Monkeypox virus-associated meningoencephalitis diagnosed by detection of intrathecal antibody production

Since May 2022, nearly 90,000 cases of mpox have been reported within a global outbreak [1], with the major proportion of cases affecting men who have sex with men [2]. Apart from this epidemiological pattern of transmission, cases in the global outbreak frequently show a different clinical presentation from that previously described, with a predominance of anogenital lesions, as well as manifestations such as penile oedema, proctitis, and severe pain from skin and mucosal lesions [3]. The course of mpox is usually relatively benign and self-limiting, although within the current outbreak around 6% of patients have required hospitalization [2]. However, the spectrum of severe disease manifestations represents a current knowledge gap. A recent meta-analysis on neurological and psychiatric presentations of mpox reported seizures, confusion, and encephalitis in < 3% of infected individuals [4], but the studies have been small and only one included cerebrospinal fluid (CSF) results and neuroimaging [5].

The patient was a 37-year-old previously healthy man with a history of primary syphilis who received regular medication with Emtricitabine/Tenofovir as HIV pre-exposure prophylaxis. He presented to an outpatient department with a one-day history of painful genital skin lesions and oral ulcers and reported a casual sexual contact with a man in Spain nine days earlier. Mpox was suspected, and samples obtained from oral and genital lesions were positive for monkeypox virus by PCR (Supplementary material 1). The patient was afebrile and did not show signs of systemic infection. Symptomatic treatment (topical anaesthetics, paracetamol, and ibuprofen) was prescribed.

Over the next week, the patient experienced gradual improvement. On day 9–10 after symptom onset, however, he developed fever, sore throat, headache, and fatigue. On day 12, mental confusion appeared. The patient was found in a parked car, could not provide details about himself, and was brought to the emergency department by ambulance. In the emergency room, he was febrile (39 ºC) with normal respiratory rate. Blood pressure was 120/80 mmHg and heart rate was 92 beats per minute. The neck was supple. He was fully conscious but appeared confused and responded inadequately to questions about his symptoms and previous activities during the day. Neurological examination revealed normal cranial nerve function and intact strength and sensation, and the Glasgow Coma Scale (GCS) was 14/15. The previously described genital and oral ulcers as well as a few additional lesions on the lower extremities and trunk were noted. Computed tomography of the brain was performed with normal findings. Analysis of CSF showed elevated mononuclear cells (22 × 10^⁶/L) suggestive of aseptic meningitis (Table 1). The patient was admitted, and empirical treatment with intravenous acyclovir was initiated.

On the second day after admission, the patient’s condition worsened with psychomotor deceleration and increasing confusion. He moved all extremities spontaneously and had localized pain but gave no verbal or non-verbal response, and a repeated assessment revealed a GCS of 9/15. No focal neurological deficits were observed.

Magnetic resonance imaging (MRI) of the brain showed signs of encephalitis with bilateral symmetrical restricted diffusion in the cingulated gyrus and cortical regions of the insula (Fig. 1). An electroencephalogram showed generalized slow waves without epileptiform activity.

The next morning, the patient was awake and responsive, although still showing slight signs of confusion. On day four of admission, he was fully oriented and adequate. A second lumbar puncture was performed. HSV PCR was repeatedly negative, and acyclovir was discontinued. The patient was discharged from hospital five days after admission while reporting mild headache and fatigue.

After discharge, the patient was followed by regular phone calls. He reported complete recovery from day 30, which was confirmed by clinical examination at an outpatient follow-up visit on day 45.