Neuroinflammatory Disorders of the Central Nervous System Associated with Monkeypox Virus Infection: A Systematic Review and Call to Action

Background: The Monkeypox virus, a zoonotic pathogen of the Orthopoxvirus genus, has shown a marked global spread, resulting in cases of neuroinflammatory disorders. This systematic review aims to summarize the central nervous system manifestations linked to monkeypox virus infection. Methods: We conducted a systematic review according to PRISMA guidelines. Databases such as PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to September 2024. Inclusion criteria focused on monkeypox virus-positive patients with confirmed central nervous system inflammatory disorders, including encephalitis, meningitis, myelitis, and related neuroimmune diseases. Results: From 770 screened articles, 38 studies were included. Of the 20 reported monkeypox virus-infected cases with central nervous system involvement, the most common manifestations were encephalitis (40%), encephalomyelitis (30%), and meningoencephalitis (10%). Additional rarer presentations included Guillain-Barre syndrome (5%) and transverse myelitis (5%). The mean age of affected individuals was 27.9 years, and 75% were male. Fever, fatigue, and myalgia were the predominant systemic symptoms, with neurological complications often appearing within 4.6 days post-infection. Diagnoses were confirmed by quantitative reverse transcription polymerase chain reaction, magnetic resonance imaging, and cerebrospinal fluid analysis. Treatment strategies varied, with antivirals (e.g., tecovirimat) and immunomodulatory therapies (e.g., methylprednisolone, immunoglobulins, and rituximab) utilized. Conclusions: Monkeypox virus infection is associated with severe neuroinflammatory disorders, with varying outcomes from complete recovery to mortality. Increased awareness, comprehensive diagnostic approaches, and targeted therapeutic interventions are critical in managing these cases. Further research is required to elucidate the mechanisms of neuroinflammation in the monkeypox virus and establish standardized treatment protocols.