颞叶癫痫患者的诊断挑战与自身免疫性边缘叶脑炎的特征。

Diagnostic challenges in patients with temporal lobe seizures and features of autoimmune limbic encephalitis.

机构信息

Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Bochum, Germany.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.

出版信息

Eur J Neurol. 2022 May;29(5):1303-1310. doi: 10.1111/ene.15026. Epub 2021 Jul 30.

DOI:10.1111/ene.15026

PMID:34288284

Abstract

BACKGROUND AND PURPOSE

Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neuronal antibodies (Abs), but it remains unclear which clinical features should prompt neuronal Ab screening in temporal lobe epilepsy patients. The aim of the study was to investigate whether patients with temporal lobe seizures associated with additional symptoms or signs of limbic involvement may harbor neuronal Abs, and which clinical features should prompt neuronal Ab screening in these patients.

METHODS

We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal magnetic resonance imaging (MRI) hyperintensities or inflammatory cerebrospinal fluid (CSF). Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRI scans were assessed by two reviewers independently.

RESULTS

Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), psychiatric symptoms in 27/42 (64%), and both in 19/42 patients (45%). Limbic T2/fluid-attenuated inversion recovery signal hyperintensities were found in 26/46 patients (57%; unilateral: n = 22, bilateral: n = 4). Standard CSF studies were abnormal in 2/37 patients (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 patients (17%) and were directed against neuronal cell-surface targets (leucine-rich glioma inactivated protein 1: n = 1, contactin-associated protein-2: n = 1, undetermined target: n = 3) or glutamic acid decarboxylase in its 65-kD isoform (n = 3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% vs. 18/38, 47%; p = 0.01, Fisher's exact test).

CONCLUSIONS

In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% confidence interval 1.51-2.95).

摘要

背景与目的

自身免疫性边缘性脑炎（ALE）的共识标准允许在没有神经元抗体（Abs）的情况下进行诊断，但目前尚不清楚哪些临床特征应该促使颞叶癫痫患者进行神经元 Ab 筛查。本研究的目的是调查是否与边缘性受累相关的颞叶发作患者伴有其他症状或体征可能存在神经元 Abs，以及在这些患者中哪些临床特征应该促使进行神经元 Ab 筛查。

方法

我们从一家三级癫痫中心确定了 47 名患者，这些患者具有中颞叶发作和其他提示边缘性受累的特征，包括记忆缺陷、精神症状、中颞叶磁共振成像（MRI）高信号或炎症性脑脊液（CSF）。在两个独立的参考实验室（德国比勒费尔德-贝特尔和西班牙巴塞罗那）进行神经元 Ab 检测。所有脑 MRI 扫描均由两名独立的审查员进行评估。

结果

46 名患者中有 35 名（76%）伴有记忆缺陷，42 名中有 27 名（64%）伴有精神症状，42 名中有 19 名（45%）同时伴有这两种症状。26 名患者（57%；单侧：n=22，双侧：n=4）中发现中颞叶 T2/液体衰减反转恢复信号高信号。37 名患者中有 2 名（5%）标准 CSF 研究异常。47 名患者中有 8 名（17%）在血清和/或 CSF 中证实存在神经元 Abs，这些 Abs 针对神经元细胞表面靶标（亮氨酸丰富的胶质瘤失活蛋白 1：n=1，接触蛋白相关蛋白-2：n=1，未确定的靶标：n=3）或谷氨酸脱羧酶的 65-kD 同工型（n=3，均为高滴度）。与 Ab 阴性患者相比，那些携带神经元 Abs 的患者更有可能出现单侧或双侧中颞叶 MRI 改变（8/8，100% vs. 18/38，47%；p=0.01，Fisher 精确检验）。