Neurosciences Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom.
Ann Neurol. 2012 Aug;72(2):241-55. doi: 10.1002/ana.23577. Epub 2012 Apr 4.
A study was undertaken to describe the clinical spectrum, voltage-gated potassium channel (VGKC) complex antibody specificities, and central nervous system localization of antibody binding in 29 patients diagnosed with Morvan syndrome (MoS).
Clinical data were collected using questionnaires. Radioimmunoassay, cell-based assays, and mouse brain immunohistochemistry were used to characterize the serum antibodies.
Neuromyotonia (100%), neuropsychiatric features (insomnia 89.7%, confusion 65.5%, amnesia 55.6%, hallucinations 51.9%), dysautonomia (hyperhidrosis 86.2%, cardiovascular 48.3%), and neuropathic pain (62.1%) were the most common manifestations. A total of 93.1% of MoS patients were male. VGKC-complex antibodies were present in 23 of 29 (79%) MoS patients at referral; 24 of 27 available sera had CASPR2, LGI1, or both CASPR2 and LGI1 antibodies (3 also with contactin-2 antibodies). CASPR2 antibodies were generally higher titer than LGI1 antibodies. Tumors (41.4%), mainly thymomas, were associated with CASPR2 antibodies and a poor prognosis, whereas LGI1 antibodies were associated with serum hyponatremia. In brain tissue regions including the hypothalamus, raphe, and locus coeruleus, commercial antibodies to LGI1 bound to neuronal cell bodies including the antidiuretic hormone-secreting and orexin-secreting hypothalamic neurons, whereas CASPR2 commercial antibodies bound more often to the neuropil. MoS antibodies bound similarly, but there was evidence of additional antibodies in some sera that were not adsorbed by LGI1- or CASPR2-expressing cells and bound to mouse Caspr2(-/-) tissue.
MoS is clinically distinct from other VGKC-complex antibody-associated conditions, and usually is associated with high-titer CASPR2 antibodies, often accompanied by lower-titer LGI1 antibodies. CASPR2 and LGI1 antibodies bind to multiple brain regions, which helps to explain the multifocal clinical features of this disease, but other antibodies are likely to play a role in some patients and need to be characterized in future studies.
本研究旨在描述 29 例被诊断为莫旺综合征（MoS）患者的临床特征、电压门控钾通道（VGKC）复合物抗体特异性和抗体结合的中枢神经系统定位。
使用问卷收集临床数据。使用放射免疫分析、基于细胞的测定和小鼠脑免疫组织化学来表征血清抗体。
神经肌痛（100%）、神经精神特征（失眠 89.7%、意识混乱 65.5%、健忘 55.6%、幻觉 51.9%）、自主神经功能障碍（多汗症 86.2%、心血管 48.3%）和神经性疼痛（62.1%）是最常见的表现。MoS 患者中，93.1%为男性。在转诊时，29 例 MoS 患者中有 23 例（79%）存在 VGKC 复合物抗体；27 例可获得的血清中有 24 例（3 例还有接触蛋白 2 抗体）存在 CASPR2、LGI1 或两者均有的抗体。CASPR2 抗体的滴度通常高于 LGI1 抗体。肿瘤（41.4%），主要是胸腺瘤，与 CASPR2 抗体有关，预后不良，而 LGI1 抗体与血清低钠血症有关。在包括下丘脑、中缝核和蓝斑核在内的脑组织区域，LGI1 的商业抗体结合到包括抗利尿激素分泌和食欲素分泌的下丘脑神经元在内的神经元胞体，而 CASPR2 商业抗体则更常结合到神经原纤维。MoS 抗体结合情况类似，但一些血清中存在未被 LGI1 或 CASPR2 表达细胞吸附的额外抗体，并且结合到小鼠 Caspr2（-/-）组织。
MoS 与其他 VGKC 复合物抗体相关疾病在临床上明显不同，通常与高滴度的 CASPR2 抗体有关，通常伴有低滴度的 LGI1 抗体。CASPR2 和 LGI1 抗体结合到多个脑区，这有助于解释该疾病的多灶性临床特征，但其他抗体可能在一些患者中起作用，需要在未来的研究中进行表征。
