Encephalomyelitis Present in Acute Monkeypox Virus Cases in the US

Two cases of encephalomyelitis linked to monkeypox has been identified in previously healthy young gay men in the US.

During the summer of 2022, 2 cases of encephalomyelitis were associated with acute monkeypox virus (MPVX) infection in the United States — in Colorado and the District of Columbia — according to a report published in the Morbidity and Mortality Weekly Report (MMWR).

MPVX typically causes a febrile illness with lymphadenopathy and a diffuse vesiculopustular rash; neurologic complications associated with the virus are rare. The current MPVX outbreak differs both clinically and epidemiologically from prior outbreaks, with little known about any potential neurologic adverse events. It remains unknown whether the underlying pathophysiology of the current MPVX outbreak is the result of direct viral neuroinvasion or a parainfectious autoimmune disease process.

MPVX is an orthopoxvirus in the Poxviridae family. The current multinational MPVX outbreak has now spread to 96 countries that have not historically reported cases of monkeypox, with most of the cases occurring among gay, bisexual, and other men who have sex with men. The first case of monkeypox reported in the United States was in May 2022 in Massachusetts. MPVX has now been reported in all 50 US states, in the District of Columbia, and in 1 US territory.

The current report describes 2 cases of encephalomyelitis among patients with monkeypox that were reported during the latest outbreak.

The first case — Patient A — occurred in a previously healthy, presumably immunocompetent gay man in his 30s in Colorado. The individual acutely developed fever, chills, and malaise in July 2022. At 3 days after the onset of symptoms, an itchy vesiculopustular rash appeared on his face, then spread to his extremities and scrotum over the next few days. At 9 days after symptom onset, Patient A developed progressive left upper and lower extremity weakness and numbness, urinary retention, and intermittent priapism, and was hospitalized. Magnetic resonance imaging (MRI) of the brain and spine revealed lesions in a number of sites.

Patients A and B had confirmed systemic MPXV infections with encephalomyelitis appearing within 5 and 9 days, respectively, of illness onset.

After 2 weeks of hospitalization, plasma exchange (PLEX) was initiated because of persistent leg weakness, which began to improve. He was discharged to outpatient rehabilitation therapy, and at the 1-month follow-up, he could walk with an assistive device.

The second case of MPVX-linked encephalomyelitis was reported in a previously healthy, presumably immunocompetent gay man in his 30s in Washington, DC — Patient B. In July 2022, he acutely developed fever and myalgia, followed by an eruption of a diffuse vesiculopustular rash on his face, extremities, trunk, and perianal region. At

5 days after onset of symptoms, he developed bowel and bladder incontinence, along with progressive flaccid weakness of both lower extremities, and was hospitalized. Following hospitalization, his condition progressed to altered mental status and obtundation over the next 2 days.

Pulsed IV methylprednisolone was administered, with no immediate clinical improvement in weakness but mild improvement in cognition. Following a course of PLEX, Patient B began to improve substantially. He received 5 sessions of PLEX, exhibited cognitive improvement, and had improvement in his lower extremities. Patient B was later discharged to acute inpatient rehabilitation and could walk with an assistive device.

The researchers noted that “Patients A and B had confirmed systemic MPXV infections with encephalomyelitis appearing within 5 and 9 days, respectively, of illness onset.” Although the underlying pathology behind this remains to be elucidated, it might represent either MPVX invasion of the central nervous system (CNS) or a parainfectious autoimmune process triggered by systemic MPVX infection. Both of the patients had some clinical and radiographic features of acute disseminated encephalomyelitis (ADEM) — which is typically a monophasic parainfectious autoimmune demyelinating disease of the CNS that affects primarily children but can also occur in adults.

Neither patient was found to have MPVX nucleic acid in the CSF, which would have proven MPVX neuroinvasion. Absence of detectable nucleic acid in the CSF, however, is not uncommon among CNS viral infections. Since the pathologic mechanism for encephalomyelitis in these 2 cases is unknown, the best diagnostic workup and treatment course for similar cases remain unclear.

“Clinicians and public health professionals should be aware of the range of possible clinical presentations of MPVX infections and potential treatments,” the researchers concluded.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Pastula DM, Copeland MJ, Hannan MC, et al. Two cases of monkeypox-associated encephalomyelitis — Colorado and the District of Columbia, July–August 2022. MMWR Morb Mortal Wkly Rep. Published online September 13, 2022. doi:10.15585/mmwr.mm7138e1