Morvan syndrome associated with CASPR2 and LGI1 antibodies in a child

Abstract

A 16-year-old boy presented with a 3-week history of back pain, insomnia, profuse sweating, and constipation following a respiratory infection. Physical examination revealed tachycardia, arterial hypertension, muscle weakness, and postural tremor. After hospital admission, he showed almost complete insomnia and massive hyperhidrosis, forcing him to change clothes every 15 minutes and drink up to 12 L/d. He deteriorated, with confusion, hallucination, and additional motor symptoms like fasciculations, areflexia, and muscle cramps/stiffness of both legs that prevented walking. His modified Rankin Scale (mRS) score was 4. Initial blood chemistry only revealed mild hyponatremia. Repeated neuroimaging and extended screening for infectious and neoplastic disease were unremarkable. Electroneurography revealed demyelinating peripheral neuropathy and EMG showed rare spontaneous discharges without the full picture of peripheral nerve hyperexcitability. Serum catecholamine levels were elevated and CSF analysis revealed high protein levels with normal cell count and without oligoclonal bands. Antineuronal antibody screening in serum detected antibodies against the voltage-gated potassium channel (VGKC) complex by radioimmunoassay (RIA, 283 pmol/L) and high titers (1:10,000) against contactin-associated protein 2 (CASPR2) by a commercial cell-based assay (CBA; indirect immunofluorescence on BIOCHIP-Mosaic, Euroimmun, Lübeck, Germany). As the CNS was strongly affected, we analyzed CSF reactivity with a tissue-based assay (TBA). CSF incubation on murine brain sections and subsequent visualization with fluorescent-labeled antihuman immunoglobulin G antibodies revealed a strong signal in the neuropil, mainly of hippocampus and cerebellum (figure, A–D). The CBA confirmed a low CSF anti-CASPR2 antibody titer (1:10) without intrathecal synthesis (table e-1, [links.lww.com/WNL/A71][1], for full diagnostic results). [1]: http://links.lww.com/WNL/A71