Neuropathology in the North American sudden unexpected death in epilepsy registry.
Neuropathology in the North American sudden unexpected death in epilepsy registry.
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DOI：
10.1093/braincomms/fcab192
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发表时间：
2021
影响因子：
4.8
通讯作者：
Devinsky O
中科院分区：
文献类型：
--
作者：
Leitner DF;Faustin A;Verducci C;Friedman D;William C;Devore S;Wisniewski T;Devinsky O
癫痫猝死是癫痫相关死亡的主要类别，其潜在机制尚不完全清楚。危险因素包括近期病史和全身性强直阵挛性癫痫发作的频率较高，这会抑制发作后的大脑活动，损害呼吸、唤醒和保护性反射。癫痫病例突然意外死亡的神经病理学结果与其他癫痫患者的结果相似，在癫痫相关死亡中没有新的结构或机制。很少有大型研究全面审查此类患者的全脑检查。我们对 92 例北美癫痫猝死登记病例进行了全脑神经病理学检查，由委员会认证的神经病理学家对判定的死因不知情，平均每个病例检查 16 个脑区。这 92 例病例中包括 61 例癫痫意外猝死（40 例确诊、9 例确诊+、6 例可能、6 例可能）和 31 例癫痫控制但死于其他原因的患者。平均死亡年龄为 34.4 岁，其中 65.2% (60/92) 为男性。癫痫病例中突发意外死亡的平均死亡年龄比癫痫对照者更年轻（30.0岁与39.6岁；P=0.006），并且性别分布没有差异（67.3%男性与64.5%，P=0.8）。在癫痫意外死亡病例中，癫痫发病年龄较早与死亡年龄较小呈正相关（P = 0.0005），与癫痫持续时间呈负相关（P = 0.001）。我们队列中 83.7% 的病例发现了神经病理学结果。最常见的发现是齿状回发育不全（癫痫中突然意外死亡 50.9%，癫痫控制者 54.8%）和局灶性皮质发育不良 (FCD)（癫痫中突然意外死亡 41.8%，癫痫控制者 29.0%）。癫痫突然意外死亡的神经病理学发现与癫痫对照的神经病理学发现相似，包括总神经病理学发现的频率以及齿状回的具体发现、与神经发育有关的发现（例如 FCD、异位）和脑干的发现（例如髓弓或橄榄发育不全）。因此，与之前的研究一样，我们没有发现在癫痫病例中意外死亡中更常见的神经病理学发现。未来评估癫痫和对照人群中更大的意外猝死的神经病理学研究将受益于纳入不同的癫痫综合征和详细的表型信息、病理学家之间的共识，特别是对于观察结果可能不一致的更主观的发现，以及识别癫痫风险或发病机制中意外猝死标志物的分子方法。莱特纳等人。北美 SUDEP 登记 (NASR) 队列中报告称，与非 SUDEP 癫痫病例相比，癫痫猝死 (SUDEP) 中没有更常见的神经病理学发现。未来的研究可能会从更大的 SUDEP 和具有详细临床信息的对照队列中确定与 SUDEP 风险相关的发现。
Sudden unexpected death in epilepsy is the leading category of epilepsy-related death and the underlying mechanisms are incompletely understood. Risk factors can include a recent history and high frequency of generalized tonic-clonic seizures, which can depress brain activity postictally, impairing respiration, arousal and protective reflexes. Neuropathological findings in sudden unexpected death in epilepsy cases parallel those in other epilepsy patients, with no implication of novel structures or mechanisms in seizure-related deaths. Few large studies have comprehensively reviewed whole brain examination of such patients. We evaluated 92 North American Sudden unexpected death in epilepsy Registry cases with whole brain neuropathological examination by board-certified neuropathologists blinded to the adjudicated cause of death, with an average of 16 brain regions examined per case. The 92 cases included 61 sudden unexpected death in epilepsy (40 definite, 9 definite plus, 6 probable, 6 possible) and 31 people with epilepsy controls who died from other causes. The mean age at death was 34.4 years and 65.2% (60/92) were male. The average age of death was younger for sudden unexpected death in epilepsy cases than for epilepsy controls (30.0 versus 39.6 years; P = 0.006), and there was no difference in sex distribution respectively (67.3% male versus 64.5%, P = 0.8). Among sudden unexpected death in epilepsy cases, earlier age of epilepsy onset positively correlated with a younger age at death (P = 0.0005) and negatively correlated with epilepsy duration (P = 0.001). Neuropathological findings were identified in 83.7% of the cases in our cohort. The most common findings were dentate gyrus dysgenesis (sudden unexpected death in epilepsy 50.9%, epilepsy controls 54.8%) and focal cortical dysplasia (FCD) (sudden unexpected death in epilepsy 41.8%, epilepsy controls 29.0%). The neuropathological findings in sudden unexpected death in epilepsy paralleled those in epilepsy controls, including the frequency of total neuropathological findings as well as the specific findings in the dentate gyrus, findings pertaining to neurodevelopment (e.g. FCD, heterotopias) and findings in the brainstem (e.g. medullary arcuate or olivary dysgenesis). Thus, like prior studies, we found no neuropathological findings that were more common in sudden unexpected death in epilepsy cases. Future neuropathological studies evaluating larger sudden unexpected death in epilepsy and control cohorts would benefit from inclusion of different epilepsy syndromes with detailed phenotypic information, consensus among pathologists particularly for more subjective findings where observations can be inconsistent, and molecular approaches to identify markers of sudden unexpected death in epilepsy risk or pathogenesis. Leitner et al. report no neuropathological findings more common in sudden unexpected death in epilepsy (SUDEP) compared to non-SUDEP epilepsy cases in the North American SUDEP Registry (NASR) cohort. Future studies may identify findings associated with SUDEP risk from larger SUDEP and control cohorts with detailed clinical information.
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影响因子：
9.9
作者：
Leitner DF;Mills JD;Pires G;Faustin A;Drummond E;Kanshin E;Nayak S;Askenazi M;Verducci C;Chen BJ;Janitz M;Anink JJ;Baayen JC;Idema S;van Vliet EA;Devore S;Friedman D;Diehl B;Scott C;Thijs R;Wisniewski T;Ueberheide B;Thom M;Aronica E;Devinsky O
通讯作者：
Devinsky O
影响因子：
12.7
作者：
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通讯作者：
Baulac, Stephanie
影响因子：
2.2
作者：
Bayat, Arezou;Joshi, Sweta;Koubeissi, Mohamad Z.
通讯作者：
Koubeissi, Mohamad Z.
影响因子：
11.2
作者：
Liu, RSN;Lemieux, L;Duncan, JS
通讯作者：
Duncan, JS
影响因子：
2.6
作者：
Lacuey, Nuria;Martins, Rita;Lhatoo, Samden
通讯作者：
Lhatoo, Samden