Inflammatory neuropathies with pathogenic involvement of the nodes of Ranvier through autoantibodies have been increasingly characterized in the past years.The so-called anti-pan-NF-associated neuropathies caused by the simultaneous existence of anti-Neurofascin-186/-140 and -155-antibodies are extremely rare and cause life-threatening symptoms. Therapeutic strategies are needed as symptoms may be life-threatening and may not respond to standard first-line CIDP treatment. We report a case of a 52-year-old male with a rare anti-pan-neurofascin (NF) (-155, -186/-140)-associated neuropathy. The initial presentation was subacute with mild paresthesia leading to a fulminant "locked-in"-like syndrome requiring mechanical ventilation within the first eight weeks despite treatment with intravenous immunoglobulins. Nerve conduction studies revealed non-excitable nerves with acute spontaneous activity in electromyography. High titers of anti-Neurofascin-155, À186/À140-antibodies were detected in serum and cerebrospinal fluid. A combination of aggressive immunotherapy consisting of intravenous immunoglobulins, plasma exchange, rituximab and bortezomib resulted in clinical improvement with ambulation and non-detectable anti-neurofascin-antibodies within the following 3 months. The follow-up nerve conduction studies showed normalized amplitudes of the peripheral nerves with signs of reinnervation in electromyography. We conclude that an early aggressive immunotherapy consisting of a combination of rituximab and bortezomib could be considered as a therapeutic option for anti-pan-NF-associated neuropathies.

Background and ObjectivesNodo-paranodopathies are peripheral neuropathies with dysfunction of the node of Ranvier. Affected patients who are seropositive for antibodies against adhesion molecules like contactin-1 and neurofascin show distinct clinical features and a disruption of the paranodal complex. An axoglial dysjunction is also a characteristic finding of diabetic neuropathy. Here, we aim to investigate a possible association of antibody-mediated nodo-paranodopathy and diabetes mellitus (DM).MethodsWe retrospectively analyzed clinical data of 227 patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome from multiple centers in Germany who had undergone diagnostic testing for antiparanodal antibodies targeting neurofascin-155, pan-neurofascin, contactin-1–associated protein 1, and contactin-1. To study possible direct pathogenic effects of antiparanodal antibodies, we performed immunofluorescence binding assays on human pancreatic tissue sections.ResultsThe frequency of DM was 33.3% in seropositive patients and thus higher compared with seronegative patients (14.1%, OR = 3.04, 95% CI = 1.31–6.80). The relative risk of DM in seropositive patients was 3.4-fold higher compared with the general German population. Seropositive patients with DM most frequently harbored anti–contactin-1 antibodies and had higher antibody titers than seropositive patients without DM. The diagnosis of DM preceded the onset of neuropathy in seropositive patients. No immunoreactivity of antiparanodal antibodies against pancreatic tissue was detected.DiscussionWe report an association of nodo-paranodopathy and DM. Our results suggest that DM may be a potential risk factor for predisposing to developing nodo-paranodopathy and argue against DM being induced by the autoantibodies. Our findings set the basis for further research investigating underlying immunopathogenetic connections.