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Separating the wheat from the chaff - Optimizing the diagnosis of enterovirus-associated meningitis
Or Kriger1, Merav Weil2, Ilana S Fratty2
1Clinical Microbiology, Sheba Medical Center, Ramat-Gan, Israel.
Background:
Enteroviruses (EV) comprise the single most common cause of aseptic meningitis with variable geographical and temporal epidemiology. While EV-PCR in CSF is considered a gold standard for diagnosis, it is not-uncommon to use stool EV as a surrogate. Our aim was to assess the clinical significance of EV-PCR-positive CSF and stool in the investigation of patients with neurological symptoms.
Methods:
In this retrospective study from Sheba Medical centre, the largest tertiary hospital in Israel, we collected demographic, clinical and laboratory data of patients with EV-PCR-positive between 2016 and 2020. A comparison between various combinations of EV-PCR-positive CSF and stool was conducted. Data regarding EV strain-type and cycle threshold (Ct) were crossed with clinical symptoms and temporal kinetics.
Results:
Between 2016-2020, 448 CSF samples with positive EV-PCR were recorded from unique patients, the vast majority of which were diagnosed with meningitis (98%, 443/448). Unlike the diverse strain types of EV background activity, meningitis-related EV showed a clear epidemic pattern. In comparison with the EV CSF+/Stool+ group, the EV CSF-/Stool+ group had frequently more alternative pathogens detected and a higher stool Ct-value. Clinically, EV CSF-/Stool+ patients were less febrile and more lethargic and convulsive.
Discussion:
The comparison of the EV CSF+/Stool+ and CSF-/Stool+ groups suggests that putative diagnosis of EV meningitis is prudent in the febrile, non-lethargic non-convulsive patients with an EV-PCR-positive stool. Otherwise, the detection of stool EV only, in a non-epidemic setup, especially with a high Ct-value, may be incidental and mandate a continuous diagnostic effort for an alternative culprit.
Insights
Enterovirus (EV) PCR in cerebrospinal fluid (CSF) is key for meningitis diagnosis. Positive stool EV without CSF detection may indicate other pathogens, especially with high cycle threshold values.
Area of Science:
- Neurology
- Infectious Diseases
- Virology
Background:
- Enteroviruses (EV) are the most common cause of aseptic meningitis.
- Cerebrospinal fluid (CSF) EV PCR is the gold standard, but stool EV PCR is often used as a surrogate.
- The clinical significance of positive EV PCR in CSF and stool requires further investigation.
Purpose of the Study:
- To assess the clinical significance of EV PCR-positive CSF and stool in patients with neurological symptoms.
- To compare the diagnostic utility of combined CSF and stool EV PCR testing.
- To correlate EV strain types and cycle threshold (Ct) values with clinical presentation.
Main Methods:
- Retrospective study of patients with positive EV PCR at Sheba Medical Centre (2016-2020).
- Collected demographic, clinical, and laboratory data.
- Compared outcomes for EV PCR-positive CSF and stool, analyzing strain types and Ct values against clinical data.
Main Results:
- 448 unique patients had positive EV PCR in CSF, predominantly with meningitis (98%).
- Meningitis-related EV exhibited an epidemic pattern, unlike background EV strains.
- Patients with positive stool EV but negative CSF EV (EV CSF-/Stool+) showed more alternative pathogens, higher stool Ct values, and presented with less fever but more lethargy and convulsions.
Conclusions:
- Positive stool EV PCR in febrile, non-lethargic, non-convulsive patients warrants consideration for EV meningitis.
- Isolated positive stool EV PCR, particularly with high Ct values outside epidemic periods, may be incidental, necessitating further diagnostic workup for alternative causes.
