{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:35:47Z","timestamp":1791894947193,"version":"4.3.4"},"reference-count":54,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:sec id=\"ab-nrv220006-1\"><jats:title>Importance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-nrv220006-2\"><jats:title>Observations<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-nrv220006-3\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2022.3491","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T15:02:24Z","timestamp":1663686144000},"page":"1180","source":"Crossref","is-referenced-by-count":72,"title":["Neurologic Complications of Smallpox and Monkeypox"],"prefix":"10.1001","volume":"79","author":[{"given":"B. Jeanne","family":"Billioux","sequence":"first","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver Tshiani","family":"Mbaya","sequence":"additional","affiliation":[{"name":"Institut National de Recherche Biom\u00e9dicale, Kinshasa, Democratic Republic of Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Sejvar","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avindra","family":"Nath","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"4","key":"nrv220006r2","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/j.wem.2021.08.003","article-title":"The disease ecology, epidemiology, clinical manifestations, management, prevention, and control of increasing human infections with animal orthopoxviruses.","volume":"32","author":"Diaz","year":"2021","journal-title":"Wilderness Environ Med"},{"key":"nrv220006r3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(ISSN)1555-2039","article-title":"Note on an eruption resembling that of variola in the skin of a mummy of the twentieth dynasty (1200-1100 BC).","volume":"15","author":"Ruffer","year":"1911","journal-title":"J Pathol Bacteriol"},{"issue":"4","key":"nrv220006r4","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.PoH-0004-2014","article-title":"History of smallpox and its spread in human populations.","volume":"4","author":"Th\u00e8ves","year":"2016","journal-title":"Microbiol Spectr"},{"issue":"2","key":"nrv220006r5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/0196-6553(82)90003-7","article-title":"The global eradication of smallpox.","volume":"10","author":"Strassburg","year":"1982","journal-title":"Am J Infect Control"},{"issue":"9508","key":"nrv220006r6","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S0140-6736(06)68143-9","article-title":"Smallpox.","volume":"367","author":"Moore","year":"2006","journal-title":"Lancet"},{"key":"nrv220006r7","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.634827","article-title":"Neurologic manifestations of the World Health Organization\u2019s list of pandemic and epidemic diseases.","volume":"12","author":"McEntire","year":"2021","journal-title":"Front Neurol"},{"issue":"17","key":"nrv220006r8","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1056\/NEJMra020025","article-title":"Diagnosis and management of smallpox.","volume":"346","author":"Breman","year":"2002","journal-title":"N Engl J Med"},{"issue":"1","key":"nrv220006r9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jcpa.2012.06.007","article-title":"Comparative pathology of smallpox and monkeypox in man and macaques.","volume":"148","author":"Cann","year":"2013","journal-title":"J Comp Pathol"},{"issue":"2","key":"nrv220006r11","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1093\/brain\/55.2.181","article-title":"Acute perivascular myelinoclasis (\u201cacute disseminated encephalomyelitis\u201d) in smallpox.","volume":"55","author":"Marsden","year":"1932","journal-title":"Brain"},{"issue":"10271","key":"nrv220006r12","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/S0140-6736(20)32723-9","article-title":"Acute flaccid myelitis: cause, diagnosis, and management.","volume":"397","author":"Murphy","year":"2021","journal-title":"Lancet"},{"key":"nrv220006r13","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/1824-7288-40-57","article-title":"Acute cerebellitis in varicella: a 10-year case series and systematic review of the literature.","volume":"40","author":"Bozzola","year":"2014","journal-title":"Ital J Pediatr"},{"issue":"7","key":"nrv220006r14","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1001\/archneur.60.7.925","article-title":"Encephalitis complicating smallpox vaccination.","volume":"60","author":"Miravalle","year":"2003","journal-title":"Arch Neurol"},{"issue":"8","key":"nrv220006r15","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1212\/01.WNL.0000063319.64515.6B","article-title":"Smallpox and smallpox vaccination: neurological implications.","volume":"60","author":"Booss","year":"2003","journal-title":"Neurology"},{"key":"nrv220006r16","first-page":"241","article-title":"Smallpox and vaccinia: the pathologic histology.","volume":"10","author":"Lillie","year":"1930","journal-title":"Arch Pathol (Chic)"},{"issue":"21","key":"nrv220006r17","doi-asserted-by":"publisher","first-page":"2744","DOI":"10.1001\/jama.294.21.2744","article-title":"Neurologic adverse events associated with smallpox vaccination in the US, 2002-2004.","volume":"294","author":"Sejvar","year":"2005","journal-title":"JAMA"},{"key":"nrv220006r18","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/j.1699-0463.1959.tb00328.x","article-title":"A pox-like disease in cynomologous monkeys.","volume":"46","author":"Von Magnus","year":"1959","journal-title":"Acta Pathol Microbiol Scand"},{"key":"nrv220006r19","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1111\/j.1749-6632.1960.tb50015.x","article-title":"A pox disease of monkeys.","volume":"85","author":"Prier","year":"1960","journal-title":"Ann N Y Acad Sci"},{"key":"nrv220006r20","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3389\/fpubh.2018.00241","article-title":"Emergence of monkeypox as the most important orthopoxvirus infection in humans.","volume":"6","author":"Sklenovsk\u00e1","year":"2018","journal-title":"Front Public Health"},{"issue":"7","key":"nrv220006r21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066071","article-title":"Pathogen-host associations and predicted range shifts of human monkeypox in response to climate change in central Africa.","volume":"8","author":"Thomassen","year":"2013","journal-title":"PLoS One"},{"issue":"11","key":"nrv220006r22","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.3390\/v12111257","article-title":"Monkeypox virus in Nigeria: infection biology, epidemiology, and evolution.","volume":"12","author":"Alakunle","year":"2020","journal-title":"Viruses"},{"issue":"22","key":"nrv220006r23","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2022.27.22.2200421","article-title":"Epidemiological, clinical, and virological characteristics of 4 cases of monkeypox support transmission through sexual contact, Italy, May 2022.","volume":"27","author":"Antinori","year":"2022","journal-title":"Euro Surveill"},{"issue":"28","key":"nrv220006r24","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2022.27.28.2200503","article-title":"Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022.","volume":"27","author":"Peir\u00f3-Mestres","year":"2022","journal-title":"Euro Surveill"},{"issue":"3","key":"nrv220006r25","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.jaad.2006.05.061","article-title":"Monkeypox: an epidemiologic and clinical comparison of African and US disease.","volume":"55","author":"Sale","year":"2006","journal-title":"J Am Acad Dermatol"},{"issue":"8","key":"nrv220006r26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001769","article-title":"Urgent need for a nondiscriminatory and nonstigmatizing nomenclature for monkeypox virus.","volume":"20","author":"Happi","year":"2022","journal-title":"PLoS Biol"},{"issue":"8","key":"nrv220006r27","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1038\/s41591-022-01907-y","article-title":"Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus.","volume":"28","author":"Isidro","year":"2022","journal-title":"Nat Med"},{"issue":"27","key":"nrv220006r28","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2022.27.27.2200471","article-title":"Monkeypox outbreak predominantly affecting men who have sex with men, Madrid, Spain, 26 April to 16 June 2022.","volume":"27","author":"I\u00f1igo Mart\u00ednez","year":"2022","journal-title":"Euro Surveill"},{"issue":"9","key":"nrv220006r29","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1016\/S1473-3099(22)00411-X","article-title":"Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.","volume":"22","author":"Girometti","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"nrv220006r30","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1056\/NEJMoa2207323","article-title":"Monkeypox virus infection in humans across 16 countries\u2014April-June 2022.","volume":"387","author":"Thornhill","year":"2022","journal-title":"N Engl J Med"},{"issue":"1","key":"nrv220006r31","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2217\/17460913.2.1.17","article-title":"Human monkeypox: an emerging zoonotic disease.","volume":"2","author":"Parker","year":"2007","journal-title":"Future Microbiol"},{"issue":"2","key":"nrv220006r32","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1093\/infdis\/156.2.293","article-title":"Human monkeypox: clinical features of 282 patients.","volume":"156","author":"Jezek","year":"1987","journal-title":"J Infect Dis"},{"key":"nrv220006r33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2022.07.005","article-title":"Monkeypox outbreak in Madrid (Spain): clinical and virological aspects.","author":"Orviz","journal-title":"J Infect"},{"issue":"11","key":"nrv220006r34","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1093\/infdis\/jiab133","article-title":"Clinical and epidemiological findings from enhanced monkeypox surveillance in Tshuapa Province, Democratic Republic of the Congo during 2011-2015.","volume":"223","author":"Whitehouse","year":"2021","journal-title":"J Infect Dis"},{"issue":"8","key":"nrv220006r35","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/S1473-3099(19)30294-4","article-title":"Outbreak of human monkeypox in Nigeria in 2017-18: a clinical and epidemiological report.","volume":"19","author":"Yinka-Ogunleye","year":"2019","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"nrv220006r36","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1016\/S1473-3099(22)00228-6","article-title":"Clinical features and management of human monkeypox: a retrospective observational study in the UK.","volume":"22","author":"Adler","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"nrv220006r37","doi-asserted-by":"publisher","first-page":"e210","DOI":"10.1093\/cid\/ciaa143","article-title":"Clinical course and outcome of human monkeypox in Nigeria.","volume":"71","author":"Ogoina","year":"2020","journal-title":"Clin Infect Dis"},{"issue":"10","key":"nrv220006r38","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1086\/jid.2004.190.issue-10","article-title":"Human monkeypox infection: a family cluster in the midwestern US.","volume":"190","author":"Sejvar","year":"2004","journal-title":"J Infect Dis"},{"key":"nrv220006r41","doi-asserted-by":"publisher","DOI":"10.1002\/ana.v92.4","article-title":"An overview of monkeypox virus and its neuroinvasive potential.","author":"Pastula","journal-title":"Ann Neurol"},{"issue":"6","key":"nrv220006r43","doi-asserted-by":"publisher","first-page":"595","DOI":"10.2217\/17460794.3.6.595","article-title":"Therapeutic and prophylactic drugs to treat orthopoxvirus infections.","volume":"3","author":"Parker","year":"2008","journal-title":"Future Virol"},{"issue":"5","key":"nrv220006r44","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1128\/AAC.01303-07","article-title":"Single-dose safety and pharmacokinetics of ST-246, a novel orthopoxvirus egress inhibitor.","volume":"52","author":"Jordan","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"nrv220006r49","doi-asserted-by":"publisher","first-page":"e00927","DOI":"10.1128\/mSphere.00927-20","article-title":"Pharmacokinetics and efficacy of a potential smallpox therapeutic, brincidofovir, in a lethal monkeypox virus animal model.","volume":"6","author":"Hutson","year":"2021","journal-title":"mSphere"},{"issue":"1","key":"nrv220006r50","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/0042-6822(90)90271-R","article-title":"Selective inhibition of human cytomegalovirus DNA synthesis by (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG).","volume":"179","author":"Neyts","year":"1990","journal-title":"Virology"},{"issue":"2","key":"nrv220006r51","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1128\/AAC.33.2.185","article-title":"Efficacy of phosphonylmethoxyalkyl derivatives of adenine in experimental herpes simplex virus and vaccinia virus infections in vivo.","volume":"33","author":"De Clercq","year":"1989","journal-title":"Antimicrob Agents Chemother"},{"issue":"22","key":"nrv220006r54","doi-asserted-by":"publisher","first-page":"734","DOI":"10.15585\/mmwr.mm7122e1","article-title":"Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: recommendations of the advisory committee on immunization practices\u2014US, 2022.","volume":"71","author":"Rao","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"nrv220006r10","volume-title":"Smallpox","author":"Rao","year":"1972"},{"key":"nrv220006r53","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-981-15-2651-0_2","volume-title":"Animal-Origin Viral Zoonoses Livestock Diseases and Management","author":"Sklenovska","year":"2020"},{"key":"nrv220006r1","unstructured":"Centers for Disease Control and Prevention. 2022 Monkeypox outbreak global map. Accessed August 22, 2022. https:\/\/www.cdc.gov\/poxvirus\/monkeypox\/response\/2022\/world-map.html"},{"key":"nrv220006r39","unstructured":"Faus? J. Spain reports second monkeypox-related death in Europe. Accessed July 30, 2022. https:\/\/www.reuters.com\/world\/europe\/spain-confirms-first-monkeypox-related-death-country-reports-2022-07-29\/"},{"key":"nrv220006r40","unstructured":"The Daily Star. Kerala reports India\u2019s first monkeypox-related death. Accessed August 5, 2022. https:\/\/www.thedailystar.net\/health\/disease\/news\/kerala-reports-indias-first-monkeypox-related-death-3084831"},{"key":"nrv220006r42","unstructured":"World Health Organization. Clinical management and infection prevention and control for monkeypox: Interim rapid response guidance, 10 June 2022. Accessed August 22, 2022. https:\/\/www.who.int\/publications\/i\/item\/WHO-MPX-Clinical-and-IPC-2022.1"},{"key":"nrv220006r45","unstructured":"SIGA Technologies, Inc. FDA advisory committee briefing document: tecovirimat for the treatment of smallpox disease. Accessed June 30, 2022. https:\/\/www.fda.gov\/media\/112808\/download"},{"key":"nrv220006r46","unstructured":"US Food and Drug Administration. Highlights of TPOXX prescribing information. Accessed June 30, 2022. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/208627s000lbl.pdf"},{"key":"nrv220006r47","unstructured":"Centers for Disease Control and Prevention. Monkeypox signs and symptoms. Accessed July 5, 2022. https:\/\/www.cdc.gov\/poxvirus\/monkeypox\/index.html"},{"key":"nrv220006r48","unstructured":"US Food and Drug Administration. FDA approves drug to treat smallpox. Accessed June 30, 2022. https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-drug-treat-smallpox"},{"key":"nrv220006r52","doi-asserted-by":"crossref","unstructured":"Akazawa? D, Ohashi? H, Hishiki? T, . Potential antimonkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments.? bioRxiv. Published online August 2, 2022. https:\/\/www.biorxiv.org\/content\/10.1101\/2022.08.02.502485v1","DOI":"10.1101\/2022.08.02.502485"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2796513\/jamaneurology_billioux_2022_rv_220006_1667929353.09349.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T16:10:00Z","timestamp":1668442200000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2796513"}},"subtitle":["A Review"],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":54,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2022.3491","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11,1]]}}}