Miller Fisher syndrome: an updated narrative review

Abstract

Introduction: Miller Fisher syndrome (MFS) is considered a rare variant of Guillain-Barré syndrome (GBS), a group of acute-onset immune-mediated neuropathies characterized by the classic triad of ataxia, areflexia, and ophthalmoparesis. The present review aimed to provide a detailed and updated profile of all aspects of the syndrome through a collection of published articles on the subject, ranging from the initial description to recent developments related to COVID-19.

Methods: We searched PubMed, Scopus, EMBASE, and Web of Science databases and gray literature, including references from the identified studies, review studies, and conference abstracts on this topic. We used all MeSH terms pertaining to "Miller Fisher syndrome," "Miller Fisher," "Fisher syndrome," and "anti-GQ1b antibody."

Results: An extensive bibliography was researched and summarized in the review from an initial profile of MFS since its description to the recent accounts of diagnosis in COVID-19 patients. MFS is an immune-mediated disease with onset most frequently following infection. Anti-ganglioside GQ1b antibodies, detected in ~85% of patients, play a role in the pathogenesis of the syndrome. There are usually no abnormalities in MFS through routine neuroimaging. In rare cases, neuroimaging shows nerve root enhancement and signs of the involvement of the central nervous system. The most consistent electrophysiological findings in MFS are reduced sensory nerve action potentials and absent H reflexes. Although MFS is generally self-limited and has excellent prognosis, rare recurrent forms have been documented.

Conclusion: This article gives an updated narrative review of MFS with special emphasis on clinical characteristics, neurophysiology, treatment, and prognosis of MFS patients.

Keywords: Miller Fisher; Miller Fisher syndrome; anti-GQ1b antibody; ataxia; ophthalmoparesis.

Figure 1

The underlying mechanism of MFS seems to be that of “molecular mimicry.” The immune system's activation of the lipo-oligosaccharides (LOS) present on the membrane of some pathogens, most frequently Campylobacter jejuni, which are similar in shape to gangliosides (GQ1b, GM1, and GD1a), would lead to the production of autoantibodies. If the antibody produced is GM1 or GD1b, the classic form of GBS with acute motor axonal neuropathy is produced, whereas if it is GQ1b, MFS is produced (29). GQ1b is a ganglioside present in the paranodal myelin, mainly at the level of oculomotor nerves (III-IV and VI cranial nerves), dorsal root ganglia (DRG), and fibers of neuromuscular spindles. The localization of the ganglioside explains the symptomatological triad of patients.

Figure 2

At the level of the nodes of Ranvier, three distinct areas can be identified. 1. Juxtaparanodal region, where the compacted myelin is tightly attached to the axolemma. 2. Paranodal region, where the myelin is attached to the axolemma but not organized as a compact structure. 3. The node of Ranvier, in which the axolemma is not lined with myelin and is in direct contact with the extracellular fluid, despite being covered by the microvillous Schwann cells. At the level of the paranode, there is a formation consisting of Contactin-1 (CNTN1) and CASPR, expressed by neurons, which bind the NF-155 counterpart and are of glial origin. This paranodal axon-glial formation is responsible for ion channel clustering, propagating the action potential, and blocking the lateral diffusion of membrane proteins in myelinated nerve fibers.