Neuropathological analysis on epileptogenesis of progressive myoclonic epilepsy

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First, we immunohistochemically examined the expressions of neurotransmitters, neuropeptides, calcium-binding proteins and/or glutamate transporters in the brainstem and cerebral cortex of autopsy cases of hereditary dentatorubral-pallidoluysian atrophy (DRPLA), which is one of the important causes of progressive myoclonus epilepsy (PME) in Japan. The subjects comprised 14 cases of clinicopathologically confirmed DRPLA, including 7 and 2 cases of juvenile and early adult types with PME, 5 cases of late adult type without PME, and 10 age-matched controls. Serial sections of the brainstem and cerebral cortex were treated with antibodies to neurotransmitters, neuropeptides, calcium-binding proteins, and excitatory amino acid transporters. Although the size of the tegmentum was small, we failed to find any PME-specific brainstem changes in the expressions of neurotransmitters, neuropeptides and calcium-binding proteins. The numbers of interneurons immunoreactive for calbindin-D28K and parv … More albumin, which are speculated to be markers of GABAergic inhibitory interneurons, were reduced throughout the cerebral cortex predominantly in cases with PME. The expressions of glutamate transporters modifying glutamate excitotoxicity were comparatively spared. Similarly, four autopsy cases of neuronal ceroid-lipofuscinosis (NCL) showed the reduced expressions of calcium-binding proteins with preserved ones of glutamate transporter in the cerebral cortex. Regarding Lafora disease, we immunohistochemically examined neurodegeneration in three autopsy cases and evaluated oxidative products in urine and serum isolated from two patients using ELISA. Increased deposition of oxidative products to DNA and lipids were recognized in both the autopsy brains and urine specimens. Although the expression of glial glutamate transporter EAAT1 was comparatively preserved, that of another glial glutamate transporter EAAT2 was reduced in three autopsy cases, irrespective of occurrence of Lafora body. These findings suggest that different pathomechanisms seem to be related to epileptogenesis in each disorder causing PME. Less