Neuropathological analysis for the development of new treatment in intractable epilepsy

除成年晚期型外，齿状体-白斑萎缩症（DRPLA）还分为青少年型和成年早期型，表现为进行性肌克隆性癫痫（PME）。我们用免疫组织化学方法检测了尸检病例中氧化产物的积累和超氧化物歧化酶（SOD）的表达。DNA的氧化产物（8-OHdG）主要在有PME的DRPLA病例中积聚在透镜状核中。DRPLA患者苍白球外段、齿状核和小脑皮层中Cu/ZnSOD的细胞质免疫反应性降低。伴有PME的DRPLA患者，其透镜状核和小脑中MnSOD的线粒体免疫反应性降低，可能与氧化应激有关。西氏综合征（WS）由癫痫性痉挛、发育迟缓和低心律失常组成。我们用免疫组织化学方法检测了4例无脑畸形和围产期低氧缺氧性缺血性脑病（HIE）以及WS和lenox - gastaut综合征（LGS）尸检患者大脑中氧化产物的积累和SOD的表达。在没有破坏性改变的情况下，WS/LGS尸检病例中，4例无脑畸形中有3例和4例HIE中有2例出现中脑氧化应激标志物对脂质的免疫反应。sod的免疫反应性在包括中脑在内的脑区保存良好。我们还使用ELISA法测量了11例WS患者尿液和脑脊液（CSF）中氧化应激标志物、8-OHdG和脂质过氧化标志物如己醇赖氨酸加合物（HEL）的水平。症状组4例患者中有3例脑脊液8-OHdG水平升高。隐原组7例患者中有2例脑脊液HEL水平升高，症状组4例患者中有2例脑脊液HEL水平升高。脂质过氧化可能与WS患者持续癫痫发作有关。

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.