Miller Fisher syndrome and Bickerstaff brainstem encephalitis: anti-GQ1b antibody syndrome

Nortina Shahrizaila DM (Dr. Shahrizaila of the University of Malaya has no relevant financial relationships to disclose.)
Nobuhiro Yuki PhD (Dr. Yuki of National University of Singapore has no relevant financial relationships to disclose.)
Raymond P Roos MD, editor. (Dr. Roos of the University of Chicago owns stock in Amgen, Best Doctors, Express Scripts, Isis, and Merck.)
Originally released December 3, 2010; last updated December 13, 2016; expires December 13, 2019

This article includes discussion of Miller Fisher syndrome and Bickerstaff brainstem encephalitis: anti-GQ1b antibody syndrome, Fisher-Bickerstaff syndrome, anti-GQ1b antibodies, Bickerstaff brainstem encephalitis, and Fisher syndrome. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Prior to the discovery of IgG antibodies against GQ1b, there were clinical variants that were considered linked to Guillain-Barré syndrome due to common clinical features shared with Guillain-Barré syndrome. The most notable are Miller Fisher syndrome, which is characterized by ophthalmoplegia and ataxia, and Bickerstaff brainstem encephalitis, in which consciousness is also affected. Following the discovery in 1992 of an association of anti-GQ1b antibodies with Miller Fisher syndrome, other neurologic presentations with similar serological profiles emerged in the literature, which include Bickerstaff brainstem encephalitis, acute ophthalmoplegia, acute ataxic neuropathy, and pharyngeal-cervical-brachial weakness. In this article, the authors discuss the current understanding behind the anti-GQ1b antibody syndrome.

Key points

 

• The anti-GQ1b antibody syndrome represents a group of disorders that share a common serological profile with links also to Guillain-Barré syndrome.

 

• The overall prognosis is good even without immunotherapy in those patients that have typical Miller Fisher syndrome or acute ophthalmoparesis, but intravenous immunoglobulin (IVIG) or plasma exchange is recommended when there is altered consciousness, limb weakness, or bulbar palsy.

 

• Important mimics to be excluded include brainstem syndromes and neuromuscular junction disorders. The presence of the anti-GQ1b antibody syndrome would make the latter disorders unlikely.

Historical note and terminology

The most recognizable variant of Guillain-Barré syndrome is Miller Fisher syndrome, which was first described in 1956 by Charles Miller Fisher. He reported 3 patients who presented with a triad of acute ophthalmoplegia, ataxia, and areflexia subsequent to upper respiratory tract infection (Fisher 1956). The presence of cerebrospinal fluid albuminocytological dissociation and antecedent infection likened Miller Fisher syndrome to Guillain-Barré syndrome.

Prior to this, in 1951, Bickerstaff and Cloake described 3 patients with brainstem signs and altered consciousness following a prodrome of infective illness. The etiology of this condition was speculated to be similar to that of Guillain-Barré syndrome because of evidence of prodromal upper respiratory infection, areflexia, and CSF albuminocytological dissociation (Bickerstaff and Cloake 1951). Six years later, Bickerstaff extended his observations to include an additional 5 cases with similar patterns of brainstem signs, emphasizing the benign outcomes in all but 1 patient, who died following a seizure (Bickerstaff 1957). This condition has since been referred to as Bickerstaff brainstem encephalitis.

In 1992, Chiba and colleagues identified IgG antibodies against GQ1b in patients with Miller Fisher syndrome (Chiba et al 1992). At the time, the anti-GQ1b antibodies were considered serological markers of Miller Fisher syndrome. However, the antibodies were also detected in patients with Bickerstaff brainstem encephalitis (Yuki et al 1993; Ito et al 2008). The latter findings supported the continuity between the 2 syndromes, with Miller Fisher syndrome representing 1 end of the spectrum and Bickerstaff brainstem encephalitis the other, with involvement of the CNS. Patients with milder clinical features, such as ophthalmoparesis without ataxia (Yuki 1996), or more extensive involvement with limb weakness (Mori et al 2001), were also found to have anti-GQ1b antibodies present on serological testing. In view of the common serological profile shared by this group of patients, it has been referred to as the "anti-GQ1b antibody syndrome" (Shahrizaila and Yuki 2013).

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