Neuroinvasive Potential of Monkeypox Virus: A 25-Year Systematic Review

Monkeypox (MPX) is a zoonotic disease, caused by the MPX virus. Clinical symptoms and signs of the disease are similar to, but less severe than, smallpox, presenting with fever, headache, lymphadenopathy, back pain, myalgia, and skin rash. MPX can affect the central nervous system causing different complications, including encephalitis, cerebral edema, and intracranial hemorrhage. This study aimed to assess the neurological sequelae of MPX infection focusing on the available literature. An extensive data search was conducted in September 2024, covering the period from January 2000 to August 2024, using PubMed Central and Google Scholar. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) strategy was employed along with a combination of keywords to enlist all articles with data on MPX and its neurological manifestations, diagnosis, and treatment. All open-access case reports, case series, and original research articles in the English language, providing data on confirmed cases of MPX virus infection with documented neurological manifestations involving the brain, were reviewed. A total of 25 studies containing data on 758 patients were included in this systematic review. The mean age and standard deviation of included patients was 26.77±12.17 years, with a female predominance (65.27%). Most of the cases (87.05%) were transmitted by animal/human contact. Fatigue/malaise (34.37%) was the most common presentation, followed by fever and headache accounting for 31.27% and 29.84%, respectively. Limb weakness/numbness (20.83%) was the most common examination finding. About 26.32% had normal glucose levels and 21.05% reported raised white blood cells on CSF routine examination. T2 hyperintensities and fluid-attenuated inversion recovery (FLAIR) hyperintensities were reported on magnetic resonance imaging in 18.75% of the cases, each. Brainstem involvement, cortical, and thalamic involvement were seen in 18.60%, 16.28%, and 13.95% of cases, respectively. About 34.61% of the patients were inadvertently given antibiotics. The emerging MPX neurological involvement is alarming and requires a prompt response. The neurotropism of MPXV is still in debate and needs to be explored. Early identification and interventions by healthcare providers can significantly impact the trajectory of MPX spread.