Infantile Spasms

Description

Other Names

West syndrome, hypsarrhythmia, lightning spasms

Diagnosis Coding

ICD-10

G40.821, epileptic spasms not intractable, with status epilepticus

G40.822, epileptic spasms not intractable, without status epilepticus

G40.823, epileptic spasms intractable, with status epilepticus

G40.824, epileptic spasms intractable, without status epilepticus

Further coding details can be found by using the search feature at ICD10Data.com.

Description

Infantile spasms (IS) are a type of seizure seen in infancy that occur as the main feature of a seizure syndrome known as West syndrome. Though the terms West syndrome and IS are used interchangeably, IS is preferred. Infantile spasms generally consist of an acute onset of stiffening of the legs and arms while bending forward and may be asymmetrical. They are brief but tend to occur in clusters lasting several minutes or more at a time. They do not usually occur during sleep, but are often observed upon awakening in the morning or after a nap. They can be subtle and are sometimes confused with the Moro reflex or colic. IS may appear as:
  • Extension/stiffening of the trunk, arms, and legs
  • Flexing at the waist, especially obvious when sitting
  • Thrusting arms to side or across chest
  • Repetitive head bobbing or nodding
  • Drawing up of legs to the chest when lying down.
Infants with IS may also demonstrate a delay in or loss of previously achieved developmental milestones. Findings may include poor tone, poor head control, loss of eye contact, decreased responsiveness to sounds and eye contact, and a decrease in alertness.
West syndrome/IS is diagnosed when an infant, approximately 3-6 months of age, has spasms that are present in clusters and in great numbers (up to 100 spasms in a cluster and sometimes many clusters a day), developmental delay, and a characteristic EEG pattern called hypsarrhythmia (high amplitude chaotic abnormal pattern). See EEG example of hysarrhthymia (Epilepsy.com) for an example of this EEG pattern. Other seizure types are also seen in 30 to 50% of infants with this syndrome. Spasms usually stop as the infant gets older, but other seizure types often take their place (see the Prognosis section, below).

There are two kinds of IS, symptomatic and idiopathic, and they have dramatically different prognoses. In symptomatic IS, a specific etiology can be identified through history, physical exam, or testing. Tuberous sclerosis and perinatal asphyxia are the most common symptomatic etiologies. Other causes include cortical brain malformations, metabolic disorders (e.g., maple syrup urine disease, pyridoxine dependency, nonketotic hyperglycemia, phenylketonuria), chromosomal abnormalities, other neurocutaneous syndromes, infection, including prenatal infections (e,g, congenital CMV), and brain tumors. Of children with IS, 85-90% of children with IS have the symptomatic type. [Pellock: 2010]

Infants with idiopathic IS have normal development and neurologic exams at the onset of spasms and a higher likelihood of "growing out" of them, particularly if the spasms respond well to medication. This suggests that early diagnosis and treatment may affect the outcome in children with idiopathic IS, although children who do and do not respond to medication may represent different populations that we are yet unable to otherwise differentiate. [You: 2009]

Some neurologists identify a third group, cryptogenic IS, in which children at the onset of the spasms are either delayed developmentally or have an abnormal neurologic exam at the onset of the spasms but no specific cause can be identified.

Prevalence

0.15 to 0.2 per 1000 children 10 years of age or younger. [Mackay: 2004]

Genetics

Many of the causes of infantile spasms are genetic in origin; including tuberous sclerosis, metabolic disorders, and chromosomal abnormalities. The ARX and CDKL5 genes are associated with infantile spasms in some infants with cryptogenic IS. [Guerrini: 2007] [Bahi-Buisson: 2008]

Prognosis

Overall:
The prognosis for children with IS depends on the etiology of the spasms and whether or not there is developmental delay or an abnormal neurologic exam at the time of presentation. A good outcome is associated with a lack of identifiable etiology, normal neurologic exam and development at the time of presentation, older age at onset, and a relatively quick and complete response to treatment of the spasms. Most infants with IS have poor outcomes. Overall, 70-90% of children with IS will have intellectual disability, usually severe to profound. About 50% will develop some signs of cerebral palsy, and a smaller percentage of children will demonstrate autistic symptoms. [Partikian: 2009] [Mackay: 2004] Development may be improved with early, effective treatment, although the optimal regimen is not known. [Hamano: 2007] [Kivity: 2004] Between 40 and 60% of children with IS will develop Lennox-Gastaut syndrome, a refractory epilepsy syndrome of childhood. [Zupanc: 2009] The evolution from IS to Lennox-Gastaut syndrome may be decreased by early, effective treatment, although there is only circumstantial evidence for this. [You: 2009]

By group:
Treatment is more likely to result in complete or near-complete recovery in those with idiopathic IS than in symptomatic or cryptogenic IS. [Partikian: 2009] [Mackay: 2004]

Roles Of The Medical Home

Although treatment of infantile spasms (IS) will usually be initiated by a pediatric neurologist, the Medical Home clinician will provide ongoing care and monitoring for side effects during treatment. Concerns about developmental abilities will be addressed through the Medical Home; developmental monitoring and referral to outside agencies such as Early Intervention programs are crucial.

Practice Guidelines

Go CY, Mackay MT, Weiss SK, Stephens D, Adams-Webber T, Ashwal S, Snead OC 3rd.
Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
Neurology. 2012;78(24):1974-80. PubMed abstract / Full Text

Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, Gaillard WD, Gibson PA, Holmes GL, Nordl DR, O'Dell C, Shields WD, Trevathan E, Wheless JW.
Infantile spasms: a U.S. consensus report.
Epilepsia. 2010;51(10):2175-89. PubMed abstract

Hancock EC, Osborne JP, Edwards SW.
Treatment of infantile spasms.
Cochrane Database Syst Rev. 2008(4):CD001770. PubMed abstract

Helpful Articles

PubMed search for articles on Infantile Spasms in children for the last 3 years

Shields WD.
Infantile Spasms: Little Seizures, BIG Consequences.
Epilepsy Curr. 2006;6(3):63-9. PubMed abstract / Full Text

Wheless JW, Gibson PA, Rosbeck KL, Hardin M, O'Dell C, Whittemore V, Pellock JM.
Infantile spasms (West syndrome): update and resources for pediatricians and providers to share with parents.
BMC Pediatr. 2012;12:108. PubMed abstract / Full Text

Nabbout R, Dulac O.
Epileptic syndromes in infancy and childhood.
Curr Opin Neurol. 2008;21(2):161-6. PubMed abstract

Clinical Assessment

Overview

Primary care providers should consider a diagnosis of infantile spasms in an infant with unusual movements that cluster on awakening, especially if the infant already has developmental delay. If EEG confirms the diagnosis, an etiology for the spasms should be sought. Almost anything that causes brain damage can be associated with infantile spasms; an etiology can be found for about 3/4 of infants with IS. Etiology often determines prognosis for seizure cessation and for eventual developmental outcome. Specific therapies exist for a few of the underlying disorders including pyridoxine-dependent seizures and focal cortical dysplasias (treated with vitamin B6 and surgical resection, respectively). The Infantile Spasms Diagnostic Algorithm (Pediatric Neurology Division, University of Utah/Primary Children's Medical Center, Salt Lake City, UT) (PDF Document 53 KB) may guide the workup. The diagnostic evaluation should be tailored to the individual child, so not all studies are recommended for all children.

After they are diagnosed, infants with infantile spasms (IS) will undergo treatment with the goal of eliminating the spasms. Ongoing assessment will be needed to determine if the treatment is working and to monitor health, growth, and development during treatment. Assessment will vary depending on treatment. Children on high dose steroids will need monitoring for side effects, including weight changes, blood pressure increases, etc. The frequency of follow-up appointments for infants with IS who are undergoing treatment will vary depending on treatment choice and resources available. For instance, an infant receiving high dose steroids should be seen at least weekly, though some of these visits may be replaced by a visit by a nurse during a home health visit.

Screening

There is no screening for IS.

Presentations

Although spasms may begin as early as a month or two after birth or as late as two years of age, in most affected children they begin between 4 and 6 months and, in approximately 90%, within their first year of life. Characteristic symptoms include rapid muscular contractions of extremities in any of several patterns, including flexion, extension, and mixed patterns. These can be easily confused with other movements (e.g., Moro reflex, Sandifer syndrome). Individual spasms last only 1 to 2 seconds each and usually occur in clusters of from just a few to 100. Clusters may occur many times a day, are common when the child is awakening in the morning or after a nap, and may be accompanied by irritability and crying. The child's developmental trajectory often slows or reverses around the time of spasm onset; families may notice a decrease in developmental progress and a decrease in interaction with the environment.

Diagnostic Criteria

IS refers to the seizures as described above and is often used somewhat interchangeably with West syndrome. To meet full criteria for West syndrome, the child must demonstrate the triad of spasms, intellectual disability/developmental delay, and hypsarrhythmia on EEG. See EEG example of hysarrhthymia (Epilepsy.com).

Differential Diagnosis

IS are diagnosed by the appearance of the seizures (the seizure "semiology"), the characteristic age at which they appear, and distinct abnormalities on EEG. If an EEG obtained in a child with suspected IS is normal, the diagnosis should be reconsidered. Other entities to consider include:

The Moro reflex is a normal finding in infants up to about 3 or 4 months. When the infant is quickly moved, he/she will look startled, fling his/her arms out (palms up), and then draw the arms back to the body, and relax. See Moro reflex (MedlinePlus) and Moro reflex (picture) (MedlinePlus).

The bobble-headed doll syndrome is a movement disorder seen in children where there is episodic up and down or side-to-side movement at 2-3 Hz. This disorder is often associated with third ventricle tumors, aqueductal stenosis, communicating hydrocephalus and other structural brain disorders that can be diagnosed with brain MRI.

Spasmus nutans is a disorder seen in infants and young children. It consists of rapid, uncontrolled eye movements, head bobbing, and sometimes abnormal head positioning. Although an MRI of the brain is often performed to rule out brain abnormalities, a cause for this movement disorder is rarely found and it usually resolves without treatment after several months. [Dugdale: 2009]

Other seizure types - Although IS may appear similar to myoclonic and tonic seizures, they are distinct and will require different treatment. It may be helpful for the family to record episodes on video and to look for the initial contraction followed by a longer tonic phase that is typical for IS. Look for the combination of developmental delay and the characteristic EEG pattern.

Sandifer syndrome is body stiffening due to GE reflux, but may look similar to the tonic spasms seen in IS. Differentiating them may require additional workup, including a pH probe and an upper GI series. Sandifer’s may be seen with severe reflux and lacks the EEG findings of IS.

Pearls & Alerts

Clusters on awakening

IS clusters on awakening, whether in the morning or after a nap. If the family describes unusual movements in their infant with this pattern, IS should be strongly considered.

IS and vaccines

Although it will sometimes seem to families that the onset of IS was caused by vaccine administration, there is no convincing evidence to support causality. [Willmore: 2009]

Developmental assessments

Even a child who is developing typically when the manifestations of IS begin may show a slowing of milestone achievement or even regression. The Medical Home provider should consider frequent developmental evaluation while IS continue. Developmental assessments may be available through Early Intervention programs (See Services below).

History & Examination

Clues to the etiology should be looked for when conducting the initial history and exam.

Family History

Inquire about a family history of neurocutaneous disorders, seizures, and developmental delay/intellectual disability.

Pregnancy Or Perinatal History

Inquire about problems during pregnancy that might have led to hypoxic ischemic encephalopathy such as intrauterine growth retardation, maternal illness, and toxin exposures. Ask about a history of, or symptoms of, CNS infection, possibly prenatal, such as CMV, herpes simplex, or meningitis/encephalitis. About 50% of IS cases are due to a prenatal cause. [Pellock: 2010]

Current & Past Medical History

Ensure newborn sceening was performed and results are normal. Inquire about symptoms that might signal metabolic disease, e.g. unusual smelling urine, episodes of hypoglycemia or unresponsiveness, vomiting. Ask about any previous illnesses. Infants should be monitored for irritability, history of infections, and evidence of heart failure, including fatigue, listlessness, sweating or tiring easily while eating. Look for increased thirst and wet diapers as a sign of hydration.

Developmental & Educational Progress

It is important to take a full developmental history. IS may interfere with developmental progress in children with IS and/or IS may occur in a child with developmental delay. Development will need to be followed closely in the Medical Home.

Social & Family Functioning

Ask about finances, distance from pediatric medical care, and the presence of support systems - the care of a child with IS can put significant strains on a family. IS and its treatment can be emotionally difficult and financially burdensome for the family. Coping skills and resources should be assessed periodically.

Physical Exam

General

Check for dysmorphic features. Chromosomal and genetic abnormalities that have been associated with IS include trisomy 21, Miller-Dieker syndrome, CDKL5, and ARX mutations.Look for alertness, level of interaction with the environment, irritability, signs of infection

Vital Signs

As a baseline before medications. BP should be checked weekly for infants on high dose steroids

Growth Parameters

Ht | Wt | OFC Excessive weight gain may occur in infants on high dose steroids, weight should be monitored weekly

Skin

Look for unusual skin coloration abnormalities, especially the swirling pattern of hyperpigmented skin seen in Incontinentia pigmenti (NINDS) or the hypomelanotic ash-leaf macules associated with tuberous sclerosis. These may be difficult to see in light-skinned infants, so at least one exam using a Woods lamp should be performed in all infants with IS.

Neurologic Exam

Screening neurologic exam for asymmetries, tone problems, eye movement abnormalities, etc.

Testing

Sensory Testing

Hearing and vision testing is recommended, especially in the setting of developmental delay.

Laboratory Testing

If no structural cause is found for IS, a battery of tests is generally ordered to look for a metabolic cause. These may include CBC with differential, plasma amino acids, biotinidase, lactate and pyruvate, anion gap, and urine for organic acids, uric acid, and others. A lumbar puncture (LP) will often be performed to test cerebrospinal fluid for cell count, protein, and glucose (with a near simultaneous blood glucose), lactate, amino acids, 5-Methyltetrahydrofolate (a form of folic acid), and pyridoxal 5-phosphate (a form of vitamin B6). These tests are aimed at identifying treatable metabolic disorders, infection, and glucose transporter deficiency. Screen for fecal occult blood and urine for glucose periodically in infants on high dose steroids.

Imaging

MRI - brain (sedated) - Looking for signs of tuberous sclerosis, brain malformations, evidence of past hypoxia-ischemia, etc.Indicated if a genetic entity is thought to be responsible.

Other Testing

EEG - wake and sleep. It is particularly helpful to have an EEG recording during the episodes thought to be infantile spasms. EEG demonstrates hypsarrhthymia, a very high-voltage chaotic pattern, or modified hypsarrhthymia, in a majority of cases. Multifocal spike discharges (MSD) are found in the remainder of EEGs. A followup EEG may be requested by the treating pediatric neurologist to assess treatment response.

Ophthalmologic assessment: If the infant is on vigabatrin, ophthalmological assessment to follow for retinal changes associated with vision loss is performed at about 3 month intervals after baseline evaluation.

Subspecialist Collaborations & Other Resources

Pediatric Neurology (see Services below for relevant providers)

Generally, children with infantile spasms should be evaluated and treated by a pediatric neurologist. Infants who are probably having infantile spasms may be admitted for the initial evaluation in order to expedite testing and treatment or if appropriate, infants may be seen urgently in outpatient clinic. If you are considering infantile spasms as a diagnosis, contact pediatric neurology to arrange for evaluation as quickly as possible.

Pediatric Genetics (see Services below for relevant providers)

A small percentage of children with IS may have associated or causative genetic abnormalities. Genetic evaluation should be coordinated with Pediatric Neurology.

Developmental Pediatrics (see Services below for relevant providers)

Referral may be helpful for developmental evaluation and to identify strategies for improving delays. Treatment of infants with IS will generally be carried out in conjunction with pediatric neurology, and often by protocol. See ACTH Prescribing Protocol (Pediatric Neurology Division, University of Utah/Primary Children's Medical Center, Salt Lake City, UT) (PDF Document 41 KB) for an example.

Pediatric Ophthalmology (see Services below for relevant providers)

Ophthalmology referrals may be helpful for diagnosis and monitoring of vision, and will be necessary if the infant is on vigabatrin.

Early Intervention Programs (see Services below for relevant providers)

Infants with IS should be enrolled in Early Intervention programs to follow and provide support for developmental progress.

Treatment & Management

Pearls & Alerts

Immunizations

Immunizations should be postponed until at least a month after discontinuing high dose steroids used to treat IS.

Cessation of IS

Complete cessation of seizures is the goal when treating infantile spasms. Developmental outcome may be better if the spasms are controlled quickly. [You: 2009]

Specific treatment for IS with known etiologies

A few causes of IS have specific treatments including pyridoxine-dependent epilepsy and glucose transporter deficiency.

Systems

Neurology

Treatment is generally provided by a pediatric neurologist in communication with the Medical Home provider. Although the pediatric neurologist is responsible for the evaluation and initiation of treatment, monitoring during treatment, particularly if the child lives far away from the neurologist's office, will be up to the Medical Home. Treatment is pursued early and aggressively in infants with IS as the prognosis is extremely poor without treatment and early treatment may affect the outcome. [You: 2009] The goal of IS treatment is cessation of IS and normalization of the EEG. Treatment options include ACTH, prednisolone/prednisone, vigabatrin (Sabril), the Ketogenic Diet, [Kossoff: 2008] and anticonvulsants such as topiramate. Vigabatrin, which has been used in Europe for many years, appears to be particularly helpful in IS associated with tuberous sclerosis. [Fattal-Valevski: 2009] [Vigevano: 1997] [Pellock: 2010] Other medications have been tried, and may occasionally help, but in general have been unsuccessful in stopping IS. Surgery may also be an option in a minority of patients. Which treatment option to choose will be determined by patient characteristics and local expertise. Options are discussed below.

Oral prednisolone Because of the prohibitive cost of ACTH, oral prednisolone has recently been investigated and may be equivalent to ACTH treatment with fewer side effects and lower cost. Doses greater than 3 mg/kg/day were more effective than doses 2-3 mg/kg/day, with effective doses between 40-60 mg/day. The regimen used by Kossoff et al., is 15 mg (5 ml three times) daily at first, increased to four times daily if necessary, then decreased to twice and then once daily at two week intervals. [Kossoff: 2009]

The UKISS study showed an IS cessation rate of approximately 70% with high dose prednisolone compared to 76% with ACTH. [Lux: 2004] Infants treated with prednisolone had fewer adverse effects (53% compared to 80% with ACTH) and prednisolone was $200 for the course, whereas ACTH averaged around $70,000. [Kossoff: 2009] Other study groups have found similar results. [Azam: 2005]

ACTH at varying doses (ranging between 10 and 150 IU/m2 given either daily or every other day) has been the treatment of choice in the US for many years and continues to be used despite its escalating cost. ACTH may be particularly useful in children who have IS due to hypoxic-ischemic encephalopathy.[Vigevano: 1997] Somewhere between 50 and 91% of children stop having IS with the 40 IU/m2 dose; a higher dose may be tried in infants who respond incompletely. ACTH is typically continued for 4 weeks after the spasms stop. [Mackay: 2004] If relapses occur, sometimes a second course of ACTH may stop the spasms again or another treatment might be tried.

ACTH must be given by IM injections and has many potentially serious side effects. Infants are usually started on GI prophylaxis (e.g., ranitidine) to prevent gastrointestinal bleeding and a low salt diet to prevent hypertension. Children are monitored by Medical Home providers, sometimes with the help of home health to check weight, irritability, blood pressure, fecal occult blood, and urine glucose. Possible side effects include weight gain, hypertension, metabolic abnormalities, ulcers leading to gastric hemorrhage, irritability, sepsis, osteoporosis, and heart failure caused by dilated cardiomyopathy. (Some series show up to a 5% mortality rate.) See ACTH Prescribing Protocol (Pediatric Neurology Division, University of Utah/Primary Children's Medical Center, Salt Lake City, UT) (PDF Document 41 KB) for an example of an ACTH protocol and see ACTH manufacturer information (ACTHAR gel). Also see IS Provider Letter (Pediatric Neurology Division, University of Utah/Primary Children's Medical Center, Salt Lake City, UT) (PDF Document 55 KB) for information for the primary care clinician when a child in his or her practice is started on ACTH.

In 2009, vigabatrin was licensed by the FDA to treat IS in infants 1 month to 2 years of age. Generally, vigabatrin is thought to be more effective in infants with IS due to tuberous sclerosis, and in this case is often the first-line treatment although there are no evidence-based recommendations for appropriate dosing. [Pellock: 2010] In a study where infants with tuberous sclerosis were excluded, after two weeks of treatment only 54% of infants responded to vigabatrin therapy compared to 70% and 76% receiving prednisolone or ACTH, respectively. [Lux: 2004] However, twelve to fourteen months after initiation of treatment, percentages were similar in vigabatrin and hormone therapy treated groups. [Lux: 2005] Adverse effects were common, and excluding any effects on vision, occurred at similar rates with vigabatrin and hormonal treatments. [Lux: 2004] Because earlier control of infantile spasms may be correlated with improved developmental outcome, however, hormonal treatment may be preferable. [Lux: 2005]

Vigabatrin prescriptions are restricted to patients registered with the manufacturer due to a high incidence of vision loss in patients of all ages treated with this medication. Vision loss may be linked to taurine deficiency, and if this association is confirmed, may be amenable to dietary treatment in the future. [Jammoul: 2009] Current recommendations are that vigabatrin should be used at the lowest dose possible, for the shortest duration possible, and stopped if there is no observed benefit after 2-4 weeks of use. The goal of vigabatrin therapy, as with ACTH therapy, is cessation of IS. Dosing starts at 50 mg/kg/day in two divided doses and increases up to a maximum of 150 mg/kg/day, with a slow increase (25-50 mg/kg/day increments every 3 days) until maximized. Vigabatrin is given to families in packets of powder which they reconstitute depending on the dosage required. Vigabatrin is sent out directly to families from the pharmaceutical company program. Detailed instructions are given on the dosing information and the Medical Home clinician may need to ensure that families are giving the medication correctly. When stopping vigabatrin, the dosage should be tapered gradually. Vigabatrin prescribing information (Lundbeck SHARE program)

All patients receiving vigabatrin need to be registered in the pharmaceutical company (Lundbeck SHARE) program due to concerns about its effects on vision. See Vigabatrin prescribing information (Lundbeck SHARE program). This program mandates baseline vision screening, with retesting at three-month intervals, or as recommended by providers, and after vigabatrin therapy has been discontinued, for all individuals receiving this medication. The pediatric neurologist, not the Medical Home provider, is responsible for arranging ophthalmology follow-up for infants receiving vigabatrin. In adults, vision loss usually manifests as permanent bilateral concentric visual field constriction, leading to loss of peripheral vision. Vision loss appears to be proportional to cumulative dose, but may continue after vigabatrin has been stopped. It is difficult to measure vision loss in infants, but the retinal defects thought to correlate with vision loss in adults are found, at the earliest, about 3 months after initiating treatment, making short term use seem relatively safe. [Willmore: 2009] Ultimately, 15-30% of infants treated with vigabatrin manifest retinal defects; this percentage is probably smaller than that observed in adults. [Gaily: 2009] [Willmore: 2009]

MRI changes have also been observed in some infants receiving vigabatrin for IS. These changes, which are of uncertain significance, involve increased T2 signal and a restricted, symmetric, diffusion pattern in the thalamus, basal ganglia, brain stem and cerebellum. There is no suggested screening for these changes at the current time. Vigabatrin prescribing information (Lundbeck SHARE program) Other side effects including somnolence, fatigue, weight gain, edema, anemia, and peripheral neuropathy have been observed in adults on vigabatrin.

The ketogenic diet has been shown to be effective in studies by several different investigators. One study found it effective in fewer patients than ACTH (62% of infants became spasm-free with the ketogenic diet vs. 90% of those given ACTH), although side effects also occurred less often (31% with the ketogenic diet vs. 80% for ACTH). [Kossoff: 2008] Also see [Eun: 2006]. Since the nutritional content of infant formula is easier to control than that of a varied solid and liquid diet, the ketogenic diet is easier to manage in infants than in children. Further studies with variations of the ketogenic diet are necessary to further understand its role in the treatment of IS. [Kossoff: 2008]

High dose topiramate, at least 6 mg/kg/day, may also be effective for IS, with about one half of infants becoming seizure-free. Adverse events occurred in approximately 39%. [Zou: 2008] Also see [Peltzer: 2009].

Newer anti-epileptic medications and high-dose intravenous immunoglobulin are also being studied as possible treatments for IS.

In conclusion, in infants without tuberous sclerosis, hormonal treatments appear to be superior to vigabatrin for achieving seizure cessation in infants with IS, with short-term success in about 3/4 of infants, compared to about 1/2 with vigabatrin. Excluding effects on vision, adverse effects were similar in the hormonal groups and the vigabatrin groups. Cessation of spasms may occur more quickly in infants treated with ACTH or prednisolone, which may have a beneficial effect on development.

Evidence for the use of prednisolone instead of ACTH for treatment of infantile spasms is mounting. Although they appear to be of similar efficacy and have about the same percentage of adverse effects, prednisolone is easier to administer and much less expensive. However, treatment with ACTH has been the gold standard and further studies would help clarify this issue further. Newer options such as the ketogenic diet and topiramate also need more comparative studies in the treatment of IS, adverse effects, and developmental outcome.


For example of a treatment algorithm, see Infantile Spasms Treatment Algorithm (Pediatric Neurology Division, University of Utah/Primary Children's Medical Center, Salt Lake City, UT) (PDF Document 67 KB).

Subspecialist Collaborations & Other Resources

Pediatric Neurology (see Services below for relevant providers)

Treatment for IS will generally be initiated by pediatric neurology with collaborative monitoring for efficacy and side effects, as well as developmental progress, by the Medical Home.

Pediatric Ophthalmology (see Services below for relevant providers)

Infants on vigabatrin need pre-vigabatrin treatment screening, subsequent screening, and post-treatment screening.

Development (general)

Children who present with IS may have slow development or may have met early milestones and then show slower progress or regression after IS start. All children with IS should have periodic developmental assessment and be referred to Early Intervention. Physical, occupational, and speech therapy may be helpful for some patients.

Subspecialist Collaborations & Other Resources

Developmental Pediatrics (see Services below for relevant providers)

May be helpful for developmental progress monitoring and management suggestions.

Early Intervention Programs (see Services below for relevant providers)

Important for frequent monitoring of development and helping families support developmental progress.

Physical Therapy (see Services below for relevant providers)

If Early Intervention is not adequate, may be helpful for patients who are not meeting gross motor milestones.

Occupational Therapy, Pediatric (see Services below for relevant providers)

If Early Intervention is not adequate, may be helpful for patients who are not meeting fine motor milestones.

Speech/Language Therapy (see Services below for relevant providers)

If Early Intervention is not adequate, may be helpful for patients who are not developing language appropriately.

Frequently Asked Questions

Is it safer to use vigabatrin or ACTH?

The choice of one therapy over another should be made only after a full discussion of benefits and risks with your child's physician. Although both these treatments have potentially dangerous side effects, the consequences of untreated infantile spasms are often devastating. You might consider joining a support group of parents who have made a similar choice to get a parent perspective (See Support Groups under Resources, below).

Issues Related to Infantile Spasms

Resources

Information for Clinicians

Infantile Spasms (NIH)

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

Helpful Articles

PubMed search for articles on Infantile Spasms in children for the last 3 years

Nabbout R, Dulac O.
Epileptic syndromes in infancy and childhood.
Curr Opin Neurol. 2008;21(2):161-6. PubMed abstract

Shields WD.
Infantile Spasms: Little Seizures, BIG Consequences.
Epilepsy Curr. 2006;6(3):63-9. PubMed abstract / Full Text

Wheless JW, Gibson PA, Rosbeck KL, Hardin M, O'Dell C, Whittemore V, Pellock JM.
Infantile spasms (West syndrome): update and resources for pediatricians and providers to share with parents.
BMC Pediatr. 2012;12:108. PubMed abstract / Full Text

Clinical Tools

Algorithms/Care Processes

ACTH Prescribing Protocol (Pediatric Neurology Division, University of Utah/Primary Children's Medical Center, Salt Lake City, UT) (PDF Document 41 KB)

IS Provider Letter (Pediatric Neurology Division, University of Utah/Primary Children's Medical Center, Salt Lake City, UT) (PDF Document 55 KB)
This letter is used by the pediatric neurology division University of Utah/Primary Childrens Medical Center, Salt Lake City, UT to communicate with Medical Home clinicians regarding management of a child on ACTH.

Infantile Spasms Diagnostic Algorithm (Pediatric Neurology Division, University of Utah/Primary Children's Medical Center, Salt Lake City, UT) (PDF Document 53 KB)
A diagnostic algorithm for infantile spasms used by the Pediatric Neurology Division, University of Utah /Primary Children’s Medical Center, Salt Lake City, UT. To arrive at this algorithm, recent literature was reviewed and division members came to consensus.

Information & Support for Families

Family Diagnosis Page

Information on the Web

Epilepsy Association of Utah
For individuals with epilepsy, families, and friends, this site offers newsletters, events, links, local and youth support groups, activities for kids, first aid for seizures, and more.

Epilepsy Foundation
A national organization that provides information about epilepsy; programs to improve epilepsy treatment; materials to assist in helping people with epilepsy find jobs; activities in schools to educate the public; activities to educate policymakers; funds for research; and news about conferences and other items of interest.

Infantile Spasms (NINDS)
Information from the National Institute of Neurological Disease and Stroke including diagnosis, treatment, and clinical trials in progress.

Infantile Spasms (Epilepsy.com)
Several frequently asked questions and answers about infantile spasms.

Support National & Local

Support Groups (Epilepsy Association of Utah)

Epilepsy Association of Utah
For individuals with epilepsy, families, and friends, this site offers newsletters, events, links, local and youth support groups, activities for kids, first aid for seizures, and more.

Epilepsy Foundation
A national organization that provides information about epilepsy; programs to improve epilepsy treatment; materials to assist in helping people with epilepsy find jobs; activities in schools to educate the public; activities to educate policymakers; funds for research; and news about conferences and other items of interest.

Services for Patients & Families

Developmental Pediatrics

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Early Intervention Programs

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Occupational Therapy, Pediatric

See all Occupational Therapy, Pediatric services providers (42) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

Pediatric Immunology/Rheumatology

See all Pediatric Immunology/Rheumatology services providers (5) in our database.

Pediatric Neurology

See all Pediatric Neurology services providers (10) in our database.

Pediatric Ophthalmology

See all Pediatric Ophthalmology services providers (8) in our database.

Physical Therapy

See all Physical Therapy services providers (62) in our database.

Speech/Language Therapy

See all Speech/Language Therapy services providers (80) in our database.

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Authors

Content Last Updated: 5/2013

Bibliography

Azam M, Bhatti N, Krishin J.
Use of ACTH and prednisolone in infantile spasms: experience from a developing country.
Seizure. 2005;14(8):552-6. PubMed abstract

Bahi-Buisson N, Nectoux J, Rosas-Vargas H, Milh M, Boddaert N, Girard B, Cances C, Ville D, Afenjar A, Rio M, Héron D, N'guyen Morel MA, Arzimanoglou A, Philippe C, Jonveaux P, Chelly J, Bienvenu T.
Key clinical features to identify girls with CDKL5 mutations.
Brain. 2008;131(Pt 10):2647-61. PubMed abstract

Dugdale, DC and Hoch, DB.
Spasmus nutans.
Medline Plus (NLM.NIH.GOV); (2009) http://www.nlm.nih.gov/medlineplus/ency/article/001409.htm.

Eun SH, Kang HC, Kim DW, Kim HD.
Ketogenic diet for treatment of infantile spasms.
Brain Dev. 2006;28(9):566-71. PubMed abstract

Fattal-Valevski A, Bloch-Mimouni A, Kivity S, Heyman E, Brezner A, Strausberg R, Inbar D, Kramer U, Goldberg-Stern H.
Epilepsy in children with infantile thiamine deficiency.
Neurology. 2009;73(11):828-33. PubMed abstract

Gaily E, Jonsson H, Lappi M.
Visual fields at school-age in children treated with vigabatrin in infancy.
Epilepsia. 2009;50(2):206-16. PubMed abstract

Go CY, Mackay MT, Weiss SK, Stephens D, Adams-Webber T, Ashwal S, Snead OC 3rd.
Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
Neurology. 2012;78(24):1974-80. PubMed abstract / Full Text

Guerrini R, Moro F, Kato M, Barkovich AJ, Shiihara T, McShane MA, Hurst J, Loi M, Tohyama J, Norci V, Hayasaka K, Kang UJ, Das S, Dobyns WB.
Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus.
Neurology. 2007;69(5):427-33. PubMed abstract

Hamano S, Yoshinari S, Higurashi N, Tanaka M, Minamitani M, Eto Y.
Developmental outcomes of cryptogenic West syndrome.
J Pediatr. 2007;150(3):295-9. PubMed abstract

Hancock EC, Osborne JP, Edwards SW.
Treatment of infantile spasms.
Cochrane Database Syst Rev. 2008(4):CD001770. PubMed abstract

Jammoul F, Wang Q, Nabbout R, Coriat C, Duboc A, Simonutti M, Dubus E, Craft CM, Ye W, Collins SD, Dulac O, Chiron C, Sahel JA, Picaud S.
Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity.
Ann Neurol. 2009;65(1):98-107. PubMed abstract / Full Text

Kivity S, Lerman P, Ariel R, Danziger Y, Mimouni M, Shinnar S.
Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone.
Epilepsia. 2004;45(3):255-62. PubMed abstract

Kossoff EH, Hartman AL, Rubenstein JE, Vining EP.
High-dose oral prednisolone for infantile spasms: an effective and less expensive alternative to ACTH.
Epilepsy Behav. 2009;14(4):674-6. PubMed abstract

Kossoff EH, Hedderick EF, Turner Z, Freeman JM.
A case-control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms.
Epilepsia. 2008;49(9):1504-9. PubMed abstract

Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP.
The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial.
Lancet. 2004;364(9447):1773-8. PubMed abstract

Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP.
The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial.
Lancet Neurol. 2005;4(11):712-7. PubMed abstract

Mackay MT, Weiss SK, Adams-Webber T, Ashwal S, Stephens D, Ballaban-Gill K, Baram TZ, Duchowny M, Hirtz D, Pellock JM, Shields WD, Shinnar S, Wyllie E, Snead OC 3rd.
Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society.
Neurology. 2004;62(10):1668-81. PubMed abstract / Full Text

Nabbout R, Dulac O.
Epileptic syndromes in infancy and childhood.
Curr Opin Neurol. 2008;21(2):161-6. PubMed abstract

Partikian A, Mitchell WG.
Neurodevelopmental and Epilepsy Outcomes in a North American Cohort of Patients With Infantile Spasms.
J Child Neurol. 2009. PubMed abstract

Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, Gaillard WD, Gibson PA, Holmes GL, Nordl DR, O'Dell C, Shields WD, Trevathan E, Wheless JW.
Infantile spasms: a U.S. consensus report.
Epilepsia. 2010;51(10):2175-89. PubMed abstract
Although evidence based guidelines were published in 2004, many questions remained about the diagnosis, evaluation, and management of infantile spasms. This article develops consensus guidelines regarding some of those questions.

Peltzer B, Alonso WD, Porter BE.
Topiramate and adrenocorticotropic hormone (ACTH) as initial treatment for infantile spasms.
J Child Neurol. 2009;24(4):400-5. PubMed abstract / Full Text

Shields WD.
Infantile Spasms: Little Seizures, BIG Consequences.
Epilepsy Curr. 2006;6(3):63-9. PubMed abstract / Full Text

Vigevano F, Cilio MR.
Vigabatrin versus ACTH as first-line treatment for infantile spasms: a randomized, prospective study.
Epilepsia. 1997;38(12):1270-4. PubMed abstract

Wheless JW, Gibson PA, Rosbeck KL, Hardin M, O'Dell C, Whittemore V, Pellock JM.
Infantile spasms (West syndrome): update and resources for pediatricians and providers to share with parents.
BMC Pediatr. 2012;12:108. PubMed abstract / Full Text

Willmore LJ, Abelson MB, Ben-Menachem E, Pellock JM, Shields WD.
Vigabatrin: 2008 update.
Epilepsia. 2009;50(2):163-73. PubMed abstract

You SJ, Kim HD, Kang HC.
Factors influencing the evolution of West syndrome to Lennox-Gastaut syndrome.
Pediatr Neurol. 2009;41(2):111-3. PubMed abstract

Zou LP, Lin Q, Qin J, Cai FC, Liu ZS, Mix E.
Evaluation of open-label topiramate as primary or adjunctive therapy in infantile spasms.
Clin Neuropharmacol. 2008;31(2):86-92. PubMed abstract

Zupanc ML.
Clinical evaluation and diagnosis of severe epilepsy syndromes of early childhood.
J Child Neurol. 2009;24(8 Suppl):6S-14S. PubMed abstract