Cyclic vomiting syndrome

Cyclic vomiting syndrome also called abdominal migraine or periodic vomiting, is characterized by recurrent, prolonged attacks of severe nausea, vomiting and lethargy with no apparent cause. In some, there is severe abdominal pain. Vomiting occurs at frequent intervals for hours or days (1-4 days, most commonly). Episodes can last for hours or days and alternate with symptom-free periods. Episodes are similar, meaning that they tend to start at the same time of day, last the same length of time, and occur with the same symptoms and intensity. The episodes tend to be similar to each other in symptoms and duration, and are self-limited with return of normal health between episodes.

Cyclic vomiting syndrome is an unexplained severe vomiting disorder of children and adults that was first described by Dr. S. Gee in 1882. Cyclic vomiting syndrome can begin at any age. It can persist for months, years, or decades. Episodes may recur several times a month or several times a year. Females are affected slightly more than males. The person may be prone to motion sickness, and there is often a family history of migraine. There is a high likelihood that children’s episodes will be replaced by migraine headaches during adolescence.

Cyclic vomiting syndrome is diagnosed most often in young children around 3 to 7 years old, but it can affect people of any age. Although it’s more common in children, the number of cases diagnosed in adults is increasing. The exact prevalence of cyclic vomiting syndrome is unknown; estimates range from 4 to 2,000 per 100,000 children ¹⁾. Cyclic vomiting syndrome is diagnosed less frequently in adults, although recent studies suggest that the condition may begin in adulthood as commonly as it begins in childhood.

An affected person may vomit several times per hour, potentially leading to a dangerous loss of fluids (dehydration). Additional symptoms can include unusually pale skin (pallor), abdominal pain, diarrhea, headache, fever, and an increased sensitivity to light (photophobia) or to sound (phonophobia). In most affected people, the signs and symptoms of each attack are quite similar. These attacks can be debilitating, making it difficult for an affected person to go to work or school.

Episodes of nausea, vomiting, and lethargy can occur regularly or apparently at random, or can be triggered by a variety of factors. The most common triggers are emotional excitement and infections. Other triggers can include periods without eating (fasting), temperature extremes, lack of sleep, overexertion, allergies, ingesting certain foods or alcohol, and menstruation.

If the condition is not treated, episodes usually occur four to 12 times per year. Between attacks, vomiting is absent, and nausea is either absent or much reduced. However, many affected people experience other symptoms during and between episodes, including pain, lethargy, digestive disorders such as gastroesophageal reflux and irritable bowel syndrome, and fainting spells (syncope). People with cyclic vomiting syndrome are also more likely than people without the disorder to experience depression, anxiety, and panic disorder. It is unclear whether these health conditions are directly related to nausea and vomiting.

Cyclic vomiting syndrome is often considered to be a variant of migraines, which are severe headaches often associated with pain, nausea, vomiting, and extreme sensitivity to light and sound. Cyclic vomiting syndrome is likely the same as or closely related to a condition called abdominal migraine, which is characterized by attacks of stomach pain and cramping. Attacks of nausea, vomiting, or abdominal pain in childhood may be replaced by migraine headaches as an affected person gets older. Many people with cyclic vomiting syndrome or abdominal migraine have a family history of migraines.

Most people with cyclic vomiting syndrome have normal intelligence, although some affected people have developmental delay or intellectual disability. Autism spectrum disorder, which affects communication and social interaction, have also been associated with cyclic vomiting syndrome. Additionally, muscle weakness (myopathy) and seizures are possible. People with any of these additional features are said to have cyclic vomiting syndrome plus.

Cyclic vomiting syndrome is difficult to diagnose because vomiting is a symptom of many disorders. Treatment often involves lifestyle changes to help prevent the events that can trigger vomiting episodes. Medications, including anti-nausea and migraine therapies, may help lessen symptoms.

What are the phases of cyclic vomiting syndrome?

Cyclic vomiting syndrome has four phases:

1. Prodrome phase
2. Vomiting phase
3. Recovery phase
4. Well phase

The symptoms will vary as you go through the four phases of cyclic vomiting syndrome:

• Prodrome phase. During the prodrome phase, you feel an episode coming on. Often marked by intense sweating and nausea—with or without pain in your abdomen—this phase can last from a few minutes to several hours. Your skin may look unusually pale.
• Vomiting phase. The main symptoms of this phase are severe nausea, vomiting, and retching. At the peak of this phase, you may vomit several times an hour. You may be:
  • quiet and able to respond to people around you
  • unable to move and unable to respond to people around you
  • twisting and moaning with intense pain in your abdomen

Nausea and vomiting can last from a few hours to several days.

• Recovery phase. Recovery begins when you stop vomiting and retching and you feel less nauseated. You may feel better gradually or quickly. The recovery phase ends when your nausea stops and your healthy skin color, appetite, and energy return.
• Well phase. The well phase happens between episodes. You have no symptoms during this phase.

What may trigger an episode of cyclic vomiting?

Triggers for an episode of cyclic vomiting may include:

• emotional stress
• anxiety or panic attacks, especially in adults
• infections, such as colds, flu, or chronic sinusitis
• intense excitement before events such as birthdays, holidays, vacations, and school outings, especially in children
• lack of sleep
• physical exhaustion
• allergies
• temperature extremes of hot or cold
• drinking alcohol
• menstrual periods
• motion sickness
• periods without eating (fasting)

Eating certain foods, such as chocolate, cheese, and foods with monosodium glutamate (MSG) may play a role in triggering episodes.

Cyclic vomiting syndrome causes

Although the causes of cyclic vomiting syndrome have yet to be determined, researchers have proposed several factors that may contribute to the disorder. Some possible causes include genes, digestive difficulties, nervous system problems and hormone imbalances. Many researchers believe that cyclic vomiting syndrome is a migraine-like condition ²⁾, which suggests that it is related to changes in signaling between nerve cells (neurons) in certain areas of the brain. In one study, patients with cyclic vomiting syndrome have a significantly higher prevalence of family members with migraine headaches (82% vs 14% of control subjects with a chronic vomiting pattern) ³⁾. Furthermore, 28% of patients with cyclic vomiting syndrome whose vomiting subsequently resolved developed migraine headaches. Approximately 80% of affected patients with family histories positive for migraine respond to antimigraine therapy ⁴⁾.

Many affected individuals have abnormalities of the autonomic nervous system, which controls involuntary body functions such as heart rate, blood pressure, and digestion. Based on these abnormalities, cyclic vomiting syndrome is often classified as a type of dysautonomia ⁵⁾.

Some cases of cyclic vomiting syndrome, particularly those that begin in childhood, may be related to changes in mitochondrial DNA ⁶⁾. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA known as mitochondrial DNA or mtDNA.

Several changes in mitochondrial DNA have been associated with cyclic vomiting syndrome. Some of these changes alter single DNA building blocks (nucleotides), whereas others rearrange larger segments of mitochondrial DNA. These changes likely impair the ability of mitochondria to produce energy. Researchers speculate that the impaired mitochondria may cause certain cells of the autonomic nervous system to malfunction, which could affect the digestive system. However, it remains unclear how changes in mitochondrial function could cause episodes of nausea, vomiting, and lethargy; abdominal pain; or migraines in people with this condition.

Specific bouts of vomiting may be triggered by:

• Colds, allergies or sinus problems
• Emotional stress or excitement, especially in children
• Anxiety or panic attacks, especially in adults
• Certain foods and drinks, such as alcohol, caffeine, chocolate or cheese
• Overeating, eating right before going to bed or fasting
• Hot weather
• Physical exhaustion
• Exercising too much
• Menstruation
• Motion sickness

Identifying the triggers for vomiting episodes may help with managing cyclic vomiting syndrome.

Cyclic vomiting syndrome inheritance pattern

In most cases of cyclic vomiting syndrome, affected people have no known history of the disorder in their family. However, many affected individuals have a family history of related conditions, such as migraines, irritable bowel syndrome, or depression, in their mothers and other maternal relatives. This family history suggests an inheritance pattern known as maternal inheritance or mitochondrial inheritance, which applies to genes contained in mitochondrial DNA (mtDNA). Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.

Occasionally, people with cyclic vomiting syndrome have a family history of the disorder that does not follow maternal inheritance. In these cases, the inheritance pattern is unknown.

Risk factors for cyclic vomiting syndrome

The relationship between migraines and cyclic vomiting syndrome isn’t clear. But many children with cyclic vomiting syndrome have a family history of migraines or have migraines themselves when they get older. In adults, the association between cyclic vomiting syndrome and migraine may be lower.

Chronic use of marijuana (Cannabis sativa) also has been associated with cyclic vomiting syndrome because some people use marijuana to relieve their nausea. However, chronic marijuana use can lead to a condition called cannabis hyperemesis syndrome, which typically leads to persistent vomiting without normal intervening periods. People with this syndrome often demonstrate frequent showering or bathing behavior.

Cannabis hyperemesis syndrome can be confused with cyclic vomiting syndrome. To rule out cannabis hyperemesis syndrome, you need to stop using marijuana for at least one to two weeks to see if vomiting lessens. If it doesn’t, your doctor will continue testing for cyclic vomiting syndrome.

Cyclic vomiting syndrome prevention

Many people know what triggers their cyclic vomiting episodes. Avoiding those triggers can reduce the frequency of episodes. While you may feel well between episodes, it’s very important to take medications as prescribed by your doctor.

If episodes occur more than once a month or require hospitalization, your doctor may recommend preventive medicine, such as amitriptyline, propranolol (Inderal), cyproheptadine and topiramate.

Lifestyle changes also may help, including:

• Getting adequate sleep
• For children, downplaying the importance of upcoming events because excitement can be a trigger
• Avoiding trigger foods, such as alcohol, caffeine, cheese and chocolate
• Eating small meals and low-fat snacks daily at regular times

Cyclic vomiting syndrome symptoms

Symptoms include vomiting episodes that recur in a cyclical pattern (for example every two weeks or once a month). The vomiting episodes start suddenly, typically with nausea, and progresses to vomiting later. The episodes can sometimes wake the affected person from sleep.

Episodes may begin at any time, but often start during the early morning hours. There is relentless nausea with repeated bouts of vomiting or retching. The person is pale, listless, and resists talking. They often drool or spit and have an extreme thirst. They may experience intense abdominal pain and less often headache, low-grade fever, and diarrhea. Prolonged vomiting may cause mild bleeding from irritation of the esophagus. The symptoms are frightening to the person and family, and can be life-threatening if delayed treatment leads to severe dehydration.

The episodes are “stereotypical” which means that each episode resembles previous episodes. Other symptoms can include stomach pain, diarrhea and headache. The vomiting “attacks” can become so severe that patients become dehydrated and require medical attention in the emergency room.

In between episodes, patients feel completely well. Once an episode resolves, affected children often feel normal within hours.

Many children with cyclic vomiting syndrome also have a diagnosis of migraines or a family history of migraines.

The symptoms of cyclic vomiting syndrome often begin in the morning. Signs and symptoms include:

• Three or more recurrent episodes of vomiting that start around the same time and last for a similar length of time
• Varying intervals of generally normal health without nausea between episodes
• Intense nausea and sweating before an episode starts.

Pattern or cycle of symptoms in children

A doctor will often suspect cyclic vomiting syndrome in a child when all of the following are present ⁷⁾:

• at least five episodes over any time period, or a minimum of three episodes over a 6-month period
• episodes lasting 1 hour to 10 days and happening at least 1 week apart
• episodes similar to previous ones, tending to start at the same time of day, lasting the same length of time, and happening with the same symptoms and intensity
• vomiting during episodes happening at least four times an hour for at least 1 hour
• episodes are separated by weeks to months, usually with no symptoms between episodes
• after appropriate medical evaluation, symptoms cannot be attributed to another medical condition

Pattern or cycle of symptoms in adults

A doctor will often suspect cyclic vomiting syndrome in adults when all of the following are present ⁸⁾:

• three or more separate episodes in the past year and two episodes in the past 6 months, happening at least 1 week apart
• episodes that are usually similar to previous ones, meaning that episodes tend to start at the same time of day and last the same length of time—less than 1 week
• no nausea or vomiting between episodes, but other, milder symptoms can be present between episodes
• no metabolic, gastrointestinal, central nervous system, structural, or biochemical disorders

A personal or family history of migraines supports the doctor’s diagnosis of cyclic vomiting syndrome.

Other signs and symptoms during a vomiting episode may include:

• Abdominal pain
• Diarrhea
• Dizziness
• Sensitivity to light
• Headache
• Retching or gagging.

Your doctor may diagnose cyclic vomiting syndrome even if your pattern of symptoms or your child’s pattern of symptoms do not fit the patterns described here. Talk to your doctor if your symptoms or your child’s symptoms are like the symptoms of cyclic vomiting syndrome.

Cyclic vomiting syndrome complications

Cyclic vomiting syndrome can cause these complications:

• Dehydration. Excessive vomiting causes the body to lose water quickly. Severe cases of dehydration may need to be treated in the hospital.
• Injury to the food tube. The stomach acid that comes up with the vomit can damage the tube that connects the mouth and stomach (esophagus). Sometimes the esophagus becomes so irritated it bleeds.
• Tooth decay. The acid in vomit can corrode tooth enamel.

A study that evaluated the relationship between anxiety and health-related quality of life in children and adolescents with cyclic vomiting syndrome reported that children and adolescents with cyclic vomiting syndrome appear to be at increased risk for anxiety. Anxiety symptoms are a stronger predictor of health-related quality of life than disease characteristics in children and adolescents with cyclic vomiting syndrome. Assessment and treatment of anxiety in children and adolescents with cyclic vomiting syndrome may have a positive impact on health-related quality of life ⁹⁾.

Cyclic vomiting syndrome diagnosis

Cyclic vomiting syndrome can be difficult to diagnose. There’s no specific test to confirm the diagnosis, and vomiting is a sign of many conditions such as gastroenteritis or food poisoning that must be ruled out first.

Other causes of recurrent vomiting include:

• Gastroesophageal reflux disease (GERD)
• Stomach inflammation (gastritis)
• Pancreas inflammation (pancreatitis)
• Food allergies
• Kidney/urologic abnormalities (ureteropelvic junction obstruction)
• Stomach infections
• Cannabis abuse
• Brain tumors or other lesions in the head
• Metabolic disease

The doctor will start by asking about your child’s or your medical history and conducting a physical exam. The doctor will also want to know about the pattern of symptoms that you or your child experiences.

Triggers

Patients may not know exactly what triggers their attacks; however, many patients identify specific circumstances that seem to bring on their episodes. Colds, flus and other infections, intense excitement (birthdays, holidays, vacations), emotional stress, and menstrual periods are the most frequently reported triggers. Specific foods or anesthetics may also play a role.

After that, your doctor may often perform tests to exclude other conditions and recommend:

• Imaging studies — such as endoscopy, ultrasound or a CT scan — to check for blockages in the digestive system or signs of other digestive conditions
  • Upper GI. A patient swallows a contrast agent and a series of X-rays are performed to evaluate the esophagus, stomach, and a portion of the small intestine. Used to evaluate for an abnormal twisting of the intestine called a malrotation.
  • Abdominal ultrasound. A diagnostic imaging technique which creates images from the rebound of high-frequency sound waves in the internal organs. Used to evaluate potential diseases in the kidneys or gallbladder.
  • MRI of the brain. Magnetic resonance imaging (MRI) is an imaging procedure that uses a powerful magnet, radiofrequencies, and a computer to produce detailed images of the brain. This is to exclude possible neurologic causes of vomiting.
• Motility tests to monitor the movement of food through the digestive system and to check for digestive disorders
• Blood tests. These tests may be done during an episode to evaluate for infection, inflammation of the pancreas, thyroid problems and metabolic enzyme problems.
• Upper GI endoscopy. A test that uses a small, flexible tube with a light and a camera lens at the end (endoscope) to examine the inside your upper digestive tract. Tissue samples from inside may also be taken for examination and testing.

Cyclic vomiting syndrome treatment

There’s no cure for cyclic vomiting syndrome, though many children no longer have vomiting episodes by the time they reach adulthood. For those experiencing a cyclic vomiting episode, treatment focuses on controlling the signs and symptoms. You or your child may be prescribed:

• Anti-nausea drugs
• Pain-relieving medications
• Medications that suppress stomach acid
• Antidepressants
• Anti-seizure medications

The same types of medications used for migraines can sometimes help stop or even prevent episodes of cyclic vomiting. These medications may be recommended for people whose episodes are frequent and long lasting, or for people with a family history of migraine.

IV fluids may need to be given to prevent dehydration. Treatment is individualized based on the severity and duration of symptoms as well as the presence of complications.

Taking medicines early in prodrome phase can sometimes help stop an episode from happening. Your doctor may recommend over-the-counter medicines or prescribe medicines such as:

• ondansetron (Zofran) or promethazine (Phenergan) for nausea
• sumatriptan (Imitrex) for migraines
• lorazepam (Ativan) for anxiety
• ibuprofen for pain

Your doctor may recommend over-the-counter medicines to reduce the amount of acid your stomach makes, such as:

• famotidine (Pepcid)
• ranitidine (Zantac)
• omeprazole (Prilosec)
• esomeprazole (Nexium)

During vomiting phase, you should stay in bed and sleep in a dark, quiet room. You may have to go to a hospital if your nausea and vomiting are severe or if you become severely dehydrated. Your doctor may recommend or prescribe the following for children and adults:

• medicines for:
  • nausea
  • migraines
  • anxiety
  • pain
• medicines that reduce the amount of acid your stomach makes

If you go to a hospital, your doctor may treat you with:

• intravenous (IV) fluids for dehydration
• medicines for symptoms
• IV nutrition if an episode continues for several days

During the recovery phase, you may need IV fluids for a while. Your doctor may recommend that you drink plenty of water and liquids that contain glucose and electrolytes, such as

• broths
• caffeine-free soft drinks
• fruit juices
• sports drinks
• oral rehydration solutions, such as Pedialyte

If you’ve lost your appetite, start drinking clear liquids and then move slowly to other liquids and solid foods. Your doctor may prescribe medicines to help prevent future episodes.

During the well phase, your doctor may prescribe medicines to help prevent episodes and how often and how severe they are, such as:

• amitriptyline (Elavil)
• cyproheptadine (Periactin)
• propranolol (Inderal)
• topiramate (Topamax)
• zonisamide (Zonegran)

Your doctor may also recommend coenzyme Q10, levocarnitine (L-carnitine), or riboflavin as dietary supplements to help prevent episodes.

Medical treatment

• Prophylactic therapy (daily medication to prevent episodes). Preventive medications are normally used in patients with more than a single episode of cyclic vomiting syndrome per month. The mainstays of prophylactic therapy include the following:
  • Cyproheptadine
  • Amitriptyline
  • Anticonvulsants such as topiramate, zonisamide, and levetiracetam
  • Propranolol
  • Phenobarbital
  • Erythromycin
• Abortive therapies (therapies that stop the episode once it starts). Medications used for aborting episodes include the following:
  • Ondansetron
  • Promethazine
  • Prochlorperazine
  • Triptans
• Anti-nausea medications
• Anti-anxiety medications
• Anti-migraine treatments

Agents used in migraines, such as triptans, have also been effective in aborting attacks. If abortive therapy fails, supportive combinations such as ondansetron plus lorazepam or chlorpromazine plus diphenhydramine may attenuate an attack of cyclic vomiting in progress ¹⁰⁾. In September 2011, the US Food and Drug Administration (FDA) released an alert about the possibility of an increase in cardiac arrhythmias with the use of ondansetron, and monitoring the QT interval is recommended.

Daily prophylactic pharmacotherapy may be used to prevent episodes that occur more than once a month or if they are extremely severe and disabling (eg, lasting 3 days or longer) ¹¹⁾. Most of these drugs are non-gastrointestinal medications, such as antimigraine agents, anticonvulsants, neuroleptics, and prokinetic drugs. A family history positive for migraines predicts a high response rate (80%) to antimigraine medications; therefore, these agents are a logical first choice ¹²⁾.

The guidelines formulated by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommend cyproheptadine as first-line therapy in children younger than 5 years. However, cyproheptadine can cause substantial weight gain because of an increase in appetite. Amitriptyline is the first-line choice in children older than 5 years and adolescents ¹³⁾.

Although no randomized control trials have examined medications used in cyclic vomiting syndrome, several open-label trials and retrospective studies support the use of amitriptyline as first-line therapy in patients with cyclic vomiting syndrome who are older than 5 years. In an open-label study of 41 patients with cyclic vomiting syndrome who were followed up for 1-2 years, long-term therapy with tricyclic antidepressants (TCAs) significantly reduced the frequency and duration of episodes and the number of emergency department (ED) visits and hospitalizations ¹⁴⁾.

In this study, 80% of patients reported overall improvement of symptoms; however, one third of the patients reported mild adverse effects that did not lead to discontinuance of the medication ¹⁵⁾. After 2 years of treatment, the frequency of episodes was reduced from 17.8 episodes per year to 3.3 episodes, and the duration of an episode decreased from 6.7 days to 2.2 days. The mean number of emergency department visits and hospitalizations decreased from 15 to 3.3 over 2 years.

In a study of 132 patients with cyclic vomiting syndrome who had been monitored for 4 years, 17 subjects were identified as nonresponders to tricyclic antidepressant therapy ¹⁶⁾. When compared with responders, nonresponders were significantly more likely to have a history of migraine, coexisting psychological disorders, chronic marijuana use, and reliance on narcotics for pain control between cyclic vomiting syndrome episodes. These findings favor a multidisciplinary approach to these patients, with aggressive treatment of other comorbid illnesses.

One study used an Internet-based survey completed by subjects with cyclic vomiting syndrome or their parents to assess the efficacy of coenzyme Q10 and amitriptyline ¹⁷⁾. In all, 72% of the 162 patients receiving amitriptyline and 68% of the 22 patients receiving coenzyme Q10 reported at least a 50% reduction in the frequency, duration, or severity of episodes. Patients receiving coenzyme Q10 did not have any side effects, whereas one half of the patients receiving amitriptyline reported side effects.

In this study, 21% of patients on amitriptyline discontinued treatment because of side effects ¹⁸⁾. The same author reported a high degree of efficacy with monitoring drug levels and titrating medications to achieve therapeutic levels in a small series of patients ¹⁹⁾. Combination therapy with amitriptyline and mitochondrial supplements such as coenzyme Q10 and L-carnitine were used in most of these patients.

In another study, 20 adult patients with cyclic vomiting syndrome received zonisamide (median dosage, 400 mg/day) or levetiracetam (median dosage, 1000 mg/day) because TCAs alone were unsatisfactory as maintenance medications; at least moderate clinical response was reported in 15 subjects (75%), and 4 of these (20%) reported symptomatic remission during 9.5 ± 1.8 months of follow-up ²⁰⁾. Newer antiepileptic agents appeared beneficial as maintenance medications for nearly three fourths of adults with cyclic vomiting syndrome.

In a retrospective study of 101 adults with cyclic vomiting syndrome, most patients (86%) responded to treatment with tricyclic antidepressants (TCAs), anticonvulsants (topiramate), coenzyme Q10, and L-carnitine ²¹⁾. Nonresponse to therapy was associated with coalescence of symptoms, chronic opiate use, and more severe disease as characterized by longer episodes, a greater number of ED visits in the year before presentation, the presence of disability, and noncompliance on univariate analysis. On multivariate analysis, only compliance to therapy was associated with a response.

When prophylactic medication fails or is not taken because of the sporadic and infrequent occurrence of cyclic vomiting episodes (< 1/month), abortive agents may be taken at the onset of an attack to stop progression. These antinausea and antimigraine agents are best administered nasally, rectally, or parenterally because they are not usually tolerated by mouth during intractable emesis ²²⁾.

Sumatriptan, a 5-hydroxytryptamine receptor 1B/1D (5-HT1B/1D) agonist used off label, has a 46% efficacy rate when administered either intranasally or subcutaneously. The subcutaneous route has fallen out of favor because of a severe associated burning sensation in the chest and neck ²³⁾.

Ondansetron, a 5-HT3 antagonist, is a potent and effective antiemetic that acts on the chemoreceptor zone in the brainstem. In cyclic vomiting syndrome, it is more effective at a higher dose of 0.3-0.4 mg/kg every 6 hours and is rendered more effective in severe episodes with the use of a benzodiazepine or diphenhydramine as an adjunctive antinausea agent ²⁴⁾. High-dose intravenous (IV) ondansetron has a 59% efficacy rate and ameliorates episodes more often than it aborts them.

Aprepitant, a promising tachykinin (NK-1)–receptor antagonist, is used for chemotherapy-induced emesis and could be of benefit for patients with cyclic vomiting syndrome ²⁵⁾.

When both prophylactic and abortive therapy fails, supportive care becomes an essential aspect of treatment during acute episodes.

IV glucose-containing fluids may diminish the severity of episodes by as much as 42% ²⁶⁾. Glucose may serve as the active ingredient by truncating the ketosis. However, the abdominal pain may be severe enough to necessitate the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotics once a surgical abdomen has been excluded. Caution must be exercised when narcotics are administered for moderate to severe pain and patients must be monitored to ensure that they do not become dependent on or addicted to these agents.

Chronic opiate use can result in hyperalgesia, for which various mechanisms have been proposed. Sustained morphine administration increased substance P and NK-1 receptor expression in the spinal dorsal. Morphine-induced hyperalgesia was reversed by spinal administration of NK-1 receptor antagonists in rats and mice and was observed in wild-type NK-1 receptor positive mice but not in NK-1 receptor knockout (KO) mice ²⁷⁾.

The transient receptor potential vanilloid 1 (TRPV1) receptor, a molecular sensor of noxious heat, also plays an important role in the development of hyperalgesia. Administration of morphine via subcutaneously implanted morphine pellets elicited both thermal and tactile hypersensitivity in TRPV1 wild-type mice but not in TRPV1 KO mice ²⁸⁾. Moreover, oral administration of a TRPV1 antagonist reversed both thermal and tactile hypersensitivity induced by sustained morphine administration in mice and rats.

Sedatives such as diphenhydramine, lorazepam, and chlorpromazine have been administered to permit sleep and to provide temporary respite from unrelenting nausea ²⁹⁾. The combination of lorazepam and ondansetron appears to be more effective than ondansetron alone.

Psychological treatment

Some patients may have cyclic vomiting episodes triggered by psychological stress — these can be negative stressors (such as taking a test) or positive (such as vacation or holidays). Additionally, cyclic vomiting syndrome is a stressful illness. Therefore, many patients benefit from counseling to promote relaxation.

Avoidance of triggers

In some cases of cyclic vomiting syndrome, avoiding identified dietary triggers such as chocolate, cheese, and monosodium glutamate (MSG) can prevent episodes without the use of medication ³⁰⁾. If psychological stressors trigger episodes, stress management techniques or benzodiazepine anxiolytics (eg, lorazepam or diazepam) may help to abort attacks in the early stages. However, avoiding common triggers such as car rides and infection may be impractical or impossible.

Sleep deprivation is also cited as a common trigger for patients with cyclic vomiting syndrome and proper sleep hygiene should also be emphasized. Interestingly, a 70% decrease in frequency of episodes (placebo effect) on consultation and lifestyle changes without drug therapy has been noted ³¹⁾.

Lifestyle and home remedies

Lifestyle changes can help control the signs and symptoms of cyclic vomiting syndrome. People with cyclic vomiting syndrome generally need to get adequate sleep. Once vomiting begins, it may help to stay in bed and sleep in a dark, quiet room.

When the vomiting phase has stopped, it’s very important to drink fluids, such as an oral electrolyte solution (Pedialyte) or a sports drink (Gatorade, Powerade, others) diluted with 1 ounce of water for every ounce of sports drink.

Some people may feel well enough to begin eating a normal diet soon after they stop vomiting. But if you don’t or your child doesn’t feel like eating right away, you might start with clear liquids and then gradually add solid food.

If vomiting episodes are triggered by stress or excitement, try during a symptom-free interval to find ways to reduce stress and stay calm. Eating small meals and low-fat snacks daily, instead of three large meals, also may help.

Alternative medicine

Alternative and complementary treatments may help prevent vomiting episodes, although none of these treatments has been well-studied. These treatments include:

• Coenzyme Q10 (ubiquinone), a natural substance made in the body that is available as a supplement. Coenzyme Q10 assists with the basic functions of cells.
• L-carnitine, a natural substance that is made in the body and is available as a supplement. L-carnitine helps your body turn fat into energy.
• Riboflavin (vitamin B-2), a vitamin found in certain foods and available as a supplement. Riboflavin plays a role in the body’s mitochondrial processes.

Coenzyme Q10, L-carnitine and riboflavin may work by helping your body overcome difficulty in converting food into energy (mitochondrial dysfunction). Some researchers believe mitochondrial dysfunction may be a factor causing both cyclic vomiting syndrome and migraine.

Be sure to see a doctor and have the diagnosis of cyclic vomiting syndrome confirmed before starting any supplements. Always check with your doctor before taking any supplements to be sure you or your child is taking a safe dose and that the supplement won’t adversely interact with any medications you’re taking. Some people may experience side effects from coenzyme Q10, L-carnitine and riboflavin that are similar to the symptoms of cyclic vomiting syndrome, including nausea, diarrhea and loss of appetite.

Coping and support

Because you never know when the next episode might occur, cyclic vomiting syndrome can be difficult for the whole family. Children may be especially concerned, and may worry constantly that they’ll be with other children when an episode happens.

You or your child may benefit from connecting with others who understand what it’s like to live with the uncertainty of cyclic vomiting syndrome. Families are encouraged to contact the Cyclic Vomiting Syndrome Association (http://cvsaonline.org), which is an international voluntary organization that serves the needs of cyclic vomiting syndrome patients in the United States and Canada, for ongoing support and information. Ask your doctor about support groups in your area.

Cyclic vomiting syndrome prognosis

Once patients are properly diagnosed and treated, most improve. Additionally, many children “outgrow” the diagnosis before adulthood.

Most published series indicate that cyclic vomiting syndrome lasts an average of 2.5-5.5 years, resolving in late childhood or early adolescence. A few patients continue to be symptomatic through adulthood.

As early as 1898, clinicians observed that some patients went on to develop migraine headaches. That some children with cyclic vomiting syndrome progress to abdominal migraines and then to migraine headaches implies that there may be a sequential progression of age-dependent manifestations of migraine.

A survey by Abu-Arafeh et al ³²⁾ found the mean ages of children with cyclic vomiting syndrome, abdominal migraines, and migraine headaches to be 5.3 years, 10.3 years, and 11.5 years, respectively. This finding supports the developmental progression from vomiting to abdominal pain to headache. In unpublished data, Li and Hayes determined that nearly one third of patients develop migraines after resolution of cyclic vomiting syndrome and predicted that nearly 75% would develop migraines by age 18 years.

A study of 31 patients with cyclic vomiting syndrome by Hikita et al ³³⁾ found that the median overall duration of the disorder was 66 months and that 44% of the patients seen for follow-up (25 patients) developed migraine. The authors also found abnormally high adrenocorticotropic hormone and antidiuretic hormone levels among the 25 patients for whom follow-up data were available. Significant correlations between attack duration and adrenocorticotropic hormone levels and attack duration and antidiuretic hormone levels were noted.

Although patients are well about 90% of the time, cyclic vomiting syndrome can be medically and socially disabling. More than 50% of patients require intravenous (IV) fluids, compared with less than 1% of patients with rotavirus gastroenteritis. The average annual cost of testing, treatment, and absenteeism totals $17,000. Children miss an average of 24 school days per year and often need home tutoring or, occasionally, home schooling. Additionally, because of its frequency during times of excitement, cyclic vomiting syndrome has ruined many birthdays, holidays, and vacations ³⁴⁾.

In adults, substantial morbidity is associated with cyclic vomiting syndrome, perhaps because of lack of awareness and resultant delays in diagnosis. In a study of 41 cyclic vomiting syndrome patients, Fleisher found that 32% were completely disabled at the time of diagnosis ³⁵⁾. A total of 293 procedures were performed in the 41 patients, and none were indicative of organic etiology. In addition, 17 surgical procedures, including 10 cholecystectomies, appendectomies, exploratory laparotomies, a pyloroplasty, and a hysterectomy, were performed without any therapeutic benefit.

Adults and children with cyclic vomiting syndrome also have multiple emergency department (ED) visits (see Table 1 below), and the diagnosis is often unrecognized ³⁶⁾.

Table 1. Characteristics of emergency department visits in patients with cyclic vomiting syndrome

Characteristic	Adults (n = 104)	Children (n = 147)
Number of emergency department visits per patient with cyclic vomiting syndrome (median)	15 (range, 1-200)	10 (range, 1-175)
Number of emergency department visits before diagnosis of cyclic vomiting syndrome (median)	7 (range, 1-150)	5 (range, 0-65)
Diagnosis not made in emergency department	89 (93%)	119 (93%)
Diagnosis not recognized in emergency department in patients with established diagnosis of cyclic vomiting syndrome	84 (88%)	97 (80%)
Number of different emergency departments visited (mean ± standard deviation)	4.69 ± 4.72	2.6 ± 2.42

Brain tumor in children

Brain and spinal cord tumors in children tend to be different from those in adults. In general, children diagnosed with a malignant tumor will have a better outlook than adults. They often form in different places, develop from different cell types, and may have a different treatment and prognosis (outlook). In general, brain tumors in children are very rare. Brain and spinal cord tumors are the second most common cancers in children (after leukemia). They account for about 1 out of 4 childhood cancers. More than 4,000 brain and spinal cord tumors are diagnosed each year in children and teens. The incidence rate (number of tumors per 100,000 children) has not changed much in recent years.

Malignant (fast-growing) brain and spinal cord tumors are slightly more common in boys, while non-malignant tumors are slightly more common in girls.

About 3 out of 4 children with brain tumors (all types combined) survive at least 5 years after being diagnosed. But the outlook can vary a great deal based on the type of tumor, where it is, and other factors.

Brain tumors can directly destroy brain cells. They can also indirectly damage cells by pushing on other parts of the brain. This leads to swelling and increased pressure inside the skull.

Brain tumors are not a single kind of tumor, but include several different tumor types. As a group, these are the most common solid tumors in children less than 15 years of age, and account for approximately 20% of all cancers diagnosed in this population. Other important facts about tumors that occur in the brain and spinal cord include the following:

• Tumors can arise at any age in any area of the brain and spinal cord, although some specific types of pediatric tumors tend to occur more often in certain parts of the brain.
• Brain tumors are categorized by the type of malignant cell and by the area of the brain in which they develop.
• The terms “benign” and “malignant” as usually applied to tumors are not as useful when describing CNS tumors. Because the brain and skull are located inside a fixed amount of space, even “benign” or slow-growing tumors can cause serious problems.
• Most brain tumors tend NOT to “metastasize” or spread to distant areas to other parts of the body outside the brain and/or spinal cord (central nervous system). They do, however, tend to recur locally, or spread to other areas of the central nervous system (CNS).

Tumors in any part of the brain might raise the pressure inside the skull (known as intracranial pressure). This can be caused by growth of the tumor, swelling in the brain, or blocked flow of cerebrospinal fluid. Increased pressure can lead to general symptoms such as:

• Headache. Headaches that get worse over time and worse in the morning are a common symptom of brain tumors. But not all brain tumors cause headaches, and most headaches are not caused by tumors.
• Nausea
• Vomiting
• Crossed eyes or blurred vision
• Balance problems
• Behavior changes
• Seizures. In some children, seizures are the first symptom of a brain tumor. Most seizures in children are not caused by brain tumors, but if your child has a seizure, your child’s doctor may refer you to a neurologist (a doctor who specializes in brain and nervous system problems) to make sure it wasn’t caused by a brain tumor or other serious disease.
• Drowsiness or even coma.

In the first few years of life, other symptoms of tumors can include:

• Irritability
• Loss of appetite
• Developmental delays
• Drop in intellectual and/or physical abilities
• Increased head size, sometimes along with bulging of the soft spots of the skull (fontanelles)

In the school-aged child, other general symptoms of tumors can include poor school performance, fatigue, and personality changes.

If the child can cooperate, the doctor can sometimes tell if pressure inside the skull is increased by looking inside the child’s eyes for swelling of the optic nerve (known as papilledema).

Treatment for childhood brain cancer may involve:

• Surgery
• Chemotherapy
• Radiotherapy
• Steroids may also be given to decrease the swelling caused by the tumor.

Your child may undergo some or all of these treatments, depending on their tumor type and grade, your child’s age, overall health and medical history, and your family preferences.

In many children, treatment will cause all signs of the cancer to disappear (remission). Because a child’s nervous system is still developing, some children may have a physical, behavioral or learning disability as a result of the tumor or treatment.

Brain tumor in children key points

• Brain tumors are the most common solid tumors affecting children and adolescents, with close to 5,000 children diagnosed each year.
• There are more than 120 different kinds of brain tumors, depending on where they occur and what kinds of cells they are made of. For instance, meningiomas form in the meninges, and gliomas are composed of glial cells.
• Some forms of brain cancer can be life-threatening. But not all brain tumors are life-threatening. Meningiomas, the most common brain tumor, are often benign and can be treated with surgery.
• Tumor grading is a way of ranking how serious the tumor is – how likely it is to grow and spread.
• Proper diagnosis is essential in determining the best course of treatment for you. Treatment may involve imaging, biopsy and other tests.
• Because of their location, some pediatric brain tumors and their required treatments can cause significant long-term impairment to intellectual and neurological function.

What are the differences between cancers in adults and children?

The types of cancers that develop in children are often different from the types that develop in adults. Unlike many cancers in adults, childhood cancers are not strongly linked to lifestyle or environmental risk factors. And only a small number of childhood cancers are caused by DNA (gene) changes that are passed from parents to their child.

• Treatment is often more successful: With some exceptions, childhood cancers tend to respond better to certain treatments. This might be because of differences in the cancers themselves, as well as because children often get more intense treatments. Also, children usually don’t have many of the other health problems that adults with cancer might have, which can often get worse with treatment.
• Long-term side effects are more of a concern: On the other hand, children’s bodies are still growing, and they’re more likely to have side effects from some types of treatment. For example, children (especially very young children) are more likely to be affected by radiation therapy. Many cancer treatments also can cause long-term side effects, so children who have had cancer will need careful follow-up for the rest of their lives.
• Children with cancer are treated at pediatric cancer centers: In the United States, most children and teens with cancer are treated at a center that is a member of the Children’s Oncology Group (https://childrensoncologygroup.org). All of these centers are associated with a university or children’s hospital. These centers offer the advantage of being treated by a team of specialists who know the differences between adult and childhood cancers, as well as the unique needs of children and teens with cancer and their families. This team usually includes pediatric oncologists (childhood cancer doctors), surgeons, radiation oncologists, pediatric oncology nurses, physician assistants and nurse practitioners. These centers also have psychologists, social workers, child life specialists, nutritionists, rehabilitation and physical therapists, and educators who can support and educate the entire family.

Can brain and spinal cord tumors in children be found early?

Screening is testing for a disease (such as brain or spinal cord tumors) in people without any symptoms. At this time there are no widely recommended screening tests for most children to look for brain or spinal cord tumors before they start to cause symptoms. These tumors usually are found as a result of signs or symptoms the child is having.

Most often, the outlook for children with brain or spinal cord tumors depends more on the type of tumor and its location than on how early it is detected. But as with any disease, earlier detection and treatment is likely to be helpful.

For children with certain inherited syndromes that put them at higher risk for brain tumors, such as neurofibromatosis or tuberous sclerosis, doctors often recommend frequent physical exams and other tests. These tests might find tumors when they are still small. Not all tumors related to these syndromes may need to be treated right away, but finding them early might help doctors monitor them so that they can be treated quickly if they begin to grow or cause problems.

The central nervous system

To understand brain and spinal cord tumors, it helps to know about the normal structure and function of the central nervous system (CNS), which is the medical name for the brain and spinal cord.

The brain is the center of thought, feeling, memory, speech, vision, hearing, movement, and much more. The spinal cord and special nerves in the head, called cranial nerves, carry messages between the brain and the rest of the body. These messages tell our muscles how to move, transmit information gathered by our senses, and help coordinate the functions of our internal organs.

The brain is protected by the skull. Likewise, the spinal cord is protected by the bones (vertebrae) of the spinal column.

The brain, like the spinal cord, is composed of gray and white matter. Gray matter—the seat of the neurosomas, dendrites, and synapses—forms a surface layer called the cortex over the cerebrum and cerebellum, and deeper masses called nuclei surrounded by white matter. White matter lies deep to the cortical gray matter in most of the brain, opposite from the relationship of gray and white matter in the spinal cord. As in the spinal cord, white matter is composed of tracts, or bundles of axons, which here connect one part of the brain to another and to the spinal cord.

The brain and spinal cord are surrounded and cushioned by a liquid called cerebrospinal fluid (CSF). Cerebrospinal fluid is made by the choroid plexus, which is in spaces in the brain called ventricles. The ventricles and the spaces around the brain and spinal cord are filled with CSF.

The main areas of the brain include the cerebrum, cerebellum, and brain stem. Each area has a special function.

• Cerebrum: The cerebrum is the large, outer part of the brain. It is made up of 2 hemispheres (halves) and controls reasoning, thought, emotion, and language. It is also responsible for planned (voluntary) muscle movements (throwing a ball, walking, chewing, etc.) and for taking in and interpreting sensory information such as vision, hearing, smell, touch, and pain.
• Cerebellum: The cerebellum lies under the cerebrum at the back part of the brain. It helps coordinate movement.
• Brain stem: The brain stem is the lower part of the brain that connects to the spinal cord. It has bundles of very long nerve fibers that carry signals controlling muscles and sensation or feeling between the cerebrum and the rest of the body. Special centers in the brain stem also help control breathing and the heart beating. In addition, most cranial nerves (described below) start in the brain stem. Because the brain stem is a small area that is so essential for life, it might not be possible to surgically remove tumors in this area.
  • The brain stem is divided into 3 main parts: the midbrain, pons, and medulla oblongata.
• Cranial nerves: The cranial nerves extend directly out of the base of the brain (as opposed to coming out of the spinal cord). These nerves carry signals directly between the brain and the face, eyes, tongue, mouth, and some other areas. The most common cranial nerve tumors in children are called optic gliomas, which are tumors of the optic nerve (the large nerve that runs between the brain and each eye).
• Spinal cord: The spinal cord has bundles of very long nerve fibers that carry signals that control muscles, sensation or feeling, and bladder and bowel control.

Figure 1. Human brain

Figure 2. Medial aspect of the human brain

Figure 3. Ventricles of the brain

Figure 4. Meninges of the brain

Types of cells and body tissues in the brain and spinal cord

The brain and spinal cord have many kinds of tissues and cells, which can develop into different types of tumors.

• Neurons (nerve cells): These are the cells in the brain that help determine thought, memory, emotion, speech, muscle movement, sensation, and just about everything else that the brain and spinal cord do. They do this by transmitting chemical and electric signals through their nerve fibers (axons). Axons in the brain tend to be short, while those in the spinal cord can be as long as several feet. Unlike many other types of cells that can grow and divide to repair damage from injury or disease, neurons in the brain and spinal cord largely stop dividing about a year after birth (with a few exceptions). Neurons do not usually form tumors, but they can be damaged by tumors that start nearby.
• Glial cells: Glial cells are the supporting cells of the brain. Most brain and spinal cord tumors develop from glial cells. These tumors are sometimes referred to as a group called gliomas.
  • There are 3 main types of glial cells:
    1. Astrocytes help support and nourish neurons. When the brain is injured, astrocytes form scar tissue that helps repair the damage. The main tumors starting in these cells are called astrocytomas or glioblastomas.
    2. Oligodendrocytes make myelin, a fatty substance that surrounds and insulates the nerve cell axons of the brain and spinal cord. This helps neurons send electric signals through the axons. Tumors starting in these cells are called oligodendrogliomas.
    3. Ependymal cells line the ventricles (fluid-filled areas) within the central part of the brain and form part of the pathway through which cerebrospinal fluid (CSF) flows. Tumors starting in these cells are called ependymomas.
    4. A fourth type of cell, called microglia, are the infection-fighting cells of the central nervous system. They are part of the immune system and are not truly glial cells.
• Neuroectodermal cells: These are very early forms of nervous system cells that are probably involved in brain cell development. They are found throughout the brain. The most common tumors that come from these cells are called medulloblastomas, which start in the cerebellum.
• Meninges: These are layers of tissue that cover and protect the brain and spinal cord. The meninges help form the spaces through which CSF travels. The most common tumors that start in these tissues are called meningiomas.
• Choroid plexus: The choroid plexus is the area of the brain within the ventricles that makes CSF, which nourishes and protects the brain. Tumors that start here include choroid plexus papillomas and choroid plexus carcinomas.
• Pituitary gland and hypothalamus: The pituitary is a small gland at the base of the brain. It is connected to a part of the brain called the hypothalamus. Both make hormones that help regulate the activity of several other glands in the body. For example, they control the amount of thyroid hormone made by the thyroid gland, the production and release of milk by the breasts, and the amount of male or female hormones made by the testicles or ovaries. They also make growth hormone, which stimulates body growth, and vasopressin, which regulates water balance by the kidneys. The growth of tumors in or near the pituitary or hypothalamus, as well as surgery and/or radiation therapy in this area, can affect these functions. For example, tumors starting in the pituitary gland sometimes make too much of a certain hormone, which can cause problems. On the other hand, a child may have low levels of one or more hormones after treatment and may need to take hormones to make up for this.
• Pineal gland: The pineal gland is not really part of the brain. It is a small endocrine gland that sits between the cerebral hemispheres. It makes melatonin, a hormone that regulates sleep, in response to changes in light. The most common tumors of the pineal gland are called pineoblastomas.
• Blood-brain barrier: The inner lining of the small blood vessels (capillaries) in the brain and spinal cord creates a very selective barrier between the blood and the tissues of the central nervous system. This barrier normally helps maintain the brain’s metabolic balance and keeps harmful toxins from getting into the brain. Unfortunately, it also keeps out most chemotherapy drugs that are used to kill cancer cells, which in some cases limits their usefulness.

Brain tumor in children types

Brain tumors can be categorized as:

• Primary: Primary brain tumor starts with an abnormal brain cell and grows in the brain.
• Metastatic: Metastatic (secondary) tumor starts as a cancer in another part of the body and then spreads to the brain, where it forms a new tumor.
• Benign: Slow-growing; non-cancerous. Benign tumors can still be difficult to treat if they are growing in or around certain structures of the brain.
• Malignant: Cancerous. Unlike benign tumors that tend to stay contained, malignant tumors can be very aggressive. They grow rapidly and can spread to areas near the original tumor and to other areas in the brain.
• The type of tumor (based on the type of cell it starts from): Tumors can form in almost any type of tissue or cell in the brain or spinal cord. Some tumors have a mix of cell types. Different types of tumors tend to start in certain parts of the brain or spinal cord, and tend to grow in certain ways.
• The grade of the tumor: Some types of brain and spinal cord tumors are more likely to grow into nearby tissues (and to grow quickly) than are others. Brain and spinal cord tumors are typically divided into 4 grades (using Roman numerals I to IV), based largely on how the tumor cells look under a microscope. The higher the grade, the more quickly the tumor is likely to grow:
  • Lower grade (grade 1 or 2) tumors tend to grow more slowly and are less likely to grow into (invade or infiltrate) nearby tissues.
  • Higher grade (grade 3 or 4) tumors tend to grow quickly and are more likely to grow into nearby tissues. These tumors often require more intensive treatment.
• Gene changes in the tumor cells: Even for a specific type of tumor, the changes in the genes of the tumor cells can be different. For example, many types of tumors are now divided based on whether the cells have mutations in one of the IDH genes. For a specific type of tumor, those with IDH mutations tend to have a better outlook than those without a mutation. Other gene mutations can also be important for certain types of tumors.
• The location of the tumor: Where the tumor is in the brain and spinal cord can affect what symptoms it causes, as well as which treatments might be best. Brain tumors in children are more likely to start in the lower parts of the brain, such as the cerebellum and brain stem, than they are in adults. But they can start in the upper parts of the brain as well.

Gliomas

Gliomas are not a specific type of tumor. Glioma is a general term for a group of tumors that start in glial cells (the supporting cells of the brain). A number of tumors can be considered gliomas, including:

• Astrocytomas (which include glioblastomas)
• Oligodendrogliomas
• Ependymomas
• Brain stem gliomas
• Optic gliomas

About half of all brain and spinal cord tumors in children are gliomas.

Astrocytomas

Astrocytomas are the most common type of glioma, accounting for about half of all childhood brain tumors, most often in the cerebrum (the large upper part of the brain), but also in the cerebellum (the lower back part of the brain). Astrocytomas are most common in children between the ages of 5 and 8. Astrocytomas are tumors that start in glial cells called astrocytes, a kind of glial cell that helps support and nourish nerve cells.

The grade of an astrocytoma is important. Your child’s treatment will be based on whether or not the tumor is slow-growing (low-grade, grade 1 or 2) or fast-growing (high-grade, grade 3 or 4). Most astrocytomas in children (80 percent) are low-grade. Sometimes they begin in the spine or spread there.

Some astrocytomas can spread widely throughout the brain and blend with the normal brain tissue, which can make them hard to remove by surgery. Sometimes they spread along the cerebrospinal fluid (CSF) pathways. It is very rare for them to spread outside of the brain or spinal cord.

As with other brain tumors, astrocytomas are often grouped by grade.

Low-grade (grade 1 or 2) astrocytomas tend to grow slowly and are the most common type in children. Some types, known as non-infiltrating astrocytomas, are grade I tumors that tend to grow very slowly and do not grow into (infiltrate) nearby tissues, so they often have a good prognosis.

• Pilocytic astrocytomas are grade 1 tumors that tend to grow slowly and rarely grow into nearby tissues. Pilocytic astrocytoma is often cystic (fluid-filled). They most commonly occur in the cerebellum but can also begin in the optic nerve, hypothalamus, brain stem, or other areas. Pilocytic astrocytoma slow-growing tumor is the most common brain tumor found in children. They account for nearly 1 out of 5 brain tumors in children. When this tumor develops in the cerebellum, surgical removal is often the only treatment necessary. Pilocytic astrocytomas growing in other locations may require other therapies.
• Subependymal giant cell astrocytomas (SEGAs) occur in the ventricles (spaces in the brain). They are grade 1 tumors that tend to grow slowly and rarely grow into nearby tissues. These tumors are almost always linked with an inherited condition called tuberous sclerosis.
• Diffuse astrocytomas are also slow-growing tumors, but they are grade 2 tumors that can grow into nearby tissues, which makes them hard to remove with surgery. This brain tumor infiltrates the surrounding normal brain tissue, making complete surgical removal more difficult. Though these tumors are thought of as low grade, they tend to become more aggressive and fast growing over time. A fibrillary astrocytoma may cause seizures.
• Pleomorphic xanthoastrocytomas (PXAs) are grade 2 tumors that tend to grow slowly, and most can be cured by surgery alone.
• Optic gliomas are astrocytomas that start in the optic nerves (the nerves leading from the eyes to the brain). They usually grow slowly, and are often linked with an inherited condition called neurofibromatosis type 1. These tumors are rarely fatal, but they may cause vision loss and injury to nearby brain tissue.

High-grade (grade 3 or 4) astrocytomas tend to grow quickly and spread into the surrounding normal brain tissue. These include:

• Glioblastomas or glioblastoma multiforme, which are the fastest growing type of astrocytoma (grade 4). This is the most malignant type of astrocytoma. It grows rapidly, and often causes pressure in the brain. These tumors require a combination of treatments.
• Anaplastic astrocytomas, which are grade 3. This brain tumor is malignant. Symptoms depend on the location of the tumor. These tumors require a combination of treatments.

Oligodendrogliomas

These tumors start in brain cells called oligodendrocytes (a type of glial cell that makes a fatty substance that helps nerve cells send electric signals). These are grade II tumors that tend to grow slowly, but most of them can grow into nearby brain tissue and can’t be removed completely by surgery. Oligodendrogliomas rarely spread along the CSF pathways and even less frequently spread outside the brain or spinal cord. As with astrocytomas, they can become more aggressive over time.

Only about 1% of brain tumors in children are oligodendrogliomas.

Ependymomas

About 5% of brain tumors in children are ependymomas. These tumors start in the ependymal cells that line the ventricles or central canal of the spinal cord. They can range from fairly low-grade (slow growing) tumors to grade III (fast growing) tumors, which are called anaplastic ependymomas.

Ependymomas may spread along the CSF pathways but do not spread outside the brain or spinal cord. These tumors can block the flow of CSF out of the ventricles, causing the ventricles to become very large – a condition called hydrocephalus.

Unlike astrocytomas and oligodendrogliomas, ependymomas usually do not grow into normal brain tissue. As a result, some (but not all) ependymomas can be removed and cured by surgery. But because they can spread along ependymal surfaces and CSF pathways, treating them can sometimes be difficult.

Brain stem gliomas

A brain stem glioma is any type of glioma that starts in the brain stem. This term refers to the location of the tumor, rather than the type of cell it starts in.

• A small number of brain stem gliomas occur as tumors with very distinct edges called focal brain stem gliomas.
• More often, brain stem gliomas grow diffusely throughout the brain stem (where the tumor cells are spread throughout normal tissue), rather than growing as a focal tumor (where the tumor cells are clustered together). These are referred to as diffuse midline gliomas. These tumors most often start in the pons, where they are called diffuse intrinsic pontine gliomas. These tumors can be hard to treat.

About 10% to 20% of brain tumors in children are brain stem gliomas. Nearly all of these tumors are some type of astrocytoma.

Embryonal tumors

These tumors start in early forms of nerve cells in the central nervous system. About 10% to 20% of brain tumors in children are embryonal tumors. They are more common in younger children than older ones, and are rare in adults. Embryonal tumors tend to grow quickly and often spread throughout the CSF pathways.

Medulloblastomas are the most common type of embryonal tumor. These tumors start in the cerebellum. There are several different types of medulloblastomas, based on how the tumor cells look under a microscope, and on which gene mutations the cells have. Some types of medulloblastoma tend to have a better outlook than others, and doctors are now trying to determine how this might affect treatment.

Medulloblastomas can often be treated effectively and tend to have a better outlook than embryonal tumors in other parts of the brain.

Other, less common types of embryonal tumors include:

• Medulloepithelioma
• Atypical teratoid/rhabdoid tumor (ATRT)
• Embryonal tumor with multilayered rosettes

In the past, many embryonal tumors were referred to as primitive neuroectodermal tumors (PNETs).

Pineal tumors

Some types of tumors occur in the pineal gland (a small gland in the middle of the brain). The most common (and fastest growing) of these are called pineoblastomas. These tumors can be hard to treat.

Germ cell tumors, which are described below, can also start in the pineal gland.

Craniopharyngiomas

These slow-growing tumors start above the pituitary gland but below the brain itself. They account for about 4% of brain tumors in children. These tumors may press on the pituitary gland and the hypothalamus, causing hormone problems. Because craniopharyngiomas start very close to the optic nerves, they can also cause vision problems. This makes them hard to remove completely without damaging the child’s vision or hormone balance.

Mixed glial and neuronal tumors

Certain tumors that develop in children and young adults (and rarely in older adults) have both glial and neuronal cell components. They tend to have a fairly good outlook.

• Dysembryoplastic neuroepithelial tumors (DNETs) tend to be slow growing (grade II) tumors, and most can be cured by surgery alone.
• Ganglioglioma is a type of grade I tumor that has both mature neurons and glial cells. Most can be cured by surgery alone or surgery combined with radiation therapy.

Choroid plexus tumors

These rare tumors start in the choroid plexus, the area that makes cerebrospinal fluid (CSF) within the ventricles of the brain. Most are benign (choroid plexus papillomas) and can be cured by surgery. However, some are malignant (choroid plexus carcinomas).

Schwannomas (neurilemmomas)

These tumors start in Schwann cells that surround and insulate cranial nerves and other nerves. Schwannomas are usually benign . They often form near the cerebellum on the cranial nerve responsible for hearing and balance, in which case they are called vestibular schwannomas or acoustic neuromas. They may also develop on spinal nerves, just past the point where the nerve leaves the spinal cord. When this is the case, the tumor can press on the spinal cord, causing weakness, sensory loss, and bowel and bladder problems.

These tumors are rare in children. When schwannomas are found in a child, particularly if there are tumors on both sides of the head, it often means the child has an inherited tumor syndrome such as neurofibromatosis type 2.

Other tumors that start in or near the brain

Meningiomas

These tumors begin in the meninges, the layers of tissue that surround the outer part of the brain and spinal cord. Meningiomas cause symptoms by pressing on the brain or spinal cord. They are much less common in children than in adults.

Meningiomas are almost always benign and are usually cured by surgery. Some, however, are located very close to vital structures in the brain and can’t be cured by surgery alone.

Meningiomas are often assigned a grade based on how the tumor cells look.

• Grade 1 meningiomas, which look most like normal cells, account for most meningiomas.
• Grade 2 (atypical) meningiomas look slightly more abnormal.
• Grade 3 (anaplastic or malignant) meningiomas, which look the most abnormal, make up only about 1% to 3% of meningiomas.

Higher-grade meningiomas are more likely to come back after treatment, and some grade 3 meningiomas can spread to other parts of the body.

Chordomas

These tumors start in the bone at the base of the skull or at the lower end of the spine. Chordomas don’t start in the central nervous system, but they can injure nearby parts of the brain or spinal cord by pressing on them. These tumors tend to come back if they are not removed completely, causing more damage. They usually do not spread to other organs. Chordomas are much more common in adults than in children.

Germ cell tumors

These rare tumors develop from germ cells, which normally form egg cells in women and sperm cells in men. During normal development before birth, germ cells travel to the ovaries or testicles and develop into egg or sperm cells. But sometimes some germ cells don’t move where they should and end up in abnormal locations such as the brain. They may then develop into germ cell tumors, similar to those that can form in the ovaries or testicles.

Germ cell tumors of the nervous system usually occur in children, most often in the pineal gland or above the pituitary gland. These tumors can sometimes be diagnosed without a biopsy by measuring certain chemicals in the cerebrospinal fluid (CSF) or blood.

Types of germ cell tumors include:

• Germinomas (the most common type of brain and spinal cord germ cell tumor)
• Choriocarcinomas
• Embryonal carcinomas
• Teratomas
• Yolk sac tumors (endodermal sinus tumors)

Neuroblastomas

These nerve cell tumors are the third most common cancer in children. But neuroblastomas rarely develop in the brain or spinal cord; most develop from nerve cells inside the abdomen or chest. This type of cancer is most common during early infancy.

Lymphomas

Lymphomas are cancers that start in cells called lymphocytes, which are white blood cells that are part of the immune system. Most lymphomas start in other parts of the body, but a small portion start in the central nervous system (CNS), and are called primary CNS lymphomas. These tumors are rare in children.

Pituitary tumors

Tumors that start in the pituitary gland are almost always benign (non-cancerous). But they can still cause problems if they grow large enough to press on nearby structures or if they make too much of any kind of hormone. These tumors are more common in teens than in younger children.

Cancers that spread to the brain from other parts of the body

Sometimes tumors in the brain are found to have metastasized (spread) there from some other part of the body. Tumors that start in other organs and then spread to the brain are called metastatic or secondary brain tumors (as opposed to primary brain tumors, which start in the brain). This is important because metastatic and primary brain tumors are often treated differently.

In children, metastatic brain tumors are much less common than primary brain tumors. Childhood leukemias can sometimes spread to the CSF around the brain and spinal cord. When this happens, the cancer is still considered a leukemia (the cancer cells in the CSF are leukemia cells), so doctors use treatments directed at the leukemia.

Brain tumor in children causes

The cause of primary brain tumors in kids is usually unknown. Only a few risk factors for brain tumors are known for sure.

• Genetic conditions: Children with some genetic syndromes are more likely to develop brain tumors than other children. The syndromes are neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, ataxia telangiectasia, basal cell nevus syndrome and hereditary non-polyposis colon cancer (Gorlin syndrome). Children with these genetic conditions are more at risk for brain tumors, but these account for only a small fraction of cases. These syndromes are usually recognized early in childhood, so it is most likely that you would know if your child has one of these conditions.
• Prior radiation: Children who have received radiation therapy to the head as part of treatment for an earlier cancer are at an increased risk for a new brain tumor.
• Sex Male/Female: The patterns differ depending on the type of brain tumor. Boys and girls are equally likely to develop an astrocytoma. Boys are more likely to develop a medulloblastoma, ependymoma or germ cell tumor than girls.
• Race and Ethnicity: Caucasian children are more likely than African American children to develop a medulloblastoma or ependymoma. Other types of brain tumors affect Caucasian and African American children equally. Differences in other ethnic groups have not yet been identified.

According to the current state of medical knowledge, the following exposures have NOT been shown to increase a child’s risk of developing a brain tumor:

• Electromagnetic fields such as those from power lines and electric appliances (such as televisions)
• Mother’s consumption of alcohol during pregnancy
• Mother’s smoking during pregnancy

Risk factors for brain tumors in children

A risk factor is anything that affects a person’s chance of getting a disease such as a brain or spinal cord tumor. Different types of cancer have different risk factors.

Radiation exposure

The only well-established environmental risk factor for brain tumors is radiation exposure to the head, which most often comes from the treatment of other conditions.

For example, before the risks of radiation were well known (more than 50 years ago), children with ringworm of the scalp (a fungal infection) often received low-dose radiation therapy. This was later found to increase their risk of some types of brain tumors as they got older.

Today, most radiation-induced brain tumors are caused by radiation given to the head to treat other cancers, such as leukemia. These brain tumors usually develop around 10 to 15 years after getting radiation therapy.

Radiation-induced tumors are still fairly rare, but because of the increased risk (as well as the other possible side effects), radiation therapy is only given to the head after carefully weighing the possible benefits and risks. For most patients with cancer in or near the brain, the benefits of getting radiation therapy as part of their treatment far outweigh the small risk of developing a brain tumor years later.

The possible risk from fetal or childhood exposure to imaging tests that use radiation, such as x-rays or CT scans, is not known for sure. These tests use much lower levels of radiation than those used in radiation treatments, so if there is any increase in risk, it is likely to be very small. But to be safe, most doctors recommend that pregnant women and children not get these tests unless they are absolutely needed.

Inherited and genetic conditions

Rarely, children have inherited abnormal genes from a parent that put them at increased risk for certain types of brain tumors. In other cases, these abnormal genes are not inherited but occur as a result of changes (mutations) in the gene before birth.

People with inherited tumor syndromes often have many tumors that start when they are young. Some of the better known syndromes include:

• Neurofibromatosis type 1 (von Recklinghausen disease): This is the most common syndrome linked to brain or spinal cord tumors. It is often inherited from a parent, but it can also start in some children whose parents don’t have it. Children with this syndrome may have optic gliomas or other gliomas of the brain or spinal cord, or neurofibromas (benign tumors of peripheral nerves). Changes in the NF1 gene cause this disorder.
• Neurofibromatosis type 2: This condition is less common than von Recklinghausen disease. It can also either be inherited or may start in children without a family history. It is associated with cranial or spinal nerve schwannomas, especially vestibular schwannomas (acoustic neuromas), which almost always occur on both sides of the head. It is also linked to an increased risk of meningiomas, as well as spinal cord gliomas or ependymomas. Changes in the NF2 gene are nearly always responsible for neurofibromatosis type 2.
• Tuberous sclerosis: Children with this condition may develop subependymal giant cell astrocytomas (SEGAs), as well as other benign tumors of the brain, skin, heart, kidneys, or other organs. This condition is caused by changes in either the TSC1 or the TSC2 gene.
• Von Hippel-Lindau disease: Children with this disease tend to develop blood vessel tumors (hemangioblastomas) of the cerebellum, spinal cord, or retina, as well as tumors in the kidney, pancreas, and some other parts of the body. It is caused by changes in the VHL gene.
• Li-Fraumeni syndrome: People with this syndrome have an increased risk of gliomas, as well as breast cancer, soft tissue sarcomas, leukemia, and some other types of cancer. It is caused by changes in the TP53 gene.

Other syndromes

Other inherited conditions linked with increased risks of certain types of brain and spinal cord tumors include:

• Gorlin syndrome (basal cell nevus syndrome)
• Turcot syndrome
• Cowden syndrome
• Hereditary retinoblastoma
• Rubinstein-Taybi syndrome

Some families may have genetic disorders that are not well recognized or that could even be unique to a particular family.

Factors with uncertain, controversial, or unproven effects on brain tumor risk

Cell phone use

Cell phones give off radiofrequency (RF) rays, a form of electromagnetic energy on the spectrum between FM radio waves and those used in microwave ovens, radar, and satellite stations. Cell phones do not give off ionizing radiation, the type that can cause cancer by damaging the DNA inside cells. Still, there have been concerns that the phones, whose antennae are built-in and therefore are placed close to the head when being used, might somehow raise the risk of brain tumors.

Some studies have suggested a possible increased risk of brain tumors or of vestibular schwannomas (acoustic neuromas) in adults with cell phone use, but most of the larger studies done so far have not found an increased risk, either overall or among specific types of tumors. Still, there are very few studies of long-term use (10 years or more), and cell phones haven’t been around long enough to determine the possible risks of lifetime use. The same is true of any possible higher risks in children, who are increasingly using cell phones. Cell phone technology also continues to change, and it’s not clear how this might affect any risk.

These risks are being studied, but it will likely be many years before firm conclusions can be made. In the meantime, for people concerned about the possible risks, there are ways to lower their (and their children’s) exposure, such as using the phone’s speaker or an earpiece to move the phone itself away from the head when used.

Other factors

Exposure to aspartame (a sugar substitute), exposure to electromagnetic fields from power lines and other sources, and infection with certain viruses have been suggested as possible risk factors, but most researchers agree that there is no convincing evidence to link these factors to brain tumors. Research on these and other potential risk factors continues.

Brain tumor symptoms in children

When a child develops a brain tumor, early diagnosis is essential. The skull does not have excess room for anything other than the brain. Therefore, as brain tumors develop and expand, they cause extra pressure in this closed space. This is called intracranial pressure (ICP). Increased intracranial pressure is caused by extra tissue in the brain as well as blockage of the cerebrospinal fluid (CSF) flow pathways.

Typical symptoms of brain tumors are directly related to the location of the tumor, how fast it is growing and any associated tissue swelling that occurs in conjunction with the tumor. Parents often are the first to notice symptoms related to the development of a brain tumor. Occasionally, the child’s teacher or physician may note signs and symptoms that are worrisome.

The most common signs and symptoms that could point to a potential brain tumor are:

1. Headaches: Many children with a brain tumor experience headaches before their diagnosis. Headaches that is frequent and recurrent, especially after waking up in the morning. But a lot of children have headaches, and most of them don’t have a brain tumor. One red flag to watch out for: a headache that’s worse in the morning. This is partly because pressure in the brain increases when you’re lying down, and a tumor can make that worse.
2. Nausea and vomiting: Vomiting, especially in the morning. Nausea and vomiting are two common signs of the flu or flulike illnesses. However, in rare instances, these symptoms can be due to a brain tumor causing increased pressure inside the brain. If these symptoms persist or coincide with a headache, ask your child’s pediatrician for an expert medical opinion.
3. Sleepiness: A sleepy child isn’t usually cause for alarm. But pay attention to your gut instinct. If your child is acting lethargic, or extra sleepy, for no apparent reason, call your doctor for guidance on whether further evaluation may be necessary.
4. Vision, hearing or speech changes: Depending on a brain tumor’s location, it can affect vision, hearing and speech. Eye movement problems and/or vision changes. Of course, many children have challenges in these areas that have nothing to do with a brain tumor. Still, sudden changes in how your child sees, hears or talks should be evaluated by a medical professional.
5. Personality changes: Personality changes can be a completely normal (if frustrating) part of parenting. In rare cases, they can be due to a brain tumor that’s affecting the cerebral cortex. If your child’s mood swings or personality changes seem sudden or severe, tell your child’s pediatrician.
6. Balance problems: If a tumor sits near the brain stem, it can cause balance problems. Tumbles and falls are a regular part of life for most toddlers. But severe or worsening balance problems in young children warrant a call to your doctor. If your older child suddenly has a hard time keeping his or her balance, a doctor can help you determine why.
7. Seizures: When a brain tumor sits on the surface of the brain, it can cause seizures. Many actions can trigger a seizure, including laughing. If your child is experiencing seizures, you should see a doctor. The cause may be a tumor or something else, but seizures must always be evaluated.
8. Increased head size (macroencephaly): When babies are young, their skull bones haven’t fused or grown together yet. Because these bones are still malleable, a brain tumor could cause their head to grow in abnormal ways. If you notice a bulging on one side or any other severe changes to your baby’s head shape, your doctor can help you decide whether it requires further evaluation.

Less common symptoms include:

• Changes in eating or thirst
• Growth problems
• Dizziness
• Lethargy, irritability or other behavior changes
• Deterioration in school performance
• Loss of sensation in the arms or legs
• Loss of consciousness, without history of injury
• Changes in, or loss of control of, bowel or bladder
• Hearing loss, without evidence of infection
• Coma and death, if left untreated

Brain tissue dysfunction caused by a growing tumor may cause other symptoms, depending on the tumor’s location. For example, if a brain tumor is located in the cerebellum at the back of the head, a child may have trouble with movement, walking, balance and coordination. If the tumor affects the optic pathway, which is responsible for sight, the child may experience vision changes.

Many of these symptoms can be caused by common health conditions and that’s most often the case. However, if you’re concerned about one or more of these symptoms in your child, seek out the medical opinion of a health professional you trust. Often, an MRI scan can determine whether a brain abnormality is causing the symptoms.

If your child does have a brain tumor, advanced pediatric neurosurgery can offer effective treatment and a successful recovery for the majority of young patients who have this rare condition.

Symptoms of tumors in different parts of the brain or spinal cord

Tumors in different parts of the brain or spinal cord can cause different symptoms. But these symptoms can be caused by any abnormality in that particular location – they don’t always mean a child has a brain or spinal cord tumor.

• Tumors in the parts of the cerebrum (the large, outer part of the brain) that control movement or sensation can cause weakness or numbness in a part of the body, often on just one side.
• Tumors in or near the parts of the cerebrum responsible for language can cause problems with speech or even understanding words.
• Tumors in the front part of the cerebrum can sometimes affect thinking, personality, and language skills.
• Tumors in the cerebellum (the lower, back part of the brain that controls coordination) can cause trouble walking, trouble with precise movements of hands, arms, feet, and legs, problems swallowing or synchronizing eye movements, and changes in speech rhythm.
• Tumors in the back part of the cerebrum, or around the pituitary gland, the optic nerves, or certain other cranial nerves can cause vision problems.
• Tumors in or near other cranial nerves might lead to hearing loss (in one or both ears), balance problems, weakness of some facial muscles, facial numbness or pain, or trouble swallowing.
• Spinal cord tumors may cause numbness, weakness, or lack of coordination in the arms and/or legs (usually on both sides of the body), as well as bladder or bowel problems.

Having one or more of the symptoms above does not necessarily mean that your child has a brain or spinal cord tumor. All of these symptoms can have other causes. Still, if your child has any of these symptoms, especially if they don’t go away or get worse over time, see your child’s doctor so that the cause can be found and treated, if needed.

Brain tumor in children diagnosis

A child experiencing brain tumor symptoms should be thoroughly evaluated by a pediatrician or pediatric neurologist (a doctor specializing in medical treatment of nervous system diseases) or a neurosurgeon (a surgeon specializing in nervous system diseases), or in the emergency room to find the source of the problem.

The doctor’s evaluation usually includes imaging of the brain by an MRI scan. If the scan shows a brain tumor, the next step is a neurosurgical consultation. The pediatric neurosurgeon will work with the whole family to develop the best treatment plan for the child.

Other specialists may join the child’s treatment team, such as a pediatric oncologist (childhood cancer specialist), an ophthalmologist (if the child’s tumor affects the vision pathways), an epileptologist (to address seizures), a radiation oncologist, and advanced practitioners and technologists.

Imaging tests

Your child’s doctors may order one or more imaging tests. These tests use x-rays, strong magnets, or radioactive substances to create pictures of internal organs such as the brain and spinal cord. The pictures may be looked at by doctors specializing in this field (neurosurgeons, neurologists, and neuroradiologists) as well as by your child’s primary care doctor.

Magnetic resonance imaging (MRI) and computed tomography (CT) scans are used most often for brain diseases. These scans will almost always show a brain or spinal cord tumor, if one is present. Doctors can often also get an idea about what type of tumor it might be, based on how it looks on the scan and where it is in the brain (or spinal cord).

Magnetic resonance imaging (MRI) scan

MRI scans are very good for looking at the brain and spinal cord and are considered the best way to look for tumors in these areas. MRI images are usually more detailed than those from CT scans (described below). But they don’t show the bones of the skull as well as CT scans and therefore might not show the effects of tumors on the skull.

MRI scans use radio waves and strong magnets (instead of x-rays) to make pictures, so they don’t expose the child to radiation. A contrast material called gadolinium may be injected into a vein before the scan to help see details better.

MRI scans can take a long time, and require a person to stay still for several minutes at a time. Some children might need medicine to help them relax or even go to sleep during the test.

Special types of MRI can be useful in some situations:

• Magnetic resonance angiography (MRA) and magnetic resonance venography (MRV): These special forms of MRI may be done to look at the blood vessels in the brain, especially in and around a tumor. This can be very useful before surgery to help the surgeon plan an operation.
• Magnetic resonance spectroscopy (MRS): This test can be done as part of an MRI. It measures biochemical changes in an area of the brain (which are displayed in graph-like results called spectra). By comparing the results from a tumor to that of normal brain tissue, it can sometimes help determine the type of tumor (or how quickly it is likely to grow), although a biopsy of the tumor is often still needed to get an accurate diagnosis. MRS can also be used after treatment if another test shows an area still looks abnormal. The MRS can help determine if the area is remaining tumor or if it is more likely to be scar tissue.
• Magnetic resonance perfusion (perfusion MRI): For this test, a contrast dye is injected quickly into a vein. Then this type of MRI can show the amount of blood going through different parts of the brain and tumor. Tumors often have a bigger blood supply than normal areas of the brain. A faster growing tumor may need more blood. Perfusion MRI can give doctors an idea of the best place to take a biopsy. It can also be used after treatment to help determine if an area that still looks abnormal is remaining tumor or if it is more likely to be scar tissue.
• Functional MRI (fMRI): This test looks for tiny blood flow changes in an active part of the brain. It can be used to determine what part of the brain handles a function such as speech, thought, sensation, or movement. Doctors can use this to help determine which parts of the brain to avoid when planning surgery or radiation therapy. This test is like a regular MRI, except that your child will be asked to do certain tasks (like answering simple questions or moving their fingers) to activate different areas of the brain while the scans are being done.
• Diffusion tensor imaging (DTI), also known as tractography: This is a type of MRI test that can show the major pathways (tracts) of white matter in the brain. This information can be used by surgeons to help avoid these important parts of the brain when removing tumors.

Computed tomography (CT) scan

The CT scan uses x-rays to make detailed cross-sectional images of your child’s brain and spinal cord. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body.

For brain and spinal cord tumors, CT scans are not used as often as MRI scans, which give slightly more detailed images and do not use radiation. Still, there are instances where CT scans may have advantages over MRI scans:

• CT scans take much less time than MRIs, which can be particularly helpful for children who have trouble staying still.
• CT scans provide greater detail of the bone structures near the tumor than MRIs do.
• CT angiography (CTA), described below, can provide better details of the blood vessels in and around a tumor than MRA in some cases.

Before the scan, your child may get an injection of a contrast dye through an IV (intravenous) line. This helps better outline any tumors that are present.

• CT angiography (CTA): For this test, your child gets an injection of contrast material through an IV line while he or she is in the CT scanner. The scan creates detailed images of the blood vessels in the brain, which can help doctors plan surgery.

Positron emission tomography (PET) scan

For a PET scan, a radioactive substance (usually a type of sugar known as FDG) is injected into the blood. The amount of radioactivity used is very low and passes out of the body within a day or so. Because tumor cells in the body are growing quickly, they absorb larger amounts of the sugar than most other cells. A special camera is then used to create a picture of areas of radioactivity in the body. Some children might need medicine to help them relax or even go to sleep during the test.

The PET scan image is not as detailed as a CT or MRI scan, but it can provide helpful information about whether abnormal areas seen on other tests (such as MRIs) are likely to be tumors or not. This test is more likely to be helpful for fast-growing (high-grade tumors) than for slower-growing tumors.

This test is also useful after treatment to help determine if an area that still looks abnormal on an MRI scan is remaining tumor or if it is more likely to be scar tissue. Remaining tumor might show up on the PET scan, while scar tissue will not.

Brain or spinal cord tumor biopsy

Imaging tests such as MRI and CT scans may show that a child has a brain or spinal cord tumor. But often the type of tumor can only be determined by removing a sample of it, which is called a biopsy. A biopsy may be done as a procedure on its own for diagnosis, or it may be part of surgery to treat the tumor.

In some cases (such as for many astrocytomas or brain stem gliomas), it may not be necessary or possible to biopsy the tumor safely, so the diagnosis is made based only on how the tumor looks on imaging tests.

Biopsies can be done in different ways.

Stereotactic needle biopsy

This type of biopsy may be used if imaging tests show surgery to remove the tumor might be too risky (such as with some tumors in vital areas or deep within the brain), but a sample is still needed to make a diagnosis.

Depending on the situation, the biopsy may be done with the child awake or under general anesthesia (asleep). If the child is awake, the neurosurgeon injects a local anesthetic into areas of skin over the skull to numb them. (The skull and brain itself do not feel pain.)

The biopsy itself can be done in 2 main ways:

1. The most common approach is to get an MRI or CT scan, and then use either markers (each about the size of a nickel) placed on different parts of the scalp, or facial and scalp contours, to create a map of the inside of the head. An incision (cut) is then made in the scalp, and a small hole is drilled in the skull. An image-guidance system is then used to direct a hollow needle into the tumor to remove small pieces of tissue.
2. In an approach that’s used less often, a rigid frame is attached to the head. An MRI or CT scan is used along with the frame to help the neurosurgeon guide a hollow needle into the tumor to remove small pieces of tissue. This also requires an incision in the scalp and a small hole in the skull.

The biopsy samples are then sent to a pathologist (a doctor specializing in diagnosis of diseases by lab tests). The pathologist looks at it under a microscope (and might do other lab tests) to determine if the tumor is benign or malignant (cancerous) and exactly what type of tumor it is. This helps determine the best course of treatment and the prognosis (outlook).

Craniotomy (surgical or open biopsy)

If imaging tests show the tumor can likely be treated with surgery, the neurosurgeon may not do a needle biopsy. Instead, he or she may do an operation called a craniotomy to remove all or most of the tumor. Removing most of the tumor is known as debulking.

Small samples of the tumor are looked at right away by the pathologist while the child is still in the operating room, to get a preliminary diagnosis. This can help guide treatment, including whether further surgery should be done at that time. A final diagnosis is made a within a few days in most cases.

Lab tests of biopsy specimens

Finding out which type of tumor a child has is very important in helping to determine their outlook (prognosis) and treatment options. But in recent years, doctors have found that changes in certain genes, chromosomes, or proteins within the tumor cells can also be important. Some tumors are now tested for these types of changes. For example:

• Gliomas that are found to have IDH1 or IDH2 gene mutations tend to have a better outlook than gliomas without these gene mutations.
• Oligodendrogliomas whose cells are missing parts of certain chromosomes (known as a 1p19q co-deletion) are much more likely to be helped by chemotherapy than patients whose tumors do not.
• In high-grade gliomas, MGMT promoter methylation is linked with better outcomes and a higher chance of responding to chemotherapy, so it can sometimes be used to help guide treatment.
• For medulloblastomas, changes in certain genes can be used to divide these tumors into groups, some of which have a better prognosis (outlook) than others.

Lumbar puncture (spinal tap)

This test is used mainly to look for signs of cancer in the cerebrospinal fluid (CSF), which is the liquid that bathes the brain and spinal cord. For this test, the doctor first numbs an area in the lower part of the back over the spine. The doctor may also recommend that the child be given something to make them sleep so the lumbar puncture can be done more easily and safely. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.

The fluid is looked at under a microscope for cancer cells. The CSF can also be tested for certain substances released by some germ cell tumors.

Lumbar punctures are often used if a tumor has already been diagnosed as a type that can commonly spread through the CSF (such as a medulloblastoma). Information from the spinal tap can influence treatment.

Bone marrow aspiration and biopsy

Because some tumors (especially medulloblastomas) can spread beyond the nervous system, in some instances the doctor may recommend looking at cells in your child’s bone marrow (the soft, inner part of certain bones) to see if tumor cells have spread there.

The bone marrow aspiration and biopsy are often done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, but in some cases they may be taken from other bones.

For a bone marrow aspiration, the skin over the hip and the surface of the bone is cleaned and then numbed with local anesthetic. In most cases, the child is also given other medicines to make them drowsy or even asleep during the procedure. A thin, hollow needle is then inserted into the bone, and a syringe is used to suck out (aspirate) a small amount of liquid bone marrow.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed down into the bone. Once the biopsy is done, pressure is applied to the site to help stop any bleeding.

The specimens are then looked at under a microscope for tumor cells.

Blood and urine tests

These lab tests are rarely used to diagnose brain and spinal cord tumors, but if your child has been sick for some time they may be done to check how well the liver, kidneys, and some other organs are working. This is especially important before any planned surgery.

If your child is getting chemotherapy, blood tests will be done routinely to check blood counts and to see if the treatment is affecting other parts of the body.

Brain tumor in children treatment

In putting together the most appropriate treatment plan for a child with a brain tumor, the neurosurgery team will need to know:

• Tumor location: This is determined by a brain scan, using one or more types of imaging such as CT or MRI. Because there are many vital structures in the brain, there are places a tumor can grow that are not appropriate for surgery. The neurosurgeon’s careful evaluation will determine the accessibility of the tumor and the safest approach.
• Brain tumor type: Looking at the tumor cells under a microscope can reveal the brain tumor type, and give doctors insight on how the tumor is likely to grow or spread.
• Brain tumor grade: The grade refers to how aggressive the tumor cells appear to be. The higher the grade, the more aggressive the tumor.

Treatment for childhood brain cancer may involve:

• Surgery
• Chemotherapy
• Radiotherapy
• Steroids may also be given to decrease the swelling caused by the tumor.

Your child may undergo some or all of these treatments, depending on their tumor type and grade, your child’s age, overall health and medical history, and your family preferences.

Types of doctors who help care for children with cancer:

• Pediatric oncologist: A doctor who specializes in cancers of children. (Pediatric means dealing with the health of children. Oncology means cancer.) They generally are board-certified, which means they’ve passed written national exams. They plan and direct cancer treatment. In a teaching hospital they serve as the doctor in charge. There might be more than one on the team, in which case they might rotate or switch places from one day to the next. They often work closely with physician assistants (PAs) and nurse practitioners (discussed in the next section).
• Pediatric hematologist: A doctor who specializes in diseases of the blood and blood-forming tissues of children (Hematology means blood disease.)
• Pediatric hematology or oncology fellow: A pediatrician training to become a hematologist or oncologist
• Pediatric resident: A doctor training to become a pediatrician. They are in teaching hospitals, usually spending a certain length of time on the hematology or oncology service
• Medical students: Although not yet doctors, third and fourth year medical students in teaching hospitals are assigned monthly rotations on the hematology or oncology services and help care for patients
• Radiologist: A doctor with special training in diagnosing diseases by reading x-rays and other types of imaging studies, like CT scans and MRIs
• Pediatric surgeon: A doctor who treats medical problems in children with surgery. Some surgeons specialize in different parts of the body. For example, thoracic surgeons operate on the chest.
• Neurosurgeon: A doctor who specializes in operations on the brain, spine, or other parts of the nervous system
• Neurologist: A doctor who treats problems of the nervous system
• Orthopedic surgeon: A surgeon who specializes in diseases and injuries of the bones
• Pathologist: A doctor who specializes in diagnosing and classifying diseases by lab tests, such as looking at tissue and cells under a microscope. The pathologist decides if a tumor is cancer, and, if it is, the exact cell type.
• Psychiatrist: A medical doctor who specializes in mental health and behavioral disorders. Psychiatrists prescribe medicines and can also provide counseling.
• Endocrinologist: A doctor who specializes in diseases related to the glands of the endocrine system, such as the thyroid, pancreas, and adrenal glands
• Gynecologist: A doctor who specializes in women’s health and the female reproductive system
• Anesthesiologist: A doctor who specializes in giving medicines or other agents that prevent or relieve pain, especially during surgery

Other doctors in the medical center and its clinics may play a part in caring for children and teens with cancer, depending on the diagnosis, treatment plan, or symptoms that develop during the course of treatment. All work closely with the basic cancer care team to coordinate care.

Surgery

Most brain tumors in infants and children require surgical removal, or at least a biopsy, as part of the treatment. The surgeon may recommend surgery to remove as much of the tumor as safely possible as a first step and to relieve intracranial pressure caused by the tumor. For low-grade or slow-growing tumors, surgery may be the only intervention necessary.

Follow-up care after surgery

The recovery process is different for each child. Children who received prompt diagnosis and treatment can do well after surgery.

Some pediatric patients may experience some temporary neurological deficits, such as muscle weakness. In most cases, this goes away shortly after surgery, unless there was substantial permanent damage before the child was diagnosed. Physical, occupational and speech therapy can help improve strength, function and speed of recovery.

Regular post-operative follow-up visits with the child’s neurosurgeon are also important to monitor neurological function and side effects from treatment, and to guard against recurrence of the tumor.

Radiation Therapy

This therapy focuses beams of high-energy radiation on the tumor tissue and a small amount of surrounding tissue. Some tumors, such as medulloblastoma, require additional radiation to the entire brain and spinal cord. Radiation is used very cautiously in infants and toddlers due to their growing brains.

Chemotherapy

Chemotherapy is used for many types of brain tumors including aggressive, high-grade tumors. Chemotherapy can be administered as pills (orally), intravenously (IV, by vein), injected directly into the cerebrospinal fluid, or injected directly into the cavity left after surgical removal of a brain tumor.

Brain tumor in children survival prognosis

How well a child does depends on many things, including the type of tumor. In general, about 3 out of 4 children survive at least 5 years after being diagnosed.

Long-term brain and nervous system problems may result from the tumor itself or from treatment. Children may have problems with attention, focus, or memory. They may also have problems processing information, planning, insight, or initiative or desire to do things.

Children younger than age 7, especially younger than age 3, seem to be at greatest risk of these complications.

Parents need to make sure that children receive support services at home and at school.

Brain tumor in children survival rates

Survival rates are a way to get a general idea of the outlook (prognosis) for people with a certain type of tumor. They tell you what portion of people with the same type of tumor are still alive a certain amount of time (usually 5 years) after they were diagnosed. They can’t tell you what will happen, but they may help give you a better understanding about how likely it is that treatment will be successful. Some people will want to know about survival rates, and some people won’t. If you don’t want to know, you don’t have to.

The 5-year survival rate is the percentage of children who live at least 5 years after their cancer is diagnosed. For example, a 5-year survival rate of 80% means that an estimated 80 out of 100 children who have that type of tumor are still alive 5 years after being diagnosed. Of course, many children live much longer than 5 years (and many are cured).

Survival rates don’t tell the whole story. Survival rates are often based on previous outcomes of large numbers of people who had the disease, but they can’t predict what will happen in any child’s case. There are some limitations to keep in mind:

• The numbers below are among the most current available. But to get 5-year survival rates, doctors have to look at children who were treated at least 5 years ago. As treatments improve over time, children who are now being diagnosed with brain or spinal cord tumors may have a better outlook than these statistics show.
• The outlook for children with brain or spinal cord tumors varies by the type of tumor. But many other factors can also affect a child’s outlook, such as their age, the location and size of the tumor, and how well the tumor responds to treatment. The outlook for each child is specific to their circumstances.

Your child’s doctor can tell you how the survival rates below may apply, as he or she is familiar with your child’s situation.

The numbers below come from the Central Brain Tumor Registry of the United States ¹⁾ and are based on children aged 14 or younger who were treated between 2000 and 2014. There are some important points to note about these numbers:

• These numbers are for some of the more common types of tumors. Numbers are not readily available for all types of tumors that occur in children, often because they are rare or are hard to classify.
• In some cases, the numbers include a wide range of different types of tumors that can have different outlooks. For example, the survival rate for embryonal tumors below includes medulloblastomas, as well as other types of tumors. Medulloblastomas tend to have a better outlook than the other embryonal tumors. Therefore the actual survival rate for medulloblastomas would be expected to be higher than the number below, while the number for other embryonal tumors would likely be lower.

Table 1. Survival rates for more common brain and spinal cord tumors in children

Type of Tumor	5-Year Survival Rate
Pilocytic astrocytoma	About 95%
Diffuse astrocytoma	About 80% to 85%
Anaplastic astrocytoma	About 25%
Glioblastoma	About 20%
Oligodendroglioma	About 90%
Ependymoma/anaplastic ependymoma	About 75%
Embryonal tumors (includes medulloblastoma)	About 60% to 65%

Footnotes: Remember, these survival rates are only estimates – they can’t predict what will happen with any child. We understand that these statistics can be confusing and may lead you to have more questions. Talk to your child’s doctor to better understand your specific situation.

[Source ²⁾ ]

Fibular hemimelia

Fibular hemimelia is a birth defect where part or all of the fibular bone is partially or completely missing in the lower leg. This shortens the affected leg; there is also usually a lower leg deformity or bow and an abnormally positioned foot with missing toes. Although most of the limb abnormalities are concentrated in the lower leg and foot, the entire lower extremity (from the hip to the toes) is affected by this condition. The most inclusive medical term for this condition is post-axial hypoplasia of the lower limb. This means that one side of the limb bud (post-axial side – small toe side) was altered resulting in an abnormal growth pattern.

Children with fibular hemimelia have five main problems with their affected limb:

• limb length discrepancy
• foot and ankle deformities and deficiencies
• tibial deformity
• genu valgum or “knock-knee” (where the knees angle in and touch each other when the legs are straightened)
• knee instability

Fibular hemimelia is a congenital deficiency where part or all of the fibular bone is hypoplastic, dysplastic or aplastic associated with hypoplasia and dysplasia of the tibia and hypoplasia, dysplasia and aplasia of parts of the foot ¹⁾. Fibular hemimelia signs and symptoms have a wide spectrum of pathology, ranging from mild to severe limb length discrepancy, ankle/foot deformities with or without subtalar coalition, midfoot coalitions and absent rays. Knee ligament deficiencies and knee valgus deformity as well as associated femoral hypoplasia, dysplasia and partial aplasia are common. It is therefore part of the same spectrum of deficiency as congenital femoral deficiency. These are commonly referred to as postaxial deficiencies and are distinct in their pattern from preaxial deficiencies such as tibial hemimelia.

Fibular hemimelia is a very rare disorder, occurring in only 1 in 40,000 births. To put this into perspective, the United States of America usually averages about 4,000,000 live births per year. This results in 100 live births with fibular hemimelia per year in the United States. Bilateral fibular hemimelia (affecting both legs) is even rarer.

It is currently unknown why fibular hemimelia occurs. Research has demonstrated that if the genes guiding the formation of the limb are activated in an abnormal order, fibular hemimelia can occur. Other studies have demonstrated that isolated mutations of genes in the forming limb bud can lead to fibular hemimelia. Although genetic abnormalities are linked to fibular hemimelia, the condition is not heritable. The gene mutations and abnormalities are occurring only in the forming limb and not anywhere else, and thus cannot be transmitted to the next generation.

Furthermore, the vast majority of children born with this condition have no family history of other birth defects. Neither the parents of the child with fibular hemimelia nor the child themselves have any increased risk of producing additional children with this or other birth defects.

Children with fibular hemimelia present with three major complaints:

• Limb length discrepancy
• Foot and ankle deformities
• Knee deformity

Treatment in general depends upon the function of the hip, knee, and ankle joints, as well as the current and final projected limb length differences. Most children with fibular hemimelia will have projected differences at skeletal maturity > 2 inches. In fact, many children have final differences projected at 4-6 inches. The difference in leg lengths generally increases in proportion to the child’s overall growth so the final discrepancy can be predicted. This difference will often need to be treated because differences greater than ¾” may lead to painful problems in the future.

There is very little role for nonsurgical options for the ultimate treatment of fibular hemimelia, unless the ankle joint is essentially normal and the projected final difference between the limbs is less than ¾”. However, there are nonsurgical treatments needed for every child with fibular hemimelia.

• Physical Therapy: For every child with fibular hemimelia, physical therapy will be a necessity, whether it is to learn how to walk with a prosthesis or how to keep the knee and ankle limber during a limb lengthening surgery.
• Orthoses/Shoe lifts: Many children that are undergoing limb lengthening will need orthotics and shoe lifts to help “even out” the limb lengths during childhood. Internal shoe lifts can be made up to ½”. Lifts greater than ½” need to be placed outside of shoes, because the heel will not fit in the shoe otherwise. In addition, the child may need a brace such as a supramalleolar orthosis (SMO) or ankle foot orthosis (AFO). Supramalleolar orthosis provides side to side ankle support, while ankle foot orthosis provides more support to the bottom of the ankle. Your physician will prescribe the appropriate brace for your child.
• Prosthetic Fitting: If limb ablation is ultimately the decision made to treat a child with fibular hemimelia, then they will need long term care with a prosthetist. A pediatric prosthetist with experience working with children after amputations for fibular hemimelia is certainly preferable. Prosthetic technology continues to advance at a rapid rate. In addition, as the child ages, the prosthetic options also increase over time.

In general, the goal for children with differences in limb lengths is to have two limbs nearly equal in length and as functional and pain-free as possible by the time a child is fully grown. To achieve this goal, first the surgeon must examine the child for the function of his/her surrounding joints, and then calculate an estimated final projected difference. Based on this information, the decision then is made between the orthopaedic surgeon and the family whether a limb lengthening and reconstruction is the best option for treatment, or possibly a limb ablation (amputation) and prosthetic fitting. If limb reconstruction is chosen, your doctor will walk you through a “life plan” that discusses the surgical procedures recommended for your child and the anticipated timing of these surgeries.

The decision for limb ablation (amputation) versus reconstruction is obviously a very critical decision and should be discussed thoroughly with an orthopedic surgeon familiar at managing these limb length differences. The greater the projected difference, the more limb lengthening surgeries are needed to even out the limbs. In addition, most of the time, for the limbs that are very short initially in comparison to the other side, the joint may be more abnormal, and even if they can be “fixed” they may be painful and not as functional as a prosthesis. Again, there are many, many factors that weigh in to this decision, and consultation with a limb deformity specialist is recommended.

Surgical treatment:

• Limb Ablation – If the decision is made to amputate the limb in a growing children, amputations are typically made through a joint rather than through a bone itself. The two most common types of amputations are either a Symes or a Boyd amputation through the ankle joint. Both of these preserve the heel pad to provide a good surface to interface with the prosthetic. Once the child heals from the amputation surgery, he/she is fitted for a prosthesis. The surgery can be performed as young as 10 months, right before the child is pulling up to stand. If needed, the surgery can be delayed as well, especially if a family needs more time making this decision.
• Epiphysiodesis surgery – An epiphysiodesis is a surgery performed to stop the growth on the longer leg. This procedure “shortens” the longer leg. It is typically recommended for projected limb length differences between 2-5 cm (3/4”-2”), while lengthening is preferred for differences of greater than 2”. In this procedure, the growth area (physis) is drilled surgically. The growth area is made of cartilage, and after the surgery, the cartilage hole heals itself, but fills in with bone. Once bone fills up this hole, the bone can no longer grow. Some surgeons also use metal implants as a part of this procedure. The surgeon may also recommend epiphysiodesis as part of the “life plan”. For example, if a child has a projected 12 cm limb length difference, the surgeon may recommend 2 separate 5 cm limb lengthenings, and then an epiphysiodesis of the longer (normal) side when there is 2 cm left of growth to make up the remainder of the difference.
• Limb lengthening and reconstruction
  • Ankle reconstruction: The term “superankle” was first coined by Dr. Dror Paley in 1996 ²⁾. The surgery itself has been modified from time to time since then. Nonetheless, the superankle surgery refers to an ankle joint reconstruction performed prior to limb lengthening. Prior to any limb lengthening, whether it is for fibular hemimelia, femoral deficiency, etc., the joints need to be in as normal of a position as possible. Specific to fibular hemimelia, as mentioned above, the ankle joints are often abnormal. Many have contractures that point the foot down and out (equinus and eversion), and many times there is a tarsal coalition in which two of the foot bones (typically the calcaneus and talus bones) are stuck together. During this ankle reconstruction surgery, the gastrocnemius muscle and peroneal muscles are often lengthened, the tarsal coalition is released, and many times, the bottom portion of the ankle joint is realigned (known as a supramalleolar osteotomy). Lastly, a portion of the anlage (the cartilaginous remnant of the fibula bone) is also removed. After the surgery, the surgeon may place a child in a cast and allow the ankle to heal. Some surgeons will place an external fixator on at this time and begin the limb lengthening process. There are pluses and minuses to each method, and further details should be discussed with the surgeon.
  • Limb lengthening with external fixator.
  • Limb lengthening with internal lengthening nail.

What are the chances that a second child in the same family will have fibular hemimelia?

The chances of a second child having fibular hemimelia are the same as the first, 1 in 40,000. Since this genetic mutation is spontaneous, there is no increased risk of having a second child with fibular hemimelia.

What are the chances that a person with fibular hemimelia will have a child with fibular hemimelia?

A person with fibular hemimelia has a 1 in 40,000 chance of having a child with fibular hemimelia. Since this genetic mutation is spontaneous, there is no increased risk of fibular hemimelia being passed down to the next generation.

Will a child with fibular hemimelia learn to walk?

The children do just fine and nothing stops them from walking. Even with a severe foot and ankle deformity and a leg length discrepancy, a child will adapt and walk usually between 12 and 16 months of age. If weight bearing on the affected limb appears to be placing forces across the foot and ankle that push the foot into a more deformed position, then a small lower leg brace will be used as mentioned above. This is a temporary problem due to the fact that the initial reconstruction is performed at the age of 18 to 24 months.

Fibular hemimelia types

Fibular hemimelia is not one condition where all of the cases have the same amount of deformity or deficiency or limb length discrepancy. Consequently, to facilitate the physicians’ recommendation of a specific treatment, fibular hemimelia is classified into different groups according to degree of severity. There are numerous classifications of fibular hemimelia ³⁾, with the majority of these limited by the fact that they were developed at a time when surgical reconstruction for fibular hemimelia was unsuccessful and when amputation was the primary or only consideration for treatment. Therefore, the different groups of fibular hemimelia that have been described in the various classifications do not relate to the different types of treatment that are currently available. Most are only descriptive and recommend Syme’s amputation independent of the type of fibular hemimelia. The most commonly used classification is that of Achterman and Kalamchi ⁴⁾, which describes the amount of fibular deficiency. Experts now know that the amount of leg length discrepancy and foot deformity, which are the two biggest problems in fibular hemimelia, do not correlate to the amount of fibula that is missing. The best prognostic factor is the foot deformity itself. Therefore, a classification based on the foot deficiency is needed. Birch et al. ⁵⁾ classified fibular hemimelia according to the number of rays of the foot and recommended amputation for most cases with less than three rays.

The Paley classification (Figure 2) is the first classification of fibular hemimelia to be designed with reconstructive surgery options in mind ⁶⁾. It is based on the patho-anatomy and deformities of the ankle and subtalar joint. Each Paley classification type has a different surgical treatment; it is independent of the number of rays or the leg length discrepancy. The Paley classification of fibular hemimelia describes of four types of fibular hemimelia, with type 3 subdivided into three subtypes, as shown in the following list.

• Type 1 Stable ankle. In many cases the ankle of type 1 cases appears completely normal, and the fibula is only slightly shorter at its upper end compared to the opposite side. There are some type 1 cases with complete fibular aplasia. The predicted leg length discrepancy in type 1 cases is typically less than 5 cm (2 in.).
• Type 2 Dynamic valgus. The foot in these cases can be brought into a plantigrade position. There is no fixed equino-valgus. Most feet have a ball and socket ankle joint with a fibula that is relatively short compared to the tibia at the level of the ankle joint. The normal fibula has its distal physis at the level of the ankle mortise. When the fibula is short distally, its distal physis is proximal to the ankle joint. While the foot can be placed plantigrade, the ankle naturally rolls outwards, and the patient stands and walks in valgus. There is often limited dorsiflexion in this group but not fixed equinus.
• Type 3 Fixed equino-valgus. There is a fixed deformity of equino-valgus. In some cases the foot can be brought out of equinus with obligatory valgus. When the heel is held out of valgus in a neutral position, there is a fixed equinus deformity. This fixed equino-valgus can be divided into three groups:
  • Type 3A Ankle type. The fixed equino-valgus deformity is due to a malorientation of the ankle joint (distal tibial epiphysis is in procurvatum-valgus; the LDTA is decreased and ADTA is increased).
  • Type 3B Subtalar type. There is a malunited subtalar coalition. The calcaneus is located lateral to the talus and is often tilted into valgus relative to the body of the talus. If there is a fibula with distal fibular physis and lateral malleolus present (3B1), it is proximally migrated and articulates with the dorsal surface of the calcaneus. The same deformity can occur without a fibula (3B2).
  • Type 3c Combined subtalar and ankle type. Both distal tibial malorientation and malunited subtalar coalition are present.
• Type 4 Fixed equino-varus. The only difference between type 3B or 3C and type 4 is that the subtalar coalition is malunited in varus in the former. In most of these cases the distal tibia is also maloriented into procurvatum and valgus. This type can be misdiagnosed as a clubfoot. It its resistant to Ponsetti casting as well as clubfoot releases of the subtalar joint since there is a subtalar coalition.

Figure 1. Normal leg bones

Footnote: Fibular hemimelia is a partial or total absence of the fibula, which is the smaller bone in your lower leg.

Figure 2. Fibular hemimelia types

Footnote: Paley classification of fibular hemimelia. Type 1 Stable ankle, Type 2 dynamic valgus ankle, Type 3 fixed equinovalgus ankle, 3A Ankle type, 3B subtalar type, 3C combined ankle/subtalar, Type 4 fixed equino-varus ankle. LAT = lateral.

[Source ⁷⁾ ]

Fibular hemimelia causes

The exact cause of fibular hemimelia remains unknown and in most cases it is usually not an inheritable condition, with the vast majority of children born with this condition having no family history of other birth defects ⁸⁾. A spontaneous genetic error occurs during limb bud development. This growth abnormality occurs during the development of the lower limb bud at six to eight weeks after conception. This “blue print” error resides only in the cells of the limb bud of the developing fetus, not in any reproductive cells from the parents.

The exception to this is when fibular hemimelia is associated with deficiency in more than one limb; for example, bilateral fibular hemimelia is often an autosomal dominant condition. When multiple limbs are affected by a limb deficiency, one can often assume that this was either an autosomal-dominant gene disorder (inherited or new mutation) or related to a teratologic agent (drug, radiation, virus, etc.). Fibular hemimelia has been reproduced in a mouse model ⁹⁾, suggesting that in most cases it may be a somatic gene mutation, although this theory has not been confirmed.

Fibular hemimelia signs and symptoms

Many children with fibular hemimelia can be diagnosed at birth or soon thereafter. Fibular hemimelia does not cause pain. The difference in limb lengths is often noticeable at birth.

The severity of fibular hemimelia has a wide spectrum. For example, one child may have a predicted 5-cm (2-inch) mild leg length discrepancy, five toes/rays present on the foot, and mild instability of the ankle. However, another child might have a predicted leg length discrepancy of 30 cm (12 inches), two or three toes present on the foot, and a very stiff ankle joint. Usually patients with a more severe form of fibular hemimelia will have more effects in the hip joint, femur and knee joint.

The most obvious effects of fibular hemimelia are limb shortening, lower leg deformity or bow, and an abnormally positioned foot with missing toes. However, there are other effects that are more subtle and do not become obvious until later in life. The hip joint can be mildly dysplastic, meaning the cup of the hip joint is shallow. There usually is a difference in length between the normal femur (thigh bone) and the femur with fibular hemimelia. This length difference can be minimal or very significant. The femur usually has an outward twist termed external femoral torsion, which can result in an out-toeing gait. The knee is always unstable to some degree due to the absence or abnormality of the ligaments inside the knee joint. The tibia (shin bone) is always shorter on the affected side with an abnormally positioned ankle and/or foot. The tibia usually has a dimple on the front side of the leg marking the bow or deformity in the tibia.

The fibula (small bone in the lower leg) can be partially or totally absent. When the fibula is totally absent on the X-rays, there is always a fibrous remnant connected to the calcaneus (heel bone) that is very tight and contracted. This fibrous fibula remnant is termed the fibular anlage. This tight band of tissue causes the foot and ankle to rotate outwards and the lower leg to grow in a valgus (knocked knee) direction. The foot’s toe down position (equinus contracture) is caused by the malalignment (misdirection) of the ankle joint and the tight heel cord/calf muscle. The ankle joint not only points down, but it also points in an outward direction. This is termed ankle valgus. When severe ankle valgus is present, this gives the appearance that the patient is walking on the inner side of the ankle. The ankle position is a combination of the above stated factors that are all related to fibular hemimelia.

The foot in fibular hemimelia is affected in various ways. The most obvious is the absence of the lateral digits or rays. The number of digits present on the foot with fibular hemimelia is extremely variable. Some patients retain all five digits whereas others might have only two digits. There is a common misconception among pediatric orthopedic doctors that the number of toes determines the functionality of the foot. The International Center for Limb Lengthening doctors strongly disagree with this thought process. Every foot with fibular hemimelia is unique and must be examined carefully to determine the functionality. Simply counting existing toes does not allow anyone to predict the function of the foot in the future.

Another foot anomaly that is very consistent in fibular hemimelia is called tarsal coalition. A tarsal coalition is when some of the bones in the foot are not separated. In fibular hemimelia, the ankle bone (talus) is usually fused or coalesced to the heel bone (calcaneus). This results in the absence of the subtalar joint. The subtalar joint is the joint between the ankle bone and heel bone that allows the foot and ankle to rock side to side. In response to the bones in the foot being fused, the ankle joint will form into a ball-in-socket type of configuration instead of the normal hinge joint.

The ball-in-socket configuration allows for all of the normal ankle motion of toe up (dorsiflexion) and toe down (plantar flexion) along with the side to side rocking motion (eversion and inversion) to come from one joint instead of two joints in a normal ankle. The benefit of this ball-in-socket adaptation is to allow all “normal” motion that a normal ankle would possess. The disadvantage of this ball-in-socket ankle joint is the potential for the foot and ankle to angle outward giving a “squashed” foot/ankle appearance that is termed dynamic ankle valgus. Dynamic means that the deformity appears when the joint is stressed by weight bearing. Ankle valgus means a “knocked knee” appearance of the ankle.

The tarsal coalition (fusion of the foot bones) in patients with fibular hemimelia creates a second issue besides the ball-in-socket adaptation of the ankle joint. The ankle bone (talus) and heel bone (calcaneus) are usually fused in an abnormal position with the heel bone (calcaneus) lying next to the ankle bone (talus) instead of underneath the ankle bone. This awkward position of the ankle and heel bones exaggerates the pushed out appearance of the foot.

In the same way that the number of digits varies among patients, the amount of motion at the ankle joint is also variable. Some patients will have normal motion at the ankle while others will have very stiff and immobile ankle joints. Once again, many orthopedists will decide the foot and ankle cannot be reconstructed due to stiffness in the ankle joint. The International Center for Limb Lengthening doctors strongly disagree. A foot and stiff ankle joint that has correct alignment is a very stable and functional limb. During the reconstruction and lengthening, the amount of ankle motion that a patient starts with is approximately the same ankle motion that the limb will have at the end of reconstruction.

Limb length discrepancy

Unilateral fibular hemimelia leads to a limb length discrepancy due to inhibition of growth of the tibia and foot. In addition, many children with fibular hemimelia have some femoral growth inhibition (congenital femoral deficiency). The foot grows shorter in height, contributing to limb length discrepancy, but it is also shorter in length. This limb length discrepancy follows a Shapiro 1a curve, meaning its growth inhibition remains constant ¹⁰⁾. This characteristic makes the leg length discrepancy of fibular hemimelia predictable using the Anderson and Green ¹¹⁾, Moseley straight line graph ¹²⁾, Amstutz method ¹³⁾ or Paley Multiplier method ¹⁴⁾. The limb length discrepancy with fibular hemimelia ranges from very mild to very severe inhibition, ranging at maturity of the patient from 2 to 25 cm in the absence of femoral deficiency discrepancy. With combined inhibition of the femur and tibia the magnitude of leg length discrepancy at maturity can be >30 cm.

Foot and ankle deformities

Foot and ankle deformities have been the most challenging and disabling problems with fibular hemimelia. Fibular hemimelia foot deformity has many components. At the ankle there is a dysplasia of the distal tibia and of the talus, which ranges from mild valgus of the distal tibia to severe dysplasia with flat malformed, maloriented joint surfaces. The distal tibial physis is more affected then the proximal tibial physis, with the former being often wedge shaped. The joint surface of the distal tibia ranges from a normal plafond with a 90° lateral distal tibial angle (LDTA) and 80° anterior distal tibial angle (ADTA) to a valgus plafond with an lateral distal tibial angle of <90° and an anterior distal tibial angle of >80° (procurvatum). The distal tibial articular surface is often concave in the frontal plane as part of a ball and socket ankle joint. The talus too ranges in its articular shape from normal to ball shaped in the frontal plane and from round to nearly flat in the sagittal plane. The talar neck may be very short and have little concave offset. The ankle joint function with fibular hemimelia may range from: normal range of motion, stable, no valgus instability, and no deformity; to, limited arc of motion, unstable with valgus instability, and fixed equino-valgus or varus deformity. Part of this deformity and instability is related to the fibular deficiency and part to the subtalar pathology. The fibula normally contributes to the lateral stability of the ankle. If the fibula is absent or deficient, then the ankle will sublux or roll into valgus. The subtalar joint pathology ranges from a normal subtalar joint to a subtalar joint with subtalar coalition. This subtalar coalition usually involves the posterior facet and is often malunited into equino-valgus. In a small minority of cases the subtalar coalition is malunited into equino-varus (clubfoot type). The combination of a malunited coalition, with valgus ankle joint instability, with a maloriented distal tibia produces a very significant magnitude of equino-valgus deformity of the foot and ankle. This foot malorientation is also associated with contractures of the tendo-Achilles and peroneal tendons. A further tether into equino-valgus may come from the fibular remnant referred to as the anlage. This anlage may be fibrous or both fibrous and cartilaginous. In some cases there is coalition of the cartilaginous fibular anlage to the calcaneus. Much of this patho-anatomy can be well visualized using magnetic resonance imaging (MRI).

Beyond the hindfoot deformities there can be deformities of the midfoot. When midfoot deformity is present it is most commonly abductus and rockerbottom. Most midfoot deformities are most commonly related to coalition between the cuboid and calcaneus. Talo-navicular joint coalition can also be present. One or more rays may be missing, making the foot narrower. Absence or weakness of the peroneus longus may lead to overpull of the tibialis anterior and elevation of the first metatarsal with compensatory flexion of the first metatarsophalangeal joint (dorsal bunion). A bracket first metatarsal or a bracket conjoined first and second metatarsal with hallux varus is not uncommon. Syndactaly between some or all of the toes is also common.

Tibial deformity

There is often a mild to severe diaphyseal tibial deformity of the valgus-procurvatum. A skin dimple is usually present over the apex of this angulation. The fibular anlage is located like the string of a bow in a straight line opposite the concavity of this deformity. This thick fibro-cartilagenous remnant may contribute to this angulation by tethering the growth of the tibia on its posterior-lateral side.

Knee joint deformities

The knee joint frequently has a valgus deformity. This valgus is related both to the distal femur and the proximal tibia. The lateral epiphysis of the proximal tibia may be delayed in its ossification compared to the normal opposite side.

Knee instability

Many patients with fibular hemimelia have hypoplasia or aplasia of the anterior and or posterior cruciate ligaments. The tibia may be subluxed anteriorly relative to the femur. The ligament deficiency and subluxation are often not symptomatic at a young age, but these become a bigger problem when the child becomes taller and heavier. Patients with anterior subluxation may have associated a rounded posterior aspect of the proximal tibial epiphysis. Whether this is primary (congenital) or secondary (developmental) is unclear.

Fibular hemimelia diagnosis

Fibular hemimelia diagnosis is based on clinical examination and X-rays.

Physical examination

The major physical hallmarks of fibular hemimelia are the following:

• Limb length difference
• Possible absence of toes
• Abnormal ankle joint

On exam, the lower leg (knee to ankle) is smaller and thinner. There is often a curve in the lower leg, and sometimes there is an associated dimple on the skin. Often, the thigh is shorter in length as well. The knee joint often has no anterior cruciate ligament (ACL), and so it will feel “loose” on exam. The ankle joint may be stiff, and it may be pointed down and out (everted). There may be absent toes on the outer portion of the foot as well.

Imaging studies

The orthopaedic surgeon will likely x-rays from hips to ankles. On these x-rays, the doctor can measure the difference in limb length, the crookedness of the limb, and evaluate for abnormalities in the foot and ankle. Radiographs are repeated often as the child grows. When the child is younger, it is possible that the surgeon may recommend an MRI of the ankle joint, and possibly the knee joint. There are times when bones in the foot and ankle are “stuck together” (known as a tarsal coalition), and prior to reconstructive surgery, the doctor may want a better look at this joint.

Fibular hemimelia treatment

A child with fibular hemimelia is usually seen in the first year of life. At the initial visit, X-rays are obtained to evaluate the exact configuration of the skeletal anatomy of the lower legs and to determine the amount of discrepancy in length between the legs. The current leg length discrepancy is used to predict the final leg length discrepancy at the end of growth. This predicted leg length discrepancy will allow the doctor to create a general treatment plan. Also, the predicted amount of limb lengthening required determines the number of surgical procedures required.

The initial clinical exam identifies the shape and position of the foot and ankle. Also, the range of motion and stability of the hip, knee, and ankle are assessed and recorded. At this point, our doctors look for a concurrent congenital femoral deficiency and hip joint shallowing in the X-rays. Clinically, the doctor assesses the stability and range of motion of the knee joint. The hip and knee are always involved to some degree in fibular hemimelia. If the involvement of the hip and knee are severe, then the overall reconstruction plan is altered by planning either concurrent hip/knee reconstruction or sequential reconstruction. Most commonly, the significantly involved hip and knee would be addressed first between the ages of 18 and 24 months (superhip/superknee procedure). The ankle reconstruction (superankle procedure) would then occur 6 to 12 months after the hip and knee reconstruction.

However, if the growth abnormality is mainly concentrated in the lower leg, then the superankle reconstruction is performed with or without concurrent lengthening between the ages of 18 and 24 months. The decision to lengthen during the first reconstructive surgery is determined by the amount of ankle motion present. If the ankle is inherently stiff, then a 5-cm (2-inch) lengthening is performed at the same surgical setting. If the ankle is very mobile, then the initial surgery concentrates on positioning the foot and ankle in a stable or corrected position while concurrently correcting the bowing in the lower leg. The mobile ankle scenario falls into a two-stage initial reconstruction plan. The second stage would be a 5-cm (2-inch) lengthening of the tibia performed 6 to 12 months after the first surgery.

The number of subsequent lengthenings is determined by the overall predicted lengthening goal. The subsequent lengthenings are performed at intervals of 4 to 6 years apart for a total of up to three lengthenings for the most severe types of fibular hemimelia. The first lengthening usually achieves a 5-cm (2-inch) gain in length. Subsequent lengthenings can achieve between 5 and 7 cm (2 and 2.8 inches) of length.

Fibular hemimelia treatment goals

The goals of treatment are to create a lower limb with a stable hip, knee, and ankle that is equal in length to the opposite lower limb. Also, all deformities in the lower limb are corrected during the treatment. The crucial goal in fibular hemimelia is the reconstruction of the ankle and foot. Contrary to many doctors’ opinions, the amount of length needed does not predict the success of reconstruction or the ability to reconstruct the lower limb. In the same way, the number of toes or rays of the foot does not predict the success of reconstruction or the function of the foot. Most doctors use predicted leg length discrepancy or the number toes on the foot to determine whether to recommend amputation/ablation and prosthetic reconstruction.

The success of reconstruction treatment is mainly determined by the foot and ankle reconstruction. This success is not determined by the final ankle motion. The goal is to create a stable ankle and a foot in a normal plantigrade (foot flat) position. This is achieved with the superankle procedure that will be explained in great detail below.

The amount of final ankle motion is usually predetermined by the amount of motion already present at the ankle joint. If a patient presents with a very stiff and deformed ankle, the goal is to achieve a plantigrade (foot flat) position with a stiff but stable ankle. The misconception is that a stiff ankle is a failure of reconstruction. Our doctors believe a stiff ankle in the correct position is a good and functional base for a plantigrade foot. On the other hand, if a patient has a deformed foot and ankle with good ankle motion, then the reconstruction is tailored to both correct the foot and ankle position and maintain ankle motion.

The amount of leg length difference predicted to occur by the end of growth does not determine whether a successful reconstruction is possible. There is no set limit to the amount of overall lengthening that can be performed. However, the overall lengthening amount does determine how many treatments or lengthenings will be needed to equalize the leg lengths at maturity. For example, if a 2-year-old boy has a 2.5-cm (1-in) leg length discrepancy, his predicted leg length difference at maturity would be 6.5 cm (2.6 in) when calculated using the Multiplier method. This amount of lengthening could be accomplished with one lengthening procedure.

On the other hand, a 2-year-old girl with a 6-cm (2.4-in) leg length difference would be predicted to have a 14.5 cm (5.7 in) difference at the end of growth. This amount of difference would require two lengthenings to accomplish about 11 to 12 cm (4.3 to 4.7 in) of lengthening. The remaining 2.5 to 3.5 cm ( .98 in to 1.4 in) of difference can be corrected either by a smaller third lengthening at the end of growth or a slowing down procedure of the long leg at the age of about 10 or 11 years. These types of strategies will be explained in greater detail below. The main point is that the total amount of length needed does not determine whether the reconstruction can be performed, but rather how many interventions or surgical procedures will be needed to successfully complete the reconstruction.

Step 1: Predicting leg length discrepancy and determining the number of lengthening surgeries

The first step is measuring the leg length discrepancy using standing radiographs of both lower limbs, with the short leg on a lift of known amount ¹⁵⁾. The total leg length discrepancy at skeletal maturity and the separate bone segment (femur, tibia, foot height) discrepancy at maturity can be calculated using the multiplier method for limb length discrepancy prediction ¹⁶⁾. The multiplier method has been validated for accuracy in the prediction of congenital limb length discrepancy, including for fibular hemimelia ¹⁷⁾. It is now possible to do this method using smart phone apps [App name 1: Paley Growth (OS1 only); App name 2: Multiplier (OS1 and Android)]. Once the predicted leg length discrepancy at skeletal maturity has been calculated, a determination of the number of limb length equalization procedures can be made.

Under the age of 4 years it is safe to lengthen up to 5.0 cm in the tibia; lengthening of >5.0 cm can lead to growth inhibition in young children ¹⁸⁾. Subsequent lengthenings can be performed preferably 4 years apart as needed to achieve limb length equalization at skeletal maturity. Lengthenings performed at an older age can safely achieve up to 8.0 cm of lengthening. Therefore, one lengthening by age 4 years and one at age 8 years would achieve a total lengthening of 13 cm (5.1 in.) (5.0 + 8.0 cm). One lengthening by age 4 years plus one at age 8 years and one at age 12 years would achieve a total lengthening of 21.0 cm (8.25 in.) (5 + 8 + 8 cm). If additional equalization is required, epiphysiodesis of the opposite proximal tibia can always be considered. Epiphysiodesis is typically performed at a specific age calculated with the Paley multiplier formulae and is usually recommended for up to 5.0 cm (2 in.) of limb length equalization. Therefore, leg length equalization up to 26.0 cm can be achieved with three lengthenings (21 cm) plus an epiphysiodesis (5 cm). This treatment covers the majority of cases with limb length discrepancy due to fibular hemimelia. It is rarely ever necessary to perform more than three limb lengthening procedures to equalize limb length discrepancy due to fibular hemimelia. Cases that present with discrepancies of >25.0 cm usually have some shortening in the femur, which can be treated with simultaneous or independent lengthening of the femur. This treatment will be discussed in a later section.

Step 2: Determining the Paley type of fibular hemimelia

The next step is to determine what type of fibular hemimelia. This distinction is based on the clinical exam of the foot and ankle. If there is a fixed equino-valgus foot deformity, then it is a type 3. If there is a fixed equino-varus foot deformity, then it is a type 4. If the ankle deformity is dynamic, then it is a type 2. If there is no foot deformity and the ankle is stable, then it is a type 1. An MRI is not necessary to separate types 1, 2, 3 and 4; these types can be determined by clinical and radiographic examination. An MRI examination is helpful to subdivide the type 3 fibular hemimelia into subtypes a, b or c.

Step 3: Determining the surgical procedures required

Most patients with type 1 fibular hemimelia do not require any foot surgery; rather, treatment consists of lengthening the tibia and fibula with no foot fixation. Most patients with type 2 will require a shortening realignment osteotomy of the distal tibia to correct the valgus and stabilize the ankle. This procedure is called the SHORDT (‘shortening osteotomy realignment distal tibia’). After the SHORDT, or together with it, the tibia can be lengthened. Types 3 and 4 fibular hemimelia have fixed deformities that should be corrected early to allow the patient to walk with the foot in a plantigrade position and to be able to wear a shoe properly. It is important to correct this deformity either before or at the time of tibial lengthening. Types 3 and 4 are treated by the SUPERankle procedures (SUPER being an acronym for ‘systematic utilitarian procedure for extremity reconstruction’). The SUPERankle procedure was developed in 1996 and is the most successful method to correct the fixed equino-valgus of type 3 fibular hemimelia or fixed equinovarus of type 4 fibular hemimelia. The SUPERankle procedure is performed in children between 18 and 24 months of age. It involves supramalleolar and/or subtalar osteotomies combined with soft tissue release. The SUPERankle procedure has been performed in infants as young as 12 months and in adults as old as 32 years. Lengthening is often combined with the SUPERankle procedure.

Fibular hemimelia surgery treatment plan

The surgical treatment of fibular hemimelia is designed to address all of the deformities and deficiencies and length discrepancies. The first step in this process is to create a reconstructive life plan individualized for each patient. This involves evaluating all of the surgical deformities and deficiencies, predicting the limb length discrepancy at maturity and then coming up with a surgical plan to correct these in the fewest number of surgeries spread out as much as possible throughout the child’s growing years, so that by skeletal maturity the child has achieved equal leg length, a functional plantigrade foot, excellent alignment of the hip, knee and ankle and, as needed, a stable knee joint.

Example of reconstructive life plan:

A 6-month-old boy presents with Paley type 3c fibular hemimelia. The predicted leg length discrepancy at skeletal maturity is 25.0 cm, with a valgus knee deformity. The reconstructive life plan would consist of:

• Surgery #1, at age 18 months, SUPERankle procedure combined with lengthening of 5.0 cm combined with hemiepiphysiodesis of distal femur for valgus knee correction.
• Surgery #2, at age 8 years, lengthening 7.0 cm of tibia.
• Surgery #3, at age 12 years, lengthening 8.0 cm of tibia.
• Surgery #4, at age 13 years, epiphysiodesis of the proximal tibia on long leg for correction of 5.0 cm.

Total leg length equalization = 25 cm (10 in.).

By the end of the first consultation, the child’s parents have a roadmap for the future. This allows them to plan their lives around the surgical plan. They leave the first consultation with a good understanding of what it would take to successfully correct the foot and leg deformities and to equalize the limb length discrepancy by skeletal maturity. They can now make an educated decision whether to reconstruct and lengthen their child’s leg with fibular hemimelia.

Fibular hemimelia surgery

After the initial reconstruction of the foot and ankle, the lower extremity can grow into a valgus or “knocked knee” position due to abnormal growth at the growth plates of either the distal femur or proximal tibia. The “knocked knee” deformity has also been attributed to the shape of the distal femur or the tethering effect of the residual scar-like fibular band called the fibular anlage. Genu valgus (knocked knee position) is treated by either straightening the bone during lengthening or performing hemiepiphysiodesis (guided growth).

Hemiepiphysiodesis is a minor procedure in which a small, two-hole plate is placed over the growth plate on the inner or outer aspect of the leg. This plate acts like a bracket that slows the growth on one side of the growth plate causing the bone to gradually turn as it grows, which corrects the knocked knee deformity. Once the leg is straight, the plate is removed. The placement and removal of the plate is performed during a brief outpatient surgery. The plates are called eight-Plates (manufactured by Orthofix) or Peanut Plates (manufactured by Biomet).

Sometimes a smaller revision surgery is required after the superankle procedure. After the initial correction of the foot and ankle with the superankle procedure, the foot can shift back to the outside. This gives the appearance that the child is walking on the inside ankle bone. This phenomenon can occur soon after the superankle procedure when the child returns to weight bearing or can gradually appear as the child continues to grow.

If the foot and ankle deformity returns soon after the initial procedure, then it means that an underlying bony deformity was either under corrected or unmasked by the initial reconstruction. One must understand that the initial reconstruction is a very complex set of procedures that is unique for each child. The deformity related to fibular hemimelia is the combination of contracted soft tissues and abnormally formed joints of the ankle and foot. This unmasked deformity or recurrence can be addressed with a smaller revision surgery that requires a bone cut in the distal tibia or between the ankle and heel bone. Usually the leg is placed in a cast for 4 to 6 weeks for healing and then the child is allowed to wear regular shoes.

The foot and ankle deformity that gradually reappears during early adolescence is addressed at the final surgical intervention, which usually occurs between 12 and 16 years of age. At the final surgical reconstruction, the leg lengths are equalized with a lengthening from the upper tibia and the foot/ankle position is corrected from the lower tibia. After this reconstruction is complete, the correction is permanent since the patient is nearing the end of growth.

SHortening Osteotomy Realignment Distal Tibia

The SHORDT (SHortening Osteotomy Realignment Distal Tibia) is a procedure that was designed by the Paley in 2014 to treat valgus instability of the ankle in patients who have a hypoplastic fibula where the growth plate of the distal fibula is present. Although in theory it could also be used for a fibular remnant lacking a distal physis, such remnants are so hypoplastic and have little growth potential that they are not likely to remain a successful lateral buttress.

Superankle procedure

The SUPERankle procedure achieves a stable plantigrade foot and ankle. It can be combined with lengthening, but it does not have to be. The superankle procedure is a comprehensive release of the contracted soft tissues around the ankle joint with osteotomies (bone cuts) of the distal tibia (shin bone) and hindfoot (ankle and heel bones). This procedure aligns the foot and ankle and corrects the patient’s downward and outward foot deformity (equinovalgus deformity). During the comprehensive release, the fibrous fibular anlage is removed and used to reinforce the lengthened heel cord (Achilles tendon). At the same time, a tibial osteotomy is performed to straighten the lower leg bow. The skin dimple marks the apex of the tibial deformity. This tibial bone cut can be used to straighten and lengthen the tibia. If the ankle joint is very stiff before reconstruction, then the superankle alignment procedure can be performed at the same time as the lengthening procedure. However, as stated above, if the ankle is very mobile, then the superankle alignment procedure is performed first followed by the first lengthening 6 to 12 months later. During this first lengthening procedure, the tibia can gain up to 5 cm (2 inches) of length.

If the superankle alignment procedure is performed without lengthening, then a simple Ilizarov external fixator is applied to support the leg. This type of external frame does not require adjustments. The patient is able to weight bear/walk in this frame.

If the patient is undergoing the superankle procedure and simultaneous lengthening, then a Taylor spatial frame external fixator is used. During the lengthening phase, the patient or parent adjusts the Taylor spatial frame on a daily basis to perform the lengthening and deformity correction. The patient is seen every two weeks for clinical and X-ray examination.

The lengthening phase of the treatment lasts for 2 to 3 months. Once lengthening is completed, the adjustments stop and the consolidation or healing phase begins. The consolidation phase can last from 2 to 4 months. During this period, the Taylor spatial frame remains on the leg and the patient will have X-rays taken once a month. These X-rays can be taken at another center that is close to the patient’s home and then sent to your child’s orthopedic surgeon for review. Clinic visits at your child’s orthopedic surgeon are not necessary during the consolidation phase unless issues or problems arise.

Tibial lengthening protocol for fibular hemimelia

One or multiple tibial lengthenings are performed when patients have a significant leg length discrepancy. The amount of length gained during a single lengthening treatment usually is determined by the new bone quality or the motion of the joints above and below the lengthening site. The amount of lengthening will be limited if the patient has poor bone quality or stiffness of the joints with loss of motion. In patients younger than 6 years of age, the maximum length gain during a single lengthening is 5 cm (2 inches). The total amount of lengthening in a younger patient is limited to avoid extreme pressures on the growth plate that can cause premature closure of the growth plate and loss of potential or “natural” growth. Older patients can acquire more length in a single treatment–between 6 and 7 cm (2.4 and 2.8 inches).

Typically the patient is admitted to the hospital on the day of the lengthening surgery. A circular external fixator is placed on the lower leg and foot of the involved side. The type of external fixator used is usually the Taylor spatial frame. The foot is always included in the Taylor spatial frame to ensure stability of the ankle joint and to maintain the proper foot position during the distraction or lengthening phase of the treatment. The tibia is cut through one or two small incisions after the Taylor spatial frame is applied. The Taylor spatial frame stabilizes the cut bones and maintains alignment.

After surgery, the patient stays at the hospital mainly for pain control and close observation of the neurovascular status of the limb. The initial hospitalization is usually 3 to 4 days. Postoperative pain is controlled with epidural analgesia or intravenous pain medicine on a patient control anesthesia machine. During the first two days of hospitalization, the pain control is fine-tuned with adjustments in the medicine doses or route of delivery. Also, physical therapy begins with gentle range of motion of the hip and knee on the involved side. The main goal in this part of physical therapy is to maintain full knee extension and to gain knee flexion to at least 60 to 70 degrees. The second aspect of physical therapy is to begin mobilization of the patient. This starts with simply sitting on the side of the bed or transferring to a wheelchair. Mobilization increases over the hospital stay to standing transfers and ambulation with a walker or crutches.

To lengthen the leg and correct the deformity, the patient or parent must adjust the struts on the Taylor spatial frame daily. During the first 5 to 7 days after surgery, the Taylor spatial frame is not adjusted. This allows the bone to recover from surgery and to begin to heal. After bone healing starts, the external fixator is activated and the lengthening begins. The lengthening phase is the time period where the Taylor spatial frame is adjusted on a daily basis by pulling the bone ends slowly apart (between 0.5 mm and 1.0 mm / day), which results in new bone formation. The lengthening phase lasts for 2 to 3 months depending on the amount of length needed. Younger patients can put as much weight as they can tolerate on the operated leg. Older and larger patients are kept at 50% weight bearing during the lengthening phase.

During hospitalization, a social worker will meet with the family to assess needs and to make arrangements for equipment (walker, wheelchair, etc.). Special transportation is also assessed, but it is rarely needed with the lower leg external fixation devices used for fibular hemimelia.

The patient is discharged from the hospital after the pain medications have been converted to an oral type of medicine, the patient is tolerating a regular diet with good fluid intake, the family is comfortable with the specifics on daily care, and the patient clears the physical therapy assessment for safe mobilization and transfers. Upon discharge, the family will have a supply of pain medication, antibiotic medication and dressings. Contact numbers are provided to the family so that questions and concerns can be addressed at any hour on any day during treatment.

After discharge, the outpatient portion of the lengthening treatment begins. This includes outpatient physical therapy five days a week as well as a daily exercise and stretching program. Doctor visits are necessary every two weeks. These follow-up examinations prevent major complications during this critical lengthening phase. Each doctor office visit includes a clinical examination of the operative leg and frame along with obtaining X-rays to assess the bone’s position and length gained.

Once the lengthening phase is completed and the planned length gained, the consolidation or healing phase begins. During the consolidation phase, the Taylor spatial frame remains in place for stabilization but no further adjustments are performed. Usually the consolidation phase lasts from 2 to 4 months, and patients are allowed full weight bearing. Office visits are not necessary unless concerns or problems arise. Instead, X-rays are obtained every 4 to 6 weeks in the patient’s hometown and mailed to the your orthopedic surgeon for review. The family is contacted via phone or e-mail to discuss the results of the X-rays and the next step in treatment.

Once the monthly X-rays show adequate healing of the new bone, the Taylor spatial frame removal surgery is scheduled in the following 2 to 4 weeks. This surgery is usually an outpatient procedure. After the Taylor spatial frame is removed, a long leg cast is applied for 2 to 4 weeks. The post-removal cast protects both the new bone and the pin holes left by the external fixator from potential fracture. Usually the patient may bear full weight in the post-removal cast.

Four weeks after Taylor spatial frame removal, the cast is removed and converted to a cast brace that may be weaned according to the patient’s comfort. A gradual return to normal activities occurs over the following 2 to 3 months. Contact sports to include soccer, lacrosse and football may be resumed 6 to 8 months after frame removal. Subsequent visits become annual or biannual office visits to assess the growth of the limb, recurrent limb length discrepancy, recurrent alignment problems and future reconstructive plans.

How is the lower extremity deformity and leg length discrepancy managed before or between reconstructive treatments?

Before a lengthening or reconstruction is performed, the lower leg is treated with a brace and a shoe lift as needed. The brace provides stability and the shoe lift provides additional length to the short limb. Usually a lower leg brace or ankle foot orthosis (AFO) is not needed before the initial reconstruction. Sometimes, if the deformity is severe and the leg length discrepancy is greater than 5 cm (2 inches), an AFO is used to support the foot and ankle during shoe wear.

Typically, after the initial foot and ankle reconstruction is completed, an AFO and appropriate-sized shoe lift are used temporarily. These assistive devices are usually discontinued after the patient has completed the postoperative physical therapy and the bone has healed.

In between surgical interventions, most legs do not require bracing. If a patient’s leg length discrepancy is greater than 2 cm (3/4 of an inch), a shoe lift can be used. Again, an AFO is used if the residual leg length discrepancy is greater than 5 cm (2 inches).

What is the strategy for shoe lifts?

A shoe lift is used if the leg length discrepancy is greater than 2 cm (3/4 of an inch). The height of the lift is calculated by subtracting 1 cm (0.4-in) from the total discrepancy. For example, a patient with a 4.5-cm (1.8-in) leg length discrepancy would be given a 3.5-cm (1.4-in) shoe lift. This 1-cm (0.4-in) reduction prevents the lift from catching on the ground and allows for better clearance of the shorter leg during walking.

The reason a patient with a leg length discrepancy wears a shoe lift is to prevent an ankle contracture in a toe-down direction (equinus contracture) and to improve the patient’s gait and posture. If a person with a significant leg length discrepancy does not use a shoe lift over the period of 15 to 20 years, the person may experience long-term problems such as back pain, hip joint arthritis, and knee joint arthritis. However, these long-term problems will not occur in young children if they do not use their lifts all the time.

Doctors usually recommend that the child use the prescribed lift on their most commonly used shoe (school shoe or play shoe). It is perfectly fine for a child to spend a significant portion of the day barefooted or not using a shoe lift as long as the ankle range of motion remains normal. This is especially important during the summer when sandals and flip flops are very popular.

The lift should not be used on athletic shoes or cleats. For sports, the feet should be shoed individually and the smaller fibular hemimelia foot should have a smaller, well-fitted shoe with no lift.

Knee valgus deformity

Most cases of fibular hemimelia have associated genu valgum secondary to distal femoral and/or proximal tibial valgus deformity. Valgus of the knee can negatively impact the foot. Since there is usually no subtalar joint present, genu valgum cannot be compensated by a mobile subtalar joint. The ankle joint, which is often a ball and socket type, cannot compensate for a valgus knee since it usually has valgus instability (dynamic valgus). After foot deformity correction with the SHORDT or SUPERankle procedure, knee valgus can promote recurrent ankle deformity. It is therefore important to identify and treat the knee valgus to improve the results of the foot correction and to help prevent recurrent ankle valgus. To objectively identify the level of the knee valgus, the lateral distal femoral angle (LDFA) and medial proximal tibia angle (MPTA) should both be measured off of the distal femoral joint line. In young children this line is difficult to see since most of the distal epiphysis is not ossified. It may be necessary to do a knee arthrogram to measure the lateral distal femoral angle and medial proximal tibia angle accurately. If the valgus is from the femur, hemiepiphysiodesis of the distal femur can be carried out using a screw-plate device at the time of the ankle surgery. If the deformity is from the tibia, and if tibial lengthening is carried out, then the deformity can be corrected through the lengthening osteotomy of the proximal tibia. If the tibia is not being lengthened a hemi-epiphysiodesis device can be applied to the proximal tibial physis.

Progressive genu valgum after lengthening is another cause of valgus in patients with fibular hemimelia. Paley et al. ¹⁹⁾ found that 75% of patients younger than 12 years and all patients younger than 4 years developed this problem. The deformity recurs through the proximal tibia. The origin is unclear but follows a pattern similar to that seen with the Cozen phenomenon ²⁰⁾ after proximal tibial metaphyseal fractures. In fibular hemimelia, the progressive tibial valgus may be related to the lack of growth by the fibula or may be due to soft tissue tethers on the lateral side by the fibular anlage. It may also be related to the tendency for the proximal tibial epiphysis to ossify medially but not laterally, thereby creating an intra-articular component. Intentionally deforming the tibia into 10–15° of varus at the end of the lengthening compensates for the expected rebound valgus. Another approach is to insert a hemi-epiphysiodesis plate at the end of the lengthening. A similar valgus tendency is observed with progressive valgus deformity in children with fibular hemimelia after amputation ²¹⁾. In contrast to the post lengthening tibial valgus, femoral valgus associated with fibular hemimelia is nonprogressive ²²⁾. Femoral valgus may contribute to valgus overload, which may be a factor for valgus rebound in the tibia. Distal femoral hemi-epiphysiodesis can be done at the time of the index lengthening procedure. Complete fibrous anlage resection may reduce the frequency and degree of rebound but has not eliminated the problem.

Growth inhibition has been reported after tibial lengthening for fibular hemimelia ²³⁾. Sharma et al. ²⁴⁾ concluded that this is related to complete fibular aplasia. Most of the cases presented by Sharma et al. were treated with double-level or combined femur and tibial lengthening without soft tissue release. Hope et al. ²⁵⁾, who used only single-level lengthening, could not demonstrate any growth inhibition. Sabharwal et al. ²⁶⁾ showed that growth inhibition occurred only if there had been a second tibial lengthening performed within a year of the first lengthening.

Knee ligament reconstruction

Most patients with fibular hemimelia have some knee ligament deficiency of the cruciate ligaments. If this instability is symptomatic or if the knee remains subluxed anteriorly in full extension, knee ligament reconstruction with the SUPERknee procedure ²⁷⁾ may be required together with the treatment of the ankle or at a separate time. Unlike femoral lengthening for congenital femoral deficiency, knee reconstruction or stabilization of the knee are not required in order to proceed with tibial lengthening.

Toe and metatarsal surgery

Many patients with fibular hemimelia are missing one or more toes. Some surgeons consider absence of two or more metatarsals an indication for amputation ²⁸⁾. As long as the foot is plantigrade, the foot in fibular hemimelia is very functional even with one, two, three or four rays.

Hallux varus, syndactaly and conjoint delta first metatarsals are the most common toe deformities associated with fibular hemimelia that benefit from surgical treatment of the toes. Syndactaly of the first to second toes is easily treated by release and skin grafting. Syndactaly between the middle toes does not need to be separated. Hallux varus is always associated with a short bracket (delta) first metatarsal. In most cases this is a conjoint metatarsal (fusion of first and second metatarsal) associated with syndactaly of the first and second toes. The treatment for this requires separation of the syndactaly combined with splitting of the conjoint metatarsal into two parts and reorienting of this osteotomy to realign the first metatarso-phalangeal joint surface.

Femoral lengthening

Femoral lengthening can be combined with the tibial lengthening at the same time or at a separate time to treat concomitant shortening of the femur. Simultaneous femur and tibia lengthening with external fixation is used when the femur and tibia shortening is of significant magnitude. In such cases, it is not unusual to perform the SUPERankle procedure with application of the external fixator for lengthening tibia and femur. A discussion of femoral lengthening is beyond the scope of this article, but for further information the reader is referred to published studies ²⁹⁾. If femoral lengthening is considered, it is factored into the surgical life plan discussed previously. Obviously, simultaneous femoral and tibial lengthening can yield much larger amounts of lengthening in one treatment than tibia lengthening alone. For example, simultaneous 5.0-cm femoral and 5.0-cm tibia lengthening together take a total of 5 months of external fixation, and isolated tibia lengthening of 5.0 cm also takes a total of 5 months of external fixation. Therefore, in the first example combined femoral and tibia lengthening achieve 10.0 cm (4 in.) of leg length equalization compared to only 5.0 cm (2 in.) when only the tibia is lengthened. While tibial lengthening alone requires daily physical therapy, combined femur and tibial lengthening mandates strict lengthening-specific physical therapy ³⁰⁾. There is no indication to do femoral lengthening in the absence of femoral discrepancy. The advent of internal lengthening methods makes femoral lengthening as a separate procedure much easier.

Physical therapy

Physical therapy is the most important aspect of the lengthening process. Without proper physical therapy, the lengthening goals will not be achieved and major complications will occur. Therefore, physical therapy requirements are very strict. The patient undergoing tibial lengthening must receive physical therapy 5 days per week while at the same time performing an exercise and stretching program at home. The physical therapy continues at this level of intensity for the duration of the distraction phase (2 to 3 months depending on the planned amount of lengthening). During this initial therapy, the parents are taught home exercises and stretching techniques that their child must perform every day. Also, the parents are able to observe the therapy sessions and the therapists’ techniques.

The physical therapy usually involves land and water therapy for patients undergoing lengthening. During the distraction phase, the ideal situation is to perform all physical therapy at the specialist center with experience in limb lengthening and limb reconstruction. Once the distraction phase is completed, the therapy requirements significantly decrease. At that point, the family may return home and their therapy transitions to a local therapist with guidance from the therapists at the specialist center. Even if the patient has returned home during the lengthening phase, the office visit for clinical and X-ray evaluation that occurs every 2 weeks is still mandatory.

If the family plans to return home immediately after the hospital stay, the patient must undergo at least one week of therapy at the specialist center. This is to allow the therapy team time to teach the family the lengthening stretches and prepare them for the transition to the local therapist. Again, the family choosing this strategy must still return every two weeks for the clinical and X-ray evaluations at the specialist center clinic. Doctors do not recommend this strategy due to the increased complication rate and the decreased overall length gain of the patients when compared with patients who have chosen to perform most of the therapy at the specialist center.

The relationship between the patient and the physical therapist is very important while the family is in the specialist center and becomes even more important when the family and patient return home. The therapists are the remote eyes and ears of the physician. During the daily therapy, if any concerns or complaints arise, the therapist notifies the surgeon immediately for a recommended solution or makes sure that the patient is seen in the office for a clinical check. After the patient returns home, the specialist center physical therapist will intermittently check on the patient’s progress and discuss the therapy with the local therapist. If there is a significant therapy issue, the individual therapist notifies the local therapist and provides additional instructions.

Recovery after surgery

Recovery depends upon the surgery performed.

• Epiphysiodesis: Recovery after this surgery is relatively easy. The child can go home the same day of the surgery and can typically bear full weight immediately after the surgery. After 2-3 weeks the child can typically return to full activities. Physical therapy is rarely needed.
• Limb lengthening with external fixator: This surgery is complex and the recovery extensive. The longer the lengthening, the longer the external fixator is in place, and therefore, the longer the recovery.
• Limb lengthening with internal lengthening nail: like the external fixator, lengthening with an internal lengthening nail is also an extensive process. However, for the most part, especially in older children, the nails are better accepted and less cumbersome.

Fibular hemimelia prognosis

Children who have fibular hemimelia live happy and fruitful lives, no matter whether they have a limb reconstruction or an ablation procedure. They can play sports, play with friends, and generally have normal intelligence and life expectancy. In order to optimize their leg function, they should be seen by an orthopaedic surgeon familiar with fibular hemimelia to discuss their treatment options.

Out toeing

Out-toeing is when your child’s foot points outward instead of straight ahead when he or she runs or walks. While out-toeing is often normal and will correct on its own, there are some conditions that cause out-toeing that are serious. Out-toeing is much less common than in-toeing and can occur in older children. Out-toeing can also run in families.

Out-toeing may be due to twists in the bone in the hip, thigh bone (femur), shin bone (tibia), or foot. While some of these are normal variations, a thorough history and examination are needed to make sure there is not a more serious problem.

My parents said that our pediatrician should have put our child in braces to correct the out-toeing. But our doctor said we didn’t need to?! Who is right?

When your parents were growing up, doctors used special shoes, braces, and even cables to correct in-toeing / out-toeing. However, studies have now shown that the in-toeing / out-toeing improves on its own, and the shoes and braces didn’t make it happen any faster.

When should I take my child to a doctor for in-toeing / out-toeing?

Your child should see a doctor if in-toeing / out-toeing does not improve by kindergarten, if there is pain, limp, developmental delay, or the walking is getting worse. Out-toeing in only one foot in an is very worrisome in teenagers for a problem in the hip, particularly if there is also hip, thigh, or knee pain – if this is the case your child should be evaluated with x-rays immediately.

My toddler trips a lot because of in-toeing. When should I be worried?

Many toddlers who do in-toe also trip! Remember, toddlers are learning to walk, and they do not yet have the muscle control, balance, or coordination to keep up with their busy lives. The in-toeing may make this seem worse. As your child becomes stronger and more coordinated, the tripping will improve.

Out toeing cause

Common causes of out-toeing

• External rotation contracture of the hip – During pregnancy, both of the baby’s hips are flexed up and rotated outward to fit in the mother’s womb. This position is known as hip external rotation (the feet are pointed inwards). This external rotation contracture present at birth usually goes away on its own when the child starts walking.
• External tibial torsion – This is when the shin bone (tibia) is twisted outward. Similar to the external rotation contracture of the hip, external tibial torsion is also usually due to positioning of the baby in the womb. However, unlike an external rotation contracture of the hip, external tibial torsion usually does not improve and may even get worse as the child grows. Splints, braces, special shoes, or chiropractic manipulation do NOT improve external tibial torsion.
• Flat feet – flat feet (link) occur when there is no arch in the foot. This can give the appearance of out-toeing. Flexible flat feet are normal in babies and toddlers. Out-toeing from flat feet usually improves on its own without treatment.

Less common causes of out-toeing

• Femoral retroversion – This is when the thigh bone (femur) has a twist outward compared to the hip. This is more often seen in obese children. It can also be seen in slipped capital femoral epiphysis (SCFE) in older children and adolescents.
• Perthes disease also known as Legg-Calve-Perthes – because of decreased hip rotation, some patients with Perthes disease may present with out-toeing.
• Cerebral palsy – muscle imbalance in the legs of children with cerebral palsy can lead to out-toeing. This is usually seen on one leg only, not both. A thorough history and physical exam may reveal signs of possible cerebral palsy, and referral to a neurologist or physical medicine and rehabilitation specialist is usually needed.

Out toeing symptoms

Many children with out-toeing have no pain or functional problems. Frequently, families notice that the child stands, walks, or runs with the feet point outward. Depending on the reason for the out-toeing, some children may limp and/or have pain in the hip, thigh, knee, or foot.

Out toeing diagnosis

Your doctor will take a thorough history, especially regarding birth history and developmental milestones. Any history of pain or limping should be discussed. The physical exam will include watching your child walk and run, and checking range of motion of the hips, knees, ankles, and feet. He or she will also do a neurologic examination to check muscle tightness, nerve / muscle function, and coordination.

If the history and physical examination are consistent with out-toeing as normal development in your child, no other studies are needed. If your doctor finds anything concerning, he or she may order x-rays or refer your child to a specialist.

Out toeing treatment

Treatment is dependent on the underlying diagnosis that is causing the out-toeing. Normal developmental out-toeing can be followed by your child’s pediatrician or family doctor. Occasionally, external tibial torsion or femoral retroversion may require surgery to untwist the bones if the out-toeing causes pain, limping, knee cap (patella) problems, or severe problems with walking and running when the child is older. It is important that your child’s doctor evaluates your child to make sure that there are not other serious things like slipped capital femoral epiphysis, Perthes disease or cerebral palsy that are causing the out-toeing.

Out toeing prognosis

Even though normal developmental out-toeing may not completely correct with growth, almost all children are pain free and can participate in sports and activities. Although patients with external tibial torsion and femoral retroversion may have an increased risk of hip or knee pain, long term functional problems only occur in about 1 in 1,000 children.

Will my child walking improve?

As most kids get older, their bones very gradually rotate to a normal angle. Walking, like other skills, improves with experience, so kids will become better able to control their muscles and foot position.

In-toeing and out-toeing gets better over time, but this happens very gradually and is hard to notice. So doctors often recommend using video to help parents track improvement. Parents can record their child walking, and then wait about a year to take another video. This usually makes it easy to see if the gait abnormality has improved over time. In most cases, it has. If not, parents should speak with their child’s doctor to discuss whether treatment is necessary.

In the past, special shoes and braces were used to treat gait abnormalities. But doctors found that these didn’t make in-toeing or out-toeing disappear any faster, so they’re rarely used now.

Metatarsus adductus

Metatarsus adductus is a common foot deformity noted at birth that causes the front half of the foot or forefoot, to curve inwards rather than straight ahead and occasionally the toes spread widely. The bones in the front half of the foot bend or turn in toward the side of the big toe. Metatarsus adductus is a fairly common deformity affecting the feet of newborns and young children. Metatarsus adductus is one of the reasons why people develop “in-toeing.”

Metatarsus adductus may also be referred to as “flexible” (the foot can be straightened to a degree by hand) or “nonflexible” (the foot cannot be straightened by hand). Metatarsus varus is another term usually refers to the fixed form of metatarsus adductus that requires treatment. When this is the case, your child may require leg casts, splints or braces to straighten the feet.

The cause of metatarsus adductus is not always clear, however it is thought to be related to the way the child is ‘tucked up’ in the womb. The feet will usually straighten within a year or two of birth, and the deformity usually has little effect on walking or crawling.

Babies born with metatarsus adductus rarely need treatment as they grow. They may, however, be at increased risk for developmental dysplasia of the hip also called slipped capital femoral epiphysis (SFCE), a condition of the hip joint in which the top of the thigh (femur) slips in and out of its socket, because the socket is too shallow to keep the joint intact.

Metatarsus adductus causes

The cause of metatarsus adductus is not known. It occurs in approximately 1 to 2 per 1,000 live births and is more common in first born children.

Metatarsus adductus is thought to be caused by the infant’s position inside the womb. Risks may include:

• The baby’s bottom was pointed down in the womb (breech position).
• The mother had a condition called oligohydramnios, in which she did not produce enough amniotic fluid.

There may also be a family history of the condition.

Metatarsus adductus symptoms

The front of the foot is bent or angled in toward the middle of the foot. The back of the foot and the ankles are normal. About one half of children with metatarsus adductus have these changes in both feet.

Newborns with metatarsus adductus may also have a problem called developmental dysplasia of the hip (slipped capital femoral epiphysis). This allows the thigh bone slips out of the hip socket.

(Club foot is a different problem. The foot is pointed down and the ankle is turned in.)

Metatarsus adductus diagnosis

A doctor makes the diagnosis of metatarsus adductus with a physical examination. During the examination, the doctor will obtain a complete birth history of the child and ask if other family members were known to have metatarsus adductus.

Diagnostic procedures are not usually necessary to evaluate metatarsus adductus. However, X-rays (a diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film) of the feet are often done in the case of nonflexible metatarsus adductus.

An infant with metatarsus adductus has a high arch and the big toe has a wide separation from the second toe and deviates inward. Flexible metatarsus adductus is diagnosed if the heel and forefoot can be aligned with each other with gentle pressure on the forefoot while holding the heel steady. This technique is known as passive manipulation.

If the forefoot is more difficult to align with the heel, it is considered a nonflexible, or stiff foot.

Metatarsus adductus treatment

Treatment is rarely needed for metatarsus adductus. In most children, the problem corrects itself as they use their feet normally.

In cases where treatment is being considered, the determination will depend on how rigid the foot is when the health care provider tries to straighten it. If the foot is very flexible and easy to straighten or move in the other direction, no treatment may be needed. A pediatric orthopedic surgeon should be involved in treating more severe deformities. The child will be checked regularly.

Specific treatment for metatarsus adductus will be determined by your child’s doctor based on:

• Your child’s age, overall health, and medical history
• The extent of the condition
• Your child’s tolerance for specific medications, procedures, or therapies
• Expectations for the course of the condition
• Your opinion or preference

The goal of treatment is to straighten the position of the forefoot and heel. Treatment options vary for infants, and may include:

• Observation, for those with a supple, or flexible, forefoot
• Stretching or passive manipulation exercises. These are done if the foot can be easily moved into a normal position. The family will be taught how to do these exercises at home.
• Your child may need to wear a splint or special shoes, called reverse-last shoes, for most of the day. These shoes hold the foot in the correct position.
• Casts. Rarely, your child will need to have a cast on the foot and leg. Casts work best if they are put on before your child is 8 months old. The casts will probably be changed every 1 to 2 weeks.
• Surgery. Surgery is rarely needed. Most of the time, your provider will delay surgery until your child is between 4 and 6 years old.

Studies have shown that metatarsus adductus may resolve spontaneously (without treatment) in the majority of affected children.

Your child’s doctor may instruct you on how to perform passive manipulation exercises on your child’s feet during diaper changes. A change in sleeping positions may also be recommended. Suggestions may include side-lying positioning.

In rare instances, the foot does not respond to the stretching program, long leg casts may be applied. Casts are used to help stretch the soft tissues of the forefoot. The plaster casts are changed every 1 to 2 weeks by your child’s pediatric orthopaedist.

If the foot responds to casting, straight cast shoes may be prescribed to help hold the forefoot in place. Straight last shoes are made without a curve in the bottom of the shoe.

For those infants with very rigid or severe metatarsus adductus, surgery may be required to release the forefoot joints. Following surgery, casts are applied to hold the forefoot in place as it heals.

Metatarsus adductus long-term outlook

Metatarsus adductus is a common problem in babies with more than 90% resolving on their own. When needed treatment will depend on the degree of flexibility in the affected foot.

In-toeing does not interfere with the child becoming an athlete later in life. In fact, many sprinters and athletes have in-toeing.

Femoroacetabular impingement

Femoroacetabular impingement (FAI) is a condition in which extra bone grows along one or both of the bones that form the hip joint — giving the bones an irregular shape, which can lead to premature contact between these two structures when the hip is placed in certain positions. Over time, this repeated contact can cause damage to the labrum (O-ring type structure which surrounds the hip socket) or the underlying cartilage. A normally developed hip joint is formed by the end of the thigh bone (technically called the femoral head) that normally is shaped as a ball or sphere and the socket (also referred to as the acetabulum) on either side of the pelvic bone. Femoroacetabular impingement involves abnormal contact between the end of the thigh bone and neck against the frontal part of the hip socket. In FAI, bone overgrowth — called bone spurs — develop around the femoral head and/or along the acetabulum. This extra bone causes abnormal contact between the hip bones, and prevents them from moving smoothly during activity. Because they do not fit together perfectly, the bones rub against each other during movement. Over time this friction can damage the joint this can result in tears of the labrum and breakdown of articular cartilage (osteoarthritis), causing pain and limiting activity. Femoroacetabular impingement may occur from deformities of the femur, which is called cam impingement, or from deformities of the socket which is called pincer impingement. It can also occur in children who suffer from deformities of both the thigh bone and the hip socket simultaneously. The bony morphologies of femoroacetabular impingement, classified as pincer-, cam-, or combined-type deformities, are often accompanied by chondrolabral abnormalities ¹⁾.

Femoroacetabular impingement (FAI) is increasingly recognized as a cause for hip and groin pain in the young, active patient ²⁾. The prevalence of femoroacetabular impingement in the general adult population is between 10 to 15% ³⁾. Based on clinical diagnosis, femoroacetabular impingement affects adolescents and the young adult population before radiographic signs of arthritis manifest ⁴⁾. The prevalence of symptomatic athletes has been reported to be higher than the general population at 55% ⁵⁾. There is also literature that has examined the prevalence of anatomic morphology consistent with this condition but in asymptomatic individuals; therefore, patients can have bony features of femoroacetabular impingement and not manifest with symptoms. A meta-analysis by Frank et al. reports a prevalence of 37% for cam deformity and 67% for pincer deformity in asymptomatic volunteers ⁶⁾. When accounting for the athletic population, cam deformity prevalence was 54.8% for athletes and 23.1% for non-athletes. The pincer lesion was present in 49.5% of the athletic population. Cam deformity is more prevalent in men than women, with a reported prevalence of 9 to 25% men versus 3 to 10% in women. Pincer lesions are more common in women than men, with reports of 19.6% versus 15.2% ⁷⁾.

Hip arthroscopic surgery is indicated to treat femoroacetabular impingement and related defects including labral lesions, ligamentum teres injuries, and articular cartilage delamination ⁸⁾. Compared with open approaches, hip arthroscopic surgery may result in faster recovery, lower complication rates, less pain, and less morbidity ⁹⁾. Over the past decade, hip arthroscopic surgery rates have risen exponentially ¹⁰⁾. Hip arthroscopic surgery has reduced pain and improved function in patients in most age groups, body mass indices (BMIs), sexes, income levels, and activity levels ¹¹⁾.

Negative outcomes after hip arthroscopic surgery for femoroacetabular impingement may be defined as persistent pain, looseness, and stiffness with reduced range of motion, refractory to nonsurgical treatment or reoperation ¹²⁾. Furthermore, dissatisfaction can result from an inability to return to desired activities. Failure rates for hip arthroscopic surgery range from 2.9% to 13.2% ¹³⁾. Residual or unaddressed femoroacetabular impingement is the most common cause of negative outcomes in hip arthroscopic surgery ¹⁴⁾. Other potential causes of negative outcomes include unrecognized acetabular dysplasia, soft tissue laxity, and osteoarthritis. Positive outcomes after hip arthroscopic surgery usually involve achieving the minimal clinically important difference or substantial clinical benefit on patient-reported outcome measures ¹⁵⁾. Negative outcomes after hip arthroscopic surgery for femoroacetabular impingement are typically managed with revision arthroscopic surgery or open surgical hip dislocation but sometimes require total hip arthroplasty ¹⁶⁾.

Hip joint anatomy

The hip is a ball-and-socket joint. The socket is formed by the acetabulum, which is part of the large pelvis bone. The ball is the femoral head, which is the upper end of the femur (thighbone).

A slippery tissue called articular cartilage covers the surface of the ball and the socket. It creates a smooth, low friction surface that helps the bones glide easily across each other during movement.

The acetabulum is ringed by strong fibrocartilage called the labrum. The labrum forms a gasket around the socket, creating a tight seal and helping to provide stability to the joint.

Figure 1. Hip joint anatomy (in a healthy hip, the femoral head fits perfectly into the acetabulum)

Types of FAI

There are three types of femoroacetabular impingement (FAI): pincer, cam, and combined impingement.

1. Pincer impingement. This type of impingement occurs because extra bone extends out over the normal rim of the acetabulum. The labrum can be crushed under the prominent rim of the acetabulum.
2. Cam impingement. In cam impingement the femoral head is not round and cannot rotate smoothly inside the acetabulum. A bump forms on the edge of the femoral head that grinds the cartilage inside the acetabulum.
3. Combined impingement. Combined impingement just means that both the pincer and cam types are present.

Figure 2. Femoroacetabular impingement

Footnote: (Left) Pincer impingement. (Center) Cam impingement. (Right) Combined impingement.

Figure 3. Femoroacetabular impingement types

Femoral acetabular impingement causes

The cause of femoroacetabular impingement is still under investigation; however, studies suggest that genetic factors may contribute to the abnormal hip pathology. Multiple studies have investigated single nucleotide polymorphisms such as GDF5, FRZB, DIO2, and HOX9 ¹⁷⁾. FRZB has been found by one study to contribute to a specific shape of proximal femur morphology on X-ray and increased development of osteoarthritis of the hip ¹⁸⁾. DIO2 has also correlated with specific proximal femur morphology and the increased development of hip osteoarthritis ¹⁹⁾. HOX9 was looked at in a Japanese population and found to contribute to pincer lesion formation of the acetabulum ²⁰⁾.

There is also evidence to suggest an increased incidence of femoroacetabular impingement in athletes due to cam deformity formation ²¹⁾. More specifically, adolescents engaged in high-intensity sports were found to be ten times more likely to have a cam deformity and impingement than age-matched adolescents not participating in high-intensity sports ²²⁾. There is a theory that increased stress along the growth plate of the hip leads to increased stress reaction bone formation resulting in cam deformity and subsequent impingement.

The formation of femoroacetabular impingement has also occurred in patients with a history of slipped capital femoral epiphysis (SCFE). When this primary insult happens during childhood, the epiphysis of the femoral head slips posterior and medial respective to the metaphysis, leading to a prominent metaphysis anterior and laterally. Even after surgical in situ fixation of a slipped capital femoral epiphysis, there is residual deformity, and this can cause impingement ²³⁾.

Femoroacetabular impingement occurs because the hip bones do not form normally during the childhood growing years. It is the deformity of a cam bone spur, pincer bone spur, or both, that leads to joint damage and pain.

• Cam impingement (deformity of the thigh bone) occurs when the abnormally shaped femoral head (ball) and head-neck junction jam, or run into, the hip socket during certain activities like bending over, sitting for long periods of time, or riding a bike.
• Pincer impingement is caused by direct contact between the femoral head-neck junction and the acetabular rim in conditions where the coverage of the femoral head in the anterior region is excessive (acetabular retroversion, protrusion acetabulum etc.). Impingement of a child’s hip can also be caused due to pediatric hip disorders such as Legg-Calvé-Perthes disease, slipped capital femoral epiphysis or post-traumatic deformities.

When the hip bones are shaped abnormally, there is little that can be done to prevent femoroacetabular impingement. Femoroacetabular impingement (FAI) syndrome is caused by a prominent femoral head-neck junction (ie, cam morphology) or a prominent acetabular rim (ie, pincer morphology). Patients may also present a combination of the 2 deviations, where they have both cam and pincer morphology ²⁴⁾. At motion, these morphologies have the potential to cause abnormal mechanical stresses within the hip joint, which may cause subsequent soft tissue damage ²⁵⁾.

Activities such as running, hockey, dancing, and gymnastics are not causes of FAI, but because of the increased demand these activities place on the hips, the symptoms of FAI may occur earlier than in less active children.

It is not known how many people have femoroacetabular impingement. Some people may live long, active lives with femoroacetabular impingement and never have problems. When symptoms develop, however, it usually indicates that there is damage to the cartilage or labrum and the disease is likely to progress.

Because athletic people may work the hip joint more vigorously, they may begin to experience pain earlier than those who are less active. However, exercise does not cause femoroacetabular impingement.

Risk factors for developing femoro acetabular impingement

Risk factors for developing femoro acetabular impingement:

• Consequence of Legg-Calvé-Perthes altering the shape of the ball and socket of the hip joint
• Consequence of Slipped Capital Femoral Epiphysis altering the shape of the femoral head and acetabulum
• Activities involving repetitive motion of the hip (running, weight lifting, ice skating)
• Activities involving extreme flexion of the hip (dance, gymnastics)
• Trauma to the hip

Femoroacetabular impingement symptoms

Some people with FAI can live active lives and never experience pain or hip problems. Others, especially athletic and active people, may develop pain in the hip or thigh that is usually worse in a seated position. Clicking, popping or a pinching sensation may be felt deep in the hip joint.

Pain often occurs in the groin area or hip (front, side, and/or back) aggravated by activity and/or prolonged sitting is the most common symptom of femoroacetabular impingement (FAI). Other signs or symptoms include difficulty flexing the hip and popping or clicking of the hip. Turning, twisting, and squatting may cause a sharp, stabbing pain. Sometimes, the pain is just a dull ache.

The most common symptoms of FAI include:

• Pain
• Stiffness
• Limping

Femoroacetabular impingement diagnosis

A diagnosis of femoroacetabular impingement may be suspected after a detailed history and physical examination. X-rays can help evaluate the shape of the ball and socket to look for possible causes of impingement. The findings on X-ray are often subtle, however, and may be missed by practitioners who are unfamiliar with the condition.

During your first appointment, your doctor will discuss your general health and your hip symptoms. He or she will also examine your hip.

Impingement test

As part of the physical examination, your doctor will likely conduct the impingement test. For this test, your doctor will bring your knee up towards your chest and then rotate it inward towards your opposite shoulder. If this recreates your hip pain, the test result is positive for impingement.

Imaging tests

Your doctor may order imaging tests to help determine whether you have FAI.

• X-rays. These provide good images of bone, and will show whether your hip has abnormally shaped bones of FAI. X-rays can also show signs of arthritis.
• Computed tomography (CT) scans. More detailed than a plain x-ray, CT scans help your doctor see the exact abnormal shape of your hip.
• Magnetic resonance imaging (MRI) scans. These studies can create better images of soft tissue. They will help your doctor find damage to the labrum and articular cartilage. Injecting dye into the joint during the MRI may make the damage show up more clearly.
• Local anesthetic. Your doctor may also inject a numbing medicine into the hip joint as a diagnostic test. If the numbing medicine provides temporary pain relief, it confirms that FAI is the problem.

Femoroacetabular impingement treatment

Treatment may include non-surgical options such as activity modification, physical therapy, injections and anti-inflammatory medications. For those patients that don’t respond to non-operative treatment, hip arthroscopy or a surgical dislocation of the hip may be recommended.

When symptoms first occur, it is helpful to try and identify an activity or something you may have done that could have caused the pain. Sometimes, you can just back off on your activities, let your hip rest, and see if the pain will settle down. Over-the-counter anti-inflammatory medicines, such as ibuprofen and naproxen, may help.

If your symptoms persist, you will need to see a doctor to determine the exact cause of your pain and provide treatment options. The longer painful symptoms go untreated, the more damage FAI can cause in the hip.

Nonsurgical treatment

• Activity changes. Your doctor may first recommend simply changing your daily routine and avoiding activities that cause symptoms.
• Non-steroidal anti-inflammatory medications. Drugs like ibuprofen can be provided in a prescription-strength form to help reduce pain and inflammation.
• Physical therapy. Specific exercises can improve the range of motion in your hip and strengthen the muscles that support the joint. This can relieve some stress on the injured labrum or cartilage.

If your pain continues after a period of rest and therapy, an intra-articular injection (shot inside the joint) of numbing medication (local anesthetic) and a steroid is sometimes recommended. An injection helps clarify if the pain is coming from the joint or the surrounding muscle.

Surgical treatment

If tests show joint damage caused by FAI and your pain is not relieved by nonsurgical treatment, your doctor may recommend surgery. The surgical treatment of FAI aims to correct cam and/or pincer morphologies and repair damaged soft tissue ²⁶⁾. Initially, this was performed with an open surgical approach ²⁷⁾, but arthroscopic management has now emerged as the treatment of choice ²⁸⁾.

Arthroscopy

Many FAI problems can be treated with arthroscopic surgery. Arthroscopic procedures are done with small incisions and thin instruments. The surgeon uses a small camera, called an arthroscope, to view inside the hip.

During arthroscopy, your doctor can repair or clean out any damage to the labrum and articular cartilage. He or she can correct the FAI by trimming the bony rim of the acetabulum and also shaving down the bump on the femoral head.

Some severe cases may require an open operation with a larger incision to accomplish this.

Femoroacetabular impingement prognosis

Surgery can successfully reduce symptoms caused by impingement. Correcting the impingement can prevent future damage to the hip joint. However, not all of the damage can be completely fixed by surgery, especially if treatment has been put off and the damage is severe. It is possible that more problems may develop in the future.

While there is a small chance that surgery might not help, it is currently the best way to treat painful FAI.

Positional plagiocephaly

Plagiocephaly literally means “oblique head” (from the Greek word “plagio” for oblique and “cephale” for head) and corresponds to a unilateral or bilateral occipital flattening, which may arise due to the continual influence of external forces on the immature skull (nonsynostotic posterior plagiocephaly) or because of premature fusion of one or both lambdoid sutures (synostotic posterior plagiocephaly) ¹⁾. Anterior plagiocephaly can be used to define the cranial deformation characterized by premature unilateral fusion of the coronal suture.

Positional or deformational plagiocephaly is the most common cause of plagiocephaly (prevalence of 5-48% in healthy newborn infants) ²⁾ versus an incidence of 0.003% of synostotic plagiocephaly (lamboid synostosis) ³⁾.

Positional plagiocephaly is also called non-synostotic plagiocephaly or deformational plagiocephaly, refers to a flattened, misshapen or asymmetrical (uneven) head shape caused by repeated pressure to the same area of the skull. There is another type of plagiocephaly caused by abnormal closure of the skull bones. This is called synostotic plagiocephaly or craniosynostosis, and is not addressed in this post. When the head has a flat spot at the back of the skull, this is called brachycephaly. Positional plagiocephaly does not affect the development of a baby’s brain, but if left untreated it may change their physical appearance by causing uneven growth of their face and head.

Non-synostotic plagiocephaly falls into three main groups ⁴⁾:

1. Plagiocephaly – skewed occipital flattening,
2. Brachycephaly – symmetric occipital flattening, and
3. Combined plagiocephaly/brachycephaly.

Positional plagiocephaly or deformational plagiocephaly occurs because the bones of a newborn baby’s head are thin and flexible, so the head is soft and may change shape easily. Flattening of the head in one area may happen if a baby lies with their head in the same position for a long time ⁵⁾. The incidence of positional plagiocephaly has increased with the start of ‘Back to Sleep’ campaign by the American Academy of Pediatrics ⁶⁾ and ranges from 1 in 300 live births to 22.1 percent ⁷⁾. Positional plagiocephaly or deformational plagiocephaly results from an ongoing action of gravitational forces on the occipital region, causing a flattened region of the posterior craniofacial skeleton. If no intervention is performed, the deformity can continue and, in severe cases, evolve with facial deformities. Positional plagiocephaly occurs more often on the right side (70% of cases) and affects more males. The major risk factors include: torticollis, prematurity, multiparity, and a fixed sleeping position.

Deformational plagiocephaly is very common, and can typically be diagnosed with a thorough physical evaluation by a clinician who specializes in treating craniofacial differences. Because positional plagiocephaly can be confused with craniosynostosis, especially unilateral lambdoid synostosis and unicoronal synostosis, accurate diagnosis by an experienced team is extremely important to managing your child’s condition.

Craniofacial experts will be able to differentiate readily between these conditions. In rare cases, your child’s medical team may use a CT scan to confirm the diagnosis and further evaluate your child’s condition. It is important that cases of craniosynostosis be identified early, as these conditions often require surgical treatment, and if left untreated, may result in elevated intracranial pressure.

Most babies with deformational plagiocephaly do not need any treatment at all, especially if they are active and you have plenty of one-on-one interaction with them. Positional plagiocephaly usually improves naturally as your baby grows and gains head control and can move their head by themselves. The plagiocephaly will get better if you encourage your baby to turn their head themselves when they are awake. From the age of two weeks, while you are supporting their head in your hands, your baby can slowly follow your eyes or voice around, even if one way seems harder at first.

If you have concerns about your baby’s head shape or if you notice that your baby only turns their head to one side when lying on their back, see your doctor.

If treatment is necessary, you may be referred to a specialist clinic where your baby will be treated by a team that may include a pediatrician, plastic surgeon, physiotherapist and orthotist.

The most common treatment is provided by the physiotherapist who will encourage active movement, and teach parents how to position their baby and do exercises with them to help improve the head shape.

Deformational plagiocephaly can be associated with torticollis. Torticollis literally means “a tight neck” and can be seen when there are structural anomalies such as fused or hemivertebrae, or most commonly as a completely isolated anomaly.

In the majority of cases, physical therapy to straighten and stretch the neck will straighten the head and head posture. If your child has torticollis, he may habitually sleep in one position and develop plagiocephaly. Treating the torticollis will often help to improve the plagiocephaly as your child is able to sleep more comfortably in different positions. Otherwise, helmet therapy is used.

A very small number of babies with plagiocephaly (less than one in 10) have a severe and persistent deformity, and they may need to be treated with helmet therapy.

If repositioning is not successful in addressing the problem, or if the deformation is moderate or severe and persists beyond six months, then helmet therapy may be required.

Helmet therapy works by fitting the skull tightly with a specially designed helmet in all areas except where it is flat. Leaving extra room around the flat area of the head allows the skull and brain to grow back into the normal shape that they were genetically programmed to do.

Deformational plagiocephaly key points to remember:

• Lie your baby on their back for sleep and do not use pillows in the crib.
• Vary the position of your baby’s head when putting them down to sleep, and your baby’s position when they are awake and alert. Give your baby face time and tummy time.
• Talk to your doctor if you are worried about your baby’s head shape.
• Plagiocephaly usually improves over time if your baby is active and has lots of one-on-one interaction.
• If helmet therapy is needed, it won’t hurt your baby and the outcomes are normally very good.

Figure 1. Plagiocephaly and brachycephaly

Figure 2. Normal skull of a newborn

Figure 3. Brain size versus age diagram

What is craniosynostosis?

Craniosynostosis is a birth defect of the skull characterized by the premature closure of one or more of the cranial sutures or fibrous joints between the bones of the skull (joints between the bone plates) before brain growth is complete ⁸⁾. The occurrence is approximately one for 2000 to 2500 live births ⁹⁾. The premature fusion of sutures prevents perpendicular growth of the skull, and an increase in brain volume leads to a compensatory growth of the skull parallel to this. Closure of a single suture is most common. Normally the skull expands uniformly to accommodate the growth of the brain and most cranial sutures fuse when a person is 20-30 years of age, with the exception being the metopic suture fusing around 6 months to 2 years; premature closure of a single suture restricts the growth in that part of the skull and promotes growth in other parts of the skull where sutures remain open. This results in a misshapen skull but does not prevent the brain from expanding to a normal volume. However, when many sutures close prematurely, the skull cannot expand to accommodate the growing brain, which leads to increased pressure within the skull and impaired development of the brain. Theoretically, a person can suffer consequences of an early skull suture fusion no matter what age it fuses. However, doctors usually see the most severe consequences when the fusion happens early in life, often before birth.

Craniosynostosis usually involves fusion of a single cranial suture, but can involve more than one of the sutures in your baby’s skull (complex craniosynostosis). In rare cases, craniosynostosis is caused by certain genetic syndromes (syndromic craniosynostosis).

Types of craniosynostosis are:

• Sagittal synostosis (scaphocephaly) is the most common type. It affects the main suture on the very top of the head. The early closing forces the head to grow long and narrow, instead of wide. Babies with this type tend to have a broad forehead. It is more common in boys than girls.
• Frontal plagiocephaly is the next most common type. It affects the suture that runs from ear to ear on the top of the head. It is more common in girls.
• Metopic synostosis is a rare form that affects the suture close to the forehead. The child’s head shape may be described as trigonocephaly. It may range from mild to severe.

Craniosynostosis can be gene-linked or caused by metabolic diseases (such as rickets or vitamin D deficiency) or an overactive thyroid. Some cases are associated with other disorders such as microcephaly (abnormally small head) and hydrocephalus (excessive accumulation of cerebrospinal fluid in the brain). The first sign of craniosynostosis is an abnormally shaped skull. Other features can include signs of increased intracranial pressure, developmental delays, or impaired cognitive development, which are caused by constriction of the growing brain. Seizures and blindness may also occur.

Primary craniosynostosis affects individuals of all races and ethnicities and is usually present at birth. Most forms of primary craniosynostosis affect men and women in equal numbers (although males outnumber females 2:1 for sagittal synostosis). Primary craniosynostosis affects approximately 0.6 in 100,000 people in the general population. Overall, craniosynostosis affects approximately 1 in 2,000-2,500 people in the general population. Approximately 80-90 percent of individuals with primary craniosynostosis have isolated defects. The remaining cases of primary craniosynostosis occur as part of a larger syndrome. More than 150 different syndromes have been identified that are potentially associated with craniosynostosis.

In most cases of primary craniosynostosis, affected children usually have normal intelligence and do not have other abnormalities besides the skull malformation. However, when multiple sutures are affected, the skull may be unable to expand enough to accommodate the growing brain. If left untreated, this can cause increased pressure within the skull (intracranial pressure) and can potentially result in cognitive impairment or developmental delays. Increased pressure within the skull can also cause vomiting, headaches, and decreased appetite. In some rare cases, additional symptoms can develop including seizures, misalignment of the spine, or eye abnormalities.

Treatment for craniosynostosis generally consists of surgery to improve the symmetry and appearance of the head and to relieve pressure on the brain and the cranial nerves. For some children with less severe problems, cranial molds can reshape the skull to accommodate brain growth and improve the appearance of the head.

Although neurological damage can occur in severe cases, most children have normal cognitive development and achieve good cosmetic results after surgery. Early diagnosis and treatment are key.

In this context, patients with craniosynostosis not surgically-treated can develop several complications such as ¹⁰⁾: Intracranial hypertension occurs in up to 60% of children with complex craniosynostosis and 20% of carriers of simple craniosynostosis; cognitive and developmental disorders, poor weight gain, visual, hearing, and language disorders; and psychological problems such as low self-esteem and social isolation. Therefore, the objective of surgical treatment is to prevent intracranial hypertension and to correct craniofacial abnormalities. Overall, the optimal timing of surgical correction in most cases is between 6 and 9 months of age. The motivations for performing the surgery before 1 year of age include the ability of the child younger than 1 year to completely reossify, the malleable character of the calvaria during this age, and the tremendous brain growth that occurs during the first year, which allows good remodeling of the skull ¹¹⁾. Satisfactory craniofacial form and esthetic pleasing outcomes have also been associated with craniofacial surgical interventions performed before 1 year of age ¹²⁾. It is noteworthy that the presence of intracranial hypertension signs (irritability, swelling of the papilla, bulging fontanelle, and imaging findings) may result in the need for earlier surgical intervention, to perform decompression procedures or ventricular shunt surgery if associated with hydrocephalus.

Plagiocephaly causes

Positional plagiocephaly or deformational plagiocephaly is acquired cranial asymmetry resulting from physical forces applied over a time, and refers to altered cranial shape in infants older than six weeks of age, when molding from the birth process is over ¹³⁾.  The most commonly reported risk factors are: first-born, male, limited neck rotation or preference in head position, supine sleep position, lower level of activity, and lack of tummy time ¹⁴⁾. An increase in prevalence of deformational plagiocephaly was noted in American tertiary centers the 1990s, and this was largely attributed to parents following the recommendation to place their infant supine while sleeping in order to prevent sudden infant death (SIDS) ¹⁵⁾. In a prospective cohort study from 2014, 47% of 440 healthy full-term infants seven to 12 weeks of age in Calgary were estimated to have deformational plagiocephaly ¹⁶⁾. In a prospective cohort study investigating the natural course, the prevalence of deformational plagiocephaly increased to four months, and the majority of cases reversed by two years of age ¹⁷⁾. Although deformational plagiocephaly might disappear as a child grows older and increased mobility relieves pressure on the cranium, it persists in some children. In a study of 129 children diagnosed with deformational plagiocephaly in infancy and whose parents had been given information on counter-positioning strategies, 39% had not reverted to the normal range of symmetry at mean age of four years ¹⁸⁾.

Plagiocephaly prevention

A baby’s head position needs to be varied during sleep and when they are awake to avoid them developing deformational plagiocephaly.

• Sleeping position: Your baby must always be placed on their back to sleep to reduce the risk of SIDS (Sudden Infant Death Syndrome or Cot Death). Do not use pillows in the cot for positioning.
• Head and crib position for sleep: A young baby will generally stay in the position they are placed for sleep, until they can move themselves. Alternate your baby’s head position when they sleep. Place your baby at alternate ends of the crib to sleep, or change the position of the crib in the room. Babies often like to look at fixed objects like windows or wall murals, so changing their crib position will encourage them to look at things that interest them from different angles.
• Play time: When your baby is awake and alert, play or interact with them facing you (face time) or place them lying down on their front (tummy time) or on their side from as early as one or two weeks of age. Place rattles or toys (or other people’s faces) that your baby likes to look at in different positions to encourage your baby to turn their head both ways. Even at two weeks of age your baby can follow your voice or eyes (maintain eye contact) and turn their head themselves each way if you support their head in your hands while they are awake and alert.
• Vary your holding and carrying positions of your baby: Avoid having your baby lying down too much by varying their position throughout the day, e.g. use a sling, hold them upright for cuddles, carry them over your arm on their tummy or side.

Plagiocephaly symptoms

It is quite common for a newborn baby to have an unusually shaped head. This can be either related to their position in the uterus during pregnancy, or caused by moulding (changing shape) during labour, including changes caused by instruments used during delivery. Depending on the cause of the unusual shape, most babies’ heads should go back to a normal shape within about six weeks after birth.

Sometimes a baby’s head does not return to a normal shape, or they may have developed a flattened spot at the back or side of their head. Sometimes a flat spot develops when a baby has limited neck movement and prefers resting their head in one particular position.

Plagiocephaly diagnosis

Diagnosis of positional plagiocephaly is eminently clinical and can typically be diagnosed with a thorough physical evaluation by a clinician who specializes in treating craniofacial differences. Because deformational plagiocephaly can be confused with craniosynostosis, especially unilateral lambdoid synostosis and unicoronal synostosis (unilateral fusion of the lambdoid or coronal sutures), accurate diagnosis by an experienced team is extremely important to managing your child’s condition ¹⁹⁾. Medical history and physical examination are sufficient to establish the differential diagnosis between a positional plagiocephaly and craniosynostosis in the vast majority of cases (Table 1). Classically, patients with premature fusion of the lambdoid suture already have the deformity at birth, while those with a positional deformity have a normal skull at birth and develop the deformity in the subsequent weeks or months. When asked, parents may mention that there is a preferred position of the baby’s positioning in patients with positional plagiocephaly, while in patients with synostotic plagiocephaly, there is no preferred position.

Medical history

The key questions to differentiate the craniosynostoses from the positional plagiocephaly are ²⁰⁾:

1. “Is deformity present at birth?” Craniosynostosis is present at birth, whereas deformational plagiocephaly develops in the neonatal period;
2. Is there a preferred sleep position?;
3. “Is there improvement of the deformity?” Craniosynostosis gets worse with time, whereas the deformational plagiocephaly improves as the child develops head control and the skull no longer has localized pressure for long periods”.

Table 1. Important characteristics to subsidize the differential diagnosis of positional plagiocephaly versus lamboid synostosis (craniosynostosis)

Characteristics	Positional plagiocephaly	Lambdoid craniosynostosis
Age at onset	Several weeks postnatally	Birth
Preferred position	Common	Rare
Torticollis	Present	Absent/Present
Bony ridge along the lambdoid suture	Absent	Present
Bulging mastoid	Absent	Present
Frontal bossing	Ipsilateral	Contralateral
Displacement of the ipsilateral ear	Anterior	Posterior
Skull shape	Parallelogram	Trapezoid
Diagnosis	Clinical, through medical history and physical examination	Three-dimensional computed tomography
Treatment	Clinical	Surgical

Physical examination

During the physical examination, symmetries between the skull, forehead, and ears should be carefully analyzed. Positional plagiocephaly presents a format of a parallelogram skull, while synostotic posterior plagiocephaly has the shape of a trapezoid ²¹⁾. Still, an ipsilateral bulging in the mastoid region and a ridge on the fused lambdoid suture can be seen and palpated. In moderate to severe cases in both deformities, compensatory frontal bossing can be observed, ipsilateral in positional plagiocephaly and contralateral in synostotic plagiocephaly. This involvement of the forehead may progress, leading to a facial scoliosis in both pathologies, changing the facial symmetry. In patients with lambdoid suture craniosynostosis, the ipsilateral ear stenosis tends to be in a posterior position and downwards, as if the suture pulled it. While the positional plagiocephaly tends to be in an anterior position, as if it had been pushed (Figure 4). The physical examination should also include evaluation of the cervical region and look for evidence of congenital torticollis and/or thickening of the sternocleidomastoid muscle, which are directly related to positional plagiocephaly.

Figure 4. Positional plagiocephaly

Footnote: Representation of positional plagiocephaly and true (synostotic) posterior plagiocephaly. (A) Positional plagiocephaly showing: absence of lambdoid suture stenosis, format of a parallelogram skull, ipsilateral compensatory frontal bossing, ipsilateral ear in an anterior position, as if it had been pushed. (B) True posterior plagiocephaly showing: presence of lambdoid suture stenosis, shape of a trapezoid, ipsilateral bulging in the mastoid region, contralateral compensatory frontal bossing, ipsilateral ear stenosis tends to be in a posterior position and downwards, as if the suture pulled it.

Imaging studies

In rare and difficult cases, when the examination and history are not diagnostic, a good-quality four-view radiographic series (anteroposterior, Towne and two lateral projections) might be sufficient to exclude craniosynostosis and avoid further radiation exposure ²²⁾. If it is unclear, because of the very young age of the patient, it is recommended to repeat X-skull after 1 or 2 months ²³⁾. CT is not the recommended modality for screening because of the associated radiation exposure and high imaging costs and diagnostics by pediatricians with CT is associated with further delay in referral ²⁴⁾.

After the clinical suspicion (or confirmation) of craniosynostosis, the children should be referred to a multidisciplinary team specialized in craniofacial anomalies (anesthesiologist, plastic surgeon, speech therapist, neurosurgeon, orthodontist, otorhinolaryngologist, and psychologist) ²⁵⁾. In these centers, the radiological exam of choice is the three-dimensional CT scan that contributes to elucidation of the extension of suture fusion and the consequent craniofacial deformity and subsequent surgical planning. It is noteworthy that the cephalic perimeter generally does not change due to compensatory growth of other bones in the majority of cases with simple craniosynostosis.

Plagiocephaly treatment

In most babies with deformational plagiocephaly due to sleeping position, simple repositioning of the child to place them off the flattened area will resolve the problem. The shape of your baby’s head should improve naturally over time as their skull develops and they start moving their head, rolling around and crawling.

To take pressure off the flattened part of your baby’s head:

• give your baby time on their tummy during the day – encourage them to try new positions during play time, but make sure they always sleep on their back as this is safest for them
• switch your baby between a sloping chair, a sling and a flat surface – this ensures there isn’t constant pressure on 1 part of their head
• change the position of toys and mobiles in their cot – this will encourage your baby to turn their head on to the non-flattened side
• alternate the side you hold your baby when feeding and carrying
• reduce the time your baby spends lying on a firm flat surface, such as car seats and prams – try using a sling or front carrier when practical

If treatment is necessary, you may be referred to a specialist clinic where your baby will be treated by a team that may include a pediatrician, plastic surgeon, physiotherapist and orthotist.

If your baby has difficulty turning their head, physiotherapy may help loosen and strengthen their neck muscles. The most common treatment is provided by the physiotherapist who will encourage active movement, and teach parents how to position their baby and do exercises with them to help improve the head shape.

A very small number of babies with deformational plagiocephaly (less than one in 10) have a severe and persistent deformity, and they may need to be treated with helmet therapy.

Corrective surgery may be needed if they have craniosynostosis.

Helmet therapy

Do not purchase any helmet devices on your own. Only a doctor can prescribe these helmets, and they are used in a small number of cases.

A lightweight helmet is made by an orthotist using 3D images and fitted for your baby. The helmet helps to reshape the skull by taking pressure off the flat area and allowing the skull to grow into the space provided.

Helmet therapy is most effective if treatment starts between six and eight months of age and is completed before 12 months, as this is the time of rapid growth of the skull.

Wearing the helmet doesn’t hurt and babies usually get used to it very quickly. Parents can sometimes feel quite emotional when their baby first wears the helmet. It can be helpful to know this is a common feeling and to remember treatment is temporary and outcomes are normally very good.

When your baby first gets their helmet, it will usually be worn for a two-hours-on/two-hours-off cycle for the first two days. This will allow you to monitor your baby’s skin and give your baby time to get used to the helmet. Following a review around two days after fitting, your baby will start wearing the helmet 23 hours a day. The orthotist will then review your baby about every three weeks.

Caring for your baby during helmet therapy:

• There should be some space in the helmet for your baby’s ears. Make sure their ears sit comfortably in these spaces and the helmet is not twisted.
• When you take the helmet off, check your baby’s skin to make sure there is no rubbing, blisters or broken skin. Mild redness over the high spots of the head is normal.
• You can put sorbolene cream on dry skin or mild rashes. You can buy sorbolene from a chemist or larger supermarkets. If the dry skin or rash does not get better, call your baby’s orthotist.
• Rather than taking the helmet off during hot weather, it is better to dress your baby in light clothing to keep them cool.
• Your baby’s head will become sweaty under the helmet. You should wash their hair daily and clean the inside of the helmet with a soft nailbrush or face washer and warm, soapy water. Rinse the helmet well and towel dry.

Figure 5. Plagiocephaly helmet therapy

Plagiocephaly long-term outcomes

To date, no studies have shown that the flattened area of the skull leads to any compromise in neurocognitive function. Once your baby can sit independently, the flattening will not worsen. As your child grows, you will notice that the flattening seems to improve. The head may never be symmetrical, but your child’s face will become more noticeable, his hair will grow and he will become more active. By school age, the flattening is usually no longer a cosmetic issue.

What is anencephaly

Anencephaly is a term that refers to the incomplete development of the brain, skull, and scalp and is part of a group of birth defects called neural tube defects. Anencephaly is one of the most common neural tube defects. Neural tube defects are birth defects that affect the tissue that becomes the spinal cord and brain.

Anencephaly occurs early in the development of an unborn baby. Anencephaly results when the upper part of the neural tube fails to close. This often results in a baby being born without the front part of the brain (forebrain) and the thinking and coordinating part of the brain (cerebrum). The remaining parts of the brain are often not covered by bone or skin.

Why this happens is not known. Possible causes include environmental toxins and low intake of folic acid by the mother during pregnancy.

The exact number of cases of anencephaly is unknown, because many of these pregnancies result in miscarriage. The Centers for Disease Control and Prevention (CDC) estimates that each year, about 3 pregnancies in every 10,000 in the United States will have anencephaly ¹⁾. This means about 1,206 pregnancies are affected by these conditions each year in the United States ²⁾. Having one infant with anencephaly increases the risk of having another child with neural tube defects.

There is no known cure or standard treatment for anencephaly. Almost all babies born with anencephaly will die shortly after birth.

Figure 1. Anencephaly

How many babies are born with Anencephaly?

Researchers estimate that about 1 in every 4,600 babies is born with anencephaly in the United States ³⁾.

Anencephaly causes

The causes of anencephaly among most infants are unknown. Some babies have anencephaly because of a change in their genes or chromosomes. Anencephaly might also be caused by a combination of genes and other factors, such as the things the mother comes in contact with in the environment or what the mother eats or drinks, or certain medicines she uses during pregnancy.

During pregnancy, the human brain and spine begin as a flat plate of cells, which rolls into a tube, called the neural tube. If all or part of the neural tube fails to close, leaving an opening, this is known as an open neural tube defect. This opening may be left exposed or covered with bone or skin.

Anencephaly and spina bifida are the most common open neural tube defects, while encephaloceles (where there is a protrusion of the brain or its coverings through the skull) are much rarer. Anencephaly occurs when the neural tube fails to close at the base of the skull, while spina bifida occurs when the neural tube fails to close somewhere along the spine.

Open neural tube defects happen to couples without a prior family history of these defects in the vast majority of cases. open neural tube defects result from a combination of genes inherited from both parents, coupled with environmental factors. For this reason, open neural tube defects are considered multifactorial traits, meaning many factors, both genetic and environmental, contribute to their occurrence.

Once a child has been born with an open neural tube defect in the family, the chance for an open neural tube defect to happen again is increased by 4 to 10 percent. It is important to understand that the type of neural tube defect can differ the second time. For example, one child could be born with anencephaly, while the second child could have spina bifida.

Getting enough folic acid before and during early pregnancy can help prevent neural tube defects, such as anencephaly. If you are pregnant or could get pregnant, take 400 micrograms (mcg) of folic acid every day. If you have already had a pregnancy affected by an neural tube defect, you can speak with your doctor about taking a higher dose of folic acid before pregnancy and during early pregnancy.

• Since the United States began fortifying grains with folic acid, there has been a 28% decline in pregnancies affected by neural tube defects (spina bifida and anencephaly) ⁴⁾
• In order to get the recommended 400 micrograms of folic acid every day, a woman of reproductive age can take a supplement containing folic acid or to eat foods fortified with folic acid, or both, depending on her dietary habits.

Anencephaly prevention

There is good evidence that folic acid (vitamin B9) can help reduce the risk of certain birth defects, including anencephaly. Women who are pregnant or planning to become pregnant should take a multivitamin with folic acid every day. Many foods are now fortified with folic acid to help prevent these kinds of birth defects.

Getting enough folic acid can cut the chance of neural tube defects in half.

Folic acid can help reduce the risk of certain birth defects, such as spina bifida and anencephaly.

• Women who are of childbearing age should take at least 400 micrograms (mcg) of a folic acid supplement every day in addition to that found in fortified foods.
• Pregnant women should take add 600 micrograms a day, or 1000 micrograms a day if expecting twins.

Folic acid is available in multivitamins and prenatal vitamins, supplements containing other B-complex vitamins, and supplements containing only folic acid. Common doses range from 400 to 800 mcg in supplements for adults and 200 to 400 mcg in children’s multivitamins ⁵⁾.

About 85% of supplemental folic acid, when taken with food, is bioavailable ⁶⁾. When consumed without food, nearly 100% of supplemental folic acid is bioavailable.

Table 1 lists the current Recommended Dietary Allowances (RDAs) for folate as mcg of dietary folate equivalents (DFEs). Recommended Dietary Allowance (RDA) is the average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.

The Food and Nutrition Board of the Institute of Medicine developed dietary folate equivalents (DFEs) to reflect the higher bioavailability of folic acid than that of food folate. At least 85% of folic acid is estimated to be bioavailable when taken with food, whereas only about 50% of folate naturally present in food is bioavailable ⁷⁾. Based on these values, the Food and Nutrition Board defined dietary folate equivalent (DFE) as follows:

• 1 mcg DFE = 1 mcg food folate
• 1 mcg DFE = 0.6 mcg folic acid from fortified foods or dietary supplements consumed with foods
• 1 mcg DFE = 0.5 mcg folic acid from dietary supplements taken on an empty stomach

Factors for converting mcg DFE to mcg for supplemental folate in the form of 5-methyl-THF have not been formally established ⁸⁾.

For infants from birth to 12 months, the Food and Nutrition Board of the Institute of Medicine established an Adequate Intake (intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an Recommended Dietary Allowance [RDA]) for folate that is equivalent to the mean intake of folate in healthy, breastfed infants in the United States (see Table 1).

Infants

• 0 to 6 months: 65 mcg/day*
• 7 to 12 months: 80 mcg/day*

*For infants from birth to 12 months, the Food and Nutrition Board established an Acceptable Intake (AI) for folate that is equivalent to the mean intake of folate in healthy, breastfed infants in the United States.

Children

• 1 to 3 years: 150 mcg/day
• 4 to 8 years: 200 mcg/day
• 9 to 13 years: 300 mcg/day

Adolescents and adults

• Males, age 14 and older: 400 mcg/day
• Females, age 14 and older: 400 mcg/day
• Pregnant females of all ages: 600 mcg/day
• Breastfeeding females of all ages: 500 mcg/day

Table 1: Recommended Dietary Allowances (RDAs) for Folate

Age	Male	Female	Pregnancy	Lactation
Birth to 6 months*	65 mcg DFE*	65 mcg DFE*
7–12 months*	80 mcg DFE*	80 mcg DFE*
1–3 years	150 mcg DFE	150 mcg DFE
4–8 years	200 mcg DFE	200 mcg DFE
9–13 years	300 mcg DFE	300 mcg DFE
14–18 years	400 mcg DFE	400 mcg DFE	600 mcg DFE	500 mcg DFE
19+ years	400 mcg DFE	400 mcg DFE	600 mcg DFE	500 mcg DFE

[Source ⁹⁾ ]

Food sources of folic acid (vitamin B9)

Table 2: Selected Food Sources of Folate and Folic Acid

Food	Micrograms (mcg) per serving	Percent DV*
Beef liver, braised, 3 ounces	215	54
Spinach, boiled, ½ cup	131	33
Black-eyed peas (cowpeas), boiled, ½ cup	105	26
Breakfast cereals, fortified with 25% of the DV†	100	25
Asparagus, boiled, 4 spears	89	22
Brussels sprouts, frozen, boiled, ½ cup	78	20
Lettuce, romaine, shredded, 1 cup	64	16
Avocado, raw, sliced, ½ cup	59	15
Spinach, raw, 1 cup	58	15
Rice, white, medium-grain, cooked, ½ cup†	54	14
Broccoli, chopped, frozen, cooked, ½ cup	52	13
Mustard greens, chopped, frozen, boiled, ½ cup	52	13
Green peas, frozen, boiled, ½ cup	47	12
Kidney beans, canned, ½ cup	46	12
Spaghetti, cooked, enriched, ½ cup†	45	11
Wheat germ, 2 tablespoons	40	10
Tomato juice, canned, ¾ cup	36	9
Crab, Dungeness, 3 ounces	36	9
Orange juice, ¾ cup	35	9
Bread, white, 1 slice†	32	8
Turnip greens, frozen, boiled, ½ cup	32	8
Peanuts, dry roasted, 1 ounce	27	7
Orange, fresh, 1 small	29	7
Papaya, raw, cubed, ½ cup	27	7
Banana, 1 medium	24	6
Yeast, baker’s, ¼ teaspoon	23	6
Egg, whole, hard-boiled, 1 large	22	6
Cantaloupe, raw, cubed, ½ cup	17	4
Vegetarian baked beans, canned, ½ cup	15	4
Fish, halibut, cooked, 3 ounces	12	3
Milk, 1% fat, 1 cup	12	3
Ground beef, 85% lean, cooked, 3 ounces	7	2
Chicken breast, roasted, 3 ounces	3	1

Footnotes:* DV = Daily Value. The FDA developed DVs to help consumers compare the nutrient contents of products within the context of a total diet. The Daily Value (DV) for folate used for the values in Table 2 is 400 mcg for adults and children age 4 years and older ¹⁰⁾. This Daily Value (DV), however, is changing to 400 mcg DFE as the updated Nutrition and Supplement Facts labels are implemented ¹¹⁾. Manufacturers will use the following conversion factors: 1 mcg DFE = 1 mcg naturally occurring folate = 0.6 mcg folic acid. The updated labels and DVs must appear on food products and dietary supplements beginning in January 2020, but they can be used now ¹²⁾. The FDA does not require food labels to list folate content unless a food has been fortified with this nutrient. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

† Fortified with folic acid as part of the folate fortification program.

[Source ¹³⁾ ]

Fortified means that vitamins have been added to the food. Many foods are now fortified with folic acid. Some of these are:

• Enriched breads
• Cereals
• Flours
• Cornmeals
• Pastas
• Rice
• Other grain products

There are also many pregnancy-specific products on the market that have been fortified with folic acid. Some of these are at levels that meet or exceed the RDA for folate. Women should be careful about including a high amount of these products in their diets along with their prenatal multivitamin. Taking more is not needed and does not provide any added benefit.

The tolerable upper intake level for folic acid is 1000 micrograms (mcg) a day. This limit is based on folic acid that comes from supplements and fortified foods. It does not refer to the folate found naturally in foods.

Anencephaly symptoms

The following are the most common symptoms of anencephaly. However, each child may experience symptoms differently. Symptoms may include:

• Absence of the skull
• Absence of bony covering over the back of the head
• Missing bones around the front and sides of the head
• Absence of parts of the brain
• Facial feature abnormalities
• Congenital heart defects
• Folding of the ears
• Cleft palate. A condition in which the roof of the child’s mouth does not completely close, leaving an opening that can extend into the nasal cavity.
• Some basic reflexes, but without the cerebrum, there can be no consciousness and the baby cannot survive

The symptoms of anencephaly may resemble other problems or medical conditions. Always consult your child’s doctor for a diagnosis.

Anencephaly diagnosis

Anencephaly can be diagnosed during pregnancy or after the baby is born. During pregnancy, there are screening tests (prenatal tests) to check for birth defects and other conditions. Anencephaly would result in an abnormal result on a blood or serum screening test or it might be seen during an ultrasound (which creates pictures of the body).

In some cases, anencephaly might not be diagnosed until after the baby is born.

The diagnosis of anencephaly may be made during pregnancy, or at birth by physical examination. The baby’s head often appears flattened due to the abnormal brain development and missing bones of the skull.

Diagnostic tests

Diagnostic tests performed during pregnancy to evaluate the baby for anencephaly include the following:

• Alpha-fetoprotein (AFP). An alpha-fetoprotein [AFP] is protein produced by the fetus that is excreted into the amniotic fluid. Abnormal levels of alpha-fetoprotein may indicate brain or spinal cord defects, multiple fetuses, a miscalculated due date, or chromosomal disorders.
• Amniocentesis. A test performed to determine chromosomal and genetic disorders and certain birth defects. The test involves inserting a needle through the abdominal and uterine wall into the amniotic sac to retrieve a sample of amniotic fluid.
• Ultrasound (also called sonography). A diagnostic imaging technique that uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs as they function, and to assess blood flow through various vessels.
• Blood tests.
• Urine estriol level
• A pre-pregnancy serum folic acid test may also be done.

During Pregnancy

• An ultrasound during pregnancy is done to confirm the diagnosis. The ultrasound may reveal too much fluid in the uterus. This condition is called polyhydramnios.

Figure 2. Anencephaly ultrasound

Footnote: A single intrauterine fetus at 17 weeks of gestation by AC and FL, with an absence of brain tissue and bony calvarium and a “Frog eye” appearance upon coronal section of the face.

[Source ¹⁴⁾ ]

Anencephaly survival

Anencephaly most often causes death within a few days after birth.

Anencephaly treatment

There is no current treatment. Talk to your health care provider about care decisions.

Future pregnancies

Genetic counseling may be recommended by the doctor to discuss the risk of recurrence in a future pregnancy as well as vitamin therapy (a prescription for folic acid) that can decrease the recurrence for open neural tube defects. Extra folic acid, a B vitamin, if taken one to two months prior to conception and throughout the first trimester of pregnancy, has been found to decrease the reoccurrence of open neural tube defects for couples who have had a previous child with an open neural tube defect. The CDC also recommends to avoid smoking and drinking alcohol during pregnancy.

Back pain in children

Back pain in children is not like back pain in adults. Back pain in children and adolescents is a symptom of many different conditions. Compared to an adult, a child with a back pain is more likely to have a serious underlying disorder such as malignancy (cancer) or infection. All lower back pain in children should be considered seriously and medical advice should always be sought if the pain persists longer than a few days. This is especially true if your child is 4 years old or younger, or if your child of any age has back pain accompanied by:

• Fever or weight loss
• Weakness or numbness
• Trouble walking
• Pain that radiates down one or both legs
• Bowel or bladder problems
• Pain that keeps the child from sleeping

More serious causes of back pain need early identification and treatment or they may become worse. Always see a doctor if your young child’s back pain lasts for more than several days or progressively worsens.

Fortunately, most back pain in children and teens improves with rest, analgesics and sometimes, physical therapy. But in some cases, the pain lingers or repeatedly returns. If this happens to your child, you should contact your child’s pediatrician or an orthopaedic physician for further investigation.

Back pain in children is usually assessed by pediatric physicians who specialize in diagnosing and treating spine conditions and injuries in children, teens and young adults.

In rare cases, back pain in children is a symptom of a larger problem that may need surgical intervention to treat.

Figure 1. Vertebral column (spinal column)

Footnote: Your spine is made up of small bones, called vertebrae, which are stacked on top of one another and create the natural curves of your back.

Back pain in children causes

Many things can cause low back pain or back pain in children. Your spine is a column of bones (vertebrae) held together by muscles, tendons and ligaments and cushioned by shock-absorbing disks. A problem in any part of your spine can cause back pain. A precise cause for the back pain is only identifiable in around 15% of cases.

Most back pain is what’s known as “non-specific” (there’s no obvious cause) or “mechanical” (the pain originates from the joints, bones or soft tissues in and around the spine).

A common cause of back pain is injury to a muscle (strain) or ligament (sprain). Strains and sprains can occur for many reasons, including improper lifting, poor posture and lack of regular exercise. Being overweight may increase your risk of strains and sprains affecting your back.

This type of back pain “non-specific” (there’s no obvious cause):

• tends to get better or worse depending on your position – for example, it may feel better when sitting or lying down
• typically feels worse when moving – but it’s not a good idea to avoid moving your back completely, as this can make things worse
• can develop suddenly or gradually
• might sometimes be the result of poor posture or lifting something awkwardly, but often occurs for no apparent reason
• may be due to a minor injury such as sprain (pulled ligament) or strain (pulled muscle)
• can be associated with feeling stressed or run down
• will usually start to get better within a few weeks

Back pain can also result from more-serious injuries, such as a vertebral fracture or ruptured disk; from arthritis and other age-related changes in your spine; and from certain infections.

Back pain in children is more likely to have a serious cause. The following may be present:

• Developmental disorders: Arthritis of the spine (spondylolysis) or slipping of the vertebral bodies across one another (spondylolisthesis);
• Disc herniation (slipped disc);
• Scheuermann disease: Typically in adolescent males where there is weakening of the vertebral end-plates causing crushing and painless kyphosis (increased curvature of the back producing a ‘hunch’);
• Tumors of the bone or spinal cord;
• Infection of the discs (discitis) or bone (osteomyelitis) mostly in children less than 10 years old;
• Congenital disorders such as scoliosis (lateral curvature of the spine).

Common back pain conditions in children

Muscle strain and imbalances

Musculoskeletal strain is most often responsible for back pain in children and adolescents. This type of pain frequently responds to rest, anti-inflammatory medications, and an exercise program.

Many teenagers may have more persistent back pain. This is often related to tight hamstring muscles and weak abdominal muscles. Having poor posture and carrying a heavy backpack can contribute to this pain. These children seem to improve with a physical therapy program that stresses hamstring stretching, abdominal strengthening and posture correction.

Rounded back or Scheuermann’s kyphosis

In adolescents, increased roundness of the back (when viewed from the side) also called Scheuermann’s kyphosis — is a common cause of pain in the middle of the back (the thoracic spine). Vertebrae become wedged, causing a rounded, or hunched, back. The curved part of the back may ache, and pain may get worse with activity.

Stress fracture of the spine

Spondylolysis or stress fracture, may cause lower back pain in adolescents. The pain occurs in otherwise healthy children or adolescents, and usually happens with vigorous activity. Stress fractures may occur during adolescent growth spurts or in sports that repeatedly twist and hyperextend the spine, like gymnastics, diving, and football.

Pain is usually mild and may radiate to the buttocks and legs. The pain feels worse with activity and better with rest. A child with spondylolysis may walk with a stiff legged gait and only be able to take short steps.

Most children and teens with spondylolysis can be managed with nonoperative treatment such as pain relievers. However, in some cases surgical treatment is necessary to provide pain relief.

If surgery is necessary, the procedure will most likely be a spinal fusion, or less commonly, a reconstruction of the stress fracture.

Slipped vertebra or spondylolisthesis

A slipped vertebra, or spondylolisthesis, occurs when one vertebra shifts forward on the next vertebra directly below. This may sometimes represent progression of a spondylolysis. It usually occurs at the base of the spine (lumbosacral junction). In severe cases, the bone narrows the spinal canal, which presses on the nerves.

Infection

Back pain also can be caused by an infection that involves the disc space, vertebra or the posterior part on the pelvis. In young children, infection in a disk space (diskitis) can lead to back pain. Discitis typically affects children between the ages of 1 and 5 years, although older children and teenagers can also be affected.

A child with discitis may have the following symptoms:

• Pain in the lower back or abdomen and stiffness of the spine
• Walking with a limp, or simply refusing to walk
• Squatting with a straight spine when reaching for something on the floor, rather than bending from the waist

Once diagnosed, the infection usually responds to medications. If diagnosis is delayed, an abscess can develop that may require surgical drainage.

Tumor

On rare occasion, tumors, such as osteoid osteoma, can be responsible for back pain. When they occur, tumors of the spine are most often found in the middle or lower back. Pain is constant and usually becomes worse over time. This pain is progressive; it is unrelated to activity and/or happens at night.

Scoliosis

Though not common, back pain can be caused by a form of scoliosis — including idiopathic scoliosis, congenital scoliosis, neuromuscular scoliosis and early-onset scoliosis.

In many cases, scoliosis can be treated with braces, physical therapy and medication for occasional pain. If your child is experiencing severe back pain due to scoliosis, surgical intervention may be necessary.

Treatments include spinal fusion, growing rods and, in special circumstances, vertical expandable prosthetic titanium ribs (VEPTR).

Adolescent intervertebral disc herniation

Sometimes one of the discs that cushions your child’s vertebrae ruptures or herniates. This puts pressure on your child’s spinal nerves or the spinal cord.

Although less common than the disc problems observed in adults, some adolescents do develop disc disease which can lead to considerable pain and disability.

If your child has long lasting, unrelieved pain caused by a disc herniation, he may require surgical removal of the disc.

Back pain in children diagnosis

Back pain is a symptom of many different conditions. Because of that, doctors use a variety of imaging modalities to help them better pinpoint the source of your child’s back pain.

At your first appointment, the doctor will discuss your symptoms with you and examine your back. An accurate history and physical examination are essential for evaluating acute low back pain.

Often, patients awaken with morning pain or develop pain after minor forward bending, twisting, or lifting. It is also important to note whether it is a first episode or a recurrent episode. Recurrent episodes usually are more painful with increased symptoms. Red flags are often used to distinguish a common, benign episode from a more significant problem that requires urgent workup and treatment. A recent study shows that some red flags are more important than others, and that red flags overall are poor at ruling in more serious causes of low back pain. Patients with back pain in the primary care setting (80 percent) tend to have one or more red flags, but rarely have a serious condition. There are certain signs and symptoms of more serious causes of lower back pain such as cauda equina syndrome, major intra-abdominal pathology, infections, malignancy, and fractures. Cauda equina syndrome and infections require immediate referral.

They will usually assess your ability to sit, stand, walk and lift your legs as well as test the range of movement in your back. To help them diagnose the cause of the pain, they may ask questions about any illnesses or injuries you may have had, your lifestyle and your work. Your back is a complex structure, so finding the exact cause can often be difficult.

Below are some of the questions your doctor may ask. It might be helpful to consider these before your appointment:

• When did the back pain start?
• Where are you feeling pain?
• Is your pain worse at night?
• Constant back pain that does not ease after lying down?
• Numbness (loss of feeling, or a tingling sensation) around your genitals, buttocks or anal area?
• Have you had any back problems before?
• Can you describe the pain?
• What makes the pain better or worse?
• Do you have any weakness or numbness?
• Loss of bowel or bladder function?
• Inability to pass urine
• Do you use illicit drugs (intravenous drug use)?
• Severe pain?
• Do you have fever?
• Do you have unexplained weight loss?

They will first want to make sure your pain is not being caused by a more serious condition. They will ask questions to rule out cancer, a fracture or an infection, although these conditions are uncommon.

If your doctor thinks there may be a more serious cause you will be referred for further tests.

Without signs and symptoms indicating a serious underlying condition, imaging (x-ray or an MRI scan) won’t help the diagnosis of your back pain and does not improve clinical outcomes in these patients ¹⁾.

Even with a few weaker red flags, four to six weeks of treatment is appropriate before consideration of imaging studies ²⁾. If a serious condition is suspected, magnetic resonance imaging (MRI) is usually most appropriate. Computed tomography is an alternative if MRI is contraindicated or unavailable ³⁾. Clinical correlation of MRI or computed tomography findings is essential because the likelihood of false-positive results increases with age ⁴⁾. Radiography may be helpful to screen for serious conditions, but usually has little diagnostic value because of its low sensitivity and specificity.

Laboratory tests such as complete blood count with differential, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level may be beneficial if infection or bone marrow neoplasm is suspected. These tests may be most sensitive in cases of spinal infection because lack of fever and a normal complete blood count are common in patients with spinal infection ⁵⁾. Because laboratory testing lacks specificity, MRI with and without contrast media and, in many cases, biopsy are essential for accurate diagnosis ⁶⁾.

Physical examination

During the physical examination, your doctor will carefully check the following:

• Spine. This will include feeling each vertebra and looking for deformities in the alignment and mobility of the spine. Increased roundness of the back (when viewed from the side) or a curve to the side (when viewed from the back) could be important. Your doctor will check posture and walking gait, the ability to bend over to touch the toes, and bending to the right and left. Difficulty with movement may indicate that there is a problem with the joints of the spine.
• Nerves in the back. Problems with the intervertebral disks can cause pressure on the nerves that exit the spine, so your doctor will perform specific tests for that. With your child lying face up, your doctor will raise the legs (straight leg raising test) and may also raise the legs with your child lying face down (reverse straight leg raising test). Testing reflexes and feeling in the legs will be done for the same reason.
• Muscles. The muscles in the back and legs wil be tested. Tightness of the back muscles or the hamstring muscles at the back of the thigh will show that your child is trying to protect himself or herself from movements and positions that might be painful. Tenderness of the muscles will indicate a muscle injury, such as a strain.
• Balance, flexibility, coordination, and muscle strength. Other tests may be done to ensure that the back pain is not part of a bigger picture.

Imaging tests

Pediatrician or an orthopaedic physician use a variety of imaging modalities to help them better pinpoint the source of your child’s back pain.

Imaging tests include:

• X-rays. X-rays provide images of dense structures, such as bones. X-rays of your child’s spine will show if there are fractures, displacements, or other problems within the bones.
• Computerized tomography (CT scan). This is a special x-ray technique that provides a three-dimensional image. It allows your doctor to see things that are not visible on two-dimensional x-rays, and is particularly helpful for understanding the complex anatomy of the spine.
• Magnetic resonance imaging (MRI). An MRI shows the body’s soft tissues. It can be used to see the spinal cord, nerve roots, disks, and other structures that can be very important in back pain.
• EOS imaging (3-D imaging system that scans your child standing up). EOS delivers a radiation dose that is two to three times less than a general computed radiography X-ray and 20 times less than basic computed tomography (CT) scans.
• Bone scan. A bone scan involves injecting a substance into a vein, then using a special camera to see where it is picked up. It can pinpoint inflammation, infections, tumors, and fractures. Since the anatomy of the spine is very complicated and since these disease processes are not always visible on x-ray, a bone scan can be very useful.
• Positron emission tomography (PET). PET scan can help your doctor understand more about how the body’s tissues and organs are functioning.

Laboratory tests

Blood tests, including the complete blood-cell count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), can be affected by the presence of inflammation or infection.

Back pain in children treatment

Back pain in children treatment involves treating the underlying cause of the back pain.

Most cases of back pain don’t require medical attention and can be treated with over-the-counter pain relief medication and self-care.

Most people prefer to take acetaminophen (paracetamol) or anti-inflammatory drugs such as ibuprofen.

Back pain in children prognosis

Many children who experience back pain will quickly heal and move on with their lives. For children who experienced an infection that caused the back pain, recovery is generally complete after treatment.

For children diagnosed with spine conditions — scoliosis, spondylolysis or disc herniation — that required surgery, ongoing clinical follow-up is encouraged.

Calcaneovalgus foot

Calcaneovalgus foot is one of the most common deformities of the foot seen in newborns. Babies with calcaneovalgus foot are born with their foot and ankle excessively bent up, where the toes are usually touching the shin. Calcaneovalgus foot deformity may also present in older children, but is usually a manifestation of another condition.

The axis of calcaneovalgus deformity is in the tibiotalar joint, where the foot is positioned in extreme hyperextension, with its dorsum frequently touching the distal leg ¹⁾. Females are affected more often than males, and calcaneovalgus foot deformity can be unilateral or bilateral ²⁾. Calcaneovalgus foot occurs in about 5 percent of all newborns ³⁾ and is associated with external rotation of the calcaneus, an overstretched Achilles tendon, and tight anterior leg musculature, all of which warrant treatment ⁴⁾.

On inspection, the foot has an “up and out” appearance, with the dorsal forefoot practically touching the anterior aspect of the ankle and lower leg (Figure 1). The ankle generally can be plantarflexed to only 90 degrees or less. Radiographs can confirm clinical diagnosis.

Calcaneovalgus is a positional deformity that is highly amenable to treatment. According to some authors ⁵⁾, it has an excellent natural history and can spontaneously resolve on its own. Others ⁶⁾ advocate a more aggressive approach because of the possibility of future complications, such as permanent muscle imbalance, peroneal tendon dislocation, and delayed ambulation. Generally, the more severe the limitation of ankle plantar flexion, the more treatment is warranted.

Treatment should begin as early as possible. Mild cases can be treated with stretching exercises performed at each diaper change. Stretching consists of gentle plantarflexion of the foot with mild inversion for a count of 10, repeated three times. In moderate cases or when stretching fails to correct the deformity, splinting or firm, high-top, lace-up shoes that prevent dorsiflexion can be used. For severe deformities with significant limitation of ankle plantarflexion, serial mobilization casting is performed until corrected, followed by nightly maintenance use of a bivalved cast or splinting of the posterior aspect of the leg for a two- to 10-week course ⁷⁾.

Figure 1. Calcaneovalgus foot (correctable)

Footnote: A big difference between calcaneovalgus and congenital vertical talus is whether the deformity is rigid or flexible. Therefore it is important to examine the flexibility of the foot and write this in the notes. Look at the examination above. Calcaneovalgus foot is usually flexible, vertical talus is rigid.

Calcaneovalgus foot causes

Although the true cause of calcaneovalgus foot is unknown, the theory is that this is part of intrauterine “packaging” disorder, in other words, it reflects the babies foot position in the womb during the last few months of pregnancy. Calcaneovalgus runs in families, and more girls than boys have it.

Calcaneovalgus foot symptoms

Calcaneovalgus foot is obvious at birth. The foot is usually partially corrected, so the foot can be brought to the “normal” 90 degrees ankle position. It can present as unilateral or bilateral and it may be associated with other conditions, namely: posterior-medial bowing of the tibia (the leg is curved and shorter in the affected site), vertical talus (the talus bone is not in its correct position causing the entire foot to look deformed), muscle imbalance or nerve injury (usually seen in older children).

Calcaneovalgus foot diagnosis

While most children with calcaneovalgus outgrow the deformity, it is important for a trained clinician to examine your child to rule out more serious conditions.

Pediatricians and pediatric orthopedic surgeons may examine children with calcaneovalgus foot. Your child’s doctor will perform a complete medical history, physical examination and visual evaluation of your child.

Clinicians will ask if anyone else in your family is affected, look for other associated deformities, and examine your child from head to toes.

If there are any concerns of a more complex cause for calcaneovalgus foot, further investigation may be warranted utilizing:

• X-rays, which produce images of bones.
• Ultrasound, usually used for examination of babies’ hips and spine prior to their ossification/full development

Calcaneovalgus foot treatment

For most children with typical calcaneovalgus foot, no treatment is necessary, except for some home stretching exercises. Calcaneovalgus foot usually improves within the first several weeks of life. If there are other causes or associated conditions, those will be approached and managed as indicated.

It can be hard to treat calcaneovalgus foot in an older child. So it is best if the child is diagnosed as an infant. Here is what you can expect:

• For mild cases. Your child’s doctor will prescribe stretching exercises to be done at each diaper change. The parent gently moves the foot down and in for a count of 10, repeating the stretch 3 times.
• For moderate cases or when stretching does not correct the condition. Your child’s doctor may prescribe splints or firm, high-top, lace-up shoes. These hold the foot in the correct position.
• For severe cases. Your child’s doctor may prescribe casting of the child’s legs and feet for up to several months. The casts move the child’s foot into normal position. Casts are changed every 1 to 2 weeks.

Follow-up care

Most children with calcaneovalgus feet will not need long-term follow-up care. Except for children who present the deformity later in life and have other associated conditions.

What are the long-term concerns of calcaneovalgus feet?

• If diagnosed and treated, the child’s foot often works well and looks normal.
• If it doesn’t go away, calcaneovalgus can cause problems with muscle development and walking. So your child should see their healthcare provider for regular follow-up visits to be sure the problem goes away.