Neurological and psychiatric presentations associated with human monkeypox virus infection: A systematic review and meta-analysis

James B Badenoch; Isabella Conti; Emma R Rengasamy; Cameron J Watson; Matthew Butler; Zain Hussain; Ben Carter; Alasdair G Rooney; Michael S Zandi; Glyn Lewis; Anthony S David; Catherine F Houlihan; Ava Easton; Benedict D Michael; Krutika Kuppalli; Timothy R Nicholson; Thomas A Pollak; Jonathan P Rogers

doi:10.1016/j.eclinm.2022.101644

Neurological and psychiatric presentations associated with human monkeypox virus infection: A systematic review and meta-analysis

EClinicalMedicine. 2022 Oct:52:101644. doi: 10.1016/j.eclinm.2022.101644. Epub 2022 Sep 8.

Authors

James B Badenoch^{1

2}, Isabella Conti³, Emma R Rengasamy⁴, Cameron J Watson^{2

5

6}, Matthew Butler⁷, Zain Hussain⁸, Ben Carter⁹, Alasdair G Rooney¹⁰, Michael S Zandi¹¹, Glyn Lewis¹², Anthony S David¹³, Catherine F Houlihan^{14

15}, Ava Easton^{16

17}, Benedict D Michael^{17

18

19}, Krutika Kuppalli²⁰, Timothy R Nicholson⁷, Thomas A Pollak²¹, Jonathan P Rogers^{6

12}

Affiliations

¹ Barts Health NHS Trust, Charterhouse Square, London EC1M 6BQ, UK.
² Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of Medicine, London EC1M 6BQ, UK.
³ Guy's and St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
⁴ Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
⁵ Institute of Psychiatry, Psychology and Neuroscience, King's College London, WC2R 2LS, UK.
⁶ South London and Maudsley NHS Foundation Trust, London BR3 3BX, UK.
⁷ Neuropsychiatry Research and Education Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, WC2R 2LS, UK.
⁸ Edinburgh Medical School, University of Edinburgh, Edinburgh EH16 4SB, UK.
⁹ Department of Biostatistics and Health Informatics, King's College London, London WC2R 2LS, UK.
¹⁰ Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh EH16 4SB, UK.
¹¹ UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
¹² Division of Psychiatry, University College London, London, UK.
¹³ UCL Institute of Mental Health, Maple House, 149 Tottenham Court Road, London W1T 7NF, UK.
¹⁴ UCL Department of Infection and Immunity, University College London Hospital, London NW1 2BU, UK.
¹⁵ Rare and Imported Pathogens Laboratory (RIPL), UKHSA, Porton Down SP4 0JG, UK.
¹⁶ Encephalitis Society, 32 Castlegate, Malton YO17 7DT, UK.
¹⁷ Clinical Infection Microbiology and Immunology, Institute of Infection, Veterinary, and Zoological Science, University of Liverpool, L69 3BX, UK.
¹⁸ Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool L9 7LJ, UK.
¹⁹ National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infection, University of Liverpool, L69 3BX, UK.
²⁰ Emerging Diseases and Zoonoses Unit, Department of Epidemic and Pandemic Preparedness and Prevention, Health Emergencies Programme, World Health Organisation, Geneva, Switzerland.
²¹ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London SE5 4AF, UK.

Abstract

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 I ² 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.

Keywords: Encephalitis; MPX, monkeypox; Monkeypox; Neurology; Neuropsychiatry; Psychiatry; Seizure.

Abstract

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