Spasms as a presentation of Alpers' disease

Abstract

Aim: To report an unusual presentation of Alpers’ disease due to POLG1 mutations. Method: Clinical case report with POLG1 gene testing by published techniques. Results: A developmentally normal 10-month-old male presented with explosive onset of continuous spasms (without impairment in consciousness), refractory to multiple antiepileptic medications. Five-day video–electroencephalogram monitoring showed mild background slowing without epileptiform discharges (video 1). Cerebrospinal fluid lymphocytosis (49/cmm) and increased protein (510mg/L) with normal lactates and serial brain MRI/ MRS suggested a viral or immune-mediated encephalopathy. NMDA/VGKC antibodies were negative; enterovirus was isolated in CSF and stools. The explosive onset, subtle fall-off in head growth from birth (9th to below the 0.4th percentile) and elevated cerebrospinal fluid protein prompted POLG1 testing which showed compound heterozygosity for two known pathogenic mutations (A467T/T914P). On day 33 epilepsia partialis continua emerged with periodic epileptiform discharges (video 2). There was mild liver dysfunction terminally. Death occurred on day 68. Conclusion: Continuous spasms are unusual in the initial acute phase of Alpers’ disease. Usually epilepsia partialis continua or myoclonus is seen, associated with rhythmic high amplitude delta with superimposed spikes or other electroencephalogram ictal patterns (often posterior dominant and migratory) and progressive changes in the magnetic resonance imaging. Although neuronal energy failure is a major factor in pathogenesis of POLG1 encephalopathy, the pathophysiological mechanism(s) underlying the clinical features described here remain to be elucidated.