伴顽固性低钠血症的抗Y-氨基丁酸B受体抗体相关脑炎合并小细胞肺癌:1例报告及文献复习

目的:首次报道1例伴顽固性低钠血症的抗γ-氨基丁酸B受体(gamma-aminobutyric acid B receptor,GABA_BR)抗体相关脑炎合并小细胞肺癌患者,旨在进一步认识其临床特征、可能的发生机制、诊治方法以及预后。方法:报道1例伴顽固性低钠血症的抗GABA_BR抗体相关脑炎合并小细胞肺癌患者的临床表现、辅助检查结果、诊疗经过以及预后,并结合相关文献复习,分析可能的发生机制。结果:患者为老年女性,因“发作性意识不清伴四肢抽搐”就诊,并且很快进展为癫痫持续状态,伴有精神异常和认知障碍。血和脑脊液抗GABA_BR抗体阳性,合并顽固性低钠血症。头颅MRl检查未见明显异常。PET-CT检查显示,左侧肺门及左肺下叶结节及团块影,伴¹⁸F-氟代脱氧葡萄糖(¹⁸F-fluorodeoxyglucose,¹⁸F-FDG)代谢异常增高,考虑恶性病变可能。经皮肺穿刺活检诊断为左肺小细胞癌伴纵膈淋巴结转移。给予糖皮质激素冲击治疗、静脉滴注丙种球蛋白、小细胞肺癌化疗...     

抗GABA_B R脑炎5例病例报告及文献复习

目的探讨5例抗GABABR脑炎的临床特点及诊治。方法对患者的临床表现、头部影像学、脑电图特点、脑脊液检查等进行回顾性分析及相关文献回顾。结果 5例抗GABABR脑炎患者亚急性起病、病前无感染史,均以抽搐起病,有2例伴有精神症状。1例患者头部MRI右侧海马异常高信号。脑电提示部分性发作。腰椎穿刺:CSF 2例压力升高,蛋白轻度增高或正常,白细胞(20~116×106/L,单核为主),糖正常。CSF+血抗GABABR抗体阳性。肺部CT或PET-CT扫描提示肺部占位。经糖皮质激素或丙种球蛋白治疗好转。结论 (1)头部MRI、脑电图、CSF+血抗GABABR抗体检测利于抗GABABR脑炎早期诊断;(2)抗GABABR脑炎患者应积极查找可能肿瘤,尤其肺部占位,PET-CT检查对于肺CT检查阴性者有益。     

30例抗γ氨基丁酸B受体脑炎临床特点分析

目的 探讨抗GABABR抗体脑炎的临床表现、脑脊液、头部MRI及预后特点。方法 收集我院2015年12月-2019年6月收治的抗GABABR抗体脑炎患者30例,总结其临床表现、脑脊液、头部MRI特点,并进行随访,评估预后。结果 30例患者平均发病年龄为58岁(15～84岁),男性18例,女性12例。癫痫发作为最常见的首发症状,并以癫痫发作(26例,86. 67%)、精神行为异常(26例,86. 67%)、认知功能损害(24例,80. 00%)为主要临床表现。脑脊液以淋巴细胞比例及白细胞计数升高为主要特点。头部MRI可见内侧颞叶、海马异常信号(10例,35. 71%)。易合并肺癌(特别是小细胞肺癌),在平均随访11 m后近半数患者死亡(13例,48. 15%),死亡患者大多合并肺癌(9例,69. 23%)。结论 抗GABABR抗体脑炎主要表现为癫痫发作,影像学可见颞叶内侧、海马异常信号,同肺癌(小细胞肺癌)密切相关,近半数患者预后不良。     

以癫痫发作起病的抗GABAB受体脑炎六例

目的总结抗r氨基丁酸B型(GABAB)受体脑炎的临床特征以利于早期诊断及治疗。方法对6例抗GABAB受体脑炎患者的临床、实验室、脑电图(EEG)及影像学资料进行分析,并对其进行10~19(13.5±3.1)个月的随访。结果该组患者均以癫痫发作起病,表现为部分性发作、全面强直阵挛发作。5例出现认知功能减退,4例出现精神行为异常。发作间期EEG 1例表现为右前中颞区棘慢波,余未见明显异常。头颅MRI示2例颞叶内侧、海马T2/FLAIR高信号,1例海马体积缩小。腰穿检查2例脑脊液(CSF)压力增高,1例白细胞数增多,4例蛋白升高。所有患者血清及CSF GABAB受体抗体阳性,1例患者血清Hu抗体弱阳性。胸CT示2例肺部占位、2例肺叶微结节、1例纵隔稍大淋巴结及肝脏顶部异常强化灶,4例经活检诊断为小细胞肺癌。抗癫痫药物对患者癫痫发作控制不佳,免疫治疗及抗肿瘤治疗有效。结论抗GABAB受体脑炎可以癫痫发作为首发症状,逐渐出现认知障碍和精神症状,需注意对该类患者进行肿瘤筛查及随访,早期免疫治疗及抗肿瘤治疗可以改善患者神经功能预后。     

抗GABA-B受体脑炎5例临床分析与影像学特点

目的探讨抗GABA-B(γ-氨基丁酸-B)受体脑炎的临床表现、实验室及影像学特点、治疗及预后。方法回顾性分析5例经脑脊液免疫学检查诊断为抗GABA-B受体脑炎患者的临床资料。结果 5例均呈急性起病,临床首发症状为癫痫发作,癫痫发作后出现不同程度的认知功能障碍及精神行为异常。影像学特点:病灶累及颞叶内侧、海马,头部CT呈等密度或低密度影,头部MRI呈长T_1、长T_2信号,T_2 FLAIR高信号,DWI等或高信号。2例行头部核磁增强病灶无强化。1例行PET-CT示颞叶海马低密度影,代谢增高。脑脊液及血清免疫学检查均提示脑脊液GABAB-R-AB阳性(+),血清GABAB-R-AB阳性(+)。5例均伴有NSE不同程度增高。脑电图无特异性,同患者意识状态相关。5例行肺部CT均合并纵隔淋巴结肿大,发病时合并中心性肺癌3例,其余2例随访3个月后亦发现中心性肺癌。2例行支气管镜病理活检为小细胞肺癌。结论抗GABA-B受体脑炎常以癫痫为首发症状,影像学多数以颞叶内侧、海马免疫性炎症反应信号为主要表现,同肺癌(小细胞肺癌)密切相关,结合脑脊液免疫学检查及上述特点有助诊断。     

抗Hu抗体检测在神经系统副肿瘤综合征诊断中的临床意义

目的 探讨抗Hu抗体检测在神经系统副肿瘤综合征诊断中的临床意义.方法 采用间接免疫荧光方法和蛋白免疫印迹法对送检至北京协和医院神经病理实验室的1500余例患者的血清和脑脊液进行抗Hu抗体检测,回顾性分析抗Hu抗体阳性患者的临床资料及诊断.神经系统副肿瘤综合征的诊断标准参照Graus等的诊断标准.结果 共有27例患者抗体阳性,其中血清抗Hu抗体阳性25例,脑脊液抗Hu抗体阳性8例.临床主要表现为感觉神经元神经病、亚急性小脑变性、Lambert-Eaton综合征和抗利尿激素分泌不当综合征引起的脑病等,其中20例(74.1%)患有肿瘤,包括肺癌17例,胃癌2例,不明性质腹部肿瘤1例.7例患者未发现恶性肿瘤,包括多发性肌炎和系统性红斑狼疮(SLE)合并神经肌肉病各1例.根据Graus等神经系统副肿瘤综合征的诊断标准,27例中22例可确诊神经系统副肿瘤综合征或相关的肿瘤,抗Hu抗体的阳性预测值为81.5%.结论 抗Hu抗体阳性对神经系统副肿瘤综合征的诊断具有一定意义;其相关肿瘤以肺癌,特别是小细胞肺癌最常见.其他自身免疫性疾病偶可见抗Hu抗体阳性,需要全面检查和密切随访以排除恶性肿瘤的可能.     

抗LGI1抗体脑炎和抗γ氨基丁酸-B受体脑炎的临床特点

目的对抗LGIl抗体脑炎与抗GABABR脑炎的临床特点进行比较和总结。方法选取郑州大学第一附属医院2015-06—2017-06收治的12例抗LGIl抗体脑炎和13例抗GABA-B受体脑炎患者,总结其临床表现、脑电图、实验室检查、影像学表现,并进行随访,观察预后,比较分析各自特点。结果抗LGIl抗体脑炎与抗GABABR脑炎均有智能下降、精神症状、癫痫发作的特点,对免疫治疗反应较好。抗LGIl抗体脑炎往往有FBDS,且伴有低钠血症及自主神经系统症状,总体预后抗GABAB R脑炎好;抗GABABR脑炎合并肿瘤者预后不佳,除免疫治疗外还应积极治疗肿瘤。结论两种自身免疫性脑炎均对免疫治疗反应较好,抗LGI1抗体脑炎预后优于抗GABABR脑炎,部分抗GABABR脑炎患者合并肿瘤,预后除免疫治疗外还取决于对肿瘤的治疗。     

抗富亮氨酸胶质瘤失活1蛋白和抗髓鞘少突胶质细胞糖蛋白双抗体阳性的边缘叶脑炎1例

介绍1例抗富亮氨酸胶质瘤失活1蛋白(LGI1)和抗髓鞘少突胶质细胞糖蛋白(MOG)双抗体阳性的边缘叶脑炎患者。患者为中年男性, 既往有视网膜静脉阻塞病史, 本次发病主要症状为颞叶癫痫、面臂肌张力障碍、自主神经功能障碍等;头颅磁共振成像示右侧海马长T2信号、无强化、灌注正常;脑电图示发作间期阵发性慢波、尖慢波;血抗MOG抗体、血和脑脊液抗LGI1抗体双阳性, 主要诊断为边缘叶脑炎, 给予激素和丙种球蛋白治疗后症状好转, 复查双抗体均转阴。该抗LGI1/MOG双阳性病例较罕见, 且临床症状和影像学表现并非与单一抗体阳性患者完全一致, 有其不同特点。文中对该病例临床资料进行报道以期进一步加深临床医师对该病的认识。     

儿童单纯疱疹病毒脑炎合并抗NMDAR和抗Hu抗体双重阳性自身免疫性脑炎的临床特点(附1例报告)

目的 探讨儿童单纯疱疹病毒感染合并抗N-甲基-D-天冬氨酸受体(NMDAR)和抗Hu抗体双阳性自身免疫性脑炎(autoimmune encephalitis, AE)的临床特点。方法 回顾分析作者医院神经内科收治的1例单纯疱疹病毒性脑炎合并抗NMDAR、抗Hu抗体双阳性AE患者的临床资料。结果 患者女,9岁。以发热、头痛起病,随后出现惊厥,脑脊液常规生化检测异常,脑脊液单纯疱疹病毒1型DNA(+),头颅MRI示右侧颞叶为主区域受累,诊断为单纯疱疹病毒脑炎。数周后患者再发头痛,并出现情绪异常、上肢震颤,脑脊液单纯疱疹病毒1型DNA(-),抗NMDAR抗体IgG 1∶10,抗Hu抗体IgG(+),最终诊断为AE(抗NMDAR、抗Hu双阳)。给予丙种球蛋白及激素治疗后患者情绪稳定,震颤消失,头痛缓解。结论 单纯疱疹病毒脑炎合并免疫性脑炎临床表现可能不典型,尽早完善相关抗体检测并及时复查有助于诊断,早期免疫治疗或可使患者获益。     

抗Ma2抗体相关脑炎临床和影像学分析

目的探讨抗Ma2抗体相关脑炎的临床表现、实验室检查和神经影像学特点,以期为临床诊治该病提供参考。方法回顾性收集作者医院2015年1月至2017年12月诊断的3例抗Ma2抗体相关脑炎患者的临床资料。结果3例抗Ma2抗体相关脑炎临床表现包括记忆下降、精神行为异常、癫痫发作等,1例患者存在睡眠障碍。3例患者血清抗Ma2抗体均呈阳性,脑脊液中该抗体阳性1例。3例患者均有头颅MRI多发异常信号,主要位于边缘系统和脑干上部。1例患者发现肺癌。结论抗Ma2抗体与边缘性脑炎或脑干脑炎关系密切。对于抗Ma2抗体相关脑炎患者,需要重点排查潜在恶性肿瘤。     

A new anti-neuronal antibody in a case of paraneoplastic limbic encephalitis associated with breast cancer

Paraneoplastic neurological syndromes are rare remote effects of different types of cancer. Paraneoplastic limbic encephalitis is a specific syndrome, most often associated with small cell lung carcinoma. This report describes the case of a pure limbic encephalitis in association with breast cancer. An anti-neuronal antibody was found in the serum and CSF of the patient which has not been reported so far.     

Limbic encephalitis – a review

The clinical features of limbic encephalitis are diverse and early diagnosis of the disorder is frequently difficult. Four patients with limbic encephalitis are described. An antineuronal antibody was identified in three of these patients. Antibodies directed against voltage-gated potassium channels, the N-methyl-D-aspartate receptor and an unidentified neuropil antigen were each found in one patient. The fourth patient had multifocal paraneoplastic encephalitis associated with small cell lung cancer. The clinical and imaging findings associated with these antibodies and the other antineuronal antibodies described in patients with limbic encephalitis are reviewed. An approach to the diagnosis and management of limbic encephalitis is presented.     

Paraneoplastic limbic encephalitis: diagnostic relevance of CSF analysis and total body PET scanning

We report two cases of paraneoplastic limbic encephalitis (PLE) that differed in their clinical patterns, the underlying tumours, and the associated paraneoplastic antibodies. The first patient was a young adult male, with anti-MA-2 antibodies and testicular tumour. The clinical picture was restricted to limbic involvement. The second patient was a 56-year old, female heavy smoker; with seizures and depression, but also vertigo and diplopia. A low level of serum anti-Hu antibodies led to the detection of a small cell lung carcinoma by total body PET-scanning. In both cases, intrathecal synthesis of CSF oligoclonal IgG bands and of the corresponding paraneoplastic antibodies was demonstrated.     

20例抗N-甲基-D-天冬氨酸受体脑炎患者临床特点分析

目的回顾性分析总结20例抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者的临床特点,增强对抗NMDAR脑炎的认识。方法对90例临床疑似脑炎患者的血清和脑脊液进行抗NMDAR-IgG检测,分析确诊为抗NMDAR脑炎的20例患者的临床表现、实验室检查、治疗及预后。结果抗NMDAR脑炎患者男女比例为6:14,中位年龄24岁,首发症状及主要精神症状多有不同。20例抗NMDAR脑炎患者中有12例患者血清和脑脊液中抗NMDAR-IgG抗体均阳性,其他8例仅在血清或脑脊液中检测到抗NMDAR-IgG抗体。5例盆腔检查异常,其中1例病理确诊为成熟囊性畸胎瘤。6例患者脑电图异常,7例头颅MRI异常。除1例患者未接受免疫治疗死亡外,其余患者接受免疫治疗后症状均有不同程度的缓解,其中3例未伴畸胎瘤的患者用二线免疫治疗后复检血清和脑脊液中抗NMDAR-IgG抗体水平下降。结论抗NMDAR脑炎患者中年轻女性发病率较高。二线免疫治疗可能对不伴有畸胎瘤患者的疗效更好。CSF中的抗NMDAR-IgG抗体的阳性率高于血清,同时检测血清和脑脊液中抗NMDAR抗体可以提高疾病的诊断效率。     

Characterisation of a syndrome of autoimmune adult onset focal epilepsy and encephalitis

We report a series of patients with a clinical syndrome characterised by the explosive onset in adulthood of recurrent focal seizures of frontotemporal onset and features suggestive of autoimmune encephalitis. We propose that this presentation of “autoimmune adult onset focal epilepsy and encephalitis” is a recognisable clinical syndrome, and provide evidence it may be associated with heterogeneous immunological targets. Between 2008 and 2011 we encountered six patients with new-onset epilepsy in whom we suspected an autoimmune aetiology. We first characterised the clinical, electroencephalographic, cerebrospinal fluid (CSF), imaging, and pathological findings of this syndrome. We subsequently tested them for antibodies against both intracellular and neuronal cell surface antigens. All patients presented with recurrent seizures with focal frontotemporal onset, refractory to multiple anticonvulsants. Four had focal T2-weighted hyperintensities on MRI. CSF mononuclear cells were variably elevated with positive oligoclonal bands in four. Brain biopsy in one patient demonstrated perivascular lymphocytic infiltration. Two were treated with immunosuppression and went on to achieve complete seizure control and return to baseline cognition. Three of four patients who received only pulsed steroids or no treatment had ongoing frequent seizures, with two dying of sudden unexpected death in epilepsy. Subsequently, three had antibodies identified against neuronal cell surface antigens including N-methyl-d-aspartate receptor and leucine-rich glioma inactivated 1. We suggest that patients with such a presentation should be carefully evaluated for a suspected autoimmune aetiology targeting cell surface antigens and have a therapeutic trial of immunosuppression as this may improve their long-term outcome.     

Antibodies to a subpopulation of glial cells and a 66 kDa developmental protein in patients with paraneoplastic neurological syndromes.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) are inflammatory disorders that probably depend on autoimmune processes. Several autoantibodies (anti-Hu, anti-Ri, and anti-Yo) have been characterised in PNS and proved to be helpful in the diagnosis. However, these do not account for all the cases and the possibility that other types of antibodies could be detected was investigated. METHODS AND RESULTS: Of 45 patients with PNS whose serum was probed on paraformaldehyde fixed rat brain sections, 11 patients were identified whose serum samples recognised a cytoplasmic antigen in a subpopulation of glial cells in the white matter of adult rat brainstem, cerebellum, and spinal cord that were double labelled with a monoclonal antibody specific for oligodendrocytes. All serum samples reacted with a 66 kDa protein of newborn rat brain on western blot analysis. These antibodies were designated as anti-CV2 antibodies. Only one of the 11 patients had one of the well characterised autoantibodies (anti-Hu). Five patients had cerebellar degeneration, three had limbic encephalitis, two had encephalomyelitis, and one had Lambert-Eaton myasthenic syndrome. The tumours were small cell lung cancer or undifferentiated mediastinal cancer in seven patients, uterine sarcoma in two, and malignant thymoma in two. Among 1061 control serum samples, only two patients had anti-CV2 antibodies. One had small cell lung cancer and the other malignant thymoma. CONCLUSIONS: The detection of anti-CV2 antibodies in patients with neurological disorders should be considered as an indication of the presence of an occult cancer.     

GAD65 antibody‐associated autoimmune epilepsy with unique independent bitemporal‐onset ictal asystole

Antibodies against the 65‐kDa isoform of the intracellular enzyme, glutamate decarboxylase (GAD65), have been found in patients with limbic encephalitis and drug‐resistant autoimmune epilepsy. We report a 22‐year‐old female who presented with new‐onset seizures and neuropsychiatric symptoms. Video‐EEG captured unique, independent bitemporal‐onset focal seizures with impaired awareness and ictal asystole. An autoimmune epilepsy panel revealed elevated GAD65 antibodies in the serum (225 nmol/l) and CSF (2.78 nmol/l), while [¹⁸F]‐fluoro‐deoxy‐glucose positron emission tomography showed bitemporal hypometabolism (left > right). The patient was diagnosed with GAD65 antibody‐associated autoimmune epilepsy. Our observation adds to the spectrum of neurocardiac syndromes associated with autoimmune epilepsy.     

A case of anti‐NMDA receptor encephalitis revealed by insular epilepsy

Anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system that typically manifests predominantly as a psychiatric disorder. However, other manifestations such as epileptic seizures, abnormal movements, and memory or language complications are not unusual. Here, we report the case of a young man who presented with a new‐onset epilepsy, with ictal semiology suggestive of insular involvement; this hypothesis was supported by a PET‐CT study. Anti‐NMDAR antibodies were found in the CSF, confirming the diagnosis of anti‐NMDAR encephalitis. A review of the literature reveals that epilepsy can be the first manifestation of NMDAR encephalitis, with a clear male predominance. Despite its rarity, neurologists should consider this diagnosis for any young patient developing a new‐onset epilepsy with temporal or insular features, particularly if the patient is male. Other cognitive or behavioural signs, even very subtle, should also prompt diagnosis.     

Steroid-responsive recurrent limbic encephalitis associated with small cell lung cancer and neuropil antibodies

Paraneoplastic limbic encephalitis (PLE) associated with small cell lung cancer (SCLC) often presents with antibodies to intracellular antigens and a poor outcome even after tumor resection and immunotherapy. We report a PLE patient presenting with generalized seizures, shortterm memory impairment and medial temporal lobe hyperintensity in MRI. Initial screening revealed significantly elevated thyroid antibody levels suggesting Hashimoto's encephalopathy. Following methylprednisolone treatment, her seizures ceased, MRI findings disappeared and memory impairment showed a partial resolution in 5 months. Two months later, she developed further generalized seizures. Chest X-ray showed a mass lesion, which was demonstrated by needle biopsy to be a small cell lung carcinoma (SCLC). The panel of onconeural antibodies including cell-membrane antigens was negative. However, the patient's serum and cerebrospinal fluid IgG, obtained during both exacerbations, immunolabeled cytoplasm and dendrites of Purkinje cells, cerebellar and hippocampal molecular layers, basal ganglia, thalamus, and the surface of cultured hippocampal neurons, in a manner distinct from previously identified neuropil antibodies associated with SCLC. These neuropil antibodies appear to be associated with a favorable response to treatment. Further studies are required for determination of the target antigen.     

Tr抗体介导的小脑性共济失调一例并文献复习

目的探讨Tr抗体介导的小脑性共济失调患者的临床特点。方法报告1例Tr抗体介导的小脑性共济失调患者的临床特点及随访情况。结果患者为49岁男性,隐匿起病,主要表现为2个月内逐渐进展的小脑性共济失调。既往史无特殊。实验室检查:脑脊液白细胞计数50×106/L,蛋白49 mg/dL;血清Tr抗体强阳性(+++),脑脊液Tr抗体弱阳性(+)。MRI上无小脑结构性改变,PET/CT可见双侧小脑葡萄糖代谢轻度减低。经系统排查,未发现肿瘤。先后予以糖皮质激素、静脉注射人免疫球蛋白(intravenous immunoglobulin,IVIG)治疗后,患者症状稍有缓解,脑脊液白细胞计数下降至7×106/L,蛋白下降至24 mg/dL,血清Tr抗体转为阴性。结论本例患者主要表现为进展型共济失调,脑脊液细胞数和蛋白水平轻度升高,血清和脑脊液Tr抗体均阳性,PET/CT可见双侧小脑葡萄糖代谢轻度减低,免疫治疗有效,但未查及肿瘤,在随访中应继续关注。