CSF herpes virus and autoantibody profiles in the evaluation of encephalitis.
OBJECTIVE
To report the frequency of coexisting herpes viruses (herpes simplex virus 1 [HSV-1] or HSV-2, varicella zoster virus, Epstein-Barr virus [EBV], cytomegalovirus, or human herpes virus 6 [HHV-6]) and autoantibodies in patients with encephalitis (herpes or autoimmune) in clinical laboratory service.


METHODS
Three groups were evaluated for herpes viruses and antibodies: group 1-patients whose CSF was positive for a herpes virus by real-time PCR over a period of 6 months; group 2-patients whose CSF was positive for an autoimmune encephalitis-associated antibody over 5 years (e.g., NMDA receptor [NMDA-R] antibody), and the same number of controls without autoimmune/infectious disease; and group 3-incidental autoimmune parainfectious encephalitis cases encountered over 1 year.


RESULTS
In group 1, antibodies were detected in 27 of 100 herpes PCR-positive CSF specimens (CSFs), either unclassified neural or nonneural in all but one patient with NMDA-R antibody detected after EBV infection. Antibodies were also detected in 3 of 7 CSFs submitted for repeat PCR testing (unclassified, 2; AMPA receptor, 1). In group 2, herpes viruses were detected in 1 of 77 controls (HHV-6) and 4 of 77 patients with autoimmune encephalitis (EBV, 2; HHV-6, 2); autoantibodies targeted NMDA-R in 3/4 and GABAB-R in 1/4. In group 3, NMDA-R antibody was detected in 7 patients post-HSV-1 encephalitis. Of the remaining 3 patients, 2 had unclassified neural antibodies detected, and one had GABAB-R autoimmunity. Concomitant neoplasms were discovered in 2 patients each from groups 2 and 3.


CONCLUSIONS
Autoantibodies and herpes virus DNA frequently coexist in encephalitic CSF. Some patients develop parainfectious autoimmunity following viral CNS infection (usually HSV-1 encephalitis). The significance of detecting herpes nucleic acids in others remains unclear.
Departments of Neurology (J.J.L., C.J.K., A.M.), and Laboratory Medicine and Pathology (M.J.B., M.M., C.J.K., A.M.), College of Medicine, Mayo Clinic, Rochester, MN.
Jenny J
JJ
Linnoila
Departments of Neurology (J.J.L., C.J.K., A.M.), and Laboratory Medicine and Pathology (M.J.B., M.M., C.J.K., A.M.), College of Medicine, Mayo Clinic, Rochester, MN.
Matthew J
MJ
Binnicker
Departments of Neurology (J.J.L., C.J.K., A.M.), and Laboratory Medicine and Pathology (M.J.B., M.M., C.J.K., A.M.), College of Medicine, Mayo Clinic, Rochester, MN.
Masoud
M
Majed
Departments of Neurology (J.J.L., C.J.K., A.M.), and Laboratory Medicine and Pathology (M.J.B., M.M., C.J.K., A.M.), College of Medicine, Mayo Clinic, Rochester, MN.
Christopher J
CJ
Klein
Departments of Neurology (J.J.L., C.J.K., A.M.), and Laboratory Medicine and Pathology (M.J.B., M.M., C.J.K., A.M.), College of Medicine, Mayo Clinic, Rochester, MN.
Andrew
A
McKeon