Gultekin S H, Rosenfeld M R, Voltz R, Eichen J, Posner J B, Dalmau J
Department of Neurology and the Cotzias Laboratory of Neuro-Oncology Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY, USA.
Brain. 2000 Jul;123 ( Pt 7):1481-94. doi: 10.1093/brain/123.7.1481.
Paraneoplastic limbic encephalitis (PLE) is a rare disorder characterized by personality changes, irritability, depression, seizures, memory loss and sometimes dementia. The diagnosis is difficult because clinical markers are often lacking, and symptoms usually precede the diagnosis of cancer or mimic other complications. The frequency of antineuronal antibodies in patients with PLE has not been investigated. We examined the neurological symptoms and the causal tumours in 50 patients with PLE to determine the utility of paraneoplastic antibodies and other tests. The diagnosis of PLE required neuropathological examination or the presence of the four following criteria: (i) a compatible clinical picture; (ii) an interval of <4 years between the development of neurological symptoms and tumour diagnosis; (iii) exclusion of other neuro-oncological complications; and (iv) at least one of the following: CSF with inflammatory changes but negative cytology; MRI demonstrating temporal lobe abnormalities; EEG showing epileptic activity in the temporal lobes. Of 1047 patients with neurological symptoms, whose sera or CSF were examined for paraneoplastic antibodies, 79 had the presumptive diagnosis of limbic encephalitis, dementia, cognitive dysfunction, or confusion. Fifty of these patients fulfilled our criteria for PLE. Pathological confirmation was obtained in 12 patients. The commonly associated neoplasms were of the lung (50%), testis (20%) and breast (8%). Neurological symptoms preceded the cancer diagnosis in 60% of patients (by a median of 3.5 months). Twenty-five of 44 (57%) patients with MRI studies had signal abnormalities in the limbic system. Thirty (60%) patients had antineuronal antibodies (18 anti-Hu, 10 anti-Ta, 2 anti-Ma), and 20 were antibody-negative or had uncharacterized antibodies (n = 4). The combination of symptoms, MRI findings and paraneoplastic antibodies established the diagnosis of PLE in 78% of the patients. Patients with anti-Hu antibodies usually had small-cell lung cancer (94%), multifocal neurological symptoms (78%) and a poor neurological outcome. Patients with anti-Ta (also called anti-Ma2) antibodies were young men with testicular tumours (100%), frequent hypothalamic involvement (70%) and a poor neurological outcome. In the group of patients without anti-Hu or anti-Ta antibodies, the tumour distribution was diverse, with cancer of the lung the most common (36%); 57% had positive MRI. Fifteen of 34 (44%) patients with a median follow-up of 8 months showed neurological improvement. Treatment of the tumour appeared to have more effect on the neurological outcome than the use of immune modulation. Improvement was observed in 38% of anti-Hu patients, 30% of anti-Ta patients and 64% of patients without these antibodies.
副肿瘤性边缘叶脑炎（PLE）是一种罕见的疾病，其特征为性格改变、易怒、抑郁、癫痫发作、记忆力减退，有时还会出现痴呆。诊断困难，因为常常缺乏临床标志物，而且症状通常在癌症诊断之前出现或类似其他并发症。尚未对PLE患者中抗神经元抗体的频率进行研究。我们检查了50例PLE患者的神经症状和相关肿瘤，以确定副肿瘤抗体及其他检查的效用。PLE的诊断需要进行神经病理学检查或具备以下四项标准：（i）临床表现相符；（ii）神经症状出现与肿瘤诊断之间的间隔<4年；（iii）排除其他神经肿瘤并发症；（iv）至少具备以下一项：脑脊液有炎症改变但细胞学检查阴性；MRI显示颞叶异常；脑电图显示颞叶癫痫活动。在1047例有神经症状且其血清或脑脊液接受副肿瘤抗体检查的患者中，79例初步诊断为边缘叶脑炎、痴呆、认知功能障碍或意识模糊。其中50例患者符合我们的PLE标准。12例患者获得了病理证实。常见的相关肿瘤为肺癌（50%）、睾丸癌（20%）和乳腺癌（8%）。60%的患者神经症状先于癌症诊断出现（中位时间为3.5个月）。44例接受MRI检查的患者中有25例（57%）在边缘系统有信号异常。30例患者（60%）有抗神经元抗体（18例抗Hu，10例抗Ta，2例抗Ma），20例抗体阴性或有未明确特征的抗体（n = 4）。症状、MRI表现和副肿瘤抗体的综合结果在78%的患者中确立了PLE的诊断。抗Hu抗体阳性的患者通常患有小细胞肺癌（94%）、多灶性神经症状（78%）且神经预后较差。抗Ta（也称为抗Ma2）抗体阳性的患者为患有睾丸肿瘤的年轻男性（100%），下丘脑受累频繁（70%）且神经预后较差。在无抗Hu或抗Ta抗体的患者组中，肿瘤分布多样，肺癌最为常见（36%）；57%的患者MRI呈阳性。34例患者中位随访8个月，其中15例（44%）神经症状有所改善。肿瘤治疗对神经预后的影响似乎比免疫调节更大。抗Hu抗体阳性的患者中有38%症状改善，抗Ta抗体阳性的患者中有30%症状改善，无这些抗体的患者中有64%症状改善。
