Neuronal plasticity in patients with Herpes simplex encephalitis: functional brain MRI studies and neuropsychological testing during the acute stage and at follow-up

Background: Herpes simplex virus infection of the central nervous system can manifest as potentially life- threatening necrotizing encephalitis that primarily affects the medial and inferior temporal lobe. Clinical features of acute Herpes simplex encephalitis are fever, headache, Wernicke's aphasia, epileptic seizures, confusion and reduced levels of consciousness. The affection of the temporal lobe and the limbic system may cause a significant and sometimes persisting memory impairment. However, there is evidence for a post-developmental neurogenesis in the adult human brain, especially in the temporal lobe (hippocampal dentate gyrus).

To date, no clinical studies on neuronal plasticity after Herpes simplex encephalitis are available; in particular, functional MRI (fMRI) studies have not been performed yet.

Aim of the study: In this study, functional brain MRI and neuropsychological testing will be performed in patients with Herpes simplex encephalitis and controls at two different time points to examine whether hippocampal neurogenesis and brain plasticity might play a role in the compensation of memory deficits caused by Herpes simplex encephalitis.

Study design: Patients with a definite diagnosis of Herpes simplex encephalitis (positive PCR and/or positive intrathecal specific antibody index >1.5) and age- and sex-matched controls will be tested neuropsychologically (t1=2–6 weeks after acute infection and t2=6 months after acute infection). At both time points, functional brain MRI will be performed following a dedicated protocol. A memory paradigm based on an experimental paradigm by Henke et al. (2003) will be presented to the patients. One series of 24 black-and-white full frontal portraits (12 male and 12 female faces) with annoyed/aggressive expression (round=20 minutes) with different professions (artistic or academic) typed below the faces are presented in sets of four stimuli followed by four control stimuli. Patients are asked to memorize the face-profession pairs. In a second section, faces are presented without profession, and the patients are instructed to remember the profession and to decide whether it is artistic or academic by pressing a designated key.

Interpretation of the fMRI series aims at the detection of activation changes in the expected areas (hippocampus, parahippocampal region and amygdala). First data will be presented.