Neuro-ophthalmology and the anti-GQ1b antibody syndromes

Abstract

The discovery of the association of the anti-GQ1b IgG antibody with the postinfectious clinical syndromes of ophthalmoplegia, ataxia, and areflexia helped house the phenotypes of the Miller Fisher syndrome (MFS), atypical MFS, Guillain-Barré syndrome with ophthalmoplegia, and Bickerstaff's brainstem encephalitis under one roof. The neuro-ophthalmologic signs classically predominate and may vary from case to case, but they maintain clinically recognizable patterns that assist with the diagnosis. The identification of a common lipopolysaccharide on the plasma membrane in human cranial and peripheral nerves at the GQ1b epitope and on infectious particles of bacteria and viruses (ie, Campylobacter jejuni) demonstrates molecular mimicry. The high frequency of oculomotor dysfunction is partially explained by the tissue ganglioside concentration and distribution and the attraction of antibody-stimulating complement activation. Current experimental treatment targets antibody removal and neutralization and prevents membrane attack complex formation through deactivation of complement. This article aims to bring together the historically disparate opinions on the origins of these syndromes as either a purely peripheral nervous system or central nervous system dysfunction, highlight the clinical neuro-ophthalmologic signs, discuss some of the biology of the anti-GQ1b antibody, and review imaging abnormalities and treatment of this fascinating disorder.

Bickerstaff Brainstem Encephalitis. A Rare Entity in Children

“…The clinical features of BBE is similar to those of the Miller Fisher syndrome (MFS); the common clinical signs are ophthalmoplegia, ataxia and CSF albumin-cytological dissociation [6]. However, the clinical criteria for the diagnosis of BBE must have disturbed conscious level or signs of upper motor neuron lesion, which show involvement of cortex and serious brainstem; the FS does not include these characteristics [7]. The exact mechanism of BBE is not well understood.…”

Miller Fisher Syndrome Mimicking Ocular Myasthenia Gravis

“…10 The incidence of MFS varies with geographic location, being much more common in Japan than in the United States. 6,8 MFS is more common in men and affects people of all ages, with the median age of onset being in the 5 th decade. 8 …”

“…2,8 Ataxia, characterized by unsteady gait with inability to walk heel-to-toe, is thought to originate from cerebellar involvement, although this is not proven. 6,8 Ataxia is often a presenting symptom of MFS. 8 Areflexia or hyporeflexia, seen as a loss of deep tendon reflexes, is thought to manifest from peripheral nerve dysfunction of the lower motor neurons.…”

“…There is, however, variable involvement of the peripheral and central nervous systems that accounts for the distinguishing phenotypic features of these conditions. 6 Patients with GBS can develop ophthalmoplegia, but it does not usually occur until after they have developed extremity and respiratory paralysis. Bickerstaff’s brainstem encephalitis has the same clinical features as MFS (ophthalmoplegia and ataxia), as well as impaired consciousness (e.g., coma) and pyramidal tract dysfunction (e.g., hyperreflexia or pathological reflexes).…”

“…MRI with contrast did not demonstrate cranial nerve enhancement, which may be present in MFS. 6 He was managed conservatively, without further medical intervention or investigations, and there was a gradual spontaneous improvement in his ductions over several months. However, there was a residual right eye abduction deficit with 6 prism diopters of esotropia for which prism glasses were successfully prescribed.…”