Objective:

The objective of this study is to evaluate neurologic course and outcomes in Neurofascin 186 (NF186) IgG seropositive polyradiculoneuropathies.

Background:

NF186 IgG has been reported in association with autoimmune neuropathies, but characterization of phenotypes and clinical outcomes are limited.

Design/Methods:

243 CIDP (193 classical, 50 variant), 122 other acquired neuropathies (including GBS, POEMS) and 122 controls (SLE, ALS, MGUS, and genetic neuropathies) were tested for NF186 IgG on cell-based assay (Euroimmun, Lübeck). Neurologic course and treatment outcomes were reviewed.

Results:

Two CIDP (0.8%) and two acquired neuropathies (1.6%; POEMS, painless radiculoplexus neuropathy, initially suspected to be secondary to radiation) were seropositive for NF186 IgG. One MGUS control was seropositive (0.8%). Among neuropaths, median age was 47 years old (range: 35-58) with one male and three females. Symptoms at illness nadir included distal symmetric sensory (n=4), motor (n=4), pain (n=3), respiratory dysfunction (n=3) with nocturnal BiPAP dependence (n=1) and early kinetic tremor (n=2). Wheelchair dependence was ubiquitous resulting in mRS of 4. Median INCAT disability score was 6.5. CSF protein was elevated (n=2) with overall median 62 mg/dL (48-234) without leukocytosis. Electrodiagnostics showed demyelinating features in the majority of cases (n=3, 75%). Restrictive pattern on PFT was present in all studied patients (n=3). Median time from symptom onset to diagnosis was 16 months (5-155). mRS improvement of > 1 point occurred in POEMS and CIDP cases (n=3). Median post-treatment mRS was 2.5 (1-6). Single mortality occurred despite initial favorable positive treatment response due to disease relapse and progressive neuromuscular respiratory failure.

Conclusions:

NF186 IgG seropositivity is associated with polyradiculopathy or radiculoplexus neuropathy phenotypes. The majority of seropositive patients had evidence of respiratory dysfunction out of proportion to most acquired polyradiculoneuropathies. Identification of additional NF186 IgG-positive cases will aid in further evaluation of clinical or phenotypic specificity of this antibody.