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

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Thom M, Seetah S, Sisodiya S, Koepp M, and Scaravilli F (2003) Sudden and unexpected death in epilepsy (SUDEP): Evidence of acute neuronal injury using HSP-70 and c-Jun immunohistochemistry. Neuropathol Appl Neurobiol 29:2 132– 43.

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Abstract: 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.

Keywords: epilepsy, hippocampus, HSP-70, c-Jun, sudden death, SUDEP

Context

  • Study searching for biochemical evidence of neuronal injury in acute postmortem tissue from possible SUDEP victims. The presence of two proteins, heat shock protein HSP-70 and c-Jun, was assessed in hippocampus in 18 SUDEP cases and 22 controls. Controls included epilepsy patients who died of non-SUDEP causes including status epilepticus and accidental death, non-epilepsy patients whose sudden deaths were attributed to cardiac causes, and post-temporal lobectomy patients. The number of HSP-70 labeled neurons in the hippocampus was greater in the epilepsy group, but the inclusion of patients who died during status epilepticus in the control group complicates interpretation.

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