Ariño Helena, Höftberger Romana, Gresa-Arribas Nuria, Martínez-Hernández Eugenia, Armangue Thaís, Kruer Michael C, Arpa Javier, Domingo Julio, Rojc Bojan, Bataller Luis, Saiz Albert, Dalmau Josep, Graus Francesc
Service of Neurology, Hospital Clinic, University of Barcelona, Barcelona, Spain2Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain3Institute of Neurology, Medical University of Vienna, Vienna, Austria.
JAMA Neurol. 2015 Aug;72(8):874-81. doi: 10.1001/jamaneurol.2015.0749.
Little is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment.
To report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective case series study and immunological investigations conducted in February 2014 in a center for autoimmune neurological disorders. Fifteen cases with GAD65-abs evaluated between 1995 and 2013 who fulfilled criteria of definite or possible PNS without concomitant onconeural antibodies were included in this study.
Analysis of the clinical records of 15 patients and review of 19 previously reported cases. Indirect immunofluorescence with rat hippocampal neuronal cultures and cell-based assays with known neuronal cell-surface antigens were used. One hundred six patients with GAD65-abs and no cancer served as control individuals.
Eight of the 15 patients with cancer presented as classic paraneoplastic syndromes (5 limbic encephalitis, 1 paraneoplastic encephalomyelitis, 1 paraneoplastic cerebellar degeneration, and 1 opsoclonus-myoclonus syndrome). When compared with the 106 non-PNS cases, those with PNS were older (median age, 60 years vs 48 years; P = .03), more frequently male (60% vs 13%; P < .001), and had more often coexisting neuronal cell-surface antibodies, mainly against γ-aminobutyric acid receptors (53% vs 11%; P < .001). The tumors more frequently involved were lung (n = 6) and thymic neoplasms (n = 4). The risk for an underlying tumor was higher if the presentation was a classic PNS, if it was different from stiff-person syndrome or cerebellar ataxia (odds ratio, 10.5; 95% CI, 3.2-34.5), or if the patient had coexisting neuronal cell-surface antibodies (odds ratio, 6.8; 95% CI, 1.1-40.5). Compared with the current series, the 19 previously reported cases had more frequent stiff-person syndrome (74% vs 13%; P = .001) and better responses to treatment (79% vs 27%; P = .005). Predictors of improvement in the 34 patients (current and previously reported) included presentation with stiff-person syndrome and the presence of a thymic tumor.
Patients with GAD-abs must be screened for an underlying cancer if they have clinical presentations different from those typically associated with this autoimmunity or develop classic PNS. The risk for cancer increases with age, male sex, and the presence of coexisting neuronal cell-surface antibodies.
在副肿瘤综合征背景下，谷氨酸脱羧酶抗体（GAD - abs）鲜为人知。对此类病例的临床识别将有助于肿瘤的及时诊断和恰当治疗。
报告伴有GAD - abs的副肿瘤性神经系统综合征（PNS）患者的临床和免疫学特征。
设计、地点和参与者：2014年2月在一家自身免疫性神经疾病中心进行的回顾性病例系列研究和免疫学调查。本研究纳入了1995年至2013年间评估的15例GAD65 - abs患者，这些患者符合明确或可能的PNS标准且无伴随的肿瘤神经抗体。
分析15例患者的临床记录并回顾19例先前报道的病例。采用大鼠海马神经元培养的间接免疫荧光法和已知神经元细胞表面抗原的细胞检测法。106例无癌症的GAD65 - abs患者作为对照个体。
15例癌症患者中有8例表现为典型的副肿瘤综合征（5例边缘性脑炎、1例副肿瘤性脑脊髓炎、1例副肿瘤性小脑变性和1例眼阵挛 - 肌阵挛综合征）。与106例非PNS病例相比，PNS患者年龄更大（中位年龄，60岁对48岁；P = 0.03），男性更常见（60%对
