Identify the clinical traits, neurophysiological features, and outcomes of autoimmune neuromuscular hyperexcitability spectrum disorders (ANHSD).

ANHSD encompass immune-mediated conditions marked by excessive excitability of nerve or muscle membranes, leading to potentially debilitating symptoms. Early identification of these syndromes can provide opportunities for treatment and minimize symptom burden and progression.

Retrospective review of Mayo clinic electronic medical records. 

Forty-five cases were classified as ANHSD, with the final diagnoses being immune-mediate rippling muscle disease (iRMD, 16/45; 36%), immunotherapy responsive cramp fasciculation syndrome (14/45; 31%), Isaac syndrome (5/45; 11%), Morvan syndrome (8/45; 18%), and peripheral nerve hyperexcitability with encephalitis/seizures not meeting Morvan syndrome criteria (2/45; 4%). In comparison to non-immune mediated peripheral nerve hyperexcitability (n=62), immune-mediated nerve hyperexcitability cases were associated with the presence of co-existing central nervous system involvement (p=0.03) or autonomic dysfunction (p=0.046). Among the ANHSD cases most (n=28; 62%) were seropositive. Ten tested positive for LGI1-IgG, eight for CASPR2-IgG, and sixteen for Cavin-4 IgG. Five patients were positive for both LGI1-IgG and CASPR2-IgG. In nine patients, hyperexcitability was suspected to be secondary to paraneoplastic autoimmunity, with thymoma, papillary thyroid cancer, breast cancer and small cell lung cancer in two patients each, with metastatic squamous cell cancer in one other.   Out of 40 patients with follow-up data, 35 received immunotherapy, one had thymectomy, and four received only symptomatic treatment. The majority (36/40; 90%) experienced either symptom improvement or stabilization.

In our study cohort, iRMD emerged as the most common ANHSD and should be contemplated especially when muscle hyperexcitability is electrically silent. However, combined frequency of various nerve hyperexcitability syndromes was higher than iRMD. Autoimmune nerve hyper-excitability cases often have multifocal neuroaxis involvement with co-existing dysautonomia, seizures or encephalopathy. The majority of cases were seropositive for neural specific antibodies, underscoring the importance of autoantibody evaluation in diagnosis of these cases.