Analysis of Metagenomic Next-Generation Sequencing (mNGS) in the Diagnosis of Herpes Simplex Virus (HSV) Encephalitis with Normal Cerebrospinal Fluid (CSF)

Abstract

Background

Metagenomic next-generation sequencing (mNGS) is becoming increasingly extensive in diagnosing herpes simplex encephalitis (HSE). However, many HSE patients with normal cerebrospinal fluid (CSF) diagnosed by mNGS have been found during the clinical application. This study aimed to summarize and analyze the clinical characteristics, supplementary examinations, and prognosis of patients with HSE whose cerebrospinal fluid was confirmed to be normal by mNGS.

Methods

This retrospective study evaluated the clinical characteristics, auxiliary examinations, and patient prognosis of patients with HSE that were diagnosed by mNGS but had normal CSF. Clinical data collected included baseline information, signs and symptoms upon admission, and risk factors for infection. Auxiliary examinations included indirect immunofluorescence assay (IIF), cell-based assay (CBA), and CSF testing. Prognosis was evaluated based on hospital stay and patient survival.

Results

Seven of the nine patients (77.8%) experienced headaches, and four (44.4%) had a fever of 38°C or higher. The average leukocyte count in the CSF was 2.6 ± 2.3/L. According to the mNGS, the median sequence count of HSV was 2 (1, 16). Magnetic resonance imaging (MRI) revealed one bilateral temporal lobe lesion (11.1%), two isolated bilateral frontal lobe lesions (22.2%), and one bilateral cingulate gyrus lesion (11.1%). One patient (11.1%) was admitted to the intensive care unit and passed away in the hospital. The remaining patients (88.9%) had a positive prognosis upon discharge.

Conclusion

Patients with HSE who had normal CSF were typically middle-aged women with normal immune function. They showed typical HSE clinical features, such as fever, headache and epilepsy, that did not differ from those of other HSE patients. A normal CSF result is generally associated with a low viral load and the body’s ability to mount an effective immune response. Most of these patients have a favorable prognosis.

Keywords:

• herpes simplex encephalitis
• herpes simplex virus
• cerebrospinal fluid
• metagenomic next-generation sequencing
• atypical clinical manifestations

Abbreviations

mNGS, metagenomic next-generation sequencing; HSE, Herpes simplex encephalitis; HSV, herpes simplex virus; IIF, Indirect immunofluorescence assay; CBA, Cell-based assay; CSF, cerebrospinal fluid testing; IQRs, interquartile ranges.

Data Sharing Statement

All the summarized and analyzed data during this study are included in this published article; the original data in this study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

This study was approved by the Ethics Committees of the Harrison International Peace Hospital and was performed in accordance with the 1964 Helsinki declaration. The written informed consent was obtained from each participant.

Acknowledgments

Zhihua Si and Lin Li should be regarded as co-first authors.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

There is no funding to report.