Monkeypox in Populations Presenting with Neurologic Syndromes Require Diagnosis


Included in the literature review were the known neurologic complications of smallpox, including encephalitis, transverse myelitis, and acute disseminated encephalomyelitis.

A recent review of smallpox and monkeypox manifestations suggests that clinicians should consider the possibility of monkeypox infection among high-risk populations presenting with neurologic syndromes. The study, published in JAMA Neurology, found serology and polymerase chain reaction testing of blood and spinal fluid may be needed for diagnosis.1

Monkeypox is a rare disease caused by infection with Monkeypox virus. The Monkeypox virus belongs to the Orthopoxvirus genus in the family Poxviridae. This genus also includes the variola virus (which causes smallpox), the vaccinia virus (used in the smallpox vaccine), and the cowpox virus, according to the CDC.2

The study noted that manifestations are frequently unrecognized because they are hidden by the acute systemic involvement by the infection and then later attributable to end-organ damage or pandemic-related psychosocial stresses. Because of this, the researchers reviewed the literature on orthopox viruses, including smallpox and monkeypox, focusing on neurologic complications.

The review aimed to address the neurologic consequences of both smallpox and monkeypox, because complications of smallpox may be relevant to monkeypox, although complications of monkeypox may be rarer and less severe.1

Back in September 2019, the FDA approved the first smallpox and monkeypox vaccine, live, nonreplicating (Jynneos, Bavarian Nordic) for the prevention of the 2 viruses. The effectiveness of the smallpox and monkeypox vaccine was inferred from the antibody responses in the clinical study of participants for smallpox, as well as from studies in nonhuman primates. The most reported adverse effects were pain, redness, swelling, itching, firmness at the injection site, muscle pain, headache, and fatigue.3

Included in the literature review were the known neurologic complications of smallpox, including encephalitis, transverse myelitis, and acute disseminated encephalomyelitis. Historical complications of smallpox vaccination include postvaccinal encephalomyelitis. The known neurologic complications of monkeypox are headaches and mood disturbances, in addition to encephalitis, transverse myelitis, and seizures.1

A major concern found in the review is the possibility of viral persistence and systemic complications in immunocompromised individuals. Additionally, it provided considerations for diagnosis, current treatment, and prevention of monkeypox.1

“Supportive and symptomatic care, which may be the only resources available for patients in resource-limited settings, play an important role in the management of monkeypox,” the study authors wrote. “Pain management is key and requires topical agents, oral medications, or nerve blocks. Painful lesions may respond to antiviral treatments; hence, access to them is crucial. In patients who are immunocompromised or have atypical presentations, the possibility of viral infection of the central nervous system should be considered.”1

The review highlighted that antiviral therapy should be initiated early in the course of the illness.1

“At more than 40 000 cases worldwide and spreading, neurologic complications are to be expected. Preventive measures including third-generation vaccinia vaccines are available but in short supply,” the study authors wrote. “Although they are safer than previous vaccines, health care providers should be vigilant for possible neurologic adverse reactions, as these vaccines are reaching a wide population.”1


  • Billioux BJ, Mbaya OT, Sejvar J, Nath A. Neurologic Complications of Smallpox and Monkeypox: A Review. JAMA Neurol. Published online September 20, 2022. doi:10.1001/jamaneurol.2022.3491
  • Murphy, Jill. Molecular Diagnostic Test Could Allow for Rapid Response to Monkeypox. Pharmacy Times. June 16, 2022. Accessed September 23, 2022.
  • Antrim, Aislinn. FDA Approves First Live, Nonreplicating Vaccine for Smallpox, Monkeypox. Pharmacy Times. September 24, 2019. Accessed September 23, 2022.
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