Neurological and psychiatric presentations associated with human monkeypox virus infection: a systematic review and meta-analysis
Authors: Badenoch James B , Conti Isabella , Rengasamy Emma R , Watson Cameron J , Butler Matt , Hussain Zain , Rooney Alasdair G , Zandi Michael S , Lewis Glyn , David Anthony S , Houlihan Catherine F , Easton Ava , Michael Benedict D , Kuppalli Krutika , Nicholson Timothy R , Pollak Thomas A , Rogers Jonathan P 
Published: July 2022

ABSTRACTObjectivesNeuropsychiatric presentations of monkeypox (MPX) infection have not been well characterised, Despite evidence of nervous system involvement associated with two relatedOrthopoxviruses, in the case of smallpox infection (with the variola virus) and smallpox vaccination (which contains live vaccinia virus). In this systematic review and meta-analysis, we aim to determine the prevalence and describe the spectrum of neurological and psychiatric presentations of MPX.DesignSystematic review and meta-analysisData sourcesMEDLINE, EMBASE, PsycINFO, AMED and pre-print server (MedRxiv) searched up to 31/05/2022Eligibility criteria for study selection and analysisAny study design of humans infected with MPX that reported neurological or psychiatric presentation. Studies which included more than ten individuals, and symptoms that were reported in a minimum of two separate studies were eligible for meta-analysisData synthesisResults were pooled with random-effects meta-analysis to calculate generalised linear mixed models and corresponding 95% confidence intervals for each prevalence outcome. Heterogeneity was measured with the I2statistic. All included studies are summarised through a narrative synthesis. Risk of bias was assessed with the Newcastle Ottawa Scale and the Joanna Briggs Institute quality assessment tool.ResultsFrom 1,702 unique studies, we extracted data on 19 eligible studies (1,512 participants, 1,031 with confirmed infection using CDC criteria or PCR testing) most of which were cohort studies and case series with no controlled populations. Study quality was generally moderate. Six clinical features were eligible for meta-analysis, of which the most prevalent were myalgia in 55.5% [95%CI 12.1-91.9%], headache 53.8% [30.6-75.4%], fatigue 36.2% [2.0-94.0%], seizure 2.7% [0.6-10.2%], confusion 2.4% [1.1-5.2%] and encephalitis 2.0% [0.5-8.2%]. Heterogeneity significantly varied across clinical features (I2=0%-98.7%). Other reported presentations not eligible for meta-analysis included sensory-perceptual disturbance (altered vision, dizziness, and photophobia) and psychiatric symptoms (anxiety and depression).ConclusionsThere is preliminary evidence for a range of neurological and psychiatric presentations of MPX, ranging from commonly reported and nonspecific neurological symptoms (myalgia and headache) to rarer but more severe neurological complications, such as encephalitis and seizures. There is less evidence regarding the psychiatric sequelae of MPX, and although there are multiple reports of anxiety and depression the prevalence of these symptoms is unknown. MPX-related nervous system presentations may warrant surveillance within the current MPX outbreak, with prospective longitudinal studies evaluating the mid to long-term sequelae of the virus. Robust methods to evaluate the potential causality of MPX with these clinical features are required at an individual and epidemiological level.Systematic review registrationPROSPERO ID 336649SUMMARY BOXWhat is already known on this topicNeuropsychiatric symptoms can be highly disabling and have a detrimental effect on quality of life.Neuropsychiatric manifestations of monkeypox virus infection have not been well characterised, however, there is evidence of nervous system involvement with the related smallpox virus and vaccinia vaccine.What this study addsPreliminary evidence for a range of neurological and psychiatric presentations of monkeypox infection, ranging from commonly reported and nonspecific neurological symptoms (myalgia and headache) to rarer but more severe neurological complications, such as encephalitis and seizures.There is less evidence regarding the psychiatric sequelae of monkeypox infection, and although there are multiple reports of anxiety and depression the prevalence of these symptoms is unknown.This preliminary suspicion that there are monkeypox-related nervous system manifestations may warrant both surveillance within the current monkeypox outbreak and robust methods to evaluate the potential causality.