Short summary

The brain energy metabolism is strictly dependent on glucose and oxygen for proper neuronal function and survival. However, despite adequate substrate delivery (oxygen and glucose) mitochondrial dysfunction can mimic the pattern of cerebral ischemia causing cerebral infarction. The ability to distinguish between lack of substrate and mitochondrial dysfunction is crucial since the two conditions require different treatments. Both mitochondrial dysfunction and cerebral ischemia has been described in patients with community acquired severe meningitis. This cohort observational study aims at correlating ICP, brain parenchymal oxygen tension and microdialysis with markers of neuronal damage and clinical outcome.

Rationale

The brain energy metabolism is strictly dependent on glucose and oxygen for proper neuronal function and survival. However, despite adequate substrate delivery (oxygen and glucose) mitochondrial dysfunction can mimic the pattern of cerebral ischemia causing cerebral infarction. The ability to distinguish between lack of substrate and mitochondrial dysfunction is crucial since the two conditions require different treatments. Whereas treatment of oxygen and glucose deficiency aims at restoring substrate availability (opening of occluded blood vessel, increasing PO₂ in inspiratory air, administration of glucose intravenously), treatment of mitochondrial dysfunction and mitochondrial protection can experimentally be done by administration of agents like Cyclosporin-A or its analogues. The present study focuses on measuring cerebral metabolism using cerebral microdialysis technique combined with measurements of intracranial pressure and brain parenchymal PO₂ in patients with community acquired severe meningitis. This disease is associated with a high degree of mortality and neurological sequelae in survivors despite maximal intensive treatment. Previous data suggests that some patients suffer from mitochondrial dysfunction resulting in brain damage and death. We hypothesize that it is important to identify this subgroup of patients and that correct treatment based on parenchymal microdialysis-, intracranial pressure- and O₂ tension measurements can improve neurological outcome.

The study has been approved by the National Committee on Health Research Ethics in Denmark and the Danish Data Protection Agency.

Description of the cohort

Patients in the Region of Southern Denmark diagnosed with community acquired severe meningitis (who are unconscious) and submitted to OUH Odense University Hospital. In 2012 this population consisted of 10 patients. Patients will be included over a three year period and the cohort is therefore expected to consist of 30 patients.

Data and biological material

Metabolic markers (pyrocat, glucose, lactate and glutamate) from micro dialysate and Licox O₂ tensiometer collected over 24 hours as well as measurements of intracranial pressure. Quantified S100beta levels in brain micro dialysate and corresponding blood samples are handled by OPEN. Detailed description of the intra cerebral metabolic condition. Final outcome rated by physical and neuropsychological assessment 90 days post hospitalization.

Collaborating researchers and departments

Department for Infectious Diseases, Odense University Hospital

• Professor and Consultant in Infectious Diseases Court Pedersen, DMSc
• Lykke Larsen, MD

Department of Neurosurgery, Odense University Hospital

• Consultant Neurosurgeon Frantz Rom Poulsen
• Consultant Neurosurgeon Mette Schulz
• Troels Nielsen, MD

Department of Anaesthesiology and Intensive Care, Odense University Hospital

• Clinical Associate Professor and Consultant Anesthesiologist Jens Schierbeck

Publications associated with the project

Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis, Poulsen FR, Schulz M, Jacobsen A, Andersen AB, Larsen L, Schalén W, Nielsen TH, Nordström CH. Neurocrit Care. 2014 Aug 21.

Patterns of cerebral tissue oxygen tension and cytoplasmic redox state in bacterial meningitis. Larsen L, Nielsen TH, Nordström CH, Andersen AB, Schierbeck J, Schulz MK, Poulsen FR. Acta Anaesthesiol Scand. 2018 Oct 17. doi: 10.1111/aas.13278.