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Infectious Diseases

Neurologic Complications of Smallpox and MonkeypoxA Review

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JAMA Neurology

Published Online: September 20, 2022

Review

Article Information and Disclosures

B. Jeanne Billioux, MD¹;

Oliver Tshiani Mbaya, MD²;

James Sejvar, MD³;

Avindra Nath, MD¹

Author Affiliations

¹National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
²Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo
³Centers for Disease Control and Prevention, Atlanta, Georgia

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Abstract

Importance Orthopox viruses include smallpox virus, a once feared but now eradicated virus, as well as monkeypox virus. Monkeypox is an emerging virus initially isolated in 1958, previously unrecognized outside sub-Saharan Africa until a worldwide outbreak in May 2022. It is important to review known neurologic consequences of both these viruses, as complications of smallpox may be relevant to monkeypox, though complications of monkeypox may be rarer and perhaps less severe.

Observations This was a literature review of the known neurologic complications of smallpox, which include encephalitis, transverse myelitis, and acute disseminated encephalomyelitis among others; historical complications of smallpox vaccination, including postvaccinal encephalomyelitis; and the known neurologic complications of monkeypox, which include headaches and mood disturbances, as well as rare presentations of encephalitis, transverse myelitis, and seizures. Of concern is the possibility of viral persistence and systemic complications in immunocompromised individuals. Also provided were considerations for diagnosis, current treatment, and prevention of monkeypox.

Conclusions and Relevance Monkeypox should be considered in high-risk populations who present with neurologic syndromes. Diagnosis may require serology and polymerase chain reaction testing of blood and spinal fluid. Antiviral therapy should be initiated early in the course of the illness.

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Article Information

Accepted for Publication: August 25, 2022.

Published Online: September 20, 2022. doi:10.1001/jamaneurol.2022.3491

Corresponding Author: Avindra Nath, MD, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Dr, Bldg 10, Room 7C-103, Bethesda, MD 20892 (natha@ninds.nih.gov).

Author Contributions: Dr Nath had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Billioux, Mbaya, Nath.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Billioux, Mbaya, Nath.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: All authors.

Supervision: Sejvar.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported in part by the National Institutes of Health (Drs Billioux, Mbaya, and Nath) and the Center for Disease Control and Prevention (Dr Sejvar).

Role of the Funder/Sponsor: These organizations have approved the manuscript for publication. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation or review of the manuscript; and decision to submit the manuscript for publication. The funding sources approved the manuscript for publication.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

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