Infantile spasms last a few seconds and can recur many times a day. They usually manifest in children < 1 year of age. Seizures may resolve spontaneously by about 5 years of age but are often replaced by other types of seizures.
Pathophysiology is unknown; however, infantile spasms may reflect abnormal interactions between the cortex and brain stem.
Causes
Usually, infantile spasms occur in infants with serious brain disorders and developmental abnormalities that often have already been recognized. These disorders may include
Tuberous sclerosis complex is a common cause; prognosis is sometimes better when seizures are caused by this disorder than when seizures have other identifiable causes.
Sometimes the cause of infantile spasms cannot be identified.
Symptoms and Signs
Spasms begin with a sudden, rapid, tonic contraction of the trunk and limbs, sometimes for several seconds. Spasms range from subtle head nodding to contraction of the whole body. They involve flexion, extension, or, more often, both (mixed). The spasms usually occur in clusters, often several dozen, in close succession and occur typically after children wake up and occasionally during sleep. Sometimes at first, they are mistaken for startles.
Developmental delays (see Childhood Development) are usually present. In the first stages of the disorder, developmental regression can occur (eg, children may stop smiling or lose the ability to sit up or roll over).
Rate of premature death ranges from 5 to 31% and is related to the etiology of the infantile spasms.
Diagnosis
Previous history (eg, neonatal hypoxic-ischemic encephalopathy) and/or symptoms and signs suggest the diagnosis of infantile spasms in some children. Physical and neurologic examinations are done, but often no pathognomonic findings are identified except in tuberous sclerosis complex.
EEG is done to confirm the diagnosis and check for specific abnormalities. Typically, the interictal pattern is hypsarrhythmia (chaotic, high-voltage polymorphic delta and theta waves with superimposed multifocal spike discharges). Multiple variations (eg, focal or asymmetric hypsarrhythmia) are possible. The ictal pattern is usually a sudden, marked and diffuse attenuation of electrical activity.
Neuroimaging, preferably MRI, is done if it has not already recently been done.
Tests to determine the cause
If it is not clear from neuroimaging or the previous history, tests to determine the cause may include
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Laboratory tests (eg, complete blood count with differential; measurement of serum glucose, electrolytes, blood urea nitrogen, creatinine, sodium, calcium, magnesium, phosphorus, serum amino acids, and urine organic acids; liver tests) if a metabolic disorder is suspected
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Genetic testing
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Cerebrospinal fluid (CSF) analysis to check for metabolic disorders
Treatment
Infantile spasms are not responsive to typical antiseizure drugs.
ACTH is the most effective treatment. Both high-dose (150 units/m2) ACTH and low-dose (20 units/m2) ACTH, given daily IM, have been used. Evidence that the high dose of ACTH works better is not conclusive; however, generally, if low-dose therapy has not stopped spasms within 2 weeks, the higher dose is used. ACTH therapy is typically continued at the effective dose for 2 to 3 weeks and then tapered off over 6 to 9 weeks.
Vigabatrin is the only antiseizure drug with proven efficacy. It is the drug of choice when the spasms are caused by tuberous sclerosis complex. It is also often used in children with an established preexisting serious brain injury or malformation and in those who do not tolerate or respond to ACTH. Dosage of oral vigabatrin is 25 mg/kg 2 times a day, increased gradually up to 75 mg/kg 2 times a day if needed. There is insufficient evidence that any other antiseizure drug or the ketogenic diet is effective.
Corticosteroids (eg, oral prednisone 2 mg/kg once/day) are sometimes given for 4 to 7 weeks as an alternative to ACTH.
In some patients with resistant spasms, focal cortical resection can eliminate seizures.
There is evidence that the more quickly effective therapy is initiated, the better the neurodevelopmental outcome, particularly when no cause is identified.
Key Points
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Infantile spasms last a few seconds and can recur many times a day; they may resolve spontaneously by about 5 years of age but are often replaced by other types of seizures.
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Usually, infantile spasms occur in infants with serious brain disorders and developmental abnormalities that often have already been recognized; tuberous sclerosis complex is a common cause.
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Do electroencephalography to confirm the diagnosis, and other tests (eg, brain MRI and metabolic and genetic testing) to evaluate the cause of infantile spasm.
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Adrenocorticotropic hormone (ACTH) is the most effective treatment, but vigabatrin is the drug of choice for spasms caused by tuberous sclerosis complex and is often used in children who have an established preexisting serious brain injury or malformation or who do not tolerate or respond to ACTH.
