Pan-neurofascinopathies: a subgroup that mimic other neuroimmune-mediated diseases

Pan-neurofascinopathies represent a distinct subset of inflammatory neuropathies characterized by autoantibodies that target multiple neurofascin (NF) isoforms, which are essential for nodal and paranodal architecture in peripheral nerves. These antibodies are associated with a broad clinical spectrum, often mimicking Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and exhibit significant variability depending on the immunoglobulin G (IgG) subclass involved. The IgG1 and 3 subclasses correlate with acute, fulminant presentations and complement activation, whereas IgG4-mediated cases are typically indolent but resistant to first-line therapies. Although primarily restricted to the peripheral nervous system, pan-neurofascinopathies may also mimic central demyelinating diseases and present with systemic features such as nephrotic syndrome. These atypical manifestations highlight the expanding clinical spectrum of the disease. Early identification of anti-pan-NF antibodies and their respective IgG subclasses is crucial to guide diagnosis and management. Timely recognition enables implementation of aggressive B cell depletion-based treatment strategies, which are essential to avoid long-term neurological sequelae in affected patients.