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Abstract Details

Reducing Axonal Firing Induces Sustained Pain Remission and Axonal Regrowth in SCN9A Variant Small-fiber Neuropathy
Neuromuscular and Clinical Neurophysiology (EMG)
P14 - Poster Session 14 (8:00 AM-9:00 AM)
1-006
To investigate long-term effects of sodium-channel blockade in small-fiber polyneuropathy (SFN) from sodium-channel mutation.

SFN symptoms reflect excess firing and distal degeneration of unmyelinated/thinly myelinated somatic/autonomic C-fiber and A-delta axons. Stocking-and-glove pain is common. Mutations of sodium-channels governing small-fiber excitability may model more-common painful neuropathies, such as from diabetes.

Cross-sectional, longitudinal analysis of family with missense SCN9A c.G856D.

The proband presented at 9y with 2 years of red, painful, itchy feet, distal ulcers, tachycardia, hypermobility and growth retardation. Gabapentin was ineffective, leaving him crying, depressed/anxious, and out of school. Lower-leg PGP9.5-immunolabeled skin-biopsy revealed abnormal epidermal neurite density (END) at 0.08% of predicted. Mexiletine gave immediate pain relief, and he flourished with improved functioning, growth, and resolved depression/anxiety. At 12.5y, he self-weaned medications, restarted school, and maintained nearly symptom-free remission for 3y with his 13.3y post-treatment biopsy normalized to 60.8%. His variant-bearing brother started holding and rubbing his feet at 2y. At 4.2y, his skin biopsy was normal (48.7%), but symptoms persisted and growth slowed. Initiating carbamazepine at 4.6y resolved his distress, improved his growth, and also his 6.1y skin-biopsy (54.5%). Their variant-bearing mother with milder, untreated erythromelalgia since 9y also had profound axonopathy (END <0.01%). 1.75y of mexiletine also induced continuing 3y remission, during which she delivered a 3rd variant-bearing child, asymptomatic at 8mo. Mother’s post-treatment biopsy at 37y was also normal (11.8%). Her affected father had subclinical "hot feet", erectile dysfunction, and irritable bowel since mid-40s. At 57y, his evaluation revealed reduced foot sweating and normal END (85.0%); oxcarbazepine was initiated.

In 4/4 patients, axonopathy paralleled pain severity (eg, small-fiber hyperactivity), not mutation. In 2/2, blocking excitotoxic firing resolved pain, then permitted off-medication remissions. In 3/3, treatment delayed or reversed axonopathy, aiding remissions. If confirmed, early sodium-channel blockade might become a way to protect axons and enable SFN remissions.

Authors/Disclosures
Madeleine Klein, BS (Albert Einstein College of Medicine)
PRESENTER
The institution of an immediate family member of Madeleine Klein has received research support from NIH.
No disclosure on file
Anne Louise Oaklander, MD, PhD, FÂé¶¹´«Ã½Ó³»­ (Massachusetts General Hospital) The institution of Dr. Oaklander has received research support from National Institutes of Health.