Mpox-Associated Neurological Disease

By Hai H. Hoang, MD

Assistant Professor of Clinical Neurology, Weill Cornell Medical College

SYNOPSIS: Neurological consequences of mpox (monkeypox) are rare and have not been attributed to direct viral invasion of the central nervous system.

SOURCE: Money KM, Barnett TA, Rapaka S, et al. Monkeypox-associated central nervous system disease: A case series and review. Ann Neurol 2023;93:893-905.

Mpox (monkeypox) virus (MPXV) is in the Pox viridae family of viruses, which also includes smallpox (variola virus), vaccina, and molluscum contagiosum viruses. Until recently, it largely has remained limited to central and western Africa, with most cases occurring from direct contact with infected animals or limited spread to household contacts via human-to-human transmission. However, on July 23, 2022, the World Health Organization declared MPXV a global public health emergency as the result of an unprecedented global outbreak. Most cases were occurring among men who have sex with men. Central nervous system (CNS) disease rarely has been reported as a complication of MPXV infection, and cases were largely limited to children and individuals with severe immunocompromise. However, CNS disease now has been observed in young adults during the current MPXV outbreak. The study authors now report three cases diagnosed in the United States, with comprehensive diagnostic evaluation, treatment, and follow-up.

Patient 1 was a previously healthy man who developed the classic MPXV dermatologic manifestations and then subsequently presented with left-sided weakness. Brain magnetic resonance imaging (MRI) showed right frontal lobe edema, T2 hyperintense lesions in the left frontal lobe, bilateral medial thalami basal ganglia, splenium, and pons. He had severe cervical spinal stenosis and an enhancing thoracic spinal cord lesion. He was treated with oral tecovirimat, which is used for human smallpox disease, for 14 days. There were concerns for acute demyelinating encephalomyelitis (ADEM), so he was given intravenous immunoglobulin (IVIG) and steroids. He clinically improved, as did his one-month follow-up imaging.

Patient 2 was a previously healthy man who developed the classic MPXV rash and then subsequently presented with acute onset of progressive bilateral lower extremity weakness and incontinence, which progressed and resulted in impaired cognitive function. Brain MRI showed non-enhancing T2 fluid-attenuated inversion recovery (FLAIR) lesions in the cerebellum, pons, and medulla, with enhancing lesions in the dorsal columns of the cervicothoracic spine. He was started on tecovirimat for 14 days. He also was given IV steroids because of concern for spinal cord edema. Repeat imaging showed diffusion-weighted hyperintensity in a prior area of T2 hyperintensity concerning for an autoimmune process. He was able to tolerate IVIG for only three of five scheduled doses and then was treated with plasma exchange for five sessions. He clinically improved, but at one-month follow-up, he continued to have impaired gait.

Patient 3 was a previously healthy man who presented with progressive encephalopathy over four days, with fever and flu-like symptoms. He had a seizure and was treated with antimicrobials and steroids for potential meningitis. His only dermatologic manifestation was small eschars on his shin that were not tested for MPXV. Brain MRI showed focal areas of restricted diffusion in the thalami and bilateral globus pallidi. He was given tecovirimat for 14 days and completed IV acyclovir for possible herpes zoster infection, although that never was confirmed. He never had MPXV confirmation, but his sexual partner was diagnosed with MPXV during the time of his hospitalization. At his one-month follow-up, he had returned to normal.

COMMENTARY

In all three cases of MPXV infection, the presence of virus in the cerebrospinal fluid never was confirmed. The neurologic manifestations and imaging strongly suggest a parainfectious process rather than direct viral invasion in the CNS. The imaging characteristics seem to be nonspecific, but the pattern in the brain and spine can be seen in ADEM, which commonly is thought to be a post-viral complication. Fortunately, all three cases improved, and at one-month follow-up, only one patient still had residual morbidity. The frequency of neurologic complication in patients with MPXV infections seems to be rare. Data have shown that the best method for preventing severe neurologic complications is preemptive MPXV vaccination.