Monkeypox Infection’s Psychiatric and Neurologic Presentations

Monkeypox infection has a range of neuropsychiatric presentations, including severe neurologic complications to nonspecific neurologic features.

Neuropsychiatric presentations of monkeypox infection may include encephalitis, seizure, nonspecific confusion, headache, and myalgia, according to findings published recently in eClinical Medicine.

Researchers conducted a meta-analysis and systematic review of the MEDLINE, EMBASE, PsycINFO, AMED, and the preprint server MedRxiv databases through May 2022 that included 19 studies. The incorporated studies were cohort studies (12), cross-sectional (2), case series (4), and case report (1); only 1 study used a control group. The studies were from the United States (6), Democratic Republic of Congo (5), Nigeria (5), Republic of Congo (2), and United Kingdom (1).

Out of a total 1512 participants, 1031 had monkeypox virus infection confirmed via polymerase chain reaction testing or US Centers for Disease Control criteria. The study sample size ranged from 1 to 370 (median, 21). Mean age (reported in 8 studies [n=542]) was 24.2±19.4 years (45.1% women [n=465]). Most studies that reported treatment setting (n=419) showed most patients (79.0%) were hospitalized. Only 3 studies (n=54), all of which were from the United States, reported ethnicity (85.2% White).

Researchers used an inverse variance approach for the sensitivity analysis and both the Joanna Briggs Institute quality assessment tool and the Newcastle Ottawa Scale to assess bias risk, which indicated reduced scores based on lack of control groups and lack of reported follow-up.

[S]erious neurologic manifestations—seizure, confusion and encephalitis—were present in small (<3%) but nonnegligible proportions of infected individuals.

Meta-analysis was performed on the 3 eligible clinical features: seizure (pooled prevalence [PP], 2.7%; 95% CI, 0.7-10.2%; I2, 0%), confusion (PP, 2.4%; 95% CI, 1.1-5.2%; I2, 0%) and encephalitis (PP, 2.0%; 95% CI, 0.5-8.2%; I2, 55.8%). Heterogeneity was found to be too high for estimation of PP for additional frequently reported symptoms of myalgia, headache and fatigue, anxiety and depression. Additional neuropsychiatric features included suicide, pain, altered vision, dizziness, photophobia, and encephalopathy.

Sensitivity analysis yielded similar results to the meta-analysis for point estimate of prevalence, heterogeneity, and confidence interval boundaries.

Exclusion of methodologically heterogeneous studies showed no significant difference in PP estimates based on headache, encephalitis, seizure, and myalgia.

Limitations of the study include the small sample size of the included studies, significant methodological and statistical heterogeneity between studies, the lack of studies assessing psychiatric symptoms using standardized scales, and limited reporting of neurologic investigations.

Study authors concluded, “Based on a small number of studies examining this topic, our meta-analysis found that serious neurologic manifestations—seizure, confusion and encephalitis—were present in small (<3%) but nonnegligible proportions of infected individuals.” They added, “The prevalence of other neuropsychiatric symptoms including myalgia, fatigue, headache, anxiety and depression are less clear, but several studies found at least half of individuals experiencing some of these outcomes.” They also noted knowledge gaps surrounding assumed components that effect risk of neurological and psychiatric presentations.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Badenoch JB, Conti I, Rengasamy ER, et al. Neurological and psychiatric presentations associated with human monkeypox virus infection: a systematic review and meta-analysis. eClinical Medicine. Published online September 8, 2022. doi:10.1016/j.eclinm.2022.101644