Monkeypox (MPX), which spreads through zoonotic transmission and by human-to-human contact, emerged as a new global health emergency in 2022, spreading to nonendemic countries from endemic regions like Central and West Africa. A total of 53,027 cases have been confirmed and 15 deaths have occurred as of September 5, 2022, from around 100 countries and locations around the world1,2. The signs of early infection include chills, sweats, sore throat, prostration, and lymphadenopathy. After about 1 week of infection, a febrile illness with a vesiculopustular rash develops. In the current outbreak, rashes generally appear in the facial, genital, and anal regions3.
Although there has been considerable consideration of primary manifestations such as cutaneous lesions and flu-like symptoms, the effect of the Monkeypox virus (MPXV) on other organs of the body has not been studied in detail. MPX cases are rapidly rising worldwide, and the evidence of its range of complications is not clear. Recently, many neurological manifestations were reported, including headaches, malaise, myalgia, anorexia, and altered consciousness4.
The 2 cases reported by the Center for Disease Control and Prevention (CDC) on September 13, 2022, which showed nerve damage in previously healthy patients, have caught the attention of the world’s health community. The two patients showed radiographical and clinical features of acute disseminated encephalomyelitis. Acute disseminated encephalomyelitis is characterized by inflammation in the brain and spinal cord that damages the myelin—the protective coating around axons of neurons. The underlying pathology was unclear. CDC reported that it might have occurred due to direct MPXV invasion of the central nervous system or by a parainfectious autoimmune process triggered by MPXV infection5. Till now, the underlying pathophysiology has remained a subject of prospective studies.
There are very few studies that highlight the neuroinvasive potential of MPXV. The neurological manifestations may be due to the neuroinvasive potential of MPXV. Studies on rodents have manifested the neuroinvasive potential of MPXV. Two possible transmission routes of MPXV to brain parenchyma in animal subjects were described: (i) olfactory epithelium routes and (ii) infected monocytes/macrophages transmission ways (Fig. 1). More extensive research is required to determine the exact invasion routes4.
It implies the need to identify the mechanism of neuroinvasion and neurotropism of MPXV in human subjects. Other rare complications that have been reported by the WHO are bronchopneumonia, sepsis, and infection of the cornea with ensuing loss of vision. Also, there is preliminary evidence of neurological complications and manifestations but the evidence about its neuropsychiatric aspect is highly lacking. So, it is suggested that health care workers should monitor patients with MPX for symptoms like anxiety, depression, etc6. This requires surveillance of current cases in MPX outbreaks to establish clear evidence and guidelines.
As this MPX has been labelled an epidemic, the frequency of these neurological complications has the potential to increase with rising cases worldwide. Awareness should be raised about these complications among primary and secondary health care providers. Epidemiological surveillance may help get insight into all possible neurological complications. Proper management guidelines supported by scientific evidence should be devised.
Sources of funding
M.F. was the lead author of this letter. M.M.B. and M.A.B. contributed equally to the preparation of the manuscript.
Conflicts of interest disclosure
The authors declare that they have no financial conflict of interest with regard to the content of this report.
Research registration unique identifying number (UIN)
Provenance and peer review
Not commissioned, internally reviewed.
1. Alavi-Moghaddam M. Monkeypox outbreak in non-endemic areas: will it cause a new pandemic? A letter to editor. Arch Acad Emerg Med 2022;10:e60.
2. Brewer MG, Monticelli SR, Ward BM. Monkeypox: considerations as a new pandemic looms. J Invest Dermatol 2022;142:2561–2564.
3. Philpott D. Epidemiologic and clinical characteristics of monkeypox cases—United States, May 17–July 22, 2022. MMWR Morb Mortal Wkly Rep 2022;71:1018–22.
4. Sepehrinezhad A, Ashayeri AR, Sahab-Negah S. Monkeypox virus from neurological complications to neuroinvasive properties: current status and future perspectives. J Neurol 2023;270:101–108.
5. Pastula DM. Two cases of monkeypox-associated encephalomyelitis—Colorado and the District of Columbia, July–August 2022. MMWR Morb Mortal Wkly Rep 2022;71:1212–15.
6. Badenoch JB, Conti I, Rengasamy ER, et al. Neurological and psychiatric presentations associated with human monkeypox virus.