Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
JAMA Neurol. 2013 Feb;70(2):229-34. doi: 10.1001/jamaneurol.2013.592.
To determine, in patients identified as seropositive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex.
Retrospective cohort study.
Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology.
A total of 54 853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive.
From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥ 0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥ 1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P< .001) and cortical presentations (P< .001); CASPR2 IgG was associated with peripheral motor excitability (P= .009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone.
The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined.
在被确定为神经元电压门控钾通道（VGKC）复合物自身抗体阳性的患者中，确定 VGKC 大分子复合物中作为定义性抗原性神经元靶标的亮氨酸丰富型胶质瘤失活蛋白 1（LGI1）和接触蛋白相关蛋白样 2（CASPR2）的临床特征谱和频率。
回顾性队列研究。
临床实践，梅奥诊所神经免疫实验室和神经病学系。
共评估了 54853 名患者，其中 1992 名被发现 VGKC 复合物 IgG 阳性。
从 2008 年 6 月 1 日至 2010 年 6 月 30 日，对 54853 名不明原因神经系统症状患者进行了全面的血清学评估，发现 1992 名患者（4%）的 VGKC 复合物 IgG 阳性（值≥0.03 nmol/L）。在我们机构进行临床评估的 316 名血清阳性患者中，82 名（26%）血清阳性 LGI1 IgG 和/或 CASPR2 IgG。在这 82 名患者中，27%的患者 VGKC 复合物 IgG 值较低（0.03-0.09 nmol/L），51%的患者 VGKC 复合物 IgG 值中等（0.10-0.99 nmol/L），22%的患者 VGKC 复合物 IgG 值较高（≥1.00 nmol/L）。LGI1 IgG 阳性与较高的 VGKC 复合物 IgG 值（P<.001）和皮质表现（P<.001）相关；CASPR2 IgG 与周围运动兴奋性相关（P=.009）。然而，这两种自身抗体都不是特定神经表现的特征性表现，也与癌症无显著相关性。神经表型多种多样。仅 LGI1 IgG 阳性的患者中有 76%（46 例）存在脑皮质表现（包括认知障碍和癫痫发作），仅 CASPR2 IgG 阳性的患者中有 29%（28 例）存在脑皮质表现。仅 CASPR2 IgG 阳性的患者中有 21%存在周围运动兴奋性过高，而仅 LGI1 IgG 阳性的患者中有 6.5%存在周围运动兴奋性过高。
本研究强调了 VGKC 复合物 IgG 值范围广泛、重叠的神经表型和不同的 LGI1 IgG 和 CASPR2 IgG 特异性。在 VGKC 复合物 IgG 值较低和中等的血清样本中经常发现 LGI1 IgG 和 CASPR2 IgG，支持在临床评估中重视较低值的临床意义。VGKC 大分子复合物的其他抗原性成分仍有待确定。
