By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
SYNOPSIS: All three of these syndromes — Miller Fisher, Guillain-Barré, and Bickerstaff encephalitis — occur following an acute gastrointestinal infection, with many cases of overlap syndromes, and deficits may progress during the first few days of illness.
SOURCE: Sekiguchi Y, Mori M, Misawa S, et al. How often and when Fisher syndrome is overlapped by Guillain-Barré syndrome or Bickerstaff brainstem encephalitis. Eur J Neurol 2016;23:1058-1063.
Initially reported in 1951 as “mesencephalitis and rhombencephalitis” by Bickerstaff and Cloake, patients with Bickerstaff brainstem encephalitis (BBE) presented with external ophthalmoplegia, ataxia, and altered consciousness, and recovered well, spontaneously. In 1956, Miller Fisher reported patients with external ophthalmoplegia, ataxia, and areflexia, also noting spontaneous recovery, with both papers noting a similarity to Guillain-Barré syndrome (GBS). With the finding, in 1992, of IgG anti-GQ1b antibodies in both BBE and Miller Fisher syndrome (MFS), the clinical spectrum of Fisher-Bickerstaff syndrome was created. How often does MFS overlap with BBE or GBS, and what is the clinical progression of one to the other?
Retrospective record review of 60 consecutive patients with MFS, seen between 1990-2014, at Chiba University Hospital, Chiba, Japan, was undertaken. All patients demonstrated the triad of external ophthalmoplegia, ataxia, and areflexia, with some patients noting additional pharyngeal-cervical-brachial (PCB) weakness. Pure MFS was defined as the presence of the triad, without pharyngeal, neck, or limb weakness. MFS/BBE was diagnosed if MFS patients developed alteration of consciousness, whereas MFS/GBS was diagnosed if they developed weakness of arms and legs. If only arm, pharyngeal, or neck weakness developed, MFS/PCB-GBS was diagnosed. All patients underwent nerve conduction studies and serum ganglioside antibodies measurements within two weeks of MFS onset, and patients were followed for at least six months or until disease remission. Statistical analysis comprised Chi square or Fisher’s exact test, analysis of variance with Bonferroni correction, and Dunnett’s test.
Among the 60 MFS patients, 50% (n = 30) remained purely MFS throughout their course, with the remaining 50% demonstrating an overlap of PCB-GBS in 23% (n = 14), GBS in 15% (n = 9), or BBE in 12% (n = 7). Progression from onset of MFS to these overlap syndromes developed in five, three, and three days, respectively. Incidence of prior infection, age of disease onset, and ganglioside positivity, including anti-GQ1b, was not statistically different between the groups. Overlap of MFS with BBE or GBS develops in 50% of cases, and does so within seven days, but cannot be predicted at first evaluation.
Combined IgG and IgM anti-GQ1b antibodies have been reported in two childhood cases, ages 4 and 6 years, of acute isolated bilateral ophthalmoplegia occurring shortly after Campylobacter jejuni enteritis.1 Neither child demonstrated weakness, ataxia, or deep tendon reflex abnormality. However, in a larger study encompassing 21 patients with acute ophthalmoplegia (AO), 13 with optic neuritis (ON), and 12 with MFS, none of the ON patients and only one with AO was found to have elevated GQ1b titers, compared to 11/12 with MFS.2 GQ1b was present in the cerebrospinal fluid (CSF) of two of 10 MFS patients tested, but in none of those with AO or ON. Serum GQ1b positivity is specific for MFS, but its role in AO and ON is speculative. CSF measurement of GQ1b adds nothing. Still unanswered is whether these antibodies are directly pathogenic, or an epiphenomenon, resulting from disruption of the nerve sheath with exposure of hitherto hidden antigens to immune surveillance and autoantibody production.
- Guisset F, Ferreiro C, Voets S, et al. Anti-GQ1b antibody syndrome presenting as acute isolated bilateral ophthalmoplegia: Report on two patients and review of the literature. Eur J Paediatr Neurol 2016;20;439-443.
- Spatola M, Du Pasquier R, Schleup M, et al. Serum and CSF GQ1b antibodies in isolated ophthalmologic syndromes. Neurology 2016;86;1780-1784.