The Prevalence & Spectrum of Neurological & Psychiatric Presentations of Human Monkeypox Infection

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Scientists have conducted a systematic review and meta-analysis to evaluate the prevalence of neuropsychiatric manifestations associated with monkeypox infection. The review article has recently been published in eClinicalMedicine.  


Monkeypox is a zoonotic virus belonging to the Orthopoxvirus genus of the Poxviridae family. The virus was initially endemic to Central and West Africa, with some sporadic outbreaks documented in non-endemic countries. However, since May 2022, a sharp rise in monkeypox cases has been observed in more than 90 countries, especially the USA and UK.

Monkeypox infection is mostly self-limiting and lasts for about 2 – 4 weeks. However, severe infection may occur occasionally in susceptible people, including children and immunocompromised individuals.

The most prominent symptom of monkeypox infection is mild-to-severe risk rashes or lesions. Regarding rare symptoms, a few studies have indicated monkeypox-related neuropsychiatric manifestations. Since smallpox and monkey belong to the same viral family and smallpox infection is significantly associated with neurological symptoms, a systematic analysis of monkeypox-related neuropsychiatric manifestations might be relevant.

In the current study, scientists have evaluated the prevalence of neurological and psychiatric symptoms associated with monkeypox infection. Moreover, they have described the spectrum of these manifestations.

Study Design

This systematic review and meta-analysis were conducted on studies published in various medical science databases up to May 2022. Any studies describing neuropsychiatric problems in monkeypox-infected persons were included in the analysis. Most of the studies were conducted in the USA, followed by Nigeria, the Democratic Republic of Congo, the Republic of Congo, and the UK.  

From an initial screening of 1,705 studies, 19 were included in the final analysis. Most studies were cohort studies and case series with no control groups. A total of 1,512 individuals participated in these studies, with 1031 having a laboratory-confirmed monkeypox infection. Overall, the quality of selected studies was moderate.   

The meta-analysis was conducted on neuropsychiatric manifestations reported by two or more studies.

Prevalence of Neuropsychiatric Symptoms

A wide variation in neuropsychiatric symptoms was observed between studies. The most commonly reported symptoms were headache, myalgia, seizure, confusion, encephalitis, and fatigue.

In retrospective studies selected for the analysis, case note review was mostly used to evaluate neuropsychiatric symptoms. Similarly, in prospective studies, a combination of clinical interview and questionnaire was used for symptom evaluation.  

A total of six symptoms were included in the meta-analysis. These symptoms were myalgia, headache, fatigue, seizure, confusion, and encephalitis.

The prevalence of seizure, confusion, and encephalitis was estimated to be 2.7%, 2.4%, and 2%, respectively. The prevalence of myalgia, headache, and fatigue could not be assessed because of high heterogeneity. The heterogeneity between studies could be due to differences in viral strains, time-dependent changes in symptom expression, the severity of illness, variation in inclusion criteria, and timing of symptom identification relative to acute illness.

No significant changes in prevalence were observed by excluding the studies that are different from the majority in terms of study design, inclusion criteria, data collection, symptom diagnosis, and temporality of symptoms.  

Other reported symptoms not included in the meta-analysis were depression, anxiety, suicide, dizziness, pain, altered vision, encephalopathy, and photophobia.    

For the sub-group analysis, headache was the only clinical symptom that met the eligibility criteria. However, no significant difference in the prevalence of headaches was observed between retrospective and prospective studies.

Study Significance

This systematic review and meta-analysis provide an overview of the prevalence of neurological and psychiatric symptoms among monkeypox-infected people.

The findings indicate serious neurological symptoms, including seizure, confusion, and encephalitis, in less than 3% of infected people. Although a significant proportion of study participants have mentioned experiencing myalgia, headache, and fatigue, the exact prevalence of these symptoms could be estimated because of the high heterogeneity between studies.

Regarding monkeypox-related psychiatric symptoms, many studies have reported depression and anxiety. However, the prevalence of these symptoms remains unknown.

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