Surgically Treated Intracerebral Haemorrhage : Pathophysiology and Clinical Aspects

Sammanfattning: Mortality and morbidity of intracerebral haemorrhage (ICH) is excessively high, and the case fatality rate has not improved in the last decades. Although surgery for ICH can be life-saving, no positive effect on functional outcome has been found in large cohorts of ICH patients. Increased understanding of the pathophysiology of ICH is needed to develop improved treatment strategies.In 17 ICH patients, paired cerebral microdialysis (CMD) catheters were inserted in the perihaemorrhagic zone (PHZ) and in normal uninjured cortex at time of surgery. Despite normalisation of cerebral blood flow, a persistent metabolic crisis indicative of mitochondrial dysfunction was detected in the PHZ. This metabolic pattern was not observed in the uninjured cortex.CMD was also used to sample proteins for proteomic analysis. A distinct proteome profile that changed over time was found in the PHZ when compared to the seemingly normal, uninjured cortex. However, protein adsorption to CMD membranes, which may interfere with concentration measurements, was substantial.Surgical treatment of 578 ICH patients was analysed in a nation-wide retrospective multi-centre study in Sweden over five years. Patients selected for surgery had similar age, pre-operative level of consciousness and co-morbidity profiles, but ICH volume and the proportion of deep-seated ICH differed among the six neurosurgical centres. Furthermore, there was variability in the post-operative care, including the use and duration of intracranial pressure monitoring, cerebrospinal fluid drainage and mechanical ventilation.In conclusion, the results of this thesis show that:(i) Despite surgical removal of an ICH a metabolic crisis caused by mitochondrial dysfunction, a potential future therapeutic target, persists in the perihaemorrhagic zone.(ii-iii) CMD is a valuable tool in ICH research for sampling novel biomarkers using proteomics, which may aid in the development of improved therapeutic interventions. However, caveats of the technique, such as protein adsorption to the CMD membrane, must be considered.(iv) The nation-wide study illustrates similar clinical features in patients selected for ICH surgery, but substantial variability in ICH volume and location as well as neurocritical care strategies among Swedish neurosurgical centres. Development of refined clinical guidelines may reduce such intercentre variability and lead to improved functional outcome for ICH patients.  

  Denna avhandling är EVENTUELLT nedladdningsbar som PDF. Kolla denna länk för att se om den går att ladda ner.