University of Bern

To expand understanding of the pathogenesis, presentations, and treatment of initially idiopathic small fiber polyneuropathy (SFN). We longitudinally readministered validated metrics to track disease course and treatment responses in a previously healthy woman with acute, postinfectious, skin biopsy-confirmed, idiopathic SFN. During 5 years, viral respiratory infections triggered 3 separated episodes of acute, disabling burning hand, foot, and face pain (erythromelalgia). The initial 2 resolved with high-dose prednisone, and the third responded to repeated immunoglobulin treatments. Pregnancy with miscarriage triggered a fourth exacerbation refractory to corticosteroids and cyclosporin. Immunoglobulins restored total remission for 2 months; then, 2 rituximab doses slightly improved later flaring. Subsequently, daratumumab initiated 100-day remission later maintained by belimumab, initiated to permit another pregnancy. Remission continued after gestational week 13 all-treatment withdrawal. A week 30 fifth flare responded to plasmapheresis, with healthy birth at week 40. At 11-week postpartum, as symptoms returned, restarting belimumab restored remission maintained during ≥19 months of breastfeeding. This decade of tracking characterizes a relapsing-remitting course of SFN with initially separated monophasic episodes becoming more confluent, as with multiple sclerosis. This tempo and responsiveness to 5 immunotherapies suggest dysimmune causality. Validated metrics helped define the course and track treatment efficacy, particularly during pregnancy and breastfeeding. This is a single observational study without controls. This provides Class IV evidence.

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Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels.

Amarouch MY, Abriel H

Frontiers in physiology • 2015-01-01

Voltage-gated sodium channels (Nav) are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disorders. The purpose of this review is to summarize the recently identified sodium channel mutations that are linked to hyper-excitability phenotypes and associated with the alteration of the activation process of voltage gated sodium channels. Indeed, several clinical manifestations that demonstrate an alteration of tissue excitability were recently shown to be strongly associated with the presence of mutations that affect the activation process of the Nav. These emerging genotype-phenotype correlations have expanded the clinical spectrum of sodium channelopathies to include disorders which feature a hyper-excitability phenotype that may or may not be associated with a cardiomyopathy. The p.I141V mutation in SCN4A and SCN5A, as well as its homologous p.I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively. Regardless of which sodium channel isoform is investigated, the substitution of the isoleucine to valine in the locus 141 induces similar modifications in the biophysical properties of the Nav by shifting the voltage-dependence of steady state activation toward more negative potentials.

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