Rotavirus meningitis in an adult with transient aphasia

Etiological diagnosis of meningitis may be challenging. The absence of microbial identification can lead to unnecessary probabilistic treatment. have recently shown that clinically relevant and unexpected viruses could be detected in the CSF using viral capture sequencing in cerebrospinal fluid (CSF) from 73 adults with suspected viral meningitis. They notably identified Rotavirus A as a potential causative agent in two adults, which had never been described in adults before.

In February 2022, we were directed to the case of a 37-year-old female patient who presented to our hospital for acute aphasia. She only had a medical history of visual migraine aura. She reported acute gastroenteritis starting seven days before admission, with abundant watery diarrhea and nonbilious vomiting for five days. Her household, including her husband and two children, displayed the same symptoms for a shorter period. She also reported headaches, daily fever with a temperature of 39°C, moderate shivers, and sweating. At hospital admission, she presented severe speech aphasia with paraphasia and jargon aphasia, associated with persistent headaches and neck stiffness. Blood analysis found a C-reactive protein level of 7.2 mg/l, a blood cell count in a normal range, and an alanine aminotransferase level of twice the normal. CSF analysis revealed pleocytosis of 40 white cells/µL with 98% lymphocytes, an elevated protein level (1.04 g/l), and a CSF/serum glucose ratio of >0.6. Intravenous aciclovir at 10 mg/kg three times per day was started under the suspicion of acute herpetic encephalitis. Electroencephalography revealed frontal intermittent rhythmic delta activity, which was aspecific and may not be pathological. Brain MRI did not show any signs of herpetic encephalitis and only revealed bilateral posterior occipito-parietal sulcus hypersignals in contrast-enhanced FLAIR (FLuid Attenuated Inversion Recovery) sequence, which were nonsignificant. Herpes simplex virus-1 (HSV-1), HSV-2, varicella-zona virus, enterovirus, and hepatitis E virus were undetected by polymerase chain reaction (PCR) in CSF. Serologies for Epstein-Barr virus and cytomegalovirus showed no evidence of acute infection, and serologies showed no sign of HIV or syphilis infection. Speech fully recovered in 12 hours after symptoms onset. A second lumbar puncture was performed on day three of admission, showing a normalized level of proteins and a white cell count of 78/µL (100% lymphocytes). Aciclovir was discontinued as HSV remained undetectable by PCR in CSF. A multiplex reverse transcription (RT)-PCR was performed on both CSF samples and the stool to detect enteric viruses (Amplidiag® Viral GE, Mobidiag). Both the first sample of CSF and stool were positive for Rotavirus A, within 40 cycle threshold (Ct) in CSF, which was confirmed with a second test on a different tube of the same CSF in favor of Rotavirus meningitis. Rotavirus was undetected in the second CSF. The patient was discharged on day six after admission, with a favorable outcome and the absence of neurological symptoms relapse.

We hereby report the third case to our knowledge of documented Rotavirus meningitis in an adult. The full clinical story supports the suggestion of Rotavirus as a previously undiagnosed etiological agent. Rotavirus neurological disease has previously only been reported in children in which it could cause encephalitis or meningitis in the context of Rotavirus gastroenteritis (; ). The high Ct value for Rotavirus detection in our case suggests the virus is difficult to detect in CSF in case of meningitis and could have been missed in meningitis cases associated with Rotavirus gastroenteritis. The pathophysiological mechanisms enabling the presence of viral RNA in patients’ CSF have yet to be determined. Its clinical presentation, however, supports a potential pathogeny of Rotavirus in the central nervous system (CNS). Rotavirus viremia has notably been reported in immunocompetent children, and a blood-brain barrier crossing is thus possible (). Although contamination may have led to the positive PCR result, we ruled out contamination of the sample by repeating all the processes on a different CSF tube. Each PCR run included a negative control to detect contamination. The CSF was tested separately from the stool sample. The only possibility for a contaminated PCR would be at the time of CSF collection, which is not likely.

Our patient's aphasia was initially imputed to a syndrome of transient headache and neurological deficits with CSF lymphocytosis (HaNDL) (; ). The hypothesis of an aura with the atypical presentation was rejected because of the absence of those symptoms’ occurrence in the past and their duration. Concordantly, aphasia was spontaneously resolutive, and the absence of MRI anomalies did not seem in favor of direct viral encephalitis. However, the HaNDL definition excludes cases with etiological findings. Therefore, although it may be possible that our patient presented mild Rotavirus encephalitis in addition to meningitis, this cannot be asserted with certainty.

Interestingly, HaNDL is often described as a postviral syndrome, and we have shown that Rotavirus detection in CSF is difficult. We hypothesize that at least a similar mechanism may be implied, and it may be possible that viral infection has been undetected in the CSF of patients with HaNDL. The development of metagenomic in CSF is likely to provide new insights into microbial involvement in previously undiagnosed CNS inflammatory processes (; ).

Our case confirms the possibility of Rotavirus A involvement in undocumented adult meningitis suggested by McGill et al., especially in the context of concomitant gastroenteritis. In addition, new sequencing techniques could help identify new pathogens in previously considered aseptic CSF.

The authors have no competing interests to declare.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval was not required.

Original draft preparation: NC, MM, GMB; Review and Editing: all authors