EBV causes aseptic meningitis, encephalomyeloneuritis and neuritis. The EBV neuropathies present with ophthalmoplegia, lumbosacral plexopathy, and sensory or autonomic neuropathy. Historically, the association of virus with neurological disease was suggested by a positive serum heterophile antibody titer, and later by the presence of EBV DNA, antibody or both in CSF. EBV is latent in B cells, and caution should be used in attributing neurological disease to EBV purely on the basis of a positive CSF PCR; in previously EBV-infected individuals, PCR might detect EBV DNA latent in B cells that are part of the inflammatory response induced by another agent. The presence of anti-EBV IgM or IgG antibody in CSF is more likely to be significant, particularly if there is evidence of intrathecal synthesis of EBV antibody (see below). In a comprehensive clinical, radiological and virological analysis of four patients with EBV myeloradiculitis, encephalomyeloradiculitis and meningoencephalomyeloradiculitis, the CSF contained a mononuclear pleocytosis with elevated protein and normal glucose; in two patients, MRI scans revealed an increased signal in the spinal cord and lumbosacral roots, but no brain swelling or focal changes. In all four patients, EBV DNA was found in the CSF and there were reduced serum:CSF ratios of antibody to EBV, but not to total IgG or albumin, consistent with intrathecal antibody synthesis. Residual neurological deficits were evident. Disappearance of viral DNA from CSF at the time of improvement of neurological disease, particularly before a decline in CSF white blood cells, supports the theory that CNS disease results from direct invasion of the CNS by virus. EBV DNA has been found in brain biopsies from affected patients. CSF from patients with EBV infection of the nervous system contains mainly EBV-specific CD8+ T cells, a few CD4+ T cells, and no CD19+ B cells. CD8+ cells from one patient with EBV infection were shown to contain EBV DNA, and had unrestricted cytotoxic activity. Patients with postinfectious complications of EBV infection have a low EBV load and a high CSF leukocyte count. Encephalitis is characterized by intense viral replication and vigorous inflammation, whereas CNS lymphoma is associated with a limited inflammatory response.
EBV-associated CNS lymphomas are rare in immunocompetent individuals. EBV triggers AIDS-associated primary CNS lymphoma (PCNSL) and post-transplantation lymphoproliferative disorder (PTLD). EBV DNA can be found in tumor tissue in both of these conditions and in CSF of patients with AIDS-associated PCNSL. Deficiency in cytotoxic T lymphocytes seems to permit the outgrowth of EBV-transformed B cells, resulting in PTLD. Administration of autologous EBV-specific cytotoxic T cells has been shown to produce specific killing of EBV-transformed B cells in patients with PTLD.
EBV infects B and T lymphocytes of more than 90% of the general population before adulthood. Primary infection results in transient viremia, followed by a rapid immune response. EBV replicates in the oropharynx and is transmitted through oral secretions. Primary EBV infection frequently results in infectious mononucleosis. EBV is also associated with nasopharyngeal carcinoma, Burkitt's lymphoma, Hodgkin's disease, and lymphoproliferative disease in immunocompromised individuals. It is estimated that neurological complications occur in 1–5% of individuals with infectious mononucleosis. Given the widespread prevalence of EBV infection, the burden of neurological disease is probably underestimated; for example, virtually all CNS lymphomas in AIDS patients contain EBV DNA.
EBV establishes latency in B lymphocytes, which adopt restricted patterns of EBV gene expression. EBV latency has been classified into three types: type I (Burkitt's lymphoma), in which only the EBV-encoded nuclear antigen (EBNA-1) is expressed; type II (nasopharyngeal carcinoma), in which EBNA-1 is coexpressed along with the latent membrane proteins LMP-1, LMP-2A and LMP-2B; and type III (lymphoproliferative diseases in immunosuppressed individuals), in which five EBNAs and the three LMPs are expressed. Autoactivation of gene expression by LMP-1 might be important in type II latency, and EBNA-2-dependent regulation of LMP-1 expression appears to be important in type III latency. The precise mechanism by which EBV reactivates remains unknown, however.
There is no known effective antiviral or other accepted treatment for EBV.
Nat Clin Pract Neurol. 2007;3(2):82-94. © 2007 Nature Publishing Group
Cite this: Herpesvirus Infections of the Nervous System - Medscape - Feb 01, 2007.