Infantile Spasms

Clinical

• begin by age 4-8 mos, onset usually before 1 y/o.
• contractions of neck, trunk, extremities; usually occuring in clusters and upon arousal from sleep
• brief, symmetric
• 3 Types of ~:
  1. flexor spasms: sudden flexion of neck, arms and legs onto trunk (like a 'bow'), occurs in clusters
  2. extensor spasms: extension of trunk and extremities (least common) (see also opistothonos, Sandifer syndrome)
  3. mixed: the most common type
• A cry may precede or follow an infantile spasm, accounting for the confusion of colic in a few cases
• can occur during sleep or while awake, but tend to occur while drowsy or immediately on awakening
• West syndrome = infantile spasms, hypsarrythmia, mental retardation
• PE: look at growth parameters, dysmorphisms, skin exam (incl woods lamp)

Categories

• 40% idiopathic
• 2 groups: cryptogenic and symptomatic
• Cryptogenic 10-20%
  • normal kid, normal, term birth, CT/MRI normal
  • good prognosis
• Symptomatic
  • related directly to several prenata, perinatal and post-natal factors
  • pre-peri-natal: prematurity, HIE with PVL, congenital infections, inborn errors of metabolism, neurocutaneous syndromes (i.e. tuberous sclerosis), cytoarchitectural abnormalities (lissencephaly, schizencephaly).
  • post-natal: CNS infections, head trauma (subdural hemorrhage, IVH), HIE
  • no association between pertussis vax and infantile spasms (they both occur at around 6 mos - coincidence)
  • poor prognosis: 80-90% risk of mental retardation, in addition to the underlying neuro d/o.
• Underlying cause found in 75% of cases (TS, metabolic dz, Aicardi syndrome, agenesis of the corpus callosum, chrom. abnormalities)

Pathogenesis

• many theories
  • dysfunction in monoamine transmitter system in brain stem
  • neuro-anatomical derangement
  • immune system abnormality
  • corticotropin releasing hormone (CRH) may be a neurotransmitter; specific stresses or injury to an infant during a critical period of neurodevelopment causes overproduction of CRH and neuronal hyperexcitability and seizures
• Exogenous ACTH and glucocorticoids suppress CRH synthesis, which may explain their effectiveness in treatment

Diagnosis

• EEG: hypsarrythmia: chaotic slow wave, high voltage pattern, bilateral
• chem panel, chromosomes, metabolic screen (incl lactate, pyruvate, serum aa, urine oa), TORCH titers
• LP
• MRI is preferred over CT because of higher resolution for heterotopias an focal anatomic abnormalities
• CT can better detect tuberous sclerosis, and intracranial calcifications due to intrauterine infxns.
• ~ can be an atypical presentation of pyridoxine-dependent seizures

Therapy

• ACTH is the preferred drug for the management of infantile spasms (need weekly f/u of BP, glucose, lytes, stool guiac (hemorrhagic gastritis) and signs of infxn.
• Prednisone is equally effective
• control can be expected in 70%
• Dose and duration of therapy are not uniform
  • a common schedule: ACTH 20 U IM qd x 2wk, and if no response, incr to 30, then 40 for an additional 4 weeks. If seizures persist, replace ACTH w/ prednisone, 2 mg/kg/d x 2wks. If seizures persist, continue for 4 more wks.
  • side fx of ACTH: hyperglycemia, hypertension, electrolyte abnormalities, infection, GI disturbance, transient brain shrinkage seen on CT scan
• ACTH has not been proved to affect outcome in infants whose spasms are due to pre-perinatal brain abnormalities (symptomatic)
• Alternative therapies include: topiramate, zonisamide, clonazepam, nitrazepam, tiagabine, valproate, phenobarbitol, prednisone
• a trial of pyridoxine (100 mg IV) should be given to r/o pyridoxine deficiency or dependencey.

Prognosis

• spontaneous remission of ~ has been reported but appears to be rare
• Poor developmental px
• 65-90% are developmentally delayed at time of initial dx - 10% of these will achieve normal cognitive, physical and educational development
• 55-65% of children w/ infantile spasms go on to develop other seizure types
• 23-50% develop lennox-gastaut
• Px is better in the cryptogenic group, with up to 40% having normal cognitive development and freedom from seizures on long term f/u.

Nelson's 16th Edition.
5 Minute Pediatric Consult. 3rd Edition.
CHLA Board Review 2005.