Prevalence and clinical implications of diabetes mellitus in autoimmune nodopathies: A systematic review.

Background And Aims: Autoimmune nodopathies comprise a newly-established subtype of immune-mediated peripheral neuropathies, characterized by circulating autoantibodies that target nodal-paranodal proteins, including contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), neurofascin-155 (NF155) and neurofascin-isoforms (NF140 and NF186). Emerging evidence suggests that diabetes mellitus (DM) may confer increased risk for autoimmune nodopathies.

Methods: A systematic search was performed including studies reporting on patients harboring nodal/paranodal antibodies (CNTN1, Caspr1, NF155, NF140 and NF186). We sought to evaluate: (1) the prevalence of DM among patients with autoimmune nodopathies; (2) the phenotype of DM-patients harboring different types of nodal/paranodal antibodies; (3) clinical features that allow distinction of autoimmune nodopathies from diabetic peripheral neuropathy (DPN).

Results: Five cohort studies, 3 case-reports and one case-series study were identified comprising 114 patients with autoimmune nodopathies. DM prevalence was documented to range between 10.5 % and 60 %. DM-patients harbored mostly paranodal antibodies; CNTN1: 58.3 %, followed by pan-neurofascin: 33.3 %, and Caspr1: 25 % antibodies. No significant differences in clinical phenotype were uncovered between DM-patients and their non-DM counterparts. Overall, DM patients were refractory to intravenous-immunoglobulins (IVIG), but responded well to escalation immunotherapies. Compared to DPN, distinctive features of autoimmune nodopathy comprised: (i) severe ataxia, tremor, and cranial nerve involvement; (ii) neurophysiological findings indicative of nodal-paranodal pathology, including (reversible) conduction failure and conduction velocity slowing, often accompanied by reduced compound muscle and sensory nerve action potentials; and (iii) marked protein-elevation or albuminocytological dissociation in cerebrospinal fluid analysis.

Conclusions: DM patients fall under the typical clinical phenotype of autoimmune nodopathy, displaying predominantly paranodal antibodies. Early suspicion is crucial, as unlike DPN, diagnosis of autoimmune nodopathy unfolds therapeutic perspectives.