Kobayakawa Yuko, Tateishi Takahisa, Kawamura Nobutoshi, Doi Hikaru, Ohyagi Yasumasa, Kira Jun-ichi
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University.
Rinsho Shinkeigaku. 2010 Feb;50(2):92-7. doi: 10.5692/clinicalneurol.50.92.
We reported a patient with immune-mediated encephalopathy showing refractory epilepsy and multiple brain lesions on MRI. The patient had high titers of anti-glutamic acid decarboxylase (GAD) antibody in sera and cerebrospinal fluid (CSF). A 36-year-old previously healthy woman was admitted to our hospital with onset of sudden generalized seizure that then persisted for one month. She had repeated epileptic attacks accompanied with loss of consciousness, and was refractory to valproic acid, zonisamide (200 mg/day) and phenobarbital (200 mg/day). Brain MRI showed multiple hyperintense lesions in predominantly bilateral frontal lobes, parietal lobes, occipital lobes and cingulate cortices. EEG showed epileptic activities (frequent sharp waves) in bilateral frontal regions. After admission, attacks disappeared through the administration of clonazepam (1.5 mg/day), though the patient remained slightly disoriented. As titers of anti-GAD antibody in sera and CSF were extremely high, we implemented plasma exchanges. After treatment, titers of anti-GAD antibody in sera and CSF decreased. The patient completely recovered to an alert state and the abnormal MRI lesions almost disappeared. Since GAD catalyzes production of gamma-aminobutyric acid (GABA), it is proposed that anti-GAD antibodies reduce synthesis of GABA or interferes with exocytosis of GABA in the nervous system. Anti-GAD antibodies are detected in some rare neurological disorders such as stiff-person syndrome. Recently, anti-GAD antibodies have been reported as implicated in cerebellar ataxia, palatal myoclonus, refractory epilepsy and limbic encephalitis. Epilepsy associated with the anti-GAD antibody is mostly pharmacoresistant temporal lobe epilepsy; with brain MRI showing no abnormality or only hippocampal sclerosis. It is very rare that brain MRI shows extensive abnormal lesions except in the hippocampus. This case suggests that anti-GAD antibodies could contribute to unexplained encephalopathy with extensive brain MRI lesions and drug-resistant symptomatic epilepsy.
我们报告了一例患有免疫介导性脑病的患者，该患者表现为难治性癫痫且磁共振成像（MRI）显示有多处脑损伤。患者血清和脑脊液（CSF）中抗谷氨酸脱羧酶（GAD）抗体滴度很高。一名36岁既往健康的女性因突发全身性癫痫发作入院，发作持续了一个月。她反复出现癫痫发作并伴有意识丧失，对丙戊酸、唑尼沙胺（200毫克/天）和苯巴比妥（200毫克/天）均耐药。脑部MRI显示双侧额叶、顶叶、枕叶及扣带回皮质为主的多处高信号损伤。脑电图显示双侧额叶区域有癫痫活动（频繁的尖波）。入院后，通过服用氯硝西泮（1.5毫克/天）发作消失，但患者仍有轻度定向障碍。由于血清和脑脊液中抗GAD抗体滴度极高，我们进行了血浆置换。治疗后，血清和脑脊液中抗GAD抗体滴度下降。患者完全恢复至清醒状态，MRI异常损伤几乎消失。由于GAD催化γ-氨基丁酸（GABA）的产生，因此推测抗GAD抗体可减少GABA的合成或干扰神经系统中GABA的胞吐作用。在一些罕见的神经系统疾病如僵人综合征中可检测到抗GAD抗体。最近，有报道称抗GAD抗体与小脑共济失调、腭肌阵挛、难治性癫痫和边缘叶脑炎有关。与抗GAD抗体相关的癫痫大多是药物难治性颞叶癫痫；脑部MRI显示无异常或仅有海马硬化。除海马体外，脑部MRI显示广泛异常损伤的情况非常罕见。该病例表明抗GAD抗体可能导致伴有广泛脑部MRI损伤和药物难治性症状性癫痫的不明原因脑病。
