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- Jacobsen, A., et al.
(author)
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Bedside diagnosis of mitochondrial dysfunction in aneurysmal subarachnoid hemorrhage
- 2014
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 130:3, s. 156-163
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Journal article (peer-reviewed)abstract
- Objectives - Aneurysmal subarachnoid hemorrhage (SAH) is frequently associated with delayed neurological deterioration (DND). Several studies have shown that DND is not always related to vasospasm and ischemia. Experimental and clinical studies have recently documented that it is possible to diagnose and separate cerebral ischemia and mitochondrial dysfunction bedside. The study explores whether cerebral biochemical variables in SAH patients most frequently exhibit a pattern indicating ischemia or mitochondrial dysfunction. Methods - In 55 patients with severe SAH, intracerebral microdialysis was performed during neurocritical care with bedside analysis and display of glucose, pyruvate, lactate, glutamate, and glycerol. The biochemical patterns observed were compared to those previously described in animal studies of induced mitochondrial dysfunction as well as the pattern obtained in patients with recirculated cerebral infarcts. Results - In 29 patients, the biochemical pattern indicated mitochondrial dysfunction while 10 patients showed a pattern of cerebral ischemia, six of which also exhibited periods of mitochondrial dysfunction. Mitochondrial dysfunction was observed during 5162 h. An ischemic pattern was obtained during 688 h. Four of the patients (40%) with biochemical signs of ischemia died at the neurosurgical department as compared with three patients (10%) in the group of mitochondrial dysfunction. Conclusions - The study documents that mitochondrial dysfunction is a common cause of disturbed cerebral energy metabolism in patients with SAH. Mitochondrial dysfunction may increase tissue sensitivity to secondary adverse events such as vasospasm and decreased cerebral blood flow. The separation of ischemia and mitochondrial dysfunction bedside by utilizing microdialysis offers a possibility to evaluate new therapies.
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- Nielsen, T. H., et al.
(author)
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Bedside Diagnosis of Mitochondrial Dysfunction After Malignant Middle Cerebral Artery Infarction
- 2014
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In: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 21:1, s. 35-42
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Journal article (peer-reviewed)abstract
- The study explores whether the cerebral biochemical pattern in patients treated with hemicraniectomy after large middle cerebral artery infarcts reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. The study includes 44 patients treated with decompressive hemicraniectomy (DCH) due to malignant middle cerebral artery infarctions. Chemical variables related to energy metabolism obtained by microdialysis were analyzed in the infarcted tissue and in the contralateral hemisphere from the time of DCH until 96 h after DCH. Reperfusion of the infarcted tissue was documented in a previous report. Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12 to 96 h after DCH the pyruvate level was significantly higher in the infarcted tissue than in the non-infarcted hemisphere (p < 0.05). After a prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows signs of protracted mitochondrial dysfunction, characterized by a marked increase in cerebral lactate level with a normal or increased cerebral pyruvate level resulting in an increased LP-ratio. This biochemical pattern contrasts to cerebral ischemia, which is characterized by a marked decrease in cerebral pyruvate. The study supports the hypothesis that it is possible to diagnose cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by microdialysis and bed-side biochemical analysis.
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- Nielsen, T. H., et al.
(author)
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Recirculation usually precedes malignant edema in middle cerebral artery infarcts
- 2012
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 126:6, s. 404-410
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Journal article (peer-reviewed)abstract
- Objectives - In patients with large middle cerebral artery (MCA) infarcts, maximum brain swelling leading to cerebral herniation and death usually occurs 25 days after onset of stroke. The study aimed at exploring the pattern of compounds related to cerebral energy metabolism in infarcted brain tissue. Methods - Forty-four patients with malignant MCA infarcts were included after decision to perform decompressive hemicraniectomy (DHC). Cerebral energy metabolism was in all patients monitored bedside by 13 microdialysis catheters inserted into the infarcted hemisphere during DHC. In 29 of the patients, one microdialysis catheter was also placed in the non-infarcted hemisphere. MCA blood-flow velocity was monitored bilaterally by transcranial Doppler ultrasound. Results - The interstitial glucose levels were in both sides within normal limits throughout the monitoring period. Mean lactate/pyruvate (LP) ratio was very high in infarcted tissue immediately after DHC. The ratio slowly decreased but did not reach normal level during the study period. In the infarcted hemisphere, MCA blood-flow velocities increased from approximately 42 cm/s 1 day prior to DHC (nine of nine patients) to approximately 60 cm/s at day 4. Conclusions - Normal interstitial glucose level in the infarcted hemisphere in combination with substantial MCA blood-flow velocities bilaterally even before DHC was performed indicates that malignant brain swelling usually commences when the embolus/thrombosis has been largely resolved and recirculation of the infarcted area has started. The protracted increase of the LP ratio in infarcted tissue might indicate mitochondrial dysfunction.
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- Nordström, Carl Henrik, et al.
(author)
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Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion
- 2016
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 158:7, s. 1231-1240
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Journal article (peer-reviewed)abstract
- Background: The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality? Method: The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma. Results: Compromised aerobic metabolism occurred during 38 % of the study period. The biochemical pattern indicating mitochondrial dysfunction was more common than that of ischaemia. In EDH and NML aerobic metabolism was generally close to normal. In SDH or CHC it was often severely compromised. Mortality was increased in SDH with impaired aerobic metabolism, while CHC did not exhibit a similar relation. Conclusions: Compromised energy metabolism is most frequent in patients with SDH and CHC (32 % and 49 % of the study period, respectively). The biochemical pattern of mitochondrial dysfunction is more common than that of ischaemia (32 % and 6 % of the study period, respectively). A correlation between mortality and biochemical data is obtained provided the microdialysis catheter is placed in an area where energy metabolism reflects tissue outcome in a large part of the brain.
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- Poulsen, Frantz R., et al.
(author)
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Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis
- 2015
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In: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 22:2, s. 221-228
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Journal article (peer-reviewed)abstract
- Mortality and morbidity have remained high in bacterial meningitis. Impairment of cerebral energy metabolism probably contributes to unfavorable outcome. Intracerebral microdialysis is routinely used to monitor cerebral energy metabolism, and recent experimental studies indicate that this technique may separate ischemia and non-ischemic mitochondrial dysfunction. The present study is a retrospective interpretation of biochemical data obtained in a series of patients with severe community-acquired meningitis. Cerebral energy metabolism was monitored in 15 patients with severe community-acquired meningitis utilizing intracerebral microdialysis and bedside biochemical analysis. According to previous studies, cerebral ischemia was defined as lactate/pyruvate (LP) ratio > 30 with intracerebral pyruvate level < 70 A mu mol L-1. Non-ischemic mitochondrial dysfunction was defined as LP-ratio > 30 at a normal or increased interstitial concentration of pyruvate (a parts per thousand yen70 mu mol L-1). Patients with LP-ratios < 30 were classified as no mitochondrial dysfunction. The biochemical pattern was in 8 patients (10 microdialysis catheters) classified as no mitochondrial dysfunction, in 5 patients classified as non-ischemic mitochondrial dysfunction, and in 2 patients (3 catheters) classified as ischemia. In patients with severe community-acquired meningitis, compromised cerebral energy metabolism occurs frequently and was diagnosed in 7 out of 15 cases. A biochemical pattern of non-ischemic mitochondrial dysfunction appears to be a more common underlying condition than cerebral ischemia.
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| 8. |
- Reinstrup, Peter, et al.
(author)
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Best zero level for external ICP transducer
- 2019
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 161:4, s. 635-642
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Journal article (peer-reviewed)abstract
- Background: Continuous monitoring of intracranial pressure (ICP) was introduced in the 1950s. For correct ICP recordings, the zero-reference point for the external pressure gauge must be placed next to a head anatomical structure. We evaluated different anatomical points as zero reference for the ICP device at different head positions and their relation to brain centre (BC), foramen of Monro (Monro), and brain surface. Methods: Patients referred for neuroimaging due to e.g. headache all having normal 3D MRI scans were selected. Monro, BC, Orbit(O), external auditory meatus (EAM), and orbito-meatal (OM) line were identified and projected to mid-sagittal, or axial images. Each scan was evaluated like lying supine, 45° head elevations, upright, and 45° lateral position. Distances from skin to brain surface, BC, and Monro were measured. All values are presented as mean ± SD and/or range in millimetre. For conversion to mmHg, millimetre was multiplied by 0.074. Results: Twenty MRI scans were examined. A zero reference at EAM or glabella was ideal at BC when head was strict supine or in the lateral position. At 45° head elevation, an overestimation of the BC-ICP by 4.8 ± 0.8 and in upright 5.6 ± 0.5 mmHg was found, and 45° lateral underestimated ICP-BC by 6.3 ± 1.0 mmHg. Monro was situated 45 ± 5 mm rostral to the mid-OM line and 24 (18–31) mm inferior and 13 (8–17) mm in front of BC. A zero-reference point aligned with the highest point of the head underestimated BC-ICP and Monro-ICP. If the ICP reading was added 5.9 or 6.3 mmHg, respectively, a deviation from BC-ICP was ≤ 1.8 mmHg and Monro-ICP was ≤ 0.9 mmHg in all head positions. Conclusions: EAM and glabella are defined anatomical structures representing BC when strict supine or lateral but with 12 mmHg variation with different head positions used in clinical practice. The OM line follows Monro at head elevation, but not when the head is turned. When the highest external point on the head is used, ICP values at brain surface as well as Monro and BC are underestimated. This underestimation is fairly constant and, when corrected for, provides the most exact ICP reading.
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