Bridging the Gap: Opsoclonus-Myoclonus Syndrome: Human Pegivirus Encephalomyelitis Diagnosed Through Metagenomic Next-Generation Sequencing.

This case of encephalomyelitis in a previously healthy 21-year-old man who developed opsoclonus-myoclonus demonstrates the diagnostic utility of clinically validated metagenomic next-generation sequencing (mNGS), followed by appropriate confirmation, in complex cases of encephalitis. In this patient, an extensive diagnostic workup was negative for infectious, inflammatory, demyelinating, autoimmune, and paraneoplastic etiologies. However, clinically validated mNGS of the CSF identified human pegivirus (HPgV) as a potential causative agent. A 5-day course of IV immunoglobulins (IVIg) led to the resolution of the opsoclonus-myoclonus. HPgV identification provided clinical and pathophysiologic insights: (1) a possible link between HPgV and CNS pathology, including brainstem neurotropism similar to other flaviviruses; (2) expansion of the opsoclonus-myoclonus differential to include HPgV; and (3) potential immune-mediated CNS involvement, suggested by the favorable response to IVIg. Although promising, broader mNGS use remains limited by biologic, technical, and logistic challenges.