gms | German Medical Science

Introduction: The new high-performance techniques detect a remarkable spectrum of microorganisms even in the classically considered “sterile” sites of the human body. Thus, different viruses are detected in cerebrospinal fluid (CSF), with controversial implications in central nervous system (CNS) impairment. Epstein-Barr (EBV) is one of the most frequently detected viruses.

Objectives: To evaluate the presence, frequency and associations of EBV in CSF in neurologically impaired and non-impaired human hosts.

Methods: We retrospectively analyzed CSF samples from adult patients (≥18 years old), collected between Oct 2011 and Oct 2012 in a Romanian tertiary ID hospital. The analyzed samples originated from 2 groups of patients: 1) HIV-negative patients with presumed CNS infections (acute or convalescing) and 2) HIV-positive patients (with or without CNS impairment). CSF samples were analyzed using a multiplex PCR coupled with electrospray ionization – time-of-flight mass spectrometry (Abbott Molecular) which can simultaneously detect: herpesviruses (1-5 and 8), polyomaviruses, enteroviruses, adenoviruses and parvoviruses. The patients are characterized as regards the HIV status, neurological findings (including neuroimaging techniques and routine CSF examination), comorbidities and outcome. The EBV-positive group was subsequently deeply analyzed.

Results: A number of 92 patients were analyzed, 38 patients were HIV-negative and 54 HIV-positive. The most frequently detected virus was EBV in 25 (27.2%) patients. The EBV-positive group (25 patients):

• Had a mean age of 36 years (range 19-76 years) and a male:female ratio of 13:12.
• Nineteen were HIV-positive.
• Twenty-two patients had neurologic impairment.

The CSF routine analysis showed no abnormality in 11 cases. The cellularity had a median of 4/mm^3[IQR=18], the CSF-glucose a median of 48.5 mg/dL[IQR=40]; six patients had CSF glucose less than 40 mg/dL. The CSF protein showed a median of 57mg/dL[IQR=49]. In 7 cases EBV was found as a singular agent in CSF. In 18 cases, EBV was found in association with other microorganisms (graph): other herpesviruses (6 cases), JC virus (5 cases), HIV (10 cases – out of 11 cases for which HIV viral load was available), MTB (2 cases), Cryptococcus neoformans (2 cases), Toxoplasma gondii (one case) or rapid-grow bacteria (2 cases). Imagery was performed in 18 cases and showed abnormalities in 16 cases.

As regard the etiology of the acute/subacute neurological event (totalizing the neurological signs and symptoms, CSF exams, imagery and evolution), EBV was probable involved in 7 cases, possible involved in 6 cases and “fortuitously” founded in 12 cases (3 asymptomatic HIV-positive cases and 9 cases with the symptomatology strongly attributed to another germ).

Discussions & Conclusions: EBV is the most frequent agent found in CSF, mono-detected but especially in variable and multiple associations. Even though in approximately half of the cases its pathogen role is almost proved, it remains another half, with debatable and obscure roles, when EBV acts perhaps as a local immunity enhancer.