Neuropathological analysis for the development of new treatment in intractable epilepsy

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Dentatorubral-pallidoluysian atrophy (DRPLA) is classified into juvenile and early adult types showing progressive myoclonus epilepsy (PME) in addition to late adult type. We immunohistochemically examined accumulation of oxidative products and expression of superoxide dismutase (SOD) in autopsy cases of DRPLA. Oxidative products to DNA (8-OHdG) were accumulated in the lenticulate nucleus predominantly in DRPLA cases having PME. Cytoplasmic immunoreactivity for Cu/ZnSOD was reduced in the external segment of globus pallidus, dentate nucleus and cerebellar cortex in DRPLA cases. Mitochondrial immunoreactivity for MnSOD was reduced in the lenticulate nucleus and cerebellum in DRPLA cases having PME It is likely that oxidative stress can be involved in DRPLA.West syndrome (WS) consists of epileptic spasms, developmental delay, and hypsarrhythmia on EEG. We immunohistochemically examined accumulation of oxidative products and SOD expression in the brains of 4 autopsy cases each with lissencephaly and perinatal hypoxemic ischemic encephalopathy (HIE), and suffering from both WS and Lennox-Gastaut syndrome (LGS). In the absence of destructive changes, 3 of 4 lissencephaly cases and 2 of 4 HIE cases showed neurons immunoreactive for oxidative stress marker to lipids in the midbrain in the WS/LGS autopsy cases. Immunoreactivities for SODs were well preserved in the brain area including the midbrain. We also measured the levels of oxidative stress marker, 8-OHdG and markers for lipid peroxidation such as hexanoyl-lysine adduct (HEL) in the urine and cerebral spinal fluid (CSF) of 11 WS patients using ELISA. In the CSF, 8-OHdG level was increased in 3 of 4 patients in the symptomatic group. HEL level in the CSF was increased in 2 of 7 patients in the cryptogenic group, and in 2 of 4 patients in the symptomatic group. Lipid peroxidation is likely to be involved in the persistence of epileptic seizures in patients with WS.