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Brain inflammation and spinal cord lesions associated with monkeypox were identified in two men in the U.S., according to a report published by the CDC.

In two previously healthy young gay men with confirmed systemic monkeypox virus infections, encephalomyelitis appeared within days of illness onset, reported Daniel Pastula, MD, MHS, of the University of Colorado School of Medicine in Aurora, and co-authors in

The underlying pathology was unclear but could represent either monkeypox invasion of the central nervous system or a para-infectious autoimmune process triggered by systemic monkeypox infection, the researchers wrote.

"Neurologists should be on the alert for potential neurological complications of monkeypox virus," co-author Kenneth Tyler, MD, also of the University of Colorado, told 番茄社区app.

"To date, the reported cases seem to likely represent para- or post-infectious complications rather than direct viral invasion of the central nervous system," Tyler said.

The clinical features of the two men resembled those seen in transverse myelitis or acute disseminated encephalomyelitis , he added. Lab features included lymphocytic pleocytosis in cerebrospinal fluid (CSF) and multifocal central nervous system and spinal FLAIR and T2 hyperintense lesions. Some lesions were partially enhancing.

One case was in Colorado; the other was in Washington, D.C. Both were treated with antiviral as well as immunosuppressive therapies "given concerns that this might have triggered an autoimmune reaction, similar to what you might see in ADEM," Pastula said in an interview with 番茄社区app.

Neither patient had been vaccinated against monkeypox. The Colorado man had been vaccinated against smallpox, but the smallpox vaccine status of the D.C. patient was uncertain. Neither man had known monkeypox exposure or international travel.

Nine days after the Colorado monkeypox patient developed an itchy rash and fever, he experienced numbness and weakness in his extremities, urinary retention, and intermittent priapism and was hospitalized. He had a past syphilis infection. No monkeypox virus was detected in his CSF.

The Colorado man was treated with oral tecovirimat (Tpoxx) immediately after neurologic symptoms began. Though tecovirimat is recommended as antiviral therapy for monkeypox, its degree of central nervous system penetration is unknown.

Pulsed intravenous (IV) methylprednisolone, IV immunoglobulin (IVIG), and IV penicillin (for empiric syphilis treatment) were added to his regimen. Over several days, he experienced partial improvement in numbness and weakness. His skin lesions resolved in 3 weeks. After a month, he still needed assistance walking.

The D.C. monkeypox patient developed bladder and bowel incontinence and progressive weakness in both legs 5 days after monkeypox symptoms started, and he was hospitalized. His condition worsened and he developed altered mental status. He was intubated and transferred to the intensive care unit. His CT scans showed rectal thickening with pelvic lymphadenopathy consistent with proctitis.

This patient also was treated with tecovirimat and had no monkeypox virus in CSF. Pulsed IV methylprednisolone was given with no immediate clinical improvement in weakness, but mild improvement in cognition. IVIG was started but discontinued; a course of plasma exchange was then initiated and he improved.

After five plasma exchange sessions, the D.C. man was extubated and was speaking and following commands. After 5 weeks, his proctitis resolved and skin lesions healed. He was given IV rituximab as maintenance medication and discharged to acute inpatient rehabilitation, walking with an assistive device.

"Time will tell if these men get back to 100%," Pastula said. "But they are better than they were."

Encephalomyelitis is a rare effect of viruses like monkeypox but not unheard of, he added. In a review of monkeypox and similar diseases he and Tyler published last month, "we actually found evidence of smallpox infections being described with similar things from centuries ago," Pastula noted.

"We cite a paper from the 1790s in Britain describing someone with 'pox' who developed some 'paralysis,'" he said. "It's hard to prove, but it seems like a related virus has caused this before."

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