Infantile Spasms The 5 Minute Pediatric Consult


	Infantile Spasms

Amy R. Brooks-Kayal

Database
Differential Diagnosis
Data Gathering
Physical Examination
Laboratory Aids
Therapy
Follow-Up
Common Questions and Answers
Bibliography

DATABASE

DEFINITION

Infantile spasms are myoclonic seizures, usually occurring in clusters, associated with a typical EEG pattern: high voltage, chaotic slowing, multifocal spikes, and marked asynchrony (known as hypsarrythmia). Flexor, extensor, mixed flexor/extensor, and arrest/akinetic fits occur. The combination of infantile spasms, hypsarrythmia, and mental retardation is known as West syndrome. Infantile spasms are classified as symptomatic if a specific etiology can be identified and cryptogenic if no underlying cause is found.

CAUSES

Tuberous sclerosis (TS)
Down syndrome
Aicardi syndrome
Metabolic disorders (congenital lactic acidoses, PKU)

Almost any cause of pre- or perinatal brain injury may lead to infantile spasms, including meningitis, hypoxic-ischemic injury, uremia, and congenital infection.

GENETICS

Families of probands have a higher incidence of epilepsy, suggesting multifactorial inheritance. Tuberous sclerosis may be sporadic or autosomal dominant.

EPIDEMIOLOGY

Incidence is 0.25 to 0.42 per 1,000 live births. Peak age of onset is 4 to 9 months; onset usually occurs before 1 year of age. Boys are more often affected than girls.

ASSOCIATED CONDITIONS

Intrauterine infection
Cerebral malformations
Perinatal asphyxia
Prenatal/perinatal stroke
Lennox-Gastault syndrome
Traumatic brain injury
CNS infections
Intraventricular hemorrhage
Kernicterus
Genetic conditions noted above
Forty percent of infantile spasms are idiopathic

PROGNOSIS

Infantile spasms carry a poor developmental prognosis. Approximately 65% to 90% of patients are developmentally delayed at the time of initial diagnosis, and perhaps 10% of these children will achieve normal cognitive, physical, and educational development. Approximately 55% to 65% of children with infantile spasms go on to develop other seizure types, and 23% to 50% develop Lennox-Gastault syndrome. Prognosis is better in the cryptogenic group, with up to 40% having normal cognitive development and freedom from seizures on long-term follow-up.

DIFFERENTIAL DIAGNOSIS

Nonepileptic disorders: benign myoclonus, posturing related to gastroesophageal reflux, shuddering spells
Myoclonic epilepsy of infancy
- Benign
- Severe myoclonic epilepsy (early infantile epileptic encephalopathy, or EIEE)

DATA GATHERING

HISTORY

Prenatal and perinatal history, including:
- Maternal age
- Pregnancy complications
- Perinatal difficulties
Family history of TS or previous children with infantile spasms should be elicited.
A detailed developmental history is needed to establish any preexisting developmental delay.
A detailed description of spells may be useful in differentiating spasms from nonepileptic seizures, though these may be visually indistinguishable from infantile spasms.

PHYSICAL EXAMINATION

Check general growth parameters, specifically head circumference, because microcephaly suggests preexisting brain abnormality and a poorer prognosis.
On general physical examination, look for dysmorphisms (Down stigmata, retinal defects as in Aicardi syndrome), suggesting genetic abnormalities, and hepatomegaly, suggesting inborn errors of metabolism or congenital infection.
Careful skin examination, including a Wood lamp examination, should be performed for evidence of neurocutaneous disorders, specifically the hypopigmented macules associated with TS.
On neurologic examination, particular attention should be given to level of alertness, attainment of age-appropriate developmental milestones, and motor tone.

LABORATORY AIDS

TESTS

Diagnosis depends on EEG: high voltage, chaotic slowing, multifocal spikes, marked asynchrony known as hypsarrhythmia.
Routine blood studies should include electrolytes, calcium, and glucose but are generally unrevealing. Chromosomal analysis; metabolic screening, including blood lactate and pyruvate, serum amino acids, and urine organic acids; and TORCH titers may be helpful in identifying underlying etiology.
If no cause is found, lumbar puncture to look for evidence of CNS infection or lactic acidosis
Neuroimaging studies are most helpful test to determine etiology. MRI is preferred because of higher resolution for heterotopias and focal anatomic abnormalities; however, the intracranial calcifications associated with intrauterine infections and TS may be more apparent on CT.
Infants with TS should undergo cardiologic evaluation, renal ultrasound, genetic consultation for genetic counseling, and evaluation of other family members.
Infantile spasms can be an atypical presentation of pyridoxine-dependent seizures (see Therapy).

THERAPY

DRUGS

Adrenocorticotropic hormone (ACTH) is generally considered the most effective therapy for infantile spasms. Treatment is generally initiated at 150 units/m²/d IM for 1 to 2 weeks, and then gradually tapered over a period of 1 to 6 months. Side effects of ACTH therapy include cushingoid appearance, irritability, sleep disturbance, hyperglycemia, hypertension, electrolyte abnormalities, hypertrophic cardiomyopathy, immunosuppression, gastritis/GI bleeding, osteoporosis, and growth failure. ACTH therapy has not been proved to affect outcome in infants whose spasms are due to prenatal or perinatal brain abnormalities (symptomatic infantile spasms). Alternative therapies include topiramate (at dosages up to 20–60 mg/kg/day), clonazepam (0.1–0.15 mg/kg/d), phenobarbital (3–6 mg/kg/d), valproate (at dosages up to 100 mg/kg/d), or prednisone (2 mg/kg/d). Valproate is less frequently used as a primary agent because of the increased rateof fatal hepatotoxicity in this age group. A trial of high-dose pyridoxine (100 mg IV) should be given to all. Vigabatrin (100–150 mg/kg/day) is considered the initial treatment of choice, but is not yet available in the U.S.

FOLLOW-UP

Institution of ACTH therapy necessitates weekly follow-up to monitor blood pressure, glucose, electrolytes, BUN/creatinine, and signs of infection. Weight gain, cushingoid appearance, and irritability/insomnia associated with ACTH resolve as the medicine is tapered.

PITFALLS

Hypertension and hemorrhagic gastritis occur in infants on ACTH therapy and must be anticipated by weekly follow-up visits.
Other seizure disorders may supervene after infantile spasms have remitted and may require alternate anticonvulsant therapy.

COMMON QUESTIONS AND ANSWERS

Q: Do infantile spasms ever remit spontaneously?
A: Spontaneous remission of infantile spasms has been reported but appears to be rare.

Q: What predictions can be made about prognosis of the child with idiopathic infantile spasms?
A: Periodic evaluation by a child neurologist or child developmentalist helps to detect delays in motor or cognitive development; neither the EEG nor any other laboratory test contributes prognostic information in cryptogenic infantile spasms.

ICD-9-CM 345.6

BIBLIOGRAPHY

Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics 1996; 97(3):375–379.

Chugani HT. Infantile spasms. Curr Opin Neurol 1995; 8(2):139–144.

Kramer U, Sue WC, Mikati MA. Hypsarrhythmia: frequency of variant patterns and correlation with etiology and outcome. Neurology 1997; 48(1):197–203.

Watanabe K. West syndrome: etiological and prognostic aspects. Brain Dev 1998; 20(1):1–8

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