Morvan syndrome in an adolescent: a rare clinicophysiological diagnosis

Abstract

Case Presentation: A previously healthy 16-year-old boy developed abrupt severe oral pain after fixed orthodontic appliance placement, followed within 24 hours by psychomotor agitation, behavioral changes, and near-total insomnia without daytime sleepiness. Over the next days, he developed thermoregulatory symptoms, severe xerostomia with polydipsia, compulsive cooling behaviors, and orthostatic hypotension (127 mmHg sitting to 78 mmHg standing). Sleep was limited to brief minutes, with marked restlessness and stimulus hypersensitivity. Diazepam was ineffective. There were no hallucinations, suicidal ideation, prior psychiatric symptoms, or relevant psychosocial stressors or family history. Neurological examination showed preserved cognition and strength, frontal release signs, and peripheral nerve hyperexcitability, including diffuse fasciculations, rare myokymias, and percussion-induced myotonic-like phenomena. Brain imaging, cerebrospinal fluid, and infectious workup were normal. Electroencephalography showed no epileptiform activity, tumor screening was negative, and electroneuromyography (ENMG) demonstrated diffuse membrane instability with fibrillations, positive sharp waves, and fasciculations. Morvan syndrome was diagnosed, and autoimmune encephalitis was considered. Intravenous methylprednisolone followed by intravenous immunoglobulin (IVIG) led to marked global improvement. He was re-admitted one week later with mild residual symptoms. Second-line immunotherapy with rituximab was proposed. Serum and cerebrospinal fluid samples were collected for autoimmune antibody testing. Discussion: Morvan syndrome is a rare disorder characterized by combined hyperexcitability of the central, autonomic, and peripheral nervous systems, manifesting as severe insomnia, dysautonomia, and peripheral nerve hyperexcitability. It belongs to the spectrum of peripheral nerve hyperexcitability syndromes, alongside cramp-fasciculation syndrome and Isaacs syndrome, which share electrophysiological evidence of motor nerve instability but differ in the degree of central and autonomic involvement. Diagnosis is primarily clinical, supported by ENMG findings and by exclusion of alternative etiologies. Differential diagnoses include primary psychiatric disorders, drug- or toxin-induced states, metabolic disturbances, prion disease, paraneoplastic syndromes, and autoimmune encephalitis (most frequently associated with antibodies like CASPR2 and LGI1, although seronegative cases are recognized). The clinical course may be severe but is often responsive to immunotherapy. First-line treatments include corticosteroids, IVIG, and plasma exchange. Final Comments: Morvan syndrome should be considered in patients with agrypnia excitata associated with dysautonomia and peripheral nerve hyperexcitability. A clinicophysiological approach supported by ENMG allows early diagnosis and prompt immunotherapy, even without antibody confirmation.