Abstracts

Rationale: Aicardi syndrome (AS) is a rare cause of infantile spasms, intractable epilepsy and severe developmental impact, having an X-linked dominant inheritance pattern. Characteristic findings include ocular lacunae, and corpus callosal agenesis on MRI. The spectrum of AS may be wider, with atypical cases noted that involve features such as unilateral ocular involvement, callosal dysgensis, and a less severe course. The developmental impact in children with AS may largely relate to the underlying cortical abnormality, but seizures are likely to contribute. Epilepsy surgery has been reported rarely in AS: known cases limited to larger resections (including hemispherectomy) where seizures have been generated from one hemisphere. We present a case of successful epilepsy surgery in a 23 month old girl with a history of infantile spasms from 3 months of age and the diagnosis of a restricted form of Aicardi syndrome based on unilateral ocular and cerebral manifestations. Methods: Spasms occurred from age 3 months with asymmetrical features involving the right arm. Delays in motor development were mild while delays in language were more severe. Physical findings included generalized hypotonia, chorioretinal lacunae in the left eye only, and mild facial dysmorphisms. Early EEG showed a modified hypsarrhythmia pattern, and MRI at 5 months revealed a malformation of cortical development in the left frontal lobe, nodular heterotopia deep to this area, and a small corpus callosum. The right hemisphere appeared normal. Spasms were refractory to treatments including trials of Prednisolone, Vigabatrin, Carbamazepine, Topiramate, Valproate and Levetiracetam.Results: Presurgical EEG revealed interictal epileptiform activity and slowing in the left frontal region on an otherwise organized background; during spasms a left frontal lead was noted. MRI at 3T showed no new changes. PET revealed a hypometabolic defect in the left frontal lobe concordant with the known MRI abnormality. Left frontal resection was performed as a single stage procedure guided by ECoG. Histopathology revealed polymicrogyria, cortical dysplasia and regions of nodular heterotopia. At 4 months following surgery no seizures have been noted, there have been developmental gains, and post-operative EEG is free of epileptiform activity.Conclusions: This is the first report of successful epilepsy surgery in a patient with a more localized, 'forme fruste' pattern of AS. We hypothesize that a degree of mocaicism of the putative X-linked mutation or unusual skewed X-inactivation has allowed more restricted features in our patient.This mechanism may be responsible for the apparent milder range of outcomes seen in other patients with AS. With advances in the understanding of genetic mechanisms of AS further delineation of more atypical cases may be possible. The impact of seizure cessation on development and long term outcome in our patient is awaited.