Journal Article Annotations
2022, 4th Quarter

Infectious Diseases

Annotations by Aum Pathare, MD
January, 2023

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

PUBLICATION #1 — Infectious Diseases

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

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

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.

Annotation

The finding:
This study finds that about 2-3% of patients infected with monkeypox manifest severe neuropsychiatric complications including seizures, confusion, and encephalitis. At least half of the infected patients were noted to have less severe symptoms such as myalgia, fatigue, headache, anxiety and depression, although it is unclear if these represent a systemic response to viral illness verses direct neurological changes due to infection.

Strength and weaknesses:
Dermatological manifestations of monkeypox infection have been studied more than the potential neuropsychiatric sequelae of this entity. This systematic review and metanalysis provides a preliminary understanding of the latter and uncovers the current gaps in its understanding. Limitations include the medium to low quality cohort and cross-sectional studies included in the analysis, which had small sample sizes and considerable methodological heterogeneity.

Relevance:
Monkeypox is a systemic viral zoonotic illness with prominent and well characterized cutaneous manifestations. At this time, we have limited evidence for direct neuropsychiatric problems arising from the infection outside of seizures, possible delirium, and encephalitis. However, viral illnesses also carry a psychological burden, which has only been amplified over the course of the COVID-19 pandemic. Potentially disfiguring scarring, misinformation about communicability, stigma associated with the focus on sexual transmission of illness, and harmful emphasis on the LGBTQ+ community are other factors of concern with monkeypox. C-L psychiatrists are positioned to be at the forefront of care for these patients, and their observations may help guide further understanding and research about the psychiatric sequelae of this disease. C-L involvement in relieving distress associated with such infections may also be important in developing outreach for at risk populations.