Rácz Attila, Hummel Chiara A, Becker Albert, Helmstaedter Christoph, Schuch Fabiane, Baumgartner Tobias, von Wrede Randi, Borger Valeri, Solymosi László, Surges Rainer, Elger Christian E
Department of Epileptology, University Hospital Bonn, Bonn, Germany.
Department of Neuropathology, University Hospital Bonn, Bonn, Germany.
Front Neurol. 2022 Apr 15;13:859868. doi: 10.3389/fneur.2022.859868. eCollection 2022.
Limbic encephalitis is an increasingly recognized cause of medial temporal lobe epilepsy (mTLE) and associated cognitive deficits, potentially resulting in hippocampal sclerosis (HS). For several reasons, these patients usually do not undergo epilepsy surgery. Thus, histopathologic examinations in surgical specimens of clearly diagnosed limbic encephalitis are scarce. The purpose of this study was a detailed histopathologic analysis of surgical tissue alterations, including neurodegenerative markers, in patients with limbic encephalitis undergoing epilepsy surgery.
We investigated the surgical specimens of six patients operated on with mTLE related to limbic encephalitis (among them four patients were with GAD65 and one with Ma1/2 antibodies), and compared the findings to a control group with six patients matched according to age at the time of surgery without limbic encephalitis and without early inciting events.
Histopathologic analysis in the group with limbic encephalitis revealed HS in four patients, while three of them also displayed signs of an active inflammatory reaction with lymphocytes. In one of the patients with GAD65-encephalitis who was suffering from a late-onset mTLE and a long disease course, neurodegenerative protein markers (β-amyloid and hyperphosphorylated tau) were found coexisting with inflammatory reactions and HS. Investigations in the control group did not reveal any inflammatory reaction or neurodegenerative marker.
Our findings suggest a possible link between long-lasting immune reactions in the medial temporal lobe, HS, and further toward the development of neurodegenerative diseases. Presently, however, a causal relationship between these entities cannot yet be established. Furthermore, our results suggest that an immunological etiology should always be considered in late onset (> 18 years) mTLE, also in cases of long disease duration and the presence of HS.
边缘叶脑炎是内侧颞叶癫痫（mTLE）及相关认知缺陷日益被认识到的病因，可能导致海马硬化（HS）。由于多种原因，这些患者通常不接受癫痫手术。因此，明确诊断的边缘叶脑炎手术标本的组织病理学检查很少见。本研究的目的是对接受癫痫手术的边缘叶脑炎患者的手术组织改变进行详细的组织病理学分析，包括神经退行性标志物。
我们研究了6例因边缘叶脑炎接受mTLE手术的患者的手术标本（其中4例患者有GAD65抗体，1例有Ma1/2抗体），并将结果与一个对照组进行比较，该对照组有6例患者，根据手术时的年龄匹配，无边缘叶脑炎且无早期诱发事件。
边缘叶脑炎组的组织病理学分析显示4例患者有HS，其中3例还表现出淋巴细胞活跃炎症反应的迹象。在1例患有迟发性mTLE且病程较长的GAD65脑炎患者中，发现神经退行性蛋白标志物（β-淀粉样蛋白和过度磷酸化tau蛋白）与炎症反应和HS共存。对照组的研究未发现任何炎症反应或神经退行性标志物。
我们的研究结果提示内侧颞叶长期免疫反应、HS以及进一步发展为神经退行性疾病之间可能存在联系。然而，目前这些实体之间的因果关系尚未确立。此外，我们的结果表明，对于迟发性（>18岁）mTLE，无论病程长短及是否存在HS，均应始终考虑免疫病因。
