Clinical and Radiological Heterogeneity in Anti‐Neurofascin‐155 Autoimmune Nodopathy: A Case Series Analysis

Background and Aims Autoimmune nodopathy with anti‐neurofascin‐155 (NF155) antibodies is increasingly recognized as a distinct disease entity. Although these patients have been described, not all aspects have been fully elucidated. We investigated clinical phenotypes, biomarker profiles, and treatment outcomes in patients with anti‐NF155 antibody‐positive autoimmune nodopathy. Methods We retrospectively analyzed seven Japanese patients (aged 13–27 years) with anti‐NF155 antibody‐positive autoimmune nodopathy treated at Kumamoto University Hospital between 2017 and 2020. Clinical, electrophysiological, radiological, and biomarker data were evaluated. One refractory case was followed up for over 80 months, tracking serum neurofilament light chain (sNfL) and anti‐NF155 antibody levels in the serum and cerebrospinal fluid (CSF). Results All patients exhibited severe sensory ataxia and motor dysfunction. Trigeminal nerve hypertrophy was observed in five individuals, without corresponding symptoms, and pes cavus in one patient. All patients demonstrated a pronounced demyelinating neuropathy phenotype. The mean CSF protein level was 343 mg/dL. Intravenous immunoglobulin (IVIg) had minimal efficacy, while corticosteroids produced good responses in four patients and partial responses in three patients. Rituximab markedly improved a refractory case. Anti‐NF155 antibody and sNfL levels correlated with clinical status. Magnetic resonance imaging frequently revealed persistent nerve root hypertrophy despite functional improvement. Interpretation Anti‐NF155 nodopathy is a distinct, biomarker‐trackable entity; corticosteroids and rituximab outperform IVIg, challenging conventional practice and highlighting the need for antibody testing, especially in young patients with severe demyelinating neuropathy.