Sudden and unexpected death in epilepsy (SUDEP): evidence of acute neuronal injury using HSP‐70 and c‐Jun immunohistochemistry

Sudden and unexpected death in epilepsy (SUDEP): evidence of acute neuronal injury using HSP‐70 and c‐Jun immunohistochemistry
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DOI:
10.1046/j.1365-2990.2003.00452.x
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发表时间:
2003-04
影响因子:
5
通讯作者:
Maria Thom;S. Seetah;S. Sisodiya;Matthias J Koepp;Francesco Scaravilli
Maria Thom;S. Seetah;S. Sisodiya;Matthias J Koepp;Francesco Scaravilli
中科院分区:
医学2区
文献类型:
--
作者:
Maria Thom;S. Seetah;S. Sisodiya;Matthias J Koepp;Francesco Scaravilli

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癫痫猝死(SUDEP)的尸检和神经病理学检查显示没有特定的病变,这些病例的确切死因和死亡机制仍不确定。有临床证据支持SUDEP是一种癫痫介导的事件,癫痫控制不良的患者风险较高。我们的目的是确定SUDEP病例中尸检时急性神经元损伤的任何证据,以支持最近发生的癫痫发作。我们分析了18例SUDEP病例和22例对照病例海马中热休克蛋白(HSP)-70和c-Jun免疫阳性神经元的分布和频率,这两种标志物都是非特异性的,但都是急性神经元损伤的早期和可靠指标。尸检对照组包括死因非SUDEP的癫痫患者(包括癫痫持续状态和意外死亡)和无癫痫病史的心脏性猝死患者。另一个手术对照组包括接受颞叶切除术的难治性癫痫和海马硬化患者。HSP-70染色分布的半定量分析显示,与癫痫和心脏尸检对照相比,海马亚区阳性标记神经元的SUDEP病例显著更多(P < 0.001),但与癫痫手术对照相比则无差异(P = 0.4)。在海马或海马旁回区域,HSP-70或c-Jun组间海马旁回的免疫染色模式无显著差异。SUDEP中海马中HSP-70阳性神经元的检测支持死前神经元损伤,包括死亡前最近的癫痫发作。
Post‐mortem and neuropathological examination in sudden and unexpected death in epilepsy (SUDEP) shows no specific lesions and the exact cause and mechanism of death in these cases remains undetermined. There is clinical evidence to support the fact that SUDEP is a seizure‐mediated event, and patients with poorly controlled seizures are at higher risk. We aimed to identify any evidence of acute neuronal injury in SUDEP cases at post‐mortem to support that a recent seizure had occurred. We analysed the distribution and frequency of heat shock protein (HSP)‐70 and c‐Jun immunopositive neurones in the hippocampus in 18 SUDEP cases and 22 control cases, both markers being nonspecific but early and reliable indicators of acute neuronal injury. Post‐mortem control groups included patients with epilepsy with cause of death other than SUDEP (including status epilepticus and accidental death), and patients with sudden cardiac death without an epilepsy history. An additional surgical control group included patients with refractory epilepsy and hippocampal sclerosis who had undergone temporal lobectomy. Semiquantitative analysis of the distribution of HSP‐70 staining showed significantly more SUDEP cases with positively labelled neurones in hippocampal subfields compared to epilepsy and cardiac post‐mortem controls (P < 0.001) but not compared to the epilepsy surgical controls (P = 0.4). No significant difference in immunostaining patterns between groups was seen in the parahippocampal gyrus with HSP‐70 or with c‐Jun in either the hippocampus or parahippocampal gyrus regions. The detection of HSP‐70 positive neurones in the hippocampus in SUDEP is supportive of ante‐mortem neuronal injury including a recent seizure prior to death.