NIB01
In Vivo Detection of Epstein Barr Virus in the Cerebrospinal Fluid at the Clinical Onset of Multiple Sclerosis
Molecular mimicry between the Epstein Barr virus (EBV) protein EBNA1 and the human glial cell adhesion molecule (GlialCAM) has been recently described in multiple sclerosis (MS) patients. Also, a study showed that 34 of 35 EBV seronegative patients converted into seropositive prior to developing MS, supporting a role for EBV as a disease trigger. To the best of my knowledge, there are no reports of in vivo detection of the EBV DNA in the cerebrospinal fluid (CSF) at the clinical onset MS.
Objectives:
To report the detection of EBV DNA in two patients at the time of the clinical onset of MS.
Methods:
Case series.
Results:
The CSF of 24 patients during the first MS clinical relapse was tested for EBV via polymerase chain reaction (PCR). The test was positive in 2 patients (8.3%).
A 15-year-old male presented with right optic neuritis, left wrist weakness, and left sided numbness, no preceding viral illness or vaccination. Brain MRI showed numerous contrast-enhancing and non-enhancing demyelinating lesions in the periventricular, juxtacortical, and infratentorial areas. Initial CSF showed 17 nucleated cells (NCs) (96% lymphocytes), normal protein (33 mg/dl), normal glucose (54 mg/dl), >5 unique oligoclonal bands (OCBs), normal IgG index (0.61), and 4900 copies/ml of EBV. A second relapse took place in about one month, requiring plasma exchange. Repeat CSF showed minor changes but decreased viral copies (600/ml) and increased monocytes/macrophages to 15%. He had full clinical recovery (EDSS 0), started rituximab, and remained stable 26 months later.
A 30-years-old male presented with right optic neuritis, and right-hand tingling—no preceding infection or vaccination. Brain MRI showed concurrent contrast-enhancing and non-enhancing lesions in the periventricular, juxtacortical, and infratentorial areas. CSF showed 9 NCs (80% lymphocytes and 20% monocytes/macrophages), normal protein (28 mg/dl), mildly elevated glucose (85 mg/dl), 14 OCBs, elevated IgG index (1.71), and >250 copies/ml of EBV. Atypical lymphocytes were observed but were negative for lymphoma markers. IV steroids were effective, and ocrelizumab initiation resulted in controlling MS activity. He had a complete recovery (EDSS 0) and remained stable eight months later. In both patients, serum EBV capsid antigen IgG and EBNA IgG were elevated, while EBV IgM was negative.
Conclusions:
This is the first report of in vivo detection of EBV DNA in CSF of patients with MS. This finding further supports the evidence that EBV triggers MS in some patients.