Rada Anna, Reisch Lea Marie, Hagemann Anne, Woermann Friedrich G, Bien Christian G
Department of Epileptology, Krankenhaus Mara, Bethel Epilepsy Center, Medical School OWL, Bielefeld University, Germany.
Society for Epilepsy Research, Bielefeld, Germany; and.
Neurol Neuroimmunol Neuroinflamm. 2025 Jul;12(4):e200422. doi: 10.1212/NXI.0000000000200422. Epub 2025 Jun 12.
Epilepsy associated with glutamic acid decarboxylase antibodies (GAD-abs) often presents as temporal lobe epilepsy (TLE). However, detailed data on this condition are lacking. The aim of this study was to demonstrate that TLE with GAD-abs (GAD-TLE) is distinct from other forms of TLE and to describe the subgroup of patients with epilepsy and GAD-abs but no evidence of TLE.
Inpatients from 2011 to 2022 with high serum GAD-abs (≥1:80, confirmed by a cell-based assay and typical staining pattern on a tissue-based assay) were included. The control group comprised patients with mesial TLE (EMU-mTLE) with hippocampal sclerosis or nonlesional epilepsy diagnosed on the epilepsy monitoring unit (EMU) and having negative results on a broad panel of neural antibodies. Data were retrospectively collected from first admission (visit 1 [V1]) and most recent follow-up (visit 2 [V2]). Parameters included demographic data, comorbidities, seizure characteristics, electroencephalography findings, MRI results, verbal memory performance, GAD-ab titers (V1), therapies, seizure and memory outcomes, and occupational status (V2).
Of 81 GAD-ab-positive patients, 71 (88%) had TLE. Compared with 40 EMU-mTLE controls, patients with GAD-TLE were more often female (84% vs 33%, < 0.001), more frequently had autoimmune comorbidities (46% vs 2.5%, < 0.001), musicogenic seizures (18% vs 0%, = 0.004), and seizure clusters (25% vs 5%, = 0.002) but less frequently had hippocampal sclerosis (25% vs 54%, = 0.007). At follow-up (GAD-TLE: median 5 years; EMU-mTLE: 2 years), only 14% of patients with GAD-TLE were terminally seizure-free for ≥1 year, compared with 39% of patients with EMU-mTLE ( = 0.04). Verbal memory remained stable, and occupational status was unchanged. Ten GAD-ab-positive cases without evidence of TLE were identified, including 3 with generalized features.
Epilepsy associated with GAD-abs predominantly manifests as TLE and as such is an epilepsy syndrome (GAD-TLE). In comparison with EMU-confirmed patients with mTLE without GAD-abs, the seizure outcome is inferior but the neuropsychological performance is usually normal and remains stable. A subset of patients with epilepsy with high-titer GAD-abs do not have TLE, some presenting with generalized features.
与谷氨酸脱羧酶抗体（GAD - abs）相关的癫痫常表现为颞叶癫痫（TLE）。然而，关于这种情况的详细数据尚缺乏。本研究的目的是证明伴有GAD - abs的TLE（GAD - TLE）与其他形式的TLE不同，并描述患有癫痫和GAD - abs但无TLE证据的患者亚组。
纳入2011年至2022年血清GAD - abs水平高（≥1:80，通过基于细胞的检测确认，并在基于组织的检测中有典型染色模式）的住院患者。对照组包括在癫痫监测单元（EMU）诊断为内侧颞叶癫痫（EMU - mTLE）伴海马硬化或非病灶性癫痫且一系列神经抗体检测结果为阴性的患者。数据从首次入院（就诊1 [V1]）和最近一次随访（就诊2 [V2]）进行回顾性收集。参数包括人口统计学数据、合并症、发作特征、脑电图结果、MRI结果、言语记忆表现、GAD - ab滴度（V1）、治疗方法、发作和记忆结局以及职业状况（V2）。
在81例GAD - ab阳性患者中，71例（88%）患有TLE。与40例EMU - mTLE对照组相比，GAD - TLE患者女性更常见（84%对33%，<0.001），自身免疫性合并症更频繁（46%对2.5%，<0.001），音乐源性发作（18%对0%，=0.004）和发作簇（25%对5%，=0.002）更常见，但海马硬化较少见（25%对54%，=0.007）。在随访时（GAD - TLE：中位数5年；EMU - mTLE：2年），只有14%的GAD - TLE患者连续≥1年无发作，而EMU - mTLE患者为39%（=0.04）。言语记忆保持稳定，职业状况未改变。确定了10例无TLE证据的GAD - ab阳性病例，包括3例具有全身性特征的病例。
与GAD - abs相关的癫痫主要表现为TLE，因此是一种癫痫综合征（GAD - TLE）。与EMU确诊的无GAD - abs的mTLE患者相比，发作结局较差，但神经心理学表现通常正常且保持稳定。一部分高滴度GAD - abs的癫痫患者没有TLE，一些表现为全身性特征。
