Autoimmune dementia is a novel and expanding field which subsumes neuropsychiatric disorders with predominant cognitive impairments due to an underlying autoimmune etiology. Progressive dementias with atypical clinical presentation should trigger a thorough diagnostic approach including testing for neural surface and intracellular antibodies to avoid a delay in accurate diagnosis and initiating appropriate therapy. Here, we present two emerging cases of progressive dementia with co-existing serum autoantibodies against the KCNA2 (potassium voltage-gated channel subfamily A member 2) subunit. We found various cognitive deficits with dominant impairments in the memory domain, particularly in delayed recall. One patient presented a subacute onset of then-persisting cognitive deficits, while the other patient’s cognitive impairments progressed more chronically and fluctuated. Cognitive impairments coincided with additional neuropsychiatric symptoms. Both had a potential paraneoplastic background according to their medical history and diagnostic results. We discuss the potential role of KCNA2 autoantibodies in these patients and in general by reviewing the literature. The pathogenetic role of KCNA2 antibodies in cognitive impairment is not well delineated; clinical presentations are heterogeneous, and thus a causal link between antibodies remains questionable. Current evidence indicates an intracellular rather than extracellular epitope. We strongly suggest additional prospective studies to explore KCNA2 antibodies in specifically-defined cohorts of cognitively impaired patients via a systematic assessment of clinical, neuropsychological, neuroimaging, as well as laboratory and CSF (cerebrospinal fluid) parameters, and antibody studies to (1) determine the epitope’s location (intracellular vs. extracellular), (2) the mode of action, and (3) seek co-existing, novel pathogenetic autoantibodies in sera and CSF.

中文翻译：

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KCNA2 进行性认知障碍中的自身免疫：病例系列和文献综述


自身免疫性痴呆是一个新的、不断扩展的领域，其中包括由于潜在的自身免疫病因而导致的以认知障碍为主的神经精神疾病。具有非典型临床表现的进行性痴呆应触发彻底的诊断方法，包括检测神经表面和细胞内抗体，以避免延误准确诊断和开始适当的治疗。在这里，我们介绍了两例新出现的进行性痴呆病例，同时存在针对 KCNA2（钾电压门控通道亚家族 A 成员 2）亚基的血清自身抗体。我们发现各种认知缺陷在记忆领域有显着的损害，特别是在延迟回忆方面。一名患者出现亚急性发作，随后持续存在认知缺陷，而另一名患者的认知障碍则更加慢性且波动性地进展。认知障碍与额外的神经精神症状同时发生。根据他们的病史和诊断结果，两人都有潜在的副肿瘤背景。我们通过回顾文献来讨论 KCNA2 自身抗体在这些患者中的潜在作用以及一般情况。 KCNA2 抗体在认知障碍中的致病作用尚不清楚；临床表现各不相同，因此抗体之间的因果关系仍然值得怀疑。目前的证据表明是细胞内而不是细胞外的表位。 我们强烈建议进行额外的前瞻性研究，通过对临床、神经心理学、神经影像学以及实验室和 CSF（脑脊液）参数的系统评估，在特定的认知障碍患者群体中探索 KCNA2 抗体，并进行抗体研究 (1) 确定表位的位​​置（细胞内与细胞外），（2）作用模式，（3）在血清和脑脊液中寻找共存的新型致病性自身抗体。