Tian Decai, Zhu Xiaodong, Xue Rong, Zhao Peng, Yao Yuanrong
From the Bejing-TJ Center for Neuroinflammation, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (D.T.); Department of Neurology, Neurologic Institute, Tianjin Medical University General Hospital, Tianjin, China (X.Z., R.X., P.Z.); and Department of Neurology, Guizhou Provincial People's Hospital, Medical School of Guizhou University, Zhongshan East Road 83, Guiyang 550002, China (Y.Y.).
Radiology. 2018 Jul;288(1):308-311. doi: 10.1148/radiol.2018161474.
History In November 2012, a previously healthy 31-year-old woman was admitted to our hospital with a 2-month history of right-sided numbness, diplopia, and intermittent nausea and dizziness. She did not have a history of fever, weight loss, headache, photophobia, seizure, or extremity weakness. Physical examination revealed left abduction limitation and right-sided hypoesthesia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts, normal serum chemistry, and normal immune function. Analysis of her serum was negative for antiaquaporin 4 antibody, rheumatism antibody profile, and paraneoplastic profile. Serum analysis was also negative for human immunodeficiency virus type 1 and 2 RNA, hepatitis B and C antigen or antibody profile, and fluorescent treponemal antibody absorption. Cerebrospinal fluid (CSF) analysis revealed clear fluid, a normal glucose level, an elevated protein level (45 mg/dL; normal range, 20-40 mg/dL), and an elevated white blood cell count (10/mm [0.01 ×10/L]; normal range, 0-8/mm [{0-0.008} ×10/L]; 81% lymphocytes, 19% monocytes). No CSF-specific oligoclonal bands were detected. Gram staining, acid-fast staining, and lactic acid and cryptococcal antigen test results were negative. CSF did not grow any bacteria, fungus, or acid-fast bacillus at culture. Spinal cord MRI, brain MR angiography, and CT of the chest, abdomen, and pelvis revealed normal findings (images not shown). Brain MRI and gadolinium-enhanced (20 mL gadopentetate dimeglumine, BeiLu Pharmaceutical, Beijing, China) MRI were performed ( Fig 1 ). The patient's clinical symptoms and imaging findings responded to treatment with a high dose of steroids. However, the patient's symptoms exhibited clinical and radiologic progression as she attempted to taper the steroid dose. She arbitrarily stopped taking the steroids and started traditional Chinese treatment instead. However, her condition was not controlled. [Figure: see text][Figure: see text][Figure: see text] In November 2013, she was readmitted with worsening dizziness and diplopia accompanied by hearing loss, tinnitus, slurred speech, drinking-induced cough, walking instability, and involuntary outbursts of laughter and crying. Dysmetria, ataxia, brisk tendon reflexes, pathologic reflexes, and pseudobulbar signs were observed bilaterally. Repeated biochemical and immune tests did not yield positive findings. CSF analysis revealed mild lymphocytic pleocytosis (white blood cell count, 8/mm [0.008 ×10/L]; 83% lymphocytes, 17% monocytes) and a slightly elevated total protein level (46 mg/dL). Brain PET revealed diffuse high metabolism in the midbrain and pons (images not shown). Whole-body PET was negative for malignancy (images not shown). Brain MRI and gadolinium-enhanced MRI were performed ( Fig 2 ). The patient's clinical symptoms and imaging findings improved after treatment with a high dose of steroids. Thereafter, intravenous cyclophosphamide therapy was added after her condition deteriorated again when the prednisone dose was tapered to 20 mg per day in March 2014 ( Fig 3a ). Her pontocerebral symptoms were relatively stable in the following year, with apparent diminishment of lesions in the brainstem and cerebellum observed at brain PET (images not shown). Follow-up MR images were obtained in July 2014 ( Fig 3b ). Subsequently, the patient exhibited clinical and radiologic aggravation. MR images were obtained again in July 2015 ( Fig 4 ) and February 2016 ( Fig 5 ). The patient underwent biopsy of the right frontal lobe, and a histopathologic examination was performed in August 2015. Afterward, her condition worsened, and she died in September 2016. [Figure: see text][Figure: see text][Figure: see text] [Figure: see text][Figure: see text].
病史 2012年11月，一名此前健康的31岁女性因右侧麻木、复视以及间歇性恶心和头晕2个月的病史入住我院。她无发热、体重减轻、头痛、畏光、癫痫或肢体无力病史。体格检查发现左侧外展受限及右侧感觉减退。克尼格征和布鲁津斯基征阴性，针刺反应试验结果为阴性。实验室检查显示全血细胞计数及分类、血清化学指标和免疫功能均正常。她的血清抗水通道蛋白4抗体、风湿抗体谱及副肿瘤综合征相关检查均为阴性。血清分析中，人类免疫缺陷病毒1型和2型RNA、乙肝和丙肝抗原或抗体谱以及梅毒螺旋体抗体吸收试验也均为阴性。脑脊液（CSF）分析显示脑脊液清亮，葡萄糖水平正常，蛋白水平升高（45mg/dL；正常范围20 - 40mg/dL），白细胞计数升高（10/mm³[0.01×10⁹/L]；正常范围0 - 8/mm³[{0 - 0.008}×10⁹/L]；81%为淋巴细胞，19%为单核细胞）。未检测到脑脊液特异性寡克隆带。革兰染色、抗酸染色、乳酸及隐球菌抗原检测结果均为阴性。脑脊液培养未生长任何细菌、真菌或抗酸杆菌。脊髓磁共振成像（MRI）、脑磁共振血管造影以及胸部、腹部和骨盆的CT检查均显示正常结果（未展示图像）。进行了脑部MRI及钆增强（20mL钆喷酸葡胺，北陆药业，北京，中国）MRI检查（图1）。患者的临床症状和影像学表现对高剂量类固醇治疗有反应。然而，当患者试图减少类固醇剂量时，其症状出现临床和影像学进展。她擅自停用类固醇，转而开始接受中医治疗。但她的病情未得到控制。[图：见正文][图：见正文][图：见正文] 2013年11月，她因头晕和复视加重再次入院，伴有听力丧失、耳鸣、言语不清、饮水呛咳、行走不稳以及哭笑无常。双侧均观察到辨距不良、共济失调、腱反射亢进、病理反射及假性球麻痹体征。重复的生化和免疫检查未发现阳性结果。脑脊液分析显示轻度淋巴细胞增多（白细胞计数8/mm³[0.008×10⁹/L]；83%为淋巴细胞，17%为单核细胞），总蛋白水平略有升高（46mg/dL）。脑部正电子发射断层扫描（PET）显示中脑和脑桥弥漫性高代谢（未展示图像）。全身PET检查未发现恶性肿瘤（未展示图像）。进行了脑部MRI及钆增强MRI检查（图2）。高剂量类固醇治疗后患者的临床症状和影像学表现有所改善。此后，2014年3月当泼尼松剂量减至每日mg时病情再次恶化，随后加用了静脉环磷酰胺治疗（图3a）。次年她的脑桥症状相对稳定，脑部PET显示脑干和小脑病变明显减轻（未展示图像）。2014年7月获得了随访MR图像（图3b）。随后，患者出现临床和影像学加重。2015年7月（图4）和2016年2月（图5）再次进行了MR图像检查。2015年8月患者接受了右侧额叶活检并进行了组织病理学检查。此后，她的病情恶化，于2016年9月死亡。[图：见正文][图：见正文][图：见正文][图：见正文][图：见正文]
