TY - JOUR
T1 - Neurological and psychiatric presentations associated with human monkeypox virus infection
T2 - A systematic review and meta-analysis
AU - Badenoch, James B.
AU - Conti, Isabella
AU - Rengasamy, Emma R.
AU - Watson, Cameron J.
AU - Butler, Matthew
AU - Hussain, Zain
AU - Carter, Ben
AU - Rooney, Alasdair G.
AU - Zandi, Michael S.
AU - Lewis, Glyn
AU - David, Anthony S.
AU - Houlihan, Catherine F.
AU - Easton, Ava
AU - Michael, Benedict D.
AU - Kuppalli, Krutika
AU - Nicholson, Timothy R.
AU - Pollak, Thomas A.
AU - Rogers, Jonathan P.
N1 - Funding Information:
MSZ, GL, ASD and CFH were supported by the NIHR University College London Hospitals Biomedical Research Centre. BDM is supported by the UKRI/MRC (MR/V03605X/1), the MRC-CSF (MR/V007181/1), the MRC/AMED (MR/T028750/1) and the Wellcome Trust (102186/B/13/Z). TP is supported by an NIHR Clinical Lectureship. JPR is supported by the Wellcome Trust (102186/B/13/Z).
Funding Information:
All authors have completed ICMJE uniform disclosure forms and declare; GL is supported by the UCLH BRC, is funded by NIHR, and is TSC chair for NIHR study and Wellcome Clinical PhD funding for JPR. CW receives support from the Royal College of Psychiatrists Pathfinder Fellowship and the Association of British Neurologists' Bursary. AE is a recipient of various grants for The Encephalitis Society which she is chief executive of, she has received payment for speaking and presentations from Pfizer, UCB, Bavarian Nordics, Valneva, CSL Behring and Biomerieux. MZ was supported to attend the European Academy of Neurology 2022 Encephalitis Workshop and Eisai Dec 2019 one lecture honoraria. ZH was supported to attend meetings by the Royal College of Psychiatrists Foundation Fellowship. BDM is supported by the UKRI/MRC (MR/V03605X/1), the MRCCSF (MR/V007181/1), the MRC/AMED (MR/T028750/1) and the Wellcome Trust (102186/B/13/Z).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/10
Y1 - 2022/10
N2 - Background: Neuropsychiatric presentations of monkeypox (MPX) infection have not been well characterised, despite evidence of nervous system involvement associated with the related smallpox infection. Methods: In this pre-registered (PROSPERO ID 336649) systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, AMED and the preprint server MedRxiv up to 31/05/2022. Any study design of humans infected with MPX that reported a neurological or psychiatric presentation was included. For eligible symptoms, we calculated a pooled prevalence using an inverse variance approach and corresponding 95% confidence intervals. The degree of variability that could be explained by between-study heterogeneity was assessed using the I2 statistic. Risk of bias was assessed with the Newcastle Ottawa Scale and the Joanna Briggs Institute quality assessment tool. Findings: From 1705 unique studies, we extracted data on 19 eligible studies (1512 participants, 1031 with confirmed infection using CDC criteria or PCR testing) most of which were cohort studies and case series with no control groups. Study quality was generally moderate. Three clinical features were eligible for meta-analysis: seizure 2.7% (95% CI 0.7–10.2%, I2 0%), confusion 2.4% (95% CI 1.1–5.2%, I2 0%) and encephalitis 2.0% (95% 0.5–8.2%, I2 55.8%). Other frequently reported symptoms included myalgia, headache and fatigue, where heterogeneity was too high for estimation of pooled prevalences, possibly as a result of differences in viral clades and study methodology. Interpretation: There is preliminary evidence for a range of neuropsychiatric presentations including severe neurological complications (encephalitis and seizure) and nonspecific neurological features (confusion, headache and myalgia). There is less evidence regarding the psychiatric presentations or sequelae of MPX. This 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. More evidence is necessary to explain heterogeneity in prevalence estimates. Funding: UKRI/MRC (MR/V03605X/1), MRC-CSF (MR/V007181/1), MRC/AMED (MR/T028750/1) and the Wellcome Trust (102186/B/13/Z) and (102186/B/13/Z) and UCLH BRC.
AB - Background: Neuropsychiatric presentations of monkeypox (MPX) infection have not been well characterised, despite evidence of nervous system involvement associated with the related smallpox infection. Methods: In this pre-registered (PROSPERO ID 336649) systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, AMED and the preprint server MedRxiv up to 31/05/2022. Any study design of humans infected with MPX that reported a neurological or psychiatric presentation was included. For eligible symptoms, we calculated a pooled prevalence using an inverse variance approach and corresponding 95% confidence intervals. The degree of variability that could be explained by between-study heterogeneity was assessed using the I2 statistic. Risk of bias was assessed with the Newcastle Ottawa Scale and the Joanna Briggs Institute quality assessment tool. Findings: From 1705 unique studies, we extracted data on 19 eligible studies (1512 participants, 1031 with confirmed infection using CDC criteria or PCR testing) most of which were cohort studies and case series with no control groups. Study quality was generally moderate. Three clinical features were eligible for meta-analysis: seizure 2.7% (95% CI 0.7–10.2%, I2 0%), confusion 2.4% (95% CI 1.1–5.2%, I2 0%) and encephalitis 2.0% (95% 0.5–8.2%, I2 55.8%). Other frequently reported symptoms included myalgia, headache and fatigue, where heterogeneity was too high for estimation of pooled prevalences, possibly as a result of differences in viral clades and study methodology. Interpretation: There is preliminary evidence for a range of neuropsychiatric presentations including severe neurological complications (encephalitis and seizure) and nonspecific neurological features (confusion, headache and myalgia). There is less evidence regarding the psychiatric presentations or sequelae of MPX. This 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. More evidence is necessary to explain heterogeneity in prevalence estimates. Funding: UKRI/MRC (MR/V03605X/1), MRC-CSF (MR/V007181/1), MRC/AMED (MR/T028750/1) and the Wellcome Trust (102186/B/13/Z) and (102186/B/13/Z) and UCLH BRC.
KW - Encephalitis
KW - Monkeypox
KW - Neurology
KW - Neuropsychiatry
KW - Psychiatry
KW - Seizure
UR - http://www.scopus.com/inward/record.url?scp=85139182373&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2022.101644
DO - 10.1016/j.eclinm.2022.101644
M3 - Article
AN - SCOPUS:85139182373
SN - 2589-5370
VL - 52
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 101644
ER -
