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

Abstract

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.