Lethal encephalitis caused by the Toscana virus in an elderly patient

Viral encephalitis is a life-threatening condition with prognosis mainly depending on viral pathogenicity, host immunologic state, and availability of virostatic therapy [1]. The Toscana virus (TOSV) is an arthropod-borne virus transmitted by sandflies and typically causes a transient febrile illness [2]. Recently, reports have emerged that TOSV causes not only aseptic meningitis but also serious meningoencephalitis or encephalitis without meningitis [2–8]. We present a patient who travelled around Tuscany and developed progressive fatal encephalitis. Serological positive TOSV antibodies were detected, and the autopsy revealed lymphocytic viral encephalitis. The general condition of a 73-year-old previously healthy man deteriorated rapidly a couple of days after returning from a 3 week trip to Tuscany. First symptoms were dizziness and disturbance of balance. Internal medical assessment was unremarkable at that time. As symptoms progressed he was transferred to our department of neurology. On admission he was alert but disoriented, and initially psychomotorically retarded, later agitated. Meningeal signs were negative. Cranial nerve functions and reflexes were normal except for hearing impairment on both sides. Walking and standing showed a tendency to fall to the left and were only possible with help. No impairment of the motor nerves and no sensory disturbances were found. Repeated neuroimaging examinations (cCT/cMRI) were unremarkable. EEG-studies showed generally slowed activity, but no epileptiform discharges. The body temperature fluctuated between 37–39.5 C. The laboratory studies revealed a slightly elevated CRP without a rise in WBC count. The CSF showed a slightly elevated cell count (8/3; normal \3/3) with elevated protein (757 mg/dl; normal \450), indicating a disturbance of the blood–CSF barrier. PCR for HSV, VZV and FSME virus were negative; antibody specificity tests for HSV, VZV, and FSME were within normal ranges. Serological studies on Legionella, Treponema pallidum, HIV, Hepatitis C, Borreliose were negative as were blood cultures. Serologically IgG antibodies against TOSV were positive 1:640 and IgM antibodies against TOSV were positive 1:40 using IIFT. In the CSF IgG antibodies against TOSV were tested positive 1:10. With PCR TOSV could not be detected in the CSF. As encephalitis was clinically assumed, an anti-infectious treatment course with broad antibiotics and aciclovir was implemented without clinical benefit. The patient gradually deteriorated and progressed to an akinetic–mutistic state, which persisted 2 weeks after, leading to coma and death. Post-mortem examination revealed a grossly normal brain with no signs of brain swelling. Histologic examination showed dominant perivascular cuffing of mainly lymphocytes in H & E stained sections in various brain regions (neocortex, basal ganglia, hypothalamus, thalamus, limbic areas, brain stem) and sparse infiltration of inflammatory cells in the leptomeninges, typical of viral meningoencephalitis (Fig. 1). Immunohistochemistry (IHC) with antibody CD 8 also displayed scattered S. Bartels J. G. Heckmann (&) Department of Neurology, Klinikum Landshut, Robert-Koch Str. 1, 84034 Landshut, Germany e-mail: josef.heckmann@klinikum-landshut.de