eMedicine Specialties > Neurology > Pediatric Neurology

Infantile Spasm (West Syndrome)

Author: Tracy A Glauser, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine, Children's Comprehensive Epilepsy Program, Children's Hospital Medical Center of Cincinnati
Coauthor(s): Diego A Morita, MD, Assistant Professor of Pediatrics and Neurology, Department of Pediatrics, Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati; Karen Mary Stannard, MD, FRCPC, Fellow, Pediatric Epilepsy, Cincinnati Childen's Medical Center
Contributor Information and Disclosures

Updated: Dec 7, 2009

Introduction

Background

West syndrome is composed of the triad of infantile spasms, an interictal EEG pattern termed hypsarrhythmia, and mental retardation, although the diagnosis can be made even if one of the 3 elements is missing (according to the international classification). This severe epilepsy syndrome is an age-dependent expression of a damaged brain. The term infantile spasms has been used to describe the seizure type, the epilepsy syndrome, or both. In this article, the term infantile spasms is synonymous with West syndrome.

The syndrome's namesake, Dr W J West, gave the first detailed description of infantile spasms, as they occurred in his child.¹ In a letter to the editor of The Lancet in 1841, West described the events as "bobbings" that "cause a complete heaving of the head forward towards his knees, and then immediately relaxing into the upright position … these bowings and relaxings would be repeated alternately at intervals of a few seconds, and repeated from 10 to 20 or more times at each attack, which would not continue more than 2 or 3 minutes; he sometimes has 2, 3 or more attacks in the day."²

This detailed clinical description was followed approximately 100 years later by the report of the typical interictal EEG pattern termed hypsarrhythmia. Most patients with infantile spasms have some degree of developmental retardation.

The eponym West syndrome was created in the early 1960s by Drs. Gastaut, Poirier, and Pampiglione.

Pathophysiology

Infantile spasms are believed to reflect abnormal interactions between the cortex and brainstem structures. Focal lesions early in life may secondarily affect other sites in the brain, and hypsarrhythmia may represent this abnormal activity arising from multiple brain sites. The frequent onset of infantile spasms in infancy suggests that an immature central nervous system may be important in the pathogenesis. The brain-adrenal axis also may be involved. One theory states that the effect of different stressors in the immature brain produces an abnormal excessive secretion of corticotropin-releasing hormone, causing spasms. The clinical response to adrenocorticotropic hormone (ACTH) and glucocorticoids can be explained by suppression of corticotropin-releasing hormone (CRH) production.

The understanding of the pathophysiology of infantile spasms has been limited by the lack of an appropriate animal model. However, a recent development of an animal model may provide insight into the pathogenesis of this disorder. The model uses a sodium channel blocker, tetrodotoxin (TTX), that is infused into the hippocampus of rodents. This infusion has produced clinical spasms in rats with electrographic findings similar to that seen in human infantile spasms.³

Frequency

United States

Infantile spasm constitutes 2% of childhood epilepsies but 25% of epilepsy with onset in the first year of life. The rate of infantile spasm is estimated to be 2.5-6.0 per 10,000 live births. Its prevalence rate is 1.5-2.0 per 10,000 children aged 10 years or younger.

International

Infantile spasm occurs in 0.05 (Estonia) to 0.41 (Oulu, Finland) of 1000 live births and in 1.4% (Estonia), 4.2% (Odense, Denmark), and 7.6% (Tampere, Finland) of children with epilepsy.

Mortality/Morbidity

The premature death rate ranges from 5-31%. The upper limit comes from a study of 214 Finnish children with a history of infantile spasms who were followed for a mean of 25 years (range, 20-30 y). Most of the deaths (61%) occurred at or before age 10 years, while only 10% occurred after age 20 years.

Sex

Although males are affected slightly more often than females, no significant gender difference is noted.

Age

Ninety percent of infantile spasms begin in those younger than 12 months. Peak onset is at age 4-6 months.⁴

Clinical

History

• Ictal manifestations
  • Spasms begin with a sudden, rapid, tonic contraction of trunk and limb musculature that gradually relaxes over 0.5-2 seconds.
    • Contractions can last 5-10 seconds.
    • The intensity may vary from a subtle head nodding to a powerful contraction of the body.
    • Infantile spasms usually occur in clusters, often several dozens, separated by 5-30 seconds.
    • Spasms frequently occur just before sleep or upon awakening. They can be observed during sleep, although this is rare.
  • Spasms can be flexor, extensor, or a mixture of flexion and extension.
    • Flexor spasms consist of brief contractions of the flexor muscles of the neck, trunks, and limbs, resulting in a brief jerk. They may resemble a self-hugging motion and often are associated with a cry. The patient then relaxes, and the jerk repeats. These attacks occur in clusters throughout the day and last anywhere from less than 1 minute to 10-15 minutes or longer in some patients.
    • Extensor spasms consist of contractions of the extensor musculature with sudden extension of the neck and trunk with extension and abduction of the limbs. Extensor spasms and asymmetric or unilateral spasms often are associated with symptomatic cases.
    • Mixed spasms are the most common type, consisting of flexion of the neck and arms with extension of the legs, or flexion of the legs with extension of the arms.
    • In different series the frequency of the 3 spasm types were 42-50% mixed, 34-42% flexor, and 19-23% extensor.
• Interictal manifestations: An arrest or regression in psychomotor development accompanies the onset of spasms in 70-95% of patients.
• Family history: A family history of infantile spasms is uncommon but as many as 17% of patients may have a family history of any epilepsy.

Physical

• General physical examination
  • Physical examination can be important in helping to identify specific etiologies that may have both systemic and neurological symptoms (eg, tuberous sclerosis complex).
  • Often a patient with infantile spasms has normal findings on general physical examination. No pathognomonic physical findings are present in patients with infantile spasms.
  • If abnormalities in the general physical examination are noted (eg, adenoma sebaceum, ash leaf macules), specific etiologies may be suggested.
  • Use a Wood lamp to examine the skin.
  • Patients may exhibit moderate-to-severe growth delay; this is a nonspecific finding and more a reflection of the underlying brain injury than of a specific epilepsy syndrome.
• Neurologic examination
  • The neurologic examination in patients with infantile spasms demonstrates abnormalities in mental status function, specifically deficits in cognitive function consistent with developmental delay or regression.
  • Abnormalities in level of consciousness, cranial nerve function, and motor/sensory/reflex examination are nonspecific findings and more a reflection of the underlying brain injury or effect of anticonvulsant medications than of the syndrome.
  • No pathognomonic findings are present on neurologic examination in patients with infantile spasms.

Causes

Infantile spasms (West syndrome) can be classified according to its suspected etiology as symptomatic, cryptogenic, or idiopathic.

• Symptomatic
  • Patients are diagnosed with symptomatic infantile spasms if an identifiable factor is responsible for the syndrome. Virtually any disorder that can produce brain damage can be associated with infantile spasms.
  • The list of etiologies can be subdivided into prenatal disorders, perinatal disorders, and postnatal disorders.
    • Prenatal disorders include hydrocephalus, microcephaly, hydranencephaly, schizencephaly, polymicrogyria, Sturge-Weber syndrome, incontinentia pigmenti, tuberous sclerosis, trisomy 21, hypoxic-ischemic encephalopathies, congenital infections, and trauma.
    • Perinatal disorders include hypoxic-ischemic encephalopathies, meningitis, encephalitis, trauma, and intracranial hemorrhages.
    • Postnatal disorders include pyridoxine dependency, nonketotic hyperglycinemia, maple syrup urine disease, phenylketonuria, mitochondrial encephalopathies, meningitis, encephalitis, degenerative diseases, biotinidase deficiency, and trauma. 
  • There has been an increased understanding of the role of genetic defects in the etiology of infantile spasms. Two specific genetic defects have similar phenotypic presentations with the early onset of infantile spasms. The first is an abnormality in the short arm of chromosome X. The gene ARX is associated with a wide variety of structural abnormalities and early-onset infantile spasms. The second abnormality is in the cyclin-dependent kinase-like protein 5 (CDKL5) and has simliar phenotypic presentations to those with ARX mutations.
  • Evaluating children with infantile spasms for possible tuberous sclerosis is critical, as this is the single most common disorder, comprising 10-30% of prenatal cases. Tuberosis sclerosis is an autosomally dominant inherited disease with variable manifestations including cardiac tumors, kidney tumors, cutaneous malformations such as ash-leaf hypopigmented lesions, and seizures. In more than a few patients, the family diagnosis of tuberous sclerosis is found only after a child presents with infantile spasms, and an extensive workup of the child and subsequently the family reveals the genetic disease.
  • Of patients with infantile spasms, 70-75% have symptomatic epilepsy. This percentage depends on the degree of sophistication of diagnostic studies. Development of more exquisite neurodiagnostic techniques will alter the relative proportion of symptomatic, cryptogenic, and idiopathic cases.
• Cryptogenic
  • Patients have cryptogenic infantile spasms if no cause is identified but a cause is suspected and the epilepsy is presumed to be symptomatic.
  • The proportion of cryptogenic cases varies from 8-42%. This wide range may be related to variations in the definition of the term cryptogenic and the age of diagnosis, since assessment of developmental level in early infancy is difficult.
• Idiopathic
  • Patients may be considered to have idiopathic infantile spasms if normal psychomotor development occurs prior to the onset of symptoms, no underlying disorders or definite presumptive causes are present, and no neurological or neuroradiological abnormalities exist. Some investigators use the terms idiopathic and cryptogenic interchangeably.
  • The percentage of idiopathic cases reportedly is 9-14%.
• Family history: A family history of infantile spasms is uncommon but as many as 17% of patients may have a family history of any epilepsy.

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