Monkeypox May Lead to Seizures, Confusion, and Encephalitis in Some Patients

Seizures, confusion, and encephalitis are experienced by 2-3% of patients with monkeypox.

Among some patients with monkeypox, neurologic complications such as encephalitis, seizure, confusion, headache, and myalgia are present, according to a systematic review and meta-analysis published in eClinicalMedicine.

Monkeypox is a viral infection caused by a virus in the genus Orthopoxvirus and family Poxviridae. It was first identified in monkeys and rodents in 1958 and the first human case occurred in the Democratic Republic of Congo in 1970. There is currently a world-wide outbreak of monkeypox infections that has been spreading via human-to-human transmission. Infection with monkeypox causes dermatological rash, however, there remains the possibility that some patients can present with neuropsychiatric symptoms.

“Analogous data from smallpox infection and vaccination with vaccinia indicate that neurological and psychiatric features may be significant,” researchers from the eClinicalMedicine study stated.

The researchers, from multiple institutions in the United Kingdom (UK), searched publication databases through May 2022 for studies of presentation symptoms among patients with monkeypox. Trends in neuropsychiatric symptoms were evaluated.

Analogous data from smallpox infection and vaccination with vaccinia indicate that neurological and psychiatric features may be significant.

A total of 19 studies comprising 1512 patients were included in this analysis. Among all patients, 1031 had polymerase chain reaction or Centers for Disease Control and Prevention (CDC) confirmed infection. Patients were aged mean 24.2 (standard deviation [SD], 19.4) years and 45.1% were women, in studies which reported patient-level data.

Studies were conducted in the United States (n=6), Nigeria (n=5), the Democratic Republic of Congo (n=5), Republic of Congo (n=2), and the UK (n=1). Most studies were published in 2003 (n=8).

The pooled prevalence rates of seizure were 2.7% (95% CI, 0.7-10.2%, I2, 0.0%), confusion was 2.4% (95% CI, 1.1-5.2%, I2, 0.0%), and encephalitis was 2.0% (95% CI, 0.5-8.2%, I2, 55.8%).

The proportion of patients with seizure in 2 studies was 0.03 (95% CI, 0.01-0.10; I2, 0.0%), encephalitis in 3 studies had a proportion of 0.02 (0.00-0.21; I2, 55.8%), and confusion in 2 studies had a proportion of 0.02 (95% CI, 0.01-0.05; I2, 0.0%). Studies also reported headache (n=6), myalgia (n=4), and fatigue (n=2), however, heterogeneity was too high (range, 95.5-98.7%) to perform a pooled analysis.

This study may have been limited by the lack of certain data in some studies, such as disease severity or patient characteristics.

The researchers noted that “Neuropsychiatric symptoms including myalgia, fatigue, headache, anxiety and depression are less clear, but several studies found at least half of individuals experiencing some of these outcomes,” the researchers noted. However, they acknowledged that since these symptoms are present in viral infections and patients who are hospitalized, their presence could be due to systematic illness vs neurologic injury.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Badenoch JB, Conti I, Rengasamy ER, et al. Neurological and psychiatric presentations associated with human monkeypox virus infection: a systematic review and meta-analysis. eClinicalMedicine. Published online September 8, 2022. doi:10.1016/j.eclinm.2022.101644