Morvan Syndrome

Morvan syndrome (MoS) is a rare and complex disorder of nervous system hyperexcitability. Dr. Augustine Marie Morvan, a French physician, first described MoS in April 1890 in . Morvan dubbed the syndrome (fibrillary chorea), but we now know the disorder eponymously as Morvan syndrome. In the central nervous system, hyperexcitability manifests via confusion, behavioral changes, myoclonus, and severe insomnia; hallucinosis and encephalopathy may also occur. Autonomic hyperactivity includes hyperhidrosis, constipation, labile blood pressure, hemodynamic instability, and cardiac arrhythmias. Finally, peripheral nervous system hyperexcitability is typically demonstrated by painful muscle cramps, myokymia (vermicular or continuous rippling movements, often encountered as eyelid twitching), and neuromyotonia (involuntary continuous muscle fiber activity, often seen as fasciculations, doublet and triplet discharges on electromyography). In short, MoS combines peripheral and central nervous system hyperexcitable states; myokymia, neuromyotonia, muscle fasciculations, stiffness, autonomic nervous dysfunction, severe insomnia, and encephalopathy are commonly encountered, though most patients manifest only some of the symptoms that may occur. Until the mid-1950s, etiologic theories in MoS focused on infectious causes, especially viral infections; for the second half of the 20th–century, etiologic theories focused on heavy metal toxicity. In 1999, the first report identified a new autoantibody member of the neurexin superfamily, an axonal transmembrane protein called anti-contactin-associated protein-like 2 (CASPR2). To date, approximately 60 case reports of CASPR2-associated MoS have been published in the French literature; the English language peer-reviewed medical literature boasts two case series numbering 43 patients in total. MoS is frequently paraneoplastic and is associated with malignant thymomas, in particular. It is essential to distinguish MoS from acquired neuromyotonia and limbic encephalitis. MoS can be fatal in as many as a third of cases, although a recent small case series from the Indian subcontinent reported death as an outcome in only 1 of 8 patients. A diagnosis of MoS is confirmed when serum antibody titers for CASPR2 and LGI1 are elevated. Therapeutic plasma exchange, often with immunosuppression, is the preferred treatment modality. Outcomes range from complete recovery to death, with the latter occurring in 20% of patients in a 2012 case series reported by Irani et al. Consensus in the peer-reviewed medical literature supports the efficacy of immunomodulatory treatment, especially plasmapheresis, in MoS. Little is known about the epidemiology of MoS, which is often unrecognized and thus unreported. Orphanet (accessed January 2024) reports the disease prevalence of MoS as less than one case per million. Consensus in the medical literature reveals MoS to be a strikingly male-dominated entity, with male-to-female ratios as high as 19:1 in some studies  and ranging from 70% to 90% in others.