Abstracts

Rationale: Rasmussen's encephalitis is a clinical diagnosis based on presence of refractory focal epilepsy, progressive neurological deficits and MRI evidence of unilateral cerebral atrophy. The etiology and pathophysiological basis remain unclear. Mitochondrial dysfunction in general and a more recent awareness of POLG (mitochondrial nuclear gene encoding for polymerase-γ which is responsible for maintenance of mtDNA) mutations has ushered a new understanding of the possible mechanism underlying many neurological syndromes. We report two patients with Rasmussen’s encephalitis with unusual MRI features and evidence of underlying mitochondrial dysfunction. Methods: 41 patients were found in the pediatric epilepsy monitoring unit database (1978-2008) with a clinical diagnosis of Rasmussen syndrome. Only two patients had MRI evidence of ipsilateral cerebral and cerebellar hemisphere atrophy. Details of their epilepsy evaluation and relevant test results are included below. Results: Both patients had medically refractory hemispheric epilepsy with multiple seizure types, progressive cognitive, speech and language deficits and very subtle motor impairment which precluded consideration for epilepsy surgery. They have continued medical management. Patient A (Fig 1): 11y right handed girl had seizure onset at 8.5 years age. MRI showed left cerebral and cerebellar atrophy. Blood test showed novel POLG1 mutations T251I (exon 3), and P587L (exon 10). Patient B (Fig 2): 14y right handed girl had seizure onset at 5 years age. MRI showed left cerebral and cerebellar atrophy. Skin biopsy revealed abnormal mitochondria on electron microscopy. Conclusions: Our cases manifest unusual features not described before. The ipsilateral cerebellar and cerebral involvement raises new questions about mechanism of CNS involvement and poses a challenge to pursue hemispherectomy (with resultant de-afferentation of the healthy contra lateral cerebellum) even if these patients were to develop frank hemiparesis. Associated evidence of mitochondrial dysfunction in both cases (POLG mutation in one and abnormal mitochondria in another) is suggestive of a plausible etiology and should be further investigated in patients with Rasmussen’s Syndrome.