The purpose of this study was to describe unusual variants of Alexander's disease. We studied 10 patients who did not meet previously established magnetic resonance imaging (MRI) criteria for Alexander's disease, but for whom this diagnosis was considered because of Rosenthal fibers at histological examination or presence of some MRI features suggestive of Alexander's disease. Sequence analysis of the GFAP gene was performed. In eight patients, MRI results showed predominantly posterior fossa lesions, especially multiple tumor-like brainstem lesions. One patient had asymmetrical frontal white matter abnormalities and basal ganglia abnormalities. One patient (Patient 10) developed degeneration of the frontal white matter. In nine patients, a mutation was found that was concluded to be pathogenic, because the mutation was de novo (five patients), a known mutation was found (two patients), or assembly of the glial fibrillary acidic protein was abnormal in cultured cells (two patients). In Patient 10, a DNA variation was found that was also present in the patient's clinically unaffected father and was concluded to be a polymorphism. In conclusion, DNA diagnostics is warranted in patients who display MRI features suggestive of Alexander's disease, even if they do not meet the full set of previously established MRI criteria.

Fifteen patients who experienced epileptic seizures while playing video games are described together with a review of 20 cases in the English literature. Nine of the 15 cases and all but two of the reported cases experienced their first seizure while playing video games.

A prospective study of 32 children with epileptic encephalopathies 12 years or younger revealed a high incidence of focal cortical metabolic defects on 18-fluorodeoxyglucose positron emission tomography (PET) not suspected from clinical, EEG, or magnetic resonance imaging findings. PET scans were normal in all five children with typical de novo Lennox-Gastaut syndrome but showed cortical metabolic abnormalities in three out of four with atypical de novo LennoxGastaut syndrome, five out of six with Lennox-Gastaut syndrome following infantile spasms, six out of eight with severe myoclonic epilepsy in infancy, one out of two with epilepsy with myoclonic-astatic seizures, and four out of six with an unclassified epileptic encephalopathy. This suggests that some children with epileptic encephalopathies previously thought to have primary generalised seizures or seizures due to multifocal pathology may have unifocal cortical origin for their seizures. Such an origin may be amenable to surgery.

No abstract

Juvenile Sandhoff disease (McKusick 268800) is a rare lysosomal storage disorder with only 12 cases recorded in the literature. This condition is also referred to as the subacute form of hexosaminidase deficiency. We describe 9 new cases of Pakistani origin and compare these with the other published cases. Ataxia and speech abnormalities were the commonest presentation. Constipation and urinary incontinence were frequent and may be due to autonomic neuropathy. Cherry-red spot was not noted in any of our cases. Increased lower limb reflexes were the commonest physical finding. Significant delay in diagnosis may be due to the nonspecific presentation of this condition. Diagnosis was on the basis of hexosaminidase deficiency. Residual enzyme activity did not correlate with the clinical picture. Emerging therapies make early diagnosis of this disorder important.