PDF(Pubmed)
Abstract：
Immune-mediated cerebellar ataxias (IMCAs) have diverse etiologies. Patients with IMCAs develop cerebellar symptoms, characterized mainly by gait ataxia, showing an acute or subacute clinical course. We present a novel concept of latent autoimmune cerebellar ataxia (LACA), analogous to latent autoimmune diabetes in adults (LADA). LADA is a slowly progressive form of autoimmune diabetes where patients are often initially diagnosed with type 2 diabetes. The sole biomarker (serum anti-GAD antibody) is not always present or can fluctuate. However, the disease progresses to pancreatic beta-cell failure and insulin dependency within about 5 years. Due to the unclear autoimmune profile, clinicians often struggle to reach an early diagnosis during the period when insulin production is not severely compromised. LACA is also characterized by a slowly progressive course, lack of obvious autoimmune background, and difficulties in reaching a diagnosis in the absence of clear markers for IMCAs. The authors discuss two aspects of LACA: (1) the not manifestly evident autoimmunity and (2) the prodromal stage of IMCA\'s characterized by a period of partial neuronal dysfunction where non-specific symptoms may occur. In order to achieve an early intervention and prevent cell death in the cerebellum, identification of the time-window before irreversible neuronal loss is critical. LACA occurs during this time-window when possible preservation of neural plasticity exists. Efforts should be devoted to the early identification of biological, neurophysiological, neuropsychological, morphological (brain morphometry), and multimodal biomarkers allowing early diagnosis and therapeutic intervention and to avoid irreversible neuronal loss.
摘要：
免疫介导的小脑共济失调（IMCA）具有多种病因。IMCA患者出现小脑症状，以步态共济失调为主要特征，显示急性或亚急性临床过程。我们提出了一个潜在的自身免疫性小脑共济失调（LACA）的新概念，类似于成人隐匿性自身免疫性糖尿病（LADA）。LADA是自身免疫性糖尿病的缓慢进展形式，患者通常最初被诊断为2型糖尿病。唯一的生物标志物（血清抗GAD抗体）并不总是存在或可能波动。然而,该疾病在约5年内进展为胰腺β细胞衰竭和胰岛素依赖.由于自身免疫特征不清楚,在胰岛素生产未受到严重损害的时期,临床医生往往很难得到早期诊断.LACA的特征还在于缓慢渐进的过程，缺乏明显的自身免疫背景，以及在缺乏明确的IMCA标志物的情况下难以诊断。作者讨论了LACA的两个方面：（1）不明显的自身免疫；（2）IMCA的前驱阶段，其特征是可能出现非特异性症状的部分神经元功能障碍。为了实现早期干预并防止小脑中的细胞死亡，识别不可逆神经元丢失之前的时间窗口至关重要.当存在神经可塑性的可能保留时，LACA会在此时间窗口中发生。应致力于早期识别生物，神经生理学，神经心理学，形态学（脑形态学），和多模式生物标志物允许早期诊断和治疗干预，并避免不可逆的神经元损失。
