MonkeyPox and Neurology Update [September '24]

By Dr Chandrashekhar Meshram
WFN Elected Trustee
Director, Brain and Mind Institute, Nagpur, India

Recent Monkey Pox upsurge

On 14th August 2024, World Health Organization (WHO) Director General Dr Tedros Adhanom Ghebreyesus declared Monkey Pox (mpox) outbreak a public health emergency of international concern (PHEIC). The upsurge of mpox in the Democratic Republic of the Congo and a growing number of countries in Africa has lead to this decision. Dr Tedros’s declaration came on the advice of an International Health Regulations (IHR) Emergency Committee of independent experts who met earlier in the day to review data presented by experts from WHO and affected countries. The Committee informed the Director-General that it considers the upsurge of mpox to be a PHEIC, with potential to spread further across countries in Africa and possibly outside the continent. Dr Tedros mentioned that a coordinated international response is needed to stop these outbreaks and save lives¹.

This PHEIC determination is the second in two years relating to mpox. IHR Committee Chair Professor Dimie Ogoina said, “The current upsurge of mpox in parts of Africa, along with the spread of a new sexually transmissible strain of the monkeypox virus, is an emergency, not only for Africa, but for the entire globe. Mpox, originating in Africa, was neglected there, and later caused a global outbreak in 2022. It is time to act decisively to prevent history from repeating itself.”¹

Mpox is caused by an enveloped double-stranded DNA virus of the Poxviridae family, which includes variola (the causative agent of smallpox, now eradicated), vaccinia (used in smallpox vaccination) and cowpox viruses². The first reported human case of mpox was a nine-month-old boy in the Democratic Republic of the Congo (DRC) in 1970, though the virus was discovered in Denmark (1958) in monkeys kept for research. In humans, mpox is characterized by fever, lymphadenopathy and vesiculopapular rash. The disease is considered endemic to countries in central and west Africa.

Two distinct genetic Monkey Pox Virus (MPXV) clades exist, clade I and clade II. In 2022–2023 a global outbreak of mpox was caused by a strain known as clade IIb which is a milder variant. 95,226 confirmed cases were reported in 117 countries, spreading in men who have sex with men³. 208 deaths were reported, with a case fatality ratio of 0.2 %, The current outbreak is due to clade Ia. Mpox has been reported in the DRC for more than a decade, and the number of cases reported each year has increased steadily over that period. Last year, reported cases increased significantly, and already the number of cases reported so far this year has exceeded last year’s total, with more than 15,600 cases and 537 deaths, and a case fatality ratio of 3 %. Infection levels are especially high in women who are commercial sex workers and the men who are clients⁴.

Neurological manifestations of Mpox

A wide range of neurological manifestations from less serious and nonspecific symptoms including headache, myalgia, malaise, agitation and fatigue to more severe complications including seizure and encephalitis have been reported in patients with mpox^{5, 6}. Visual changes, dizziness, ear pain and hearing loss can also occur. Out of the three family members infected with MPXV reported in the Midwestern USA, two showed mild skin rash only and one presented with severe encephalitis which required hospitalization. Headache, fatigue, myalgia, confusion and seizure were seen in the severe case. Neurological examination revealed decreased level of consciousness, pupillary dilatation, optic disc edema, loss of corneal reflexes, and reduced deep tendon reflexes. Additionally, magnetic resonance imaging (MRI) confirmed hyperintensity in the thalamus, brainstem and right posterior parietal cortex consistent with mixed cytotoxic and vasogenic brain edema. Pleocytosis was also detected in the analysis of the cerebrospinal fluid⁵. A case of longitudinally extensive transverse myelitis in a patient with recently diagnosed mpox, presenting as acute flaccid paraplegia has been described⁷.

Data from experimental studies have indicated that MPXV can gain access to the central nervous system (CNS) through the olfactory epithelium and infected circulatory monocytes/macrophages as two probable neuroinvasive mechanisms⁵. There are concerns about long term effects of MPXV on the central nervous system and evolving neurological manifestation. In view of the mpox outbreak, neurologists should be aware about its possible neurological manifestations.

The two vaccines currently in use for mpox are recommended by WHO’s Strategic Advisory Group of Experts on Immunization, and are also approved by WHO-listed national regulatory authorities, as well as by individual countries including Nigeria and the DRC.

References

1. https://www.who.int/news/item/14-08-2024-who-director-general-declares-mpox-outbreak-a-public-health-emergency-of-international-concern
2. Vakaniaki, E.H., Kacita, C., Kinganda-Lusamaki, E. et al. Sustained human outbreak of a new MPXV clade I lineage in eastern Democratic Republic of Congo. Nat Med (2024). https://doi.org/10.1038/s41591-024-03130-3
3. 2022–24 mpox (monkeypox) outbreak: global trends. World Health Organization (2024); https://worldhealthorg.shinyapps.io/mpx_global/
4. Jon Cohen – deadlier strain of mpox spreads in multiple African countries : Science, Vol 385, Issue 6709.
5. Sepehrinezhad A, Ashayeri Ahmadabad R, Sahab-Negah S. Monkeypox virus from neurological complications to neuroinvasive properties: current status and future perspectives. J Neurol. 2023 Jan;270(1):101-108. doi: 10.1007/s00415-022-11339-w. Epub 2022 Aug 21. PMID: 35989372; PMCID: PMC9393054.
6. Billioux J. et al Potential complications of monkeypox. the Lancet neurology https://doi.org/10.1016/S1474-4422(22)00340-4
7. Moore L et al transverse myelitis associated with Mpox infection doi: 10.1016/j.jneuroim.2023.578190. Epub 2023 Aug 28.