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Headaches, Mood Disturbances Among Neurologic Complications Linked With Monkeypox


Rare presentations of encephalitis and transverse myelitis are among neurologic consequences linked with orthopoxviruses of smallpox and monkeypox.

Amid the recent global public health emergency of monkeypox, a review published Tuesday in JAMA Neurology sought to explore the neurologic consequences of the disease and how these symptoms compare with smallpox, another, more severe, orthopox virus.

Associated with major socioeconomic effects and general public fear, researchers noted that long-term neurologic symptoms are historically common during pandemics.

“Yet often these manifestations go unrecognized, initially masked by the acute systemic involvement by the infection and later attributed to end-organ damage or to pandemic-related psychosocial stresses,” they said.

Until its eradication in 1980, smallpox was a highly feared, disfiguring disease. A variety of common (eg, headaches and backaches) and more rare neurologic complications (eg, encephalitis, transverse myelitis, acute disseminated encephalomyelitis) were cited in the review regarding smallpox.

Neurological manifestations were also found with smallpox vaccination, which researchers said occured more commonly in adults and can present as a postvaccinal encephalomyelitis (PVEM).

“PVEM is characterized by multifocal inflammatory demyelinating lesions occurring 7 to 14 days after vaccination,” they explained.

Headaches also proved a common neurological symptom for monkeypox, with mood disturbance, including depression and anxiety, and neuropathic pain frequently cited as well. Rare presentations of encephalitis, transverse myelitis, and seizures were reported.

“The skin lesions themselves may cause painful sores and, depending on the site involved, can cause dysphagia, rectal pain with anal fissures, etc. It is not clear if some of the painmay be dermatomal—similar to that seen with varicella zoster—but the pain can be severe.”

As these painful lesions may respond to antiviral treatments, such therapies should be initiated early in the course of the disease, said researchers. Pain management is also key, including topical agents, oral medications, or nerve blocks. But for those in resource-limited settings, supportive and symptomatic care can play an important role.

In addition, researchers said that particular attention should be placed on patients with immunocompromised conditions, such as HIV/AIDS, as it may facilitate viral neuroinvasiness. An estimated 40% of individuals with monkeypox are coinfected with HIV in the current outbreak.

Regarding diagnosis, serology or polymerase chain reaction (PCR) testing of blood and spinal fluid through one’s local health department was touted until commercial testing becomes available.

“Monkeypox should be considered in high-risk populations who present with neurologic syndromes,” concluded researchers.

“Preventive measures including third-generation vaccinia vaccines are available but in short supply. 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.”


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

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