Neurologic Complications of Smallpox and Monkeypox

Abstract

ImportanceOrthopox viruses include smallpox virus, a once feared but now eradicated virus, as well as monkeypox virus. Monkeypox is an emerging virus initially isolated in 1958, previously unrecognized outside sub-Saharan Africa until a worldwide outbreak in May 2022. It is important to review known neurologic consequences of both these viruses, as complications of smallpox may be relevant to monkeypox, though complications of monkeypox may be rarer and perhaps less severe.ObservationsThis was a literature review of the known neurologic complications of smallpox, which include encephalitis, transverse myelitis, and acute disseminated encephalomyelitis among others; historical complications of smallpox vaccination, including postvaccinal encephalomyelitis; and the known neurologic complications of monkeypox, which include headaches and mood disturbances, as well as rare presentations of encephalitis, transverse myelitis, and seizures. Of concern is the possibility of viral persistence and systemic complications in immunocompromised individuals. Also provided were considerations for diagnosis, current treatment, and prevention of monkeypox.Conclusions and RelevanceMonkeypox should be considered in high-risk populations who present with neurologic syndromes. Diagnosis may require serology and polymerase chain reaction testing of blood and spinal fluid. Antiviral therapy should be initiated early in the course of the illness.

Monkeypox encephalitis with transverse myelitis in a female patient

“… 12 Altered mental state (eg, confusion and central nervous deficits) was a recognised feature of smallpox with encephalomyelitis documented after both variola virus (ie, smallpox) and vaccinia virus (ie, post-smallpox vaccination). 9 , 10 , 13 , 14 , 15 Histological findings in people who have died of smallpox and had neurological complications showed acute perivenular demyelination. 14 Encephalitis from smallpox occurred in approximately 1 in 500 patients with variola major and 1 in 2000 patients with variola minor presenting at 6–10 days of illness.…”

“… 14 Encephalitis from smallpox occurred in approximately 1 in 500 patients with variola major and 1 in 2000 patients with variola minor presenting at 6–10 days of illness. 9 , 14 …”

“…Neurological complications have previously been documented in relation to many viral infections of epidemic potential, including SARS-CoV-2, 7 MERS-CoV, Zika virus, 8 Ebola virus, smallpox, and monkeypox. 9 Encephalopathy, seizures, stroke, and Guillain-Barré syndrome are all recognised as substantial but rare complications which increase both morbidity and mortality. 9 Three documented cases of encephalitis during the 2022 monkeypox outbreak have been fatal.…”

“… 9 Encephalopathy, seizures, stroke, and Guillain-Barré syndrome are all recognised as substantial but rare complications which increase both morbidity and mortality. 9 Three documented cases of encephalitis during the 2022 monkeypox outbreak have been fatal. 10 …”

The evolving epidemiology of monkeypox virus

“…Further studies are necessary to investigate the pathological mechanism underlying MPXV-related heart injury. Besides, there is also preliminary evidence for a wide range of neurological manifestations of monkeypox, including vomiting, nausea, anorexia, agitation, altered consciousness, fatigue, malaise, myalgia, and headache [60] , [61] . It has been reported that MPXV enters the central nervous system mainly by infected circulatory monocytes/macrophages and olfactory epithelium [62] .…”