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Adjudication committee
- First opponent: Associate Professor Marie Studahl, Institute of Biomedicine, University of Gothenburg, Sweden
- Second opponent: Professor Christian Vedeler, Institute of Clinical Medicine, University of Bergen
- Third member and chair of the evaluation committee: Associate Professor Truls Leegaard, Institute of Clinical Medicine, University of Oslo
Chair of defence
Professor Halvor Rollag, Institute of Clinical Medicine, University of Oslo
Main supervisor
Overlege Vidar Ormaasen, Oslo University Hospital, Ullevål
Summary
The aims of this prospective observational study were to evaluate the etiology, clinical presentations, immune activation, and short- and long-term outcomes in patients with acute encephalitis and aseptic meningitis (ASM). Between 2014-2018, patients admitted to Oslo University Hospital Ullevål with suspected or proven acute CNS-infection were included in the study. Encephalitis was classified according to a consortium definition. A diagnostic algorithm used for assessment of patients included a broad panel of analyses in both cerebrospinal fluid (CSF) and serum. Inflammatory markers and metabolites of the kynurenine pathway were measured in CSF and serum. Short- and long-term outcomes of the patients were assessed through semi-structured interviews, self-report questionnaires and neuropsychological testing.
In patients with encephalitis, an etiological cause was found in 53%. Compared to other patients with encephalopathy, the combination of a low level of systemic inflammatory markers, fever and nausea was associated with encephalitis. For both encephalitis and ASM, increased cytokine levels and kynurenine metabolites were revealed in the CSF, and for patients with encephalitis, a net neurotoxic ratio of kynurenine metabolites was found. At follow-up after two months, 97% of the patients with encephalitis and 63% with ASM reported persisting complaints. In encephalitis, immune activation and activation of the kynurenine pathway during the acute phase were associated with a lower Health Related Quality of Life at follow-up. After 1 year, patients with encephalitis had lower scores than ASM patients on fine motor and psychomotor skills, learning, and memory.
Overall, the etiologic range is wide for patients with encephalitis, and the diagnostic challenges are substantial. Both encephalitis and ASM are associated with a generalized immune activation in the CNS during the acute stage, and the burden of both conditions is high, at least on the short term.
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