Is human herpesviruses 6/7 detection always pathological?

*Correspondence: [e-mail].

Abstract

Case Presentation: Case A: 14-year-old female, history of headache, fever, and respiratory symptoms. COVID-19 positive through antigen-based testing. Symptoms persisted for 1 week, when the patient presented with intense headache, vomiting, and drowsiness. Upon evaluation in the emergency room, neck stiffness was noted, and ceftriaxone was initiated. Cerebrospinal fluid (CSF) showed a cell count of 1275/mm³ with predominance of neutrophils, glucose of 30 mg/dL, and protein level of 101 mg/dL. Peripheral blood culture was positive for Streptococcus constellatus. The patient developed subdural empyema and the culture of its drainage confirmed the same pathogen. Viral panel examination revealed a positive PCR result for Human herpesviruses 6/7 (HHV-6/7). Case B: 8-year-old male, history of irritability associated with ptosis of the right eyelid and altered extrinsic and intrinsic ocular motility of the same eye at around 1 year of age. Brain MRI showed hyperintense right III cranial nerve, and CSF analysis showed no cytological or biochemical changes. Pulse therapy for 5 days was performed, resulting in complete resolution. Subsequently, the CSF PCR test revealed a positive result for HHV-6/7. In the follow-up, the patient was diagnosed with recurrent painful ophthalmoplegic neuropathy, later characterized as associated with episodes of headache. At 5 years old, a repeat CSF examination showed a positive PCR result for HHV-6/7. Case C: 14-year-old male presented with bilateral visual impairment associated with bilateral ocular pain, worse on the right side, without signs of ocular redness. After 4 days, bilateral amaurosis developed. Investigation with CT angiography of the skull and brain MRI showed no abnormalities. CSF analysis showed no cytological or biochemical changes but a positive PCR result for HHV-6/7.

Discussion: We present here three cases in which the clinical relevance of HHV-6/7 detection in the CSF is questioned. There is a significant genetic similarity between these two viruses. Both have the ability to cause latency, asymptomatic reactivation, and, in the case of HHV-6, it can be integrated into chromosomal DNA. Therefore, results should be analyzed with caution to not misinterpret a positive HHV-6/7 test.

Final Comments: CSF detection of HHV6/7 is not always pathognomonic of an infection to be treated.

Publication History

Article published online:
12 May 2025