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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Vesa Kiviniemi, University of Oulu,
- Second opponent: Professor II Kathinka Dæhli Kurz, Stavanger University,
- Third member and chair of the evaluation committee: Professor II Mathias Toft, University of Oslo
Chair of the Defence
Professor II Erik Taubøll, University of Oslo
Principal Supervisor
Associate professor Geir Ringstad, University of Oslo
Summary
Impaired cerebrospinal fluid (CSF) efflux is linked to neurodegenerative diseases, such as Alzheimer’s disease. Administration of drugs directly into CSF (intrathecally) is used to treat diseases of the spinal cord. The current understanding of CSF efflux in humans is primarily based on animal studies, and there is a lack of human in vivo data on the distribution of substances within the spinal cord. We used magnetic resonance imaging to investigate the in vivo distribution and efflux routes for an injected CSF tracer substance in patients with different CSF disorders.
Contrary to animal studies, our results suggest that neither lymphatic vessels in the nasal mucosa nor the meningeal space next to the superior sagittal sinus at the vertex of the skull, the parasagittal dura (PSD), are major efflux sites for CSF in humans. We propose that the PSD could be more important as a neuroimmune interface than a clearance route.
We examined the tracer distribution in the upper cervical spinal cord and the brainstem over time. Like previous studies of the cerebral hemispheres, the tracer reached the entire parenchyma in the spinal cord and brainstem from the periphery. The clearance of the tracer from the CSF and the parenchyma was delayed in a subgroup of older patients with idiopathic normal pressure hydrocephalus. CSF tracer clearance estimations from blood samples correlated with tracer enrichment in both parenchyma and CSF.
Our findings challenge earlier assumptions about major CSF efflux routes to lymph vessels in the nasal mucosa and to large collecting vessels at the vertex of the skull. Moreover, we provide data on the distribution of an exogenous substance from the CSF to the spinal cord and brainstem. In the future, estimations of CSF clearance from blood samples could help tailor the dosage of intrathecal drug therapies.
Additional information
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