Department of Epileptology, University of Bonn Medical Center, Bonn, Germany.
Ann Neurol. 2010 Apr;67(4):470-8. doi: 10.1002/ana.21917.
Antibodies to glutamic acid decarboxylase (GAD) have been described in a few patients with temporal lobe epilepsies consistent with limbic encephalitis (LE). We studied a cohort of patients with recent-onset temporal lobe epilepsy caused by LE to test for GAD antibody positivity and response to immunotherapies.
Over a period of 3.75 years, 138 patients aged >or=18 years investigated at the Department of Epileptology, University of Bonn, for recent-onset epilepsy were prospectively collected and studied for cliniconeuroradiological features of LE, autoantibodies, and treatment responses.
Fifty-three adult patients fulfilled the criteria for LE: (1) limbic signs and symptoms for <or=5 years and (2) brain MRI revealing mediotemporal encephalitis (T2/fluid attenuated inversion recovery hyperintensity without atrophy). Nine had high-titer GAD antibodies; 10 had voltage-gated potassium channel (VGKC) antibodies. Patients with GAD antibodies were younger (median age, 23 years; range, 17-66 years) (p = 0.003) and presented with seizures only, whereas polymorphic limbic features were more common in the VGKC antibody-positive group (p < 0.001). None had tumors. Patients with GAD antibodies more frequently had cerebrospinal fluid oligoclonal bands (p = 0.009) and intrathecal secretion of the specific antibody (p = 0.01). Following monthly intravenous methylprednisolone pulses, GAD antibodies remained highly elevated in 6/6 patients, whereas VGKC antibodies normalized in 6/9 patients (p = 0.03). Despite more intense anticonvulsive treatment in the GAD antibody-positive group (p = 0.01), none of these patients became seizure free, unlike all of the patients with VGKC antibodies (p < 0.001).
High-titer GAD antibodies define a form of nonparaneoplastic LE. This is a chronic, nonremitting disorder and should be included in the differential diagnosis of patients with TLE and mediotemporal encephalitis. Therapeutic trials of other immunotherapies should be undertaken.
已在一些符合边缘性脑炎（LE）的颞叶癫痫患者中描述了谷氨酸脱羧酶（GAD）抗体。我们研究了一组由 LE 引起的近期发作性颞叶癫痫患者，以检测 GAD 抗体阳性和免疫治疗反应。
在 3.75 年的时间内，前瞻性收集了在波恩大学癫痫科就诊的年龄≥18 岁的 138 例近期发作性癫痫患者，研究其 LE 的临床神经放射学特征、自身抗体和治疗反应。
53 例成人患者符合 LE 标准：（1）边缘症状和体征<或=5 年；（2）脑 MRI 显示中颞叶脑炎（T2/液体衰减反转恢复高信号，无萎缩）。9 例患者有高滴度 GAD 抗体；10 例患者有电压门控钾通道（VGKC）抗体。GAD 抗体阳性患者更年轻（中位年龄 23 岁；范围 17-66 岁）（p=0.003），仅表现为癫痫发作，而 VGKC 抗体阳性组更常见多形性边缘特征（p<0.001）。均无肿瘤。GAD 抗体阳性患者更常出现脑脊液寡克隆带（p=0.009）和特异性抗体鞘内分泌（p=0.01）。每月静脉注射甲基强的松龙脉冲后，6/6 例患者的 GAD 抗体仍高度升高，而 6/9 例患者的 VGKC 抗体正常化（p=0.03）。尽管 GAD 抗体阳性组接受了更强烈的抗惊厥治疗（p=0.01），但与所有 VGKC 抗体阳性患者不同（p<0.001），这些患者均未无癫痫发作。
高滴度 GAD 抗体定义了一种非副肿瘤性 LE 形式。这是一种慢性、进行性疾病，应纳入 TLE 和中颞叶脑炎患者的鉴别诊断。应进行其他免疫疗法的治疗试验。
