What is already known about this topic? Monkeypox virus (MPXV) typically causes a febrile illness with lymphadenopathy and a diffuse vesiculopustular rash; neurologic complications are rare. The current monkeypox outbreak differs clinically and epidemiologically from previous outbreaks, and little is known about potential associated neurologic complications.

What is added by this report? Two U.S. cases of encephalomyelitis associated with acute MPXV infection were identified during summer 2022. Whether the underlying pathophysiology resulted from direct viral neuroinvasion or a parainfectious autoimmune process is currently unknown.

What are the implications for public health practice? Suspected cases of neurologic complications of monkeypox should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of MPXV infections during the current outbreak and treatment options.

Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak.

Details of two cases of encephalomyelitis associated with monkeypox in previously healthy young gay men in Colorado and DC are presented in this report. The University of Colorado and Georgetown University determined that this report was not subject to human subjects review because it includes only information obtained for purposes of patient clinical care and public health outbreak response. This activity was also reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.

Suggested citation for this article: 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. ePub: 13 September 2022.

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