Treatment of the catastrophic
epilepsies [
infantile spasms (IS),
Lennox-Gastaut syndrome (LGS), and
progressive myoclonic epilepsy (PME)] remains a challenge to clinicians. For IS,
adrenocorticotropic hormone has traditionally been the
drug of choice in the United States but may be associated with serious side effects in some patients.
Vigabatrin has shown promise in treating IS patients, particularly those with
tuberous sclerosis. However, the
drug is associated with visual field loss and is not commercially available in the United States. Newer antiepilepsy drugs (AEDs), such as
zonisamide,
topiramate (TPM), and
lamotrigine (LTG), may be useful in patients with IS. Although LTG, TPM, and
felbamate are approved in the United States for the treatment of LGS, the overall effectiveness of
therapy in patients with LGS is poor. For PME,
valproate is a first-line treatment.
Zonisamide and
levetiracetam also show promise. Supplementation with certain cofactors to correct deficiencies and increase mitochondrial function may be useful in some patients with PME, but response to such
therapy is not well documented. Advances in our understanding of the etiologies, mechanisms, and genetics underlying the catastrophic
epilepsies may facilitate more effective pharmacologic interventions.