Abstracts

RATIONALE: Evaluate the treatment and outcome of patients (pts) with a mitochondrial cytopathy (MITO) and infantile spasms.
METHODS: This was a retrospective study of 4 pts, 3 boys and 1 girl, who had features of a bioenergetic disorder and infantile spasms. Patients presented with infantile spasms at 3 to 7 months. All pts underwent a biochemical workup, spectrophotometric analysis of electron transport chain (ETC) activity on fresh muscle tissue, and EM evaluation of skin and muscle tissue. Multiple EEGs were performed. Pt follow-up continued for 1/2 to 3 years.
RESULTS: Four pts having epileptic spasms and EEG hypsarrhymia also had some of the features of a bioenergetic disorder, with severe axial hypotonia, appendicular hypertonia and lactate acidosis (LA). Muscle biopsy studies showed that 2 pts had ETC dysfunction, complex I (NADH-cytochrome c reductase, [lt] 2 SD) and complex III/IV (Decylubiquinol-cytochrome c reductase, [lt] 2 SD). One pt had Leigh[ssquote]s disease: LA, increased pyruvate level and MRI findings of bilateral basal ganglia cystic lesions. Pt 4 had LA, elevated pyruvate, abnormal urine organic acids, and EM of a skin biopsy showing numerous dysmorphic mitochondria.
In all pts, the EEG normalized and epileptic spasms resolved either with ACTH (40 IU) or clonazepam. In both pts with ETC dysfunction, the EEG became abnormal with return of seizure activity after ACTH withdrawal. After 1 year, the pt with the complex I disorder had an interictal EEG pattern of generalized spike and wave discharges. The pt with a complex III/IV dysfunction has an interictal EEG pattern, 3 years post ACTH, of generalized and multiregional spike and wave discharges. The pt with Leigh[ssquote]s disease began having seizures after ACTH withdrawal. Seizures were controlled on phenobarbital until the pt death 15 months after ACTH treatment. Unfortunately, an EEG was not performed after ACTH treatment. The pt controlled on clonazepam has remained seizure-free for 2 1/2 years, with the interictal EEG demonstrating only regional slowing.
CONCLUSIONS: The medical treatment of MITO remains unclear, especially in those Pts with epilepsy. In 4 pts with both an EEG pattern of hypsarrthymia, epileptic spasms and MITO, treatment with ACTH or clonazepam resulted in resolution of both EEG hypsarrhythmia and epileptic spasms. Unfortunately, withdrawal of medication resulted in the return of epilepsy in 3 out of 4 pts. Although ACTH or clonazepam may effectively treat hypsarrhythmia and epileptic spasms in pts with MITO, the long term outcome remains problematic and likely resembles other etiologies of infantile spasms.