Abstract

Isaacs syndrome (IS), commonly referred to as acquired neuromyotonia, is a rare condition characterized mainly by voltage-gated potassium channel (VGKC) antibody-mediated syndrome of peripheral nerve hyperexcitability (PNH). Few case reports have documented IS patients in the absence of both leucine-rich glioma inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies (double negative). We report a rare case of a 34-year-old healthy female, presenting with a 15-year history of paroxysmal leg cramping and stiffness, preceded by generalized hyperhidrosis and palpitations. Physical examination documented hyperhidrosis, myokymia, and hypertrophic calf muscles. Electromyogram revealed myokymic discharges and neuromyotonic discharges—findings classically seen in Isaacs syndrome. To document the presence of autoantibodies against VGKC, serum LGI1 and CASPR2 antibodies were done; however, both turned out to be absent (double negative). Diagnostic tests to search for an autoimmune or a paraneoplastic etiology were done, which also showed unremarkable results. Despite the unrevealing serologic and imaging tests, a diagnosis of Isaacs syndrome was still made due to the presenting clinical features. Full resolution of symptoms was achieved upon initiation of carbamazepine. Absence of an autoimmune and a paraneoplastic syndrome is possible in IS, especially in cases with double-negative autoantibody status. This is the fifth reported case in published literature of such autoantibody status and highlights the vital role of a physician’s clinical acumen when dealing with rare diseases such as Isaacs syndrome. Knowing the cardinal features of a disease as well as the possible phenotypic varieties allows prompt diagnosis and treatment.

中文翻译：

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卡马西平反应性双阴性VGKC复合抗体Isaacs综合征一例报告及文献复习

摘要

艾萨克斯综合征 (IS)，通常称为获得性神经肌强直，是一种罕见疾病，主要特征是电压门控钾通道 (VGKC) 抗体介导的周围神经过度兴奋 (PNH) 综合征。很少有病例报告记录 IS 患者缺乏富含亮氨酸的神经胶质瘤灭活蛋白 1 (LGI1) 和接触素相关蛋白样 2 (CASPR2) 抗体（双阴性）。我们报道了一名 34 岁健康女性的罕见病例，该病例有 15 年的阵发性腿部痉挛和僵硬病史，随后出现全身多汗和心悸。体格检查发现多汗、肌颤、小腿肌肉肥大。肌电图显示肌颤放电和神经肌强直放电——这是艾萨克斯综合征中常见的典型表现。为了记录抗 VGKC 自身抗体的存在，进行了血清 LGI1 和 CASPR2 抗体检测；然而，结果两者均缺席（双重否定）。进行了寻找自身免疫或副肿瘤病因的诊断测试，也显示出不显着的结果。尽管血清学和影像学检查结果不明确，但由于呈现的临床特征，仍被诊断为艾萨克斯综合征。开始使用卡马西平后症状完全缓解。 IS 中可能不存在自身免疫性和副肿瘤综合征，特别是在自身抗体双阴性状态的病例中。这是已发表文献中报告的第五例此类自身抗体状态的病例，凸显了医生的临床敏锐度在处理艾萨克斯综合征等罕见疾病时的重要作用。了解疾病的主要特征以及可能的表型变异可以及时诊断和治疗。