Alsalek Samir, Himstead Alexander S, Self Scott, Fote Gianna M, Vadera Sumeet, Monuki Edwin S, Perez-Rosendahl Mari, Yong William H
Kaiser Permanente Bernard J. Tyson School of Medicine, 98 S Los Robles Ave, Pasadena, CA 91101, USA.
Department of Neurosurgery, University of California, Irvine, 200 South Manchester Ave, Suite 210, Orange, CA 92868, USA.
Free Neuropathol. 2024 Aug 21;5:18. doi: 10.17879/freeneuropathology-2024-5269. eCollection 2024 Jan.
Mesial temporal lobe epilepsy (MTLE) is a common cause of seizures, and hippocampal sclerosis (HS) is the predominant subtype. mutations in MTLE-HS have only been reported infrequently. Herein, we illustrate the neurologic, radiological, and histopathological details of a patient with MTLE-HS and mutant neurons. A 31-year-old male with medically refractory epilepsy presented with magnetic resonance imaging (MRI) and electroencephalography (EEG) findings typical of mesial temporal sclerosis without a mass lesion. The surgical specimens showed ILAE Type 1 HS with neurons immunopositive for BRAFV600E mutant protein distributed along the Cornu Ammonis (CA) curvature. Instead of the normal mostly perpendicular orientation of pyramidal neurons relative to the hippocampal surface, the mutant neurons were often oriented in a parallel manner. On CD34 immunostaining, sparse clusters or nodules of CD34+ stellate cells and single immunopositive stellate cells were identified. BRAFV600E or CD34 immunopositive cells were less than 1 % of total cells. The patient responded well to surgery with no further seizures after 2 years and occasional auras. Hippocampal mutant non-expansive lesion (HBNL) has been used to describe such lesions with preserved cytoarchitecture and without overt tumor mass. Others may argue for the dual pathology of HS with early ganglioglioma. Whether pre-neoplastic lesions or early tumors, these cases are important for understanding early glioneuronal tumorigenesis and suggest that BRAFV600E studies should be routinely performed on MTLE-HS cases in the setting of clinical trials. With next-generation sequencing, a deletion was detected in almost half of the alleles in our case, suggesting that many of the histologically normal-appearing cells of the hippocampus contain this alteration. mutations can result in cytogenetic anomalies and defective DNA repair and therefore may underlie the development of a low frequency alteration.
内侧颞叶癫痫（MTLE）是癫痫发作的常见原因，海马硬化（HS）是其主要亚型。MTLE-HS中的突变仅有少量报道。在此，我们阐述了一名患有MTLE-HS和突变神经元患者的神经学、放射学和组织病理学细节。一名31岁患有药物难治性癫痫的男性患者，其磁共振成像（MRI）和脑电图（EEG）结果显示为典型的内侧颞叶硬化，无占位性病变。手术标本显示国际抗癫痫联盟（ILAE）1型HS，沿海马角（CA）曲度分布的神经元对BRAFV600E突变蛋白呈免疫阳性。与正常情况下锥体细胞相对于海马表面大多垂直排列不同，突变神经元常呈平行排列。在CD34免疫染色中，识别出CD34+星状细胞的稀疏簇或结节以及单个免疫阳性星状细胞。BRAFV600E或CD34免疫阳性细胞少于总细胞的1%。该患者术后反应良好，2年后无进一步癫痫发作，偶有先兆。海马突变非扩展性病变（HBNL）已被用于描述此类细胞结构保存且无明显肿瘤块的病变。其他人可能主张HS合并早期节细胞胶质瘤的双重病理改变。无论这些病变是肿瘤前病变还是早期肿瘤，这些病例对于理解早期神经胶质神经元肿瘤发生都很重要，并提示在临床试验背景下，应对MTLE-HS病例常规进行BRAFV600E研究。通过下一代测序技术，在我们的病例中几乎一半的等位基因中检测到一个缺失，这表明海马中许多组织学上看似正常的细胞含有这种改变。突变可导致细胞遗传学异常和DNA修复缺陷，因此可能是低频改变发生的基础。
