Shanmugarajah Priya D, Hoggard Nigel, Currie Stuart, Aeschlimann Daniel P, Aeschlimann Pascale C, Gleeson Dermot C, Karajeh Mohammed, Woodroofe Nicola, Grünewald Richard A, Hadjivassiliou Marios
Academic Department of Neurosciences, Royal Hallamshire Hospital, and University of Sheffield, Sheffield, UK.
Academic Unit of Radiology, University of Sheffield, Sheffield, UK.
Cerebellum Ataxias. 2016 Oct 3;3:17. doi: 10.1186/s40673-016-0055-1. eCollection 2016.
Alcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia. The exact pathogenic mechanisms by which alcohol leads to cerebellar damage remain unknown. Possible autoreactive immune mediated mechanisms have not been explored previously. In this study, we aim to investigate the potential role of alcohol-induced immune mediated cerebellar degeneration.
Patients with ataxia and a history of alcohol misuse were recruited from the Ataxia and Hepatology tertiary clinics at Sheffield Teaching Hospitals NHS Trust. We determined the pattern of cerebellar involvement both on clinical (SARA score) and imaging (MRI volumetry and MR spectroscopy) parameters. In addition, HLA genotyping, serological markers for gluten-related disorders and serological reactivity on rat cerebellar tissue using indirect immunohistochemistry were assessed.
Thirty-eight patients were included in the study all of whom had ataxia. The gait (97 %), stance (89 %) and heel-shin slide (89 %) were the predominant SARA elements affected. MRI volumetric and spectroscopy techniques demonstrated significant structural, volumetric and functional deficits of the cerebellum with particular involvement of the cerebellar vermis. Circulating anti-gliadin antibodies were detected in 34 % patients vs. 12 % in healthy controls. Antibodies to transglutaminase 6 (TG6) were detected in 39 % of patients and 4 % of healthy control subjects. Using immunohistochemistry, Purkinje cell and/or granular layer reactivity was demonstrated in 71 % of patient sera.
Alcohol induced tissue injury to the CNS leading to cerebellar degeneration may also involve immune mediated mechanisms, including sensitisation to gluten.
酒精相关性小脑变性是最常见的后天性小脑共济失调形式之一。酒精导致小脑损伤的确切致病机制尚不清楚。此前尚未探索可能的自身反应性免疫介导机制。在本研究中，我们旨在探讨酒精诱导的免疫介导的小脑变性的潜在作用。
从谢菲尔德教学医院国民保健服务信托基金的共济失调和肝病三级诊所招募有共济失调且有酒精滥用史的患者。我们通过临床（共济失调评定量表[SARA]评分）和影像学（MRI容积测量和磁共振波谱）参数确定小脑受累模式。此外，还评估了HLA基因分型、麸质相关疾病的血清学标志物以及使用间接免疫组织化学检测大鼠小脑组织的血清学反应性。
38例患者纳入本研究，所有患者均有共济失调。步态（97%）、站姿（89%）和跟膝胫试验（89%）是受SARA影响最主要的因素。MRI容积测量和波谱技术显示小脑存在明显的结构、容积和功能缺陷，特别是小脑蚓部受累。34%的患者检测到循环抗麦醇溶蛋白抗体，而健康对照组为12%。39%的患者和4%的健康对照者检测到抗转谷氨酰胺酶6（TG6）抗体。使用免疫组织化学方法，71%的患者血清显示浦肯野细胞和/或颗粒层有反应性。
酒精引起的中枢神经系统组织损伤导致小脑变性，可能还涉及免疫介导机制，包括对麸质的致敏。
