ObjectiveTo measure the frequency, persistence, isoform specificity, and clinical correlates of neurofascin antibodies in patients with peripheral neuropathies.MethodsWe studied cohorts of patients with Guillain-Barre syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 59), genetic neuropathy (n = 111), and idiopathic neuropathy (n = 43) for immunoglobulin (Ig) G and IgM responses to 3 neurofascin (NF) isoforms (NF140, NF155, and NF186) using cell-based assays.ResultsNeurofascin antibodies were more common in patients with GBS/CIDP (14%, 8 of 59) compared to genetic neuropathy controls (3%, 3 of 111, p = 0.01). Seven percent (3 of 43) of patients with idiopathic neuropathy also had neurofascin antibodies. NF155 IgG4 antibodies were associated with CIDP refractory to IV immunoglobulin but responsive to rituximab, and some of these patients had an acute onset resembling GBS. NF186 IgG and IgM to either isoform were less specific. A severe form of CIDP, approaching a locked-in state, was seen in a patient with antibodies recognizing all 3 neurofascin isoforms.ConclusionsNeurofascin antibodies were 4 times more frequent in autoimmune neuropathy samples compared to genetic neuropathy controls. Persistent IgG4 responses to NF155 correlated with severe CIDP resistant to usual treatments but responsive to rituximab. IgG4 antibodies against the common domains shared by glial and axonal isoforms may portend a particularly severe but treatable neuropathy. The prognostic implications of neurofascin antibodies in a subset of idiopathic neuropathy patients and transient IgM responses in GBS require further investigation.

Key Points Question Is annual residential exposure to particulate matter 2.5 μm or less in diameter (PM 2.5 ) associated with neuroimaging diffusion markers of white matter microstructure? Findings This cross-sectional study of 7602 children 9 to 10 years of age found evidence of an association between PM 2.5 exposure and hemispheric differences in white matter microstructure. In hemisphere-specific models, adjusted for confounding variables, statistically significant positive associations were observed between PM 2.5 and restricted isotropic diffusion, and statistically significant negative associations were observed between PM 2.5 and mean diffusivity. Meaning Findings from this study suggest that exposure to PM 2.5 may be associated with differences in white matter microarchitecture, supporting a need for further improvements in air quality to protect the developing brain.

No abstract