Case 508 -- A 12-year-old girl with seizures and dementia

Contributed by Widdess-Walsh P1, Prayson RP2, Cohen B3, Lachhwani D4
Departments of Pediatric Epilepsy1,4, Anatomic Pathology2, and Pediatric Neurology3Cleveland Clinic Foundation, Cleveland, Ohio.
Published on line in April 2007


The patient was the product of a normal pregnancy and birth and followed normal developmental milestones apart from some difficulty with fine motor skills. She walked and talked at 1 year of age. At the age of 7 years, she had an episode of generalized convulsive status epilepticus, and was told that she had suffered from a viral encephalitis. She developed recurrent seizures at the age of 8 years. A decline in school performance was noted around this time. At 10 years of age, the seizures became more frequent, and she developed a global developmental regression, with loss of language and cognition. She also developed a movement disorder with chorea and myoclonus.

The neurological examination showed cognitive impairment. She could not speak, but she was able to follow basic commands and follow visual cues. There were no dysmorphic features and no neurocutaneous signs. Her head size, weight and height were normal for age. She had impairment of vertical gaze and she had abnormal pursuit movements. Indirect fundoscopy was normal. She had difficulty protruding her tongue, and there was constant drooling. There was no focal motor weakness, but all purposeful movement contained chorea and myoclonus. Startle myoclonus was inducible in the facial muscles. There were no abnormalities noted in the general physical examination.

Three separate evaluations for the underlying etiology had failed to demonstrate a diagnosis before presentation to our center. Normal or unremarkable laboratory testing included amino acid and organic acid profiles, complete blood count, renal and liver function, ammonia, and lactate/pyruvate ratio. Mitochondrial analysis, including electron transport chain testing on muscle and mitochondrial DNA screening, was normal. Direct microscopy of skeletal muscle on review of an outside report was normal, although slides were not available. Her electroencephalogram (EEG) showed intermittent rhythmic slowing in the frontal regions, and a slow background consistent with an encephalopathy. EEG seizure demonstrating the abrupt onset of generalized epileptiform activity, maximal in the posterior head regions (Fig. 1). A generalized clonic seizure was recorded with a generalized ictal EEG pattern, out of sleep. Flash visual evoked responses were normal.


A brain magnetic resonance scan (MRI) showed diffuse volume loss. Sagittal T1-weighted and axial T2-weighted MRI of the brain demonstrated generalized atrophy, compensatory ventriculomegaly, and thinning of the corpus callosum (Figs. 2A and 2B).


A punch skin biopsy was obtained from the lower back area. Electron microscopy demonstrated numerous globoid filamentous inclusions within sweat gland duct epithelial cells. The filaments were tightly packed, measured approximately 10 nm, and had a randomly intersecting felt-like pattern (Fig. 3) The filaments did not appear to be membrane bound.


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