Herpes simplex virus encephalitis: chronic progressive cerebral MRI changes despite good clinical recovery and low viral load - an experimental mousestudy

Cranial magnetic resonance imaging (MRI) is a sensitive diagnostic tool for the in vivo detection of morphological abnormalities in herpes simpler vir us encephalitis (HSVE). We performed a long-term MRI study in a mouse model of HSVE. Cranial MRI findings were compared with the viral load within bra in tissue, the presence of HSV DNA in the cerebrospinal fluid (CSF), a dail y clinical assessment and post-mortem neurohistopathological studies. A 1.5 T cranial MRI scanner with standard spin-echo sequences was used. Viral lo ad within the brain and the presence of HSV DNA in cerebrospinal fluid were determined by a polymerase chain reaction assay. Clinically, animals were severely affected within the first 2 weeks and recovered thereafter. Focal histopathological and MRI abnormalities involved predominantly limbic struc tures, a pattern that mimics human disease. Severity and extent of abnormal ities had increased at 6 months despite clinical improvement. HSV DNA was p resent in CSF during the acute disease only: Brain viral load peaked at day 10 and declined thereafter. MRI as an in vivo monitoring approach may reve al chronic progressive changes in HSVE, despite clinical recovery and low v iral load in the brain. Secondary, not directly virus-mediated, mechanisms of tissue damage may contribute to tissue damage of HSVE. Eur J Neurol 6:53 1-538 (C) 1999 Lippincott Williams & Wilkins.