Infantile Spasm Seizures

What is it like?

Here’s a typical story: “At first I thought Chris was just having the little body jerks when he was moved or startled, like my other children had when they were infants. But then I knew something was wrong. The jerks became more violent, and his tiny body was thrust forward and his arms flew apart. They only lasted a few seconds but started to occur in groups lasting a few minutes. It was so hard to see such a young baby having these things.”

Infantile spasms (also called West syndrome because it was first described by Dr. West, in the 1840s) consist of a sudden jerk followed by stiffening. Often the arms are flung out as the knees are pulled up and the body bends forward (“jackknife seizures”). Less often, the head can be thrown back as the body and legs stiffen in a straight-out position, or movements can be more subtle and limited to the neck or other body parts. Each seizure lasts only a second or two but they usually occur close together in a series. Sometimes the spasms are mistaken for colic, but the cramps of colic do not occur in a series. Infantile spasms are most common just after waking up and rarely occur during sleep.

Who gets it?

Infantile spasms begin between 3 and 12 months of age and usually stop by the age of 2 to 4 years. They are uncommon, affecting only one baby out of a few thousand. About 60% of the affected infants have some brain disorder or brain injury before the seizures begin, but the others have had no apparent injury and have been developing normally. There is no evidence that family history, the baby’s sex, or factors such as immunizations are related to infantile spasms.

Tell me more

When a baby with infantile spasms has an EEG, the doctor usually will see an unusual pattern called hypsarrhythmia (HIP-sa-RITH-me-ah) when the seizures are not occurring. This chaotic, high-voltage pattern is often helpful in confirming the diagnosis.
Babies with infantile spasms seem to stop developing and may lose skills that they had already mastered, such as sitting, rolling over, or babbling.

How is it treated?

Steroid therapy (adrenocorticotropic hormone [ACTH] or prednisone) is the primary treatment for infantile spasms. Some experts recommend trying a seizure medicine such as Sabril (vigabatrin, not available in the United States), Depakote (valproate), or Topamax (topiramate) before steroid therapy. In countries where it is available, Sabril is often used as the initial therapy because it is relatively safe (especially for short-term use) and effective. It is especially effective for children with tuberous sclerosis (a disorder associated with abnormalities involving the brain, skin, heart, and other parts of the body). Sabril is associated with damage to the retina of the eye and should be used with caution in children.

What’s the outlook?

Most children with infantile spasms are mentally retarded later in life. Those whose spasms are related to an underlying developmental brain disorder or injury have a higher likelihood of moderate to severe retardation. The outlook is brighter for those who were developing normally before the spasms started: 10 to 20 percent will have normal mental function and some others may be only mildly impaired. Some children with infantile spasms develop autism. Many doctors believe that the quicker the seizures are controlled, the better the results will be.
When the spasms stop, many children later develop other kinds of epilepsy. About one-fifth of children who have had infantile spasms will have the Lennox-Gastaut syndrome.
– From Epilepsy.com

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. 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 attack would not continue more than 2 or 3 minutes; he sometimes has 2, 3 or more attacks in the day.”

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.

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.

Frequency

In the US: 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 1.6-5.0 per 10,000 live births.
Internationally: 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

As many as 5% of patients with this condition die.

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

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).
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.
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.