Abstract：
OBJECTIVE: The relationship between autologous hematopoietic stem cell transplant (aHSCT) for multiple myeloma (MM) and anti-GABAA receptor (GABAAR) encephalitis is unknown. We aimed to describe the clinical features, diagnostic process, and outcome of 3 cases of anti-GABAAR encephalitis in patients with a history of prior aHSCT for MM.
METHODS: A case series of 3 patients. Anti-GABAAR antibody was tested at the University of Pennsylvania Laboratory.
RESULTS: The patients were all male, aged 52 (case 1), 61 (case 2), and 62 (case 3) years at encephalitis symptom onset. The duration between completion of aHSCT and the onset of encephalitis was 43, 18, and 9 months, respectively. All 3 patients presented with new seizures and altered cognitive function. Other symptoms included headache and visual obscurations in cases 1 and 2 and intractable vertigo and mania in case 3. Brain MRI demonstrated nonenhancing multifocal T2-weighted/fluid-attenuated inversion recovery cortical and subcortical hyperintensities in all 3 patients. Cases 2 and 3 underwent brain biopsy before initiating immunomodulatory therapy, which demonstrated nonspecific encephalitis with astrogliosis in the white matter; these 2 patients were started on immunotherapy for the treatment of anti-GABAAR encephalitis after 22 days and 3 months, respectively, from the first presentation. Case 1 was started on empiric immunotherapy within 8 days of presentation without requiring brain biopsy, given characteristic MRI imaging. CSF analysis demonstrated the presence of anti-GABAAR antibodies in all 3 cases. Cases 1 and 3 also tested positive for anti-GABAAR antibodies in the serum (serum test was not performed in case 2). Cases 1 and 2 recovered to work full-time within 1 year. Case 3 reported occasional myoclonic-like movement.
CONCLUSIONS: We highlight the importance of considering anti-GABAAR encephalitis in patients with seizures, multifocal nonenhancing brain lesions, and a history of aHSCT for MM. Awareness in recovered post-aHSCT patients with MM may be crucial because prompt recognition can avoid brain biopsy and delays in treatment. The rapid initiation of immunotherapy while awaiting autoantibody results will likely improve functional outcomes.
METHODS: A case series of 3 patients. Anti-GABAAR antibody was tested at the University of Pennsylvania Laboratory.
RESULTS: The patients were all male, aged 52 (case 1), 61 (case 2), and 62 (case 3) years at encephalitis symptom onset. The duration between completion of aHSCT and the onset of encephalitis was 43, 18, and 9 months, respectively. All 3 patients presented with new seizures and altered cognitive function. Other symptoms included headache and visual obscurations in cases 1 and 2 and intractable vertigo and mania in case 3. Brain MRI demonstrated nonenhancing multifocal T2-weighted/fluid-attenuated inversion recovery cortical and subcortical hyperintensities in all 3 patients. Cases 2 and 3 underwent brain biopsy before initiating immunomodulatory therapy, which demonstrated nonspecific encephalitis with astrogliosis in the white matter; these 2 patients were started on immunotherapy for the treatment of anti-GABAAR encephalitis after 22 days and 3 months, respectively, from the first presentation. Case 1 was started on empiric immunotherapy within 8 days of presentation without requiring brain biopsy, given characteristic MRI imaging. CSF analysis demonstrated the presence of anti-GABAAR antibodies in all 3 cases. Cases 1 and 3 also tested positive for anti-GABAAR antibodies in the serum (serum test was not performed in case 2). Cases 1 and 2 recovered to work full-time within 1 year. Case 3 reported occasional myoclonic-like movement.
CONCLUSIONS: We highlight the importance of considering anti-GABAAR encephalitis in patients with seizures, multifocal nonenhancing brain lesions, and a history of aHSCT for MM. Awareness in recovered post-aHSCT patients with MM may be crucial because prompt recognition can avoid brain biopsy and delays in treatment. The rapid initiation of immunotherapy while awaiting autoantibody results will likely improve functional outcomes.
摘要：
目的：自体造血干细胞移植（aHSCT）治疗多发性骨髓瘤（MM）与抗GABAA受体（GABAAR）脑炎的关系尚不清楚。我们的目的是描述临床特征，诊断过程,3例抗GABAAR脑炎患者既往有MMaHSCT病史。
方法：3例患者的病例系列。在宾夕法尼亚大学实验室测试抗GABAAR抗体。
结果：患者均为男性，52岁（案例1），61（案例2），脑炎症状发作62年（病例3）。完成aHSCT和脑炎发作之间的持续时间为43、18和9个月，分别。所有3例患者均出现新的癫痫发作和认知功能改变。其他症状包括病例1和2中的头痛和视觉模糊，病例3中的顽固性眩晕和躁狂症。脑MRI显示，所有3例患者的多灶性T2加权/液体衰减倒置恢复皮质和皮质下高信号均未增强。病例2和3在开始免疫调节治疗之前接受了脑活检，这表明在白质中伴有星形胶质增生的非特异性脑炎；这2例患者在22天和3个月后开始接受免疫治疗以治疗抗GABAAR脑炎，分别,从第一次介绍。病例1在出现后8天内开始经验性免疫疗法，不需要脑活检。给定特征MRI成像。CSF分析证明在所有3例病例中均存在抗GABAAR抗体。病例1和3的血清中的抗GABAAR抗体也测试为阳性(在病例2中未进行血清测试)。病例1和2在1年内恢复全职工作。病例3报告偶有肌阵挛性运动。
结论：我们强调在癫痫发作患者中考虑抗GABAAR脑炎的重要性，多灶性非增强脑部病变，以及MM的aHSCT历史。aHSCT后康复的MM患者的意识可能至关重要，因为及时识别可以避免脑活检和治疗延误。在等待自身抗体结果的同时快速启动免疫疗法可能会改善功能结果。
方法：3例患者的病例系列。在宾夕法尼亚大学实验室测试抗GABAAR抗体。
结果：患者均为男性，52岁（案例1），61（案例2），脑炎症状发作62年（病例3）。完成aHSCT和脑炎发作之间的持续时间为43、18和9个月，分别。所有3例患者均出现新的癫痫发作和认知功能改变。其他症状包括病例1和2中的头痛和视觉模糊，病例3中的顽固性眩晕和躁狂症。脑MRI显示，所有3例患者的多灶性T2加权/液体衰减倒置恢复皮质和皮质下高信号均未增强。病例2和3在开始免疫调节治疗之前接受了脑活检，这表明在白质中伴有星形胶质增生的非特异性脑炎；这2例患者在22天和3个月后开始接受免疫治疗以治疗抗GABAAR脑炎，分别,从第一次介绍。病例1在出现后8天内开始经验性免疫疗法，不需要脑活检。给定特征MRI成像。CSF分析证明在所有3例病例中均存在抗GABAAR抗体。病例1和3的血清中的抗GABAAR抗体也测试为阳性(在病例2中未进行血清测试)。病例1和2在1年内恢复全职工作。病例3报告偶有肌阵挛性运动。
结论：我们强调在癫痫发作患者中考虑抗GABAAR脑炎的重要性，多灶性非增强脑部病变，以及MM的aHSCT历史。aHSCT后康复的MM患者的意识可能至关重要，因为及时识别可以避免脑活检和治疗延误。在等待自身抗体结果的同时快速启动免疫疗法可能会改善功能结果。
