Overell James R, Willison Hugh J
Department of Neurology, University of Glasgow, Division of Clinical Neurosciences, Southern General Hospital, Glasgow, UK.
Curr Opin Neurol. 2005 Oct;18(5):562-6. doi: 10.1097/01.wco.0000173284.25581.2f.
Miller Fisher syndrome is a localized variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, areflexia and ataxia. Bickerstaff's brainstem encephalitis is a related syndrome in which upper motor neurone features accompany the classic triad. Anti-GQ1b antibodies are uniquely found in both conditions and are believed to be pathogenic.
Infectious illnesses usually precede Miller Fisher syndrome. The clearest associations have been described with Haemophilus influenzae and Campylobacter jejuni infection. Raised cerebrospinal fluid protein is seen in 60% of patients, but clinical features and anti-GQ1b antibody testing are diagnostically more informative. Experimental studies demonstrating complement-dependent neuromuscular block may be relevant to the clinical pathophysiology of Miller Fisher syndrome. Recent neurophysiological studies suggest abnormal neuromuscular transmission occurs in some cases of Miller Fisher syndrome and Guillain-Barré syndrome. Recent mouse models have demonstrated that presynaptic neuronal membranes and perisynaptic Schwann cells are targets for anti-GQ1b antibody attack. The elimination of antiganglioside antibodies from the circulation through specific immunoadsorption therapy has the potential to ameliorate the course of Miller Fisher syndrome. This condition is typically a benign, self-limiting illness. Both plasmapheresis and intravenous immunoglobulin may be employed as treatment, especially in cases of Bickerstaff's brainstem encephalitis or those with overlapping Guillain-Barré syndrome.
Anti-GQ1b antibody testing has allowed clinicians to develop a greater understanding of the spectrum of Miller Fisher syndromes and to refine clinical diagnoses in patients with unusual presentations. Experimental studies strongly suggest anti-GQ1b antibodies are pathogenic, which in principle should direct treatments towards antibody neutralization or elimination.
米勒-费希尔综合征是吉兰-巴雷综合征的一种局部变异型，其特征为眼肌麻痹、无反射和共济失调。比克斯特费尔德脑干脑炎是一种相关综合征，其中上运动神经元特征伴随经典三联征出现。抗GQ1b抗体在这两种疾病中均独特存在，被认为具有致病性。
感染性疾病通常先于米勒-费希尔综合征出现。已明确描述与流感嗜血杆菌和空肠弯曲菌感染有最密切关联。60%的患者脑脊液蛋白升高，但临床特征和抗GQ1b抗体检测在诊断上更具信息价值。证明补体依赖性神经肌肉阻滞的实验研究可能与米勒-费希尔综合征的临床病理生理学相关。最近的神经生理学研究表明，在某些米勒-费希尔综合征和吉兰-巴雷综合征病例中存在异常的神经肌肉传递。最近的小鼠模型表明，突触前神经元膜和突触周围施万细胞是抗GQ1b抗体攻击的靶点。通过特异性免疫吸附疗法从循环中清除抗神经节苷脂抗体有可能改善米勒-费希尔综合征的病程。这种疾病通常是一种良性的自限性疾病。血浆置换和静脉注射免疫球蛋白均可用于治疗，尤其是在比克斯特费尔德脑干脑炎病例或伴有重叠吉兰-巴雷综合征的病例中。
抗GQ1b抗体检测使临床医生能够更深入地了解米勒-费希尔综合征的谱系，并对表现不寻常的患者完善临床诊断。实验研究强烈表明抗GQ1b抗体具有致病性，原则上这应将治疗导向抗体中和或清除。
