Neuropathological analysis for the development of new treatment in intractable epilepsy

齿状核-苍白球萎缩症可分为青少年型和成年型，除成年型外，还表现为进行性肌阵挛癫痫。我们用免疫组织化学方法检测了DRPLA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氧化产物(8-OHdG)主要积聚在豆状核，主要见于PME患者。DRLA患者苍白球外段、齿状核和小脑皮质中铜/锌超氧化物歧化酶的胞浆免疫反应减弱。PME患者豆状核和小脑线粒体MnSOD免疫反应性降低。提示氧化应激可能参与了DRPLA。West综合征(WS)的脑电表现为癫痫痉挛、发育迟缓和节律不齐。应用免疫组织化学方法检测了4例同时患有WS和Lennox-Gastaut综合征(LGS)的无脑和围产期缺氧缺血性脑病(HIE)尸检标本脑组织中氧化产物和超氧化物歧化酶(SOD)的表达。在无破坏性改变的情况下，在WS/LGS尸检病例中，3/4例小脑和2/4例HIE显示中脑脂质氧化应激标志物免疫反应阳性。SODS的免疫反应在包括中脑在内的大脑区域被很好地保存下来。采用双抗体夹心法检测11例WS患者尿液和脑脊液中氧化应激标志物8-OHdG和脂质过氧化标志物己酰-赖氨酸加合物(HEL)的水平。在脑脊液中，症状组4例中3例8-OHdG升高。隐源性组7例中有2例脑脊液HEL值升高，症状组4例中有2例升高。脂质过氧化可能与WS患者癫痫发作的持续性有关。

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.