Anti-GQ1b ganglioside positive Miller Fisher syndrome - evidence of paranodal pathology on nerve biopsy

BACKGROUND: Miller Fisher syndrome is a regional variant of Guillain-Barre syndrome with a characteristic clinical triad of ophthalmoplegia, areflexia and ataxia and occasionally distal limb sensory loss. 90% of patients have associated antibodies to the GQ1b ganglioside. The pathophysiology of antibody-mediated peripheral nerve impairment remains uncertain. This report includes the first description of a peripheral sensory nerve biopsy in Miller Fisher syndrome. RESULTS: A single case report is described of a 46 year old woman who presented with 2 weeks of distal glove and stocking sensory loss to both deep and superficial sensory modalities, areflexia and weight loss. This was followed by rapid onset of ataxia, ophthalmoplegia, and bulbar impairment. Peripheral neurophysiology showed reduced sensory nerve amplitudes with preserved conduction velocities in keeping with an axonal pattern of impairment. Clinical concerns of a systemic inflammatory disorder led to a diagnostic peripheral nerve biopsy from the sensory branch of the radial nerve. However she subsequently made a complete recovery over 5 weeks. Combinatorial glycoarrays confirmed restricted serum binding for GQ1b in acute serum which later resolved in a convalescent sample. The nerve biopsy showed lengthening of nodes of Ranvier, myelin splitting and macrophage internodal axonal invasion without any features of demyelination. CONCLUSIONS: The pathological features were strikingly similar to those found in acute motor axonal neuropathy and indicate the region of the node of Ranvier to be a primary focus of GQ1b induced damage in Miller Fisher syndrome, at least in this particular overlap syndrome with prominent sensory nerve involvement

A multiple sclerosis-like disorder in patients with OPA1 mutations.

We describe three unrelated patients presenting with a spinal cord syndrome and neuroimaging features consistent with multiple sclerosis (MS). All harbored a pathogenic OPA1 mutation. Although the neurological phenotype resembled neuromyelitis optica (NMO), anti-aquaporin 4 antibodies were not detected and the disorder followed a slow progressive course. The coincidental occurrence of OPA1 mutations and an MS-like disorder is likely to have modulated the phenotypic manifestations of both disorders, but unlike the previously reported association of Leber hereditary optic neuropathy and MS (Harding disease), the optic neuropathy in patients with OPA1 mutations and an MS-like disorder can be mild with a good visual prognosis.PYWM is supported by a Clinician Scientist Fellowship Award (G1002570) from the Medical Research Council (UK), and also receives funding from Fight for Sight (UK), the UK National Institute of Health Research (NIHR) as part of the Rare Diseases Translational Research Collaboration, and the NIHR Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. PFC is a Wellcome Trust Senior Fellow in Clinical Science (101876/Z/13/ Z), and a UK NIHR Senior Investigator. PFC receives additional support from the Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2), the Wellcome Trust Centre for Mitochondrial Research (096919Z/11/Z), the Medical Research Council (UK) Centre for Translational Muscle Disease (G0601943), the Medical Research Council (UK) Centre for Translational Muscle Disease research (G0601943), and EU FP7 TIRCON