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Surgically Treated Intracerebral Haemorrhage: Pathophysiology and Clinical Aspects
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.  

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. , p. 108
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1663
National Category
Anesthesiology and Intensive Care Surgery
Identifiers
URN: urn:nbn:se:liu:diva-156369DOI: 10.3384/diss.diva-156369ISBN: 9789176851272 (print)OAI: oai:DiVA.org:liu-156369DiVA, id: diva2:1305640
Public defence
2019-05-24, Berzeliussalen, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2019-04-17 Created: 2019-04-17 Last updated: 2019-04-17Bibliographically approved
List of papers
1. Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage.
Open this publication in new window or tab >>Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage.
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2018 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: We hypothesized that reduced cerebral blood flow (CBF) and/or energy metabolic disturbances exist in the tissue surrounding a surgically evacuated intracerebral hemorrhage (ICH). If present, such CBF and/or metabolic impairments may contribute to ongoing tissue injury and the modest clinical efficacy of ICH surgery.

OBJECTIVE: To conduct an observational study of CBF and the energy metabolic state in the perihemorrhagic zone (PHZ) tissue and in seemingly normal cortex (SNX) by microdialysis (MD) following surgical ICH evacuation.

METHODS: We evaluated 12 patients (median age 64; range 26-71 yr) for changes in CBF and energy metabolism following surgical ICH evacuation using Xenon-enhanced computed tomography (n = 10) or computed tomography perfusion (n = 2) for CBF and dual MD catheters, placed in the PHZ and the SNX at ICH surgery.

RESULTS: CBF was evaluated at a mean of 21 and 58 h postsurgery. In the hemisphere ipsilateral to the ICH, CBF improved between the investigations (36.6 ± 20 vs 40.6 ± 20 mL/100 g/min; P < .05). In total, 1026 MD samples were analyzed for energy metabolic alterations including glucose and the lactate/pyruvate ratio (LPR). The LPR was persistently elevated in the PHZ compared to the SNX region (P < .05). LPR elevations in the PHZ were predominately type II (pyruvate normal-high; indicating mitochondrial dysfunction) as opposed to type I (pyruvate low; indicating ischemia) at 4 to 48 h (70% vs 30%) and at 49 to 84 h (79% vs 21%; P < .05) postsurgery.

CONCLUSION: Despite normalization of CBF following ICH evacuation, an energy metabolic disturbance suggestive of mitochondrial dysfunction persists in the perihemorrhagic zone.

Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Neurology
Identifiers
urn:nbn:se:liu:diva-150994 (URN)10.1093/neuros/nyy179 (DOI)29788388 (PubMedID)
Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2019-04-17
2. Dynamic protein changes in the perihaemorrhagic zone of Surgically Treated Intracerebral Haemorrhage Patients
Open this publication in new window or tab >>Dynamic protein changes in the perihaemorrhagic zone of Surgically Treated Intracerebral Haemorrhage Patients
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 3181Article in journal (Refereed) Published
Abstract [en]

The secondary injury cascades exacerbating the initial brain injury following intracerebral haemorrhage (ICH) are incompletely understood. We used dual microdialysis (MD) catheters placed in the perihaemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) at time of surgical ICH evacuation in ten patients (range 26-70 years). Routine interstitial MD markers (including glucose and the lactate/pyruvate ratio) were analysed and remaining microdialysate was analysed by two-dimensional gel electrophoresis (2-DE) and nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS). Two time intervals were analysed; median 2-10 hours post-surgery (time A) and median 68-76 hours post-ICH onset (time B). Using 2-DE, we quantified 232 +/- 31 different protein spots. Two proteins differed between the MD catheters at time A, and 12 proteins at time B (p amp;lt; 0.05). Thirteen proteins were significantly altered between time A and time B in the SNX and seven proteins in the PHZ, respectively. Using nLC-MS/MS ca 800 proteins were identified out of which 76 were present in all samples. At time A one protein was upregulated and two downregulated, and at time B, seven proteins were upregulated, and four downregulated in the PHZ compared to the SNX. Microdialysis-based proteomics is feasible for study of secondary injury mechanisms and discovery of biomarkers after ICH.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-155569 (URN)10.1038/s41598-019-39499-2 (DOI)000459897600115 ()30816204 (PubMedID)
Note

Funding Agencies|Swedish Stroke Association (STROKE-Riksforbundet); ALF Grants of Region Ostergotland

Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-04-17
3. Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients
Open this publication in new window or tab >>Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients
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2019 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 161, no 5, p. 955-965Article in journal (Refereed) Published
Abstract [en]

Background

Supratentorial intracerebral haemorrhage (ICH) carries an excessive mortality and morbidity. Although surgical ICH treatment can be life-saving, the indications for surgery in larger cohorts of ICH patients are controversial and not well defined. We hypothesised that surgical indications vary substantially among neurosurgical centres in Sweden.

Objective

In this nation-wide retrospective observational study, differences in treatment strategies among all neurosurgical departments in Sweden were evaluated.

Methods

Patient records, neuroimaging and clinical outcome focused on 30-day mortality were collected on each operated ICH patient treated at any of the six neurosurgical centres in Sweden from 1 January 2011 to 31 December 2015.

Results

In total, 578 consecutive surgically treated ICH patients were evaluated. There was a similar incidence of surgical treatment among different neurosurgical catchment areas. Patient selection for surgery was similar among the centres in terms of patient age, pre-operative level of consciousness and co-morbidities, but differed in ICH volume, proportion of deep-seated vs. lobar ICH and pre-operative signs of herniation (p < .05). Post-operative patient management strategies, including the use of ICP-monitoring, CSF-drainage and mechanical ventilation, varied among centres (p < .05). The 30-day mortality ranged between 10 and 28%.

Conclusions

Although indications for surgical treatment of ICH in the six Swedish neurosurgical centres were homogenous with regard to age and pre-operative level of consciousness, important differences in ICH volume, proportion of deep-seated haemorrhages and pre-operative signs of herniation were observed, and there was a substantial variability in post-operative management. The present results reflect the need for refined evidence-based guidelines for surgical management of ICH.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Intracerebral haemorrhage, Surgery, Guidelines, Craniotomy, External ventricular drain, Intraventricular haemorrhage
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-156370 (URN)10.1007/s00701-019-03853-0 (DOI)000465840200018 ()30877470 (PubMedID)2-s2.0-85063056347 (Scopus ID)
Note

Funding agencies: ALF funding; Swedish Stroke Association

Available from: 2019-04-17 Created: 2019-04-17 Last updated: 2019-05-28Bibliographically approved

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