From the Department of Pathology, Yale School of Medicine, New haven, Connecticut.
Comprehensive Epilepsy Center, New York University School of Medicine, New York, New York.
J Neuropathol Exp Neurol. 2020 Mar 1;79(3):336-346. doi: 10.1093/jnen/nlz136.
Sudden unexplained death in childhood (SUDC) affects children >1-year-old whose cause of death remains unexplained following comprehensive case investigation and is often associated with hippocampal abnormalities. We prospectively performed systematic neuropathologic investigation in 20 SUDC cases, including (i) autopsy data and comprehensive ancillary testing, including molecular studies, (ii) ex vivo 3T MRI and extensive histologic brain samples, and (iii) blinded neuropathology review by 2 board-certified neuropathologists. There were 12 girls and 8 boys; median age at death was 33.3 months. Twelve had a history of febrile seizures, 85% died during apparent sleep and 80% in prone position. Molecular testing possibly explained 3 deaths and identified genetic mutations in TNNI3, RYR2, and multiple chromosomal aberrations. Hippocampal abnormalities most often affected the dentate gyrus (altered thickness, irregular configuration, and focal lack of granule cells), and had highest concordance between reviewers. Findings were identified with similar frequencies in cases with and without molecular findings. Number of seizures did not correlate with hippocampal findings. Hippocampal alterations were the most common finding on histological review but were also found in possibly explained deaths. The significance and specificity of hippocampal findings is unclear as they may result from seizures, contribute to seizure pathogenesis, or be an unrelated phenomenon.
儿童不明原因猝死 (SUDC) 影响 1 岁以上的儿童，这些儿童在全面的案例调查后死因仍未得到解释，且常与海马体异常有关。我们前瞻性地对 20 例 SUDC 病例进行了系统的神经病理学研究，包括 (i) 尸检数据和全面的辅助检查，包括分子研究，(ii) 离体 3T MRI 和广泛的组织学脑样本，以及 (iii) 由 2 名具有董事会认证的神经病理学家进行的盲法神经病理学审查。其中有 12 名女孩和 8 名男孩；死亡时的中位年龄为 33.3 个月。有 12 例有热性惊厥史，85%死于明显睡眠期间，80%死于俯卧位。分子检测可能解释了 3 例死亡，并确定了 TNNI3、RYR2 和多种染色体异常的基因突变。海马体异常最常影响齿状回（厚度改变、不规则形态和颗粒细胞局部缺失），且两位审阅者的意见一致性最高。在有和无分子发现的病例中，均以相似的频率发现了这些发现。癫痫发作的次数与海马体的发现没有相关性。海马体改变是组织学审查中最常见的发现，但也存在于可能有解释的死亡病例中。海马体发现的意义和特异性尚不清楚，因为它们可能是由癫痫发作引起的，也可能有助于癫痫发病机制，或者是一种无关的现象。
