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Sökning: WFRF:(Lewén Anders 1965 )

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1.
  • Björk, Sofie, et al. (författare)
  • Thiopental and decompressive craniectomy as last-tier ICP-treatments in aneurysmal subarachnoid hemorrhage : is functional recovery within reach?
  • 2023
  • Ingår i: Neurosurgical review. - : Springer Nature. - 0344-5607 .- 1437-2320. ; 46:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The study aimed to investigate the indication and functional outcome after barbiturates and decompressive craniectomy (DC) as last-tier treatments for elevated intracranial pressure (ICP) in aneurysmal subarachnoid hemorrhage ( aSAH). This observational study included 891 aSAH patients treated at a single center between 2008 and 2018. Data on demography, admission status, radiology, ICP, clinical course, and outcome 1-year post-ictus were collected. Patients treated with thiopental ( barbiturate) and DC were the main target group. Thirty-nine patients (4%) were treated with thiopental alone and 52 (6%) with DC. These patients were younger and had a worse neurological status than those who did not require these treatments. Before thiopental, the median midline shift was 0 mm, whereas basal cisterns were compressed/obliterated in 66%. The median percentage of monitoring time with ICP > 20 mmHg immediately before treatment was 38%, which did not improve after 6 h of infusion. Before DC, the median midline shift was 10 mm, and the median percentage of monitoring time with ICP > 20 mmHg before DC was 56%, which both significantly improved postoperatively. At follow-up, 52% of the patients not given thiopental or operated with DC reached favorable outcome, whereas this occurred in 10% of the thiopental and DC patients. In summary, 10% of the aSAH cohort required thiopental, DC, or both. Thiopental and DC are important integrated last-tier treatment options, but careful patient selection is needed due to the risk of saving many patients into a state of suffering.
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2.
  • Galos, Peter, et al. (författare)
  • Machine learning based prediction of imminent ICP insults during neurocritical care of traumatic brain injury
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background/ObjectiveIncreased intracranial pressure (ICP) is a feared secondary brain insult in neurointensive care (NIC) of traumatic brain injury (TBI). A system that predicts ICP insults before they emerge may facilitate early optimization of the physiology, which in turn may lead to that the predicted ICP insult will never occur. The aim of this study was to evaluate the performance of different AI models in predicting risk of ICP insults. MethodsThe models were trained to predict risk of ICP insults starting within 30 minutes, using the Uppsala High Frequency TBI (UHF-TBI) dataset. A restricted dataset consisting of monitoring data only was used, and an unrestricted dataset using monitoring data as well as clinical data, demographic data and radiological evaluations. Four different model classes were compared: Gaussian Process Regression (GP), Logistic Regression (LR), Random Forest classifier (RF) and Extreme Gradient Boosted Decision Trees (XGBoost).ResultsSix hundred and two TBI patients were included (total monitoring 138 411 hours). On the task of predicting upcoming ICP insults, the GP model performed similar on the UHF-TBI dataset (sensitivity 93.2% and specificity 93.9%), as in earlier smaller studies. Using a more flexible model (XGBoost) resulted in slightly better performance (sensitivity 93.8% and specificity 94.6%). Adding more clinical variables and features further improved the performance of the models slightly (XGBoost: sensitivity 94.1% and specificity of 94.6%). Using AUROC as performance measure, the XGBoost models also performed slightly better than the other models. ConclusionsAI models have potential to become valuable tools for prediction of ICP insults in advance during NIC. The fact that common off-the-shelf models, such as XGBoost, performed well in predicting ICP insults opens for new possibilities, which can lead to faster advances in the field and faster clinical implementations.
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4.
  • Lenell, Samuel, et al. (författare)
  • Cerebrovascular reactivity (PRx) and optimal cerebral perfusion pressure in elderly with traumatic brain injury
  • 2024
  • Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 166:1
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Cerebral perfusion pressure (CPP) guidance by cerebral pressure autoregulation (CPA) status according to PRx (correlation mean arterial blood pressure (MAP) and intracranial pressure (ICP)) and optimal CPP (CPPopt = CPP with lowest PRx) is promising but little is known regarding this approach in elderly. The aim was to analyze PRx and CPPopt in elderly TBI patients.METHODS: A total of 129 old (≥ 65 years) and 342 young (16-64 years) patients were studied using monitoring data for MAP and ICP. CPP, PRx, CPPopt, and ΔCPPopt (difference between actual CPP and CPPopt) were calculated. Logistic regression analyses with PRx and ΔCPPopt as explanatory variables for outcome. The combined effects of PRx/CPP and PRx/ΔCPPopt on outcome were visualized as heatmaps.RESULTS: The elderly had higher PRx (worse CPA), higher CPPopt, and different temporal patterns. High PRx influenced outcome negatively in the elderly but less so than in younger patients. CPP close to CPPopt correlated to favorable outcome in younger, in contrast to elderly patients. Heatmap interaction analysis of PRx/ΔCPPopt in the elderly showed that the region for favorable outcome was centered around PRx 0 and ranging between both functioning and impaired CPA (PRx range - 0.5-0.5), and the center of ΔCPPopt was - 10 (range - 20-0), while in younger the center of PRx was around - 0.5 and ΔCPPopt closer to zero.CONCLUSIONS: The elderly exhibit higher PRx and CPPopt. High PRx influences outcome negatively in the elderly but less than in younger patients. The elderly do not show better outcome when CPP is close to CPPopt in contrast to younger patients.
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5.
  • Rostami, Elham, 1979-, et al. (författare)
  • Prognosis in moderate-severe traumatic brain injury in a Swedish cohort and external validation of the IMPACT models
  • 2022
  • Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:3, s. 615-624
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A major challenge in management of traumatic brain injury (TBI) is to assess the heterogeneity of TBI pathology and outcome prediction. A reliable outcome prediction would have both great value for the healthcare provider, but also for the patients and their relatives. A well-known prediction model is the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) prognostic calculator. The aim of this study was to externally validate all three modules of the IMPACT calculator on TBI patients admitted to Uppsala University hospital (UUH).Method: TBI patients admitted to UUH are continuously enrolled into the Uppsala neurointensive care unit (NICU) TBI Uppsala Clinical Research (UCR) quality register. The register contains both clinical and demographic data, radiological evaluations, and outcome assessments based on the extended Glasgow outcome scale extended (GOSE) performed at 6 months to 1 year. In this study, we included 635 patients with severe TBI admitted during 2008–2020. We used IMPACT core parameters: age, motor score, and pupillary reaction.Results: The patients had a median age of 56 (range 18–93), 142 female and 478 male. Using the IMPACT Core model to predict outcome resulted in an AUC of 0.85 for mortality and 0.79 for unfavorable outcome. The CT module did not increase AUC for mortality and slightly decreased AUC for unfavorable outcome to 0.78. However, the lab module increased AUC for mortality to 0.89 but slightly decreased for unfavorable outcome to 0.76. Comparing the predicted risk to actual outcomes, we found that all three models correctly predicted low risk of mortality in the surviving group of GOSE 2–8. However, it produced a greater variance of predicted risk in the GOSE 1 group, denoting general underprediction of risk. Regarding unfavorable outcome, all models once again underestimated the risk in the GOSE 3–4 groups, but correctly predicts low risk in GOSE 5–8.Conclusions: The results of our study are in line with previous findings from centers with modern TBI care using the IMPACT model, in that the model provides adequate prediction for mortality and unfavorable outcome. However, it should be noted that the prediction is limited to 6 months outcome and not longer time interval.
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6.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Association of Arterial Metabolic Content with Cerebral Blood Flow Regulation and Cerebral Energy Metabolism-A Multimodality Analysis in Aneurysmal Subarachnoid Hemorrhage
  • 2022
  • Ingår i: Journal of Intensive Care Medicine. - : Sage Publications. - 0885-0666 .- 1525-1489. ; 37:11, s. 1442-1450
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In this study, the association of the arterial content of oxygen, carbon dioxide, glucose, and lactate with cerebral pressure reactivity, energy metabolism and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH) was investigated.Methods In this retrospective study, 60 patients with aSAH, treated at the neurointensive care (NIC), Uppsala University Hospital, Sweden, between 2016 and 2021 with arterial blood gas (ABG), intracranial pressure, and cerebral microdialysis (MD) monitoring were included. The first 10 days were divided into an early phase (day 1 to 3) and a vasospasm phase (day 4 to 10).Results Higher arterial lactate was independently associated with higher/worse pressure reactivity index (PRx) in the early phase (beta = 0.32, P = .02), whereas higher pO(2) had the opposite association in the vasospasm phase (beta = -0.30, P = .04). Arterial glucose and pCO(2) were not associated with PRx. Higher arterial lactate (beta = 0.29, P = .05) was independently associated with higher MD-glucose in the vasospasm phase, whereas higher pO(2) had the opposite association in the vasospasm phase (beta = -0.33, P = .03). Arterial glucose and pCO(2) were not associated with MD-glucose. Higher pCO(2) in the early phase, lower arterial glucose in both phases, and lower arterial lactate in the vasospasm phase were associated (P < .05) with better clinical outcome.Conclusions Arterial variables associated with more vasoconstriction (higher pO(2) and lower arterial lactate) were associated with better cerebral pressure reactivity, but worse energy metabolism. In severe aSAH, when cerebral large-vessel vasospasm with exhausted distal vasodilation is common, more vasoconstriction could increase distal vasodilatory reserve and pressure reactivity, but also reduce cerebral blood flow and metabolic supply. The MD may be useful to monitor the net effects on cerebral metabolism in PRx-targeted NIC.
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7.
  • Svedung Wettervik, Teodor, et al. (författare)
  • Autoregulatory Cerebral Perfusion Pressure Insults in Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage : The Role of Insult Intensity and Duration on Clinical Outcome
  • 2024
  • Ingår i: Journal of Neurosurgical Anesthesiology. - : Wolters Kluwer. - 0898-4921 .- 1537-1921. ; 36:3, s. 228-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This single-center, retrospective study investigated the outcome effect of the combined intensity and duration of differences between actual cerebral perfusion pressure (CPP) and optimal cerebral perfusion pressure (CPPopt), and also for absolute CPP, in patients with traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (aSAH).Methods: A total of 378 TBI and 432 aSAH patients treated in a neurointensive care unit between 2008 and 2018 with at least 24 hours of CPPopt data during the first 10 days following injury, and with 6-month (TBI) or 12-month (aSAH) extended Glasgow Outcome Scale (GOS-E) scores, were included in the study. ∆CPPopt-insults (∆CPPopt=actual CPP−CPPopt) and CPP-insults were visualized as 2-dimensional plots to highlight the combined effect of insult intensity (mm Hg) and duration (min) on patient outcome.Results: In TBI patients, a zone of ∆CPPopt ± 10 mm Hg was associated with more favorable outcome, with transitions towards unfavorable outcome above and below this zone. CPP in the range of 60 to 80 mm Hg was associated with higher GOS-E, whereas CPP outside this range was associated with lower GOS-E. In aSAH patients, there was no clear transition from higher to lower GOS-E for ∆CPPopt-insults; however, there was a transition from favorable to unfavorable outcome when CPP was <80 mm Hg.Conclusions: TBI patients with CPP close to CPPopt exhibited better clinical outcomes, and absolute CPP within the 60 to 80 mm Hg range was also associated with favorable outcome. In aSAH patients, there was no clear transition for ∆CPPopt-insults in relation to outcome, whereas generally high absolute CPP values were associated overall with favorable recovery.
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8.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Autoregulatory Management in Traumatic Brain Injury : The Role of Absolute Pressure Reactivity Index Values and Optimal Cerebral Perfusion Pressure Curve Shape
  • 2023
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:21-22, s. 2341-2352
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate if the absolute pressure reactivity index (PRx) value influenced the association between cerebral perfusion pressure (CPP) and outcome and if the optimal CPP (CPPopt) curve shape influenced the association between deviation from CPPopt and outcome in traumatic brain injury (TBI). We included 383 TBI patients treated at the neurointensive care in Uppsala between 2008 and 2018 with at least 24 h of CPP data. To determine the influence of absolute PRx values on the association between absolute CPP and outcome, the percentage of monitoring time for combinations of CPP and PRx were correlated with outcome (Extended Glasgow Outcome Scale [GOS-E]) in a heatmap. To determine the association between CPP and the relatively best PRx (CPPopt), the percentage of monitoring time of ΔCPPopt (actual CPP-CPPopt) ±5 mm Hg was analyzed in relation to GOS-E. To determine the association between CPP and the relatively best PRx within a certain absolute PRx range (curve shape), both the percentage of ΔCPPopt within the absolute limits of reactivity (PRx <0.00, < 0.15, etc.) and within certain confidence intervals of PRx-deterioration (+0.025, +0.05 etc.) from CPPopt were analyzed in relation to GOS-E. The heatmap of PRx and absolute CPP versus outcome indicated that the CPP range (55-75 mm Hg) associated with favorable outcome was wider when PRx was below 0, whereas the upper CPP-threshold decreased as PRx increased. CPPopt could be calculated during 53% of the monitoring time. Higher percentage of monitoring time with ΔCPPopt ±5 mm Hg, ΔCPPopt within the reactivity-thresholds (PRx <0.30), and ΔCPPopt within the PRx-confidence interval +0.025 were all independently associated with favorable outcome in separate logistic regressions. These regressions had similar area under receiver operating curve and were not superior to a similar regression when the CPPopt-target was replaced by the percentage of monitoring time within the traditional fixed CPP-targets 60 to 70 mm Hg. Individualized CPPopt-targets exhibited a comparable outcome association as traditional CPP targets and different definitions of the best CPPopt range based on the PRx value had a limited effect on the association between deviation from CPPopt and outcome. Since CPPopt could only be calculated during half of the time, an alternative approach would be to assess the absolute PRx to anticipate a safe CPP range
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9.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Cerebral Blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage : Relation to Neurointensive Care Targets
  • 2022
  • Ingår i: Neurocritical Care. - : Springer Nature. - 1541-6933 .- 1556-0961. ; 37:1, s. 281-292
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The primary aim was to determine to what extent continuously monitored neurointensive care unit (neuro-ICU) targets predict cerebral blood flow (CBF) and delivery of oxygen (CDO2) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO2 were associated with clinical outcome. Methods In this observational study, patients with aneurysmal subarachnoid hemorrhage treated at the neuro-ICU in Uppsala, Sweden, from 2012 to 2020 with at least one xenon-enhanced computed tomography (Xe-CT) obtained within the first 14 days post ictus were included. CBF was measured with the Xe-CT and CDO2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF < 20 mL/100 g/min, and poor CDO2 was defined as CDO2 < 3.8 mL O-2/100 g/min. Neuro-ICU variables including intracranial pressure (ICP), pressure reactivity index, cerebral perfusion pressure (CPP), optimal CPP, and body temperature were assessed in association with the Xe-CT. The acute phase was divided into early phase (day 1-3) and vasospasm phase (day 4-14). Results Of 148 patients, 27 had underwent a Xe-CT only in the early phase, 74 only in the vasospasm phase, and 47 patients in both phases. The patients exhibited cerebral hypoperfusion and poor CDO2 for medians of 15% and 30%, respectively, of the cortical brain areas in each patient. In multiple regressions, higher body temperature was associated with higher CBF and CDO2 in the early phase. In a similar regression for the vasospasm phase, younger age and longer pulse transit time (lower peripheral resistance) correlated with higher CBF and CDO2, whereas lower hematocrit only correlated with higher CBF but not with CDO2. ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO2. R-2 of these regressions were below 0.3. Lower CBF and CDO2 in the early phase correlated with poor outcome, but this only held true for CDO2 in multiple regressions. Conclusions Systemic and cerebral physiological variables exhibited a modest association with CBF and CDO2. Still, cerebral hypoperfusion and low CDO2 were common and low CDO2 was associated with poor outcome. Xe-CT imaging could be useful to help detect secondary brain injury not evident by high ICP and low CPP.
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10.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Cerebral Microdialysis Monitoring of Energy Metabolism: Relation to Cerebral Blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage
  • 2023
  • Ingår i: Journal of Neurosurgical Anesthesiology. - : Ovid Technologies (Wolters Kluwer Health). - 0898-4921 .- 1537-1921. ; 35:4, s. 384-393
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: In this study, we investigated the roles of cerebral blood flow (CBF) and cerebral oxygen delivery (CDO2) in relation to cerebral energy metabolism after aneurysmal subarachnoid hemorrhage (aSAH).Methods: Fifty-seven adult aSAH patients treated on the neurointensive care unit at Uppsala, Sweden between 2012 and 2020, with at least 1 xenon-enhanced computed tomography (Xe-CT) scan in the first 14 days after ictus and concurrent microdialysis (MD) monitoring, were included in this retrospective study. CBF was measured globally and focally (around the MD catheter) with Xe-CT, and CDO2 calculated. Cerebral energy metabolites were measured using MD.Results: Focal ischemia (CBF <20 mL/100 g/min around the MD catheter was associated with lower median [interquartile range]) MD-glucose (1.2 [0.7 to 2.2] mM vs. 2.3 [1.3 to 3.5] mM; P=0.05) and higher MD-lactate-pyruvate (LPR) ratio (34 [29 to 66] vs. 25 [21 to 32]; P=0.02). A compensated/normal MD pattern (MD-LPR <25) was observed in the majority of patients (22/23, 96%) without focal ischemia, whereas 4 of 11 (36%) patients with a MD pattern of poor substrate supply (MD-LPR >25, MD-pyruvate <120 µM) had focal ischemia as did 5 of 20 (25%) patients with a pattern of mitochondrial dysfunction (MD-LPR >25, MD-pyruvate >120 µM) (P=0.04). Global CBF and CDO2, and focal CDO2, were not associated with the MD variables.Conclusions: While MD is a feasible tool to study cerebral energy metabolism, its validity is limited to a focal area around the MD catheter. Cerebral energy disturbances were more related to low CBF than to low CDO2. Considering the high rate of mitochondrial dysfunction, treatments that increase CBF but not CDO2, such as hemodilution, may still benefit glucose delivery to drive anaerobic metabolism.
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11.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Females Exhibit Better Cerebral Pressure Autoregulation, Less Mitochondrial Dysfunction, and Reduced Excitotoxicity after Severe Traumatic Brain Injury
  • 2022
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 39:21-22, s. 1507-1517
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to investigate sex-related differences in intracranial pressure (ICP) dynamics, cerebral pressure autoregulation (PRx55-15), cerebral energy metabolism, and clinical outcome after severe traumatic brain injury (TBI). One-hundred sixty-nine adult patients with TBI, treated at the Neurointensive Care (NIC) Unit at Uppsala University Hospital between 2008 and 2020 with ICP and cerebral microdialysis (MD) monitoring were included. Of the 169 patients with TBI, 131 (78%) were male and 38 (22%) female. Male patients were more often injured by motor vehicle accidents and less often by bicycle accidents (p < 0.05). There were otherwise no differences in age, neurological status at admission, and types of intracranial hemorrhages between the sexes. The percent of monitoring time with ICP above 20 mm Hg and cerebral perfusion pressure (CPP) below 60 mm Hg were similar for both sexes. Males exhibited more disturbed cerebral pressure autoregulation (PRx55-15 [mean +/- standard deviation (SD)]; 0.28 +/- 0.18 vs. 0.17 +/- 0.23, p < 0.05) on day 1, worse cerebral energy metabolism (MD-lactate-/pyruvate-ratio [median (interquartile range)]; 25 [19-31] vs. 20 [17-25], p < 0.01) and mitochondrial dysfunction (higher burden of MD-lactate-/pyruvate-ratio >25 and MD-pyruvate >120 mu M [median (interquartile range)]; 13 [0-58] % vs. 3 [0-17] %, p < 0.05) on days 2 to 5, increased excitotoxicity (MD-glutamate median [interquartile range]; 9 [4-32] mu M vs. 5 [3-10] mu M, p < 0.05) on days 2 to 5, and higher biomarker levels of cellular injury (MD-glycerol median [interquartile range]; 103 [66-193] mu M vs. 68 [49-106] mu M, p < 0.01) most pronounced on days 6 to 10. There was no difference in mortality or the degree of favorable outcome between the sexes.Altogether, females exhibited more favorable cerebral physiology post-TBI, particularly better mitochondrial function and reduced excitotoxicity, but this did not translate into better clinical outcome compared with males. Future studies are needed to further explore potential sex differences in secondary injury mechanisms in TBI.
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12.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Higher Intracranial Pressure Variability is Associated with Lower Cerebrovascular Resistance in Aneurysmal Subarachnoid Hemorrhage
  • 2023
  • Ingår i: Journal of clinical monitoring and computing. - : Springer Nature. - 1387-1307 .- 1573-2614. ; 37:1, s. 319-326
  • Tidskriftsartikel (refereegranskat)abstract
    • Higher intracranial pressure variability (ICPV) has been associated with a more favorable cerebral energy metabolism, lower rate of delayed ischemic neurologic deficits, and more favorable outcome in aneurysmal subarachnoid hemorrhage (aSAH). We have hypothesized that higher ICPV partly reflects more compliant and active cerebral vessels. In this study, the aim was to further test this by investigating if higher ICPV was associated with lower cerebrovascular resistance (CVR) and higher cerebral blood flow (CBF) after aSAH. In this observational study, 147 aSAH patients were included, all of whom had been treated in the Neurointensive Care (NIC) Unit, Uppsala, Sweden, 2012–2020. They were required to have had ICP monitoring and at least one xenon-enhanced computed tomography (Xe-CT) scan to study cortical CBF within the first 2 weeks post-ictus. CVR was defined as the cerebral perfusion pressure in association with the Xe-CT scan divided by the concurrent CBF. ICPV was defined over three intervals: subminute (ICPV-1m), 30-min (ICPV-30m), and 4 h (ICPV-4h). The first 14 days were divided into early (days 1–3) and vasospasm phase (days 4–14). In the vasospasm phase, but not in the early phase, higher ICPV-4h (β =  − 0.19, p < 0.05) was independently associated with a lower CVR in a multiple linear regression analysis and with a higher global cortical CBF (r = 0.19, p < 0.05) in a univariate analysis. ICPV-1m and ICPV-30m were not associated with CVR or CBF in any phase. This study corroborates the hypothesis that higher ICPV, at least in the 4-h interval, is favorable and may reflect more compliant and possibly more active cerebral vessels.
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13.
  • Svedung Wettervik, Teodor, et al. (författare)
  • ICP, CPP, and PRx in traumatic brain injury and aneurysmal subarachnoid hemorrhage : association of insult intensity and duration with clinical outcome
  • 2023
  • Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 138:2, s. 446-453
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVEThe primary aim of this study was to determine the combined effect of insult intensity and duration of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and pressure reactivity index (PRx) on outcome measured with the Glasgow Outcome Scale–Extended (GOS-E) in patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (aSAH).METHODSThis observational study included all TBI and aSAH patients treated in the neurointensive care unit in Uppsala, Sweden, 2008–2018, with at least 24 hours of ICP monitoring during the first 10 days following injury and available long-term clinical outcome data. ICP, CPP, and PRx insults were visualized as 2D plots to highlight the effects of both insult intensity and duration on patient outcome.RESULTSOf 950 included patients, 436 were TBI and 514 aSAH patients. The TBI patients were younger, more often male, and exhibited worse neurological status at admission, but recovered more favorably than the aSAH patients. There was a transition from good to poor outcome with ICP above 15–20 mm Hg in both TBI and aSAH. The two diagnoses had opposite CPP patterns. In TBI patients, CPP episodes at or below 80 mm Hg were generally favorable, whereas CPP episodes above 80 mm Hg were favorable in the aSAH patients. In the TBI patients there was a transition from good to poor outcome when PRx exceeded zero, but no evident transition was found in the aSAH cohort.CONCLUSIONSThe insult intensity and duration plots formulated in this study illustrate the similarities and differences between TBI and aSAH patients. In particular, aSAH patients may benefit from much higher CPP targets than TBI patients.
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14.
  • Svedung Wettervik, Teodor, et al. (författare)
  • ICP, PRx, CPP, and ∆CPPopt in pediatric traumatic brain injury : the combined effect of insult intensity and duration on outcome
  • 2023
  • Ingår i: Child's Nervous System. - : Springer. - 0256-7040 .- 1433-0350. ; 39:9, s. 2459-2466
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeThe aim was to investigate the combined effect of insult intensity and duration, regarding intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), and optimal CPP (CPPopt), on clinical outcome in pediatric traumatic brain injury (TBI).MethodThis observational study included 61 pediatric patients with severe TBI, treated at the Uppsala University Hospital, between 2007 and 2018, with at least 12 h of ICP data the first 10 days post-injury. ICP, PRx, CPP, and increment CPPopt (actual CPP-CPPopt) insults were visualized as 2-dimensional plots to illustrate the combined effect of insult intensity and duration on neurological recovery.ResultsThis cohort was mostly adolescent pediatric TBI patients with a median age at 15 (interquartile range 12-16) years. For ICP, brief episodes (minutes) above 25 mmHg and slightly longer episodes (20 min) of ICP 20-25 mmHg correlated with unfavorable outcome. For PRx, brief episodes above 0.25 as well as slightly lower values (around 0) for longer periods of time (30 min) were associated with unfavorable outcome. For CPP, there was a transition from favorable to unfavorable outcome for CPP below 50 mmHg. There was no association between high CPP and outcome. For increment CPPopt, there was a transition from favorable to unfavorable outcome when increment CPPopt went below -10 mmHg. No association was found for positive increment CPPopt values and outcome.ConclusionsThis visualization method illustrated the combined effect of insult intensity and duration in relation to outcome in severe pediatric TBI, supporting previous notions to avoid high ICP and low CPP for longer episodes of time. In addition, higher PRx for longer episodes of time and CPP below CPPopt more than -10 mmHg were associated with worse outcome, indicating a potential role for autoregulatory-oriented management in pediatric TBI.
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15.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Intracranial lesion features in moderate-to-severe traumatic brain injury : relation to neurointensive care variables and clinical outcome
  • 2023
  • Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 165, s. 2389-2398
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The primary aim was to determine the association of intracranial hemorrhage lesion type, size, mass effect, and evolution with the clinical course during neurointensive care and long-term outcome after traumatic brain injury (TBI).Methods: In this observational, retrospective study, 385 TBI patients treated at the neurointensive care unit at Uppsala University Hospital, Sweden, were included. The lesion type, size, mass effect, and evolution (progression on the follow-up CT) were assessed and analyzed in relation to the percentage of secondary insults with intracranial pressure > 20 mmHg, cerebral perfusion pressure < 60 mmHg, and cerebral pressure autoregulatory status (PRx) and in relation to Glasgow Outcome Scale-Extended.Results: A larger epidural hematoma (p < 0.05) and acute subdural hematoma (p < 0.001) volume, greater midline shift (p < 0.001), and compressed basal cisterns (p < 0.001) correlated with craniotomy surgery. In multiple regressions, presence of traumatic subarachnoid hemorrhage (p < 0.001) and intracranial hemorrhage progression on the follow-up CT (p < 0.01) were associated with more intracranial pressure-insults above 20 mmHg. In similar regressions, obliterated basal cisterns (p < 0.001) were independently associated with higher PRx. In a multiple regression, greater acute subdural hematoma (p < 0.05) and contusion (p < 0.05) volume, presence of traumatic subarachnoid hemorrhage (p < 0.01), and obliterated basal cisterns (p < 0.01) were independently associated with a lower rate of favorable outcome.Conclusions: The intracranial lesion type, size, mass effect, and evolution were associated with the clinical course, cerebral pathophysiology, and outcome following TBI. Future efforts should integrate such granular data into more sophisticated machine learning models to aid the clinician to better anticipate emerging secondary insults and to predict clinical outcome.
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16.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Intracranial pressure- and cerebral perfusion pressure threshold-insults in relation to cerebral energy metabolism in aneurysmal subarachnoid hemorrhage
  • 2022
  • Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:4, s. 1001-1014
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The aim was to investigate the association between intracranial pressure (ICP)- and cerebral perfusion pressure (CPP) threshold-insults in relation to cerebral energy metabolism and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Methods In this retrospective study, 75 aSAH patients treated in the neurointensive care unit, Uppsala, Sweden, 2008-2018, with ICP and cerebral microdialysis (MD) monitoring were included. The first 10 days were divided into early (day 1-3), early vasospasm (day 4-6.5), and late vasospasm phase (day 6.5-10). The monitoring time (%) of ICP insults (> 20 mmHg and > 25 mmHg), CPP insults (< 60 mmHg, < 70 mmHg, < 80 mmHg, and < 90 mmHg), and autoregulatory CPP optimum (CPPopt) insults ( increment CPPopt = CPP-CPPopt < - 10 mmHg, increment CPPopt > 10 mmHg, and within the optimal interval increment CPPopt +/- 10 mmHg) were calculated in each phase. Results Higher percent of ICP above the 20 mmHg and 25 mmHg thresholds correlated with lower MD-glucose and increased MD-lactate-pyruvate ratio (LPR), particularly in the vasospasm phases. Higher percentage of CPP below all four thresholds (60/70/80//90 mmHg) also correlated with a MD pattern of poor cerebral substrate supply (MD-LPR > 40 and MD-pyruvate < 120 mu M) in the vasospasm phase and higher burden of CPP below 60 mmHg was independently associated with higher MD-LPR in the late vasospasm phase. Higher percentage of CPP deviation from CPPopt did not correlate with worse cerebral energy metabolism. Higher burden of CPP-insults below all fixed thresholds in both vasospasm phases were associated with worse clinical outcome. The percentage of ICP-insults and CPP close to CPPopt were not associated with clinical outcome. Conclusions Keeping ICP below 20 mmHg and CPP at least above 60 mmHg may improve cerebral energy metabolism and clinical outcome.
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17.
  • Svedung Wettervik, Teodor, et al. (författare)
  • Intracranial Pressure Variability : A New Potential Metric of Cerebral Ischemia and Energy Metabolic Dysfunction in Aneurysmal Subarachnoid Hemorrhage?
  • 2023
  • Ingår i: Journal of Neurosurgical Anesthesiology. - : Wolters Kluwer. - 0898-4921 .- 1537-1921. ; 35:2, s. 208-214
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It was recently reported that lower intracranial pressure variability (ICPV) is associated with delayed ischemic neurological deficits and unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to determine whether lower ICPV also correlated with worse cerebral energy metabolism after aSAH.Methods: A total of 75 aSAH patients treated in the neurointensive care unit at Uppsala University Hospital, Sweden between 2008 and 2018 and with both intracranial pressure and cerebral microdialysis (MD) monitoring during the first 10 days after ictus were included in this retrospective study. ICPV was calculated with a bandpass filter limited to intracranial pressure slow waves with a wavelength of 55 to 15 seconds. Cerebral energy metabolites were measured hourly with MD. The monitoring period was divided into 3 phases; early (days 1 to 3), early vasospasm (days 4 to 6.5), and late vasospasm (days 6.5 to 10).Results: Lower ICPV was associated with lower MD-glucose in the late vasospasm phase, lower MD-pyruvate in the early vasospasm phases, and higher MD-lactate-pyruvate ratio (LPR) in the early and late vasospasm phases. Lower ICPV was associated with poor cerebral substrate supply (LPR >25 and pyruvate <120 µM) rather than mitochondrial failure (LPR >25 and pyruvate >120 µM). There was no association between ICPV and delayed ischemic neurological deficit, but lower ICPV in both vasospasm phases correlated with unfavorable outcomes.Conclusion: Lower ICPV was associated with an increased risk for disturbed cerebral energy metabolism and worse clinical outcomes in aSAH patients, possibly explained by a vasospasm-related decrease in cerebral blood volume dynamics and cerebral ischemia.
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18.
  • Svedung Wettervik, Teodor, et al. (författare)
  • Low intracranial pressure variability is associated with delayed cerebral ischemia and unfavorable outcome in aneurysmal subarachnoid hemorrhage
  • 2022
  • Ingår i: Journal of clinical monitoring and computing. - : Springer Nature. - 1387-1307 .- 1573-2614. ; 36:2, s. 569-578
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeHigh intracranial pressure variability (ICPV) is associated with favorable outcome in traumatic brain injury, by mechanisms likely involving better cerebral blood flow regulation. However, less is known about ICPV in aneurysmal subarachnoid hemorrhage (aSAH). In this study, we investigated the explanatory variables for ICPV in aSAH and its association with delayed cerebral ischemia (DCI) and clinical outcome.MethodsIn this retrospective study, 242 aSAH patients, treated at the neurointensive care, Uppsala, Sweden, 2008–2018, with ICP monitoring the first ten days post-ictus were included. ICPV was evaluated on three time scales: (1) ICPV-1 m—ICP slow wave amplitude of wavelengths between 55 and 15 s, (2) ICPV-30 m—the deviation from the mean ICP averaged over 30 min, and (3) ICPV-4 h—the deviation from the mean ICP averaged over 4 h. The ICPV measures were analyzed in the early phase (day 1–3), in the early vasospasm phase (day 4–6.5), and the late vasospasm phase (day 6.5–10).ResultsHigh ICPV was associated with younger age, reduced intracranial pressure/volume reserve (high RAP), and high blood pressure variability in multiple linear regression analyses for all ICPV measures. DCI was associated with reduced ICPV in both vasospasm phases. High ICPV-1 m in the post-ictal early phase and the early vasospasm phase predicted favorable outcome in multiple logistic regressions, whereas ICPV-30 m and ICPV-4 h in the late vasospasm phase had a similar association.ConclusionsHigher ICPV may reflect more optimal cerebral vessel activity, as reduced values are associated with an increased risk of DCI and unfavorable outcome after aSAH.
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19.
  • Svedung-Wettervik, Teodor, et al. (författare)
  • Temperature Changes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage : Relation to Injury Pattern, Intracranial Pressure Dynamics, Cerebral Energy Metabolism, and Clinical Outcome
  • 2023
  • Ingår i: Neurocritical Care. - : Humana Press. - 1541-6933 .- 1556-0961. ; 39, s. 145-154
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim was to study the course of body temperature in the acute phase of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) in relation to the primary brain injury, cerebral physiology, and clinical outcome.Methods: In this observational study, 166 patients with aSAH treated at the neurosurgery department at Uppsala University Hospital in Sweden between 2008 and2018 with temperature, intracranial pressure (ICP), and microdialysis (MD) monitoring were included. The first 10 days were divided into the early phase (days 1-3) and the vasospasm phase (days 4-10).Results: Normothermia (temperature = 36-38 degrees C) was most prevalent in the early phase. A lower mean temperature at this stage was univariately associated with a worse primary brain injury, with higher Fisher grade and higher MD glycerol concentration, as well as a worse neurological recovery at 1 year. There was otherwise no association between temperature and cerebral physiological variables in the early phase. There was a transition toward an increased burden of hyperthermia (temperature > 38 degrees C) in the vasospasm phase. This was associated with concurrent infections but not with neurological or radiological injury severity at admission. Elevated temperature was associated with higher MD pyruvate concentration, lower rate of an MD pattern indicative of ischemia, and higher rate of poor neurological recovery at 1 year. There was otherwise no association between temperature and cerebral physiological variables in the vasospasm phase. The associations between temperature and clinical outcome did not hold true in multiple logistic regression analyses.Conclusions: Spontaneously low temperature in the early phase reflected a worse primary brain injury and indicated a worse outcome prognosis. Hyperthermia was common in the vasospasm phase and was more related to infections than primary injury severity but also with a more favorable energy metabolic pattern with better substrate supply, possibly related to hyperemia.
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20.
  • Velle, Fartein, et al. (författare)
  • Cerebral pressure autoregulation and optimal cerebral perfusion pressure during neurocritical care of children with traumatic brain injury
  • 2023
  • Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons (AANS). - 1933-0707 .- 1933-0715. ; 31:5, s. 503-513
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVEThe management of cerebral perfusion pressure (CPP) is a challenge in children with traumatic brain injury (TBI) because the normal blood pressure is age dependent and the role of cerebral pressure autoregulation (CPA) is unclear. In this study, the authors aimed to examine the pressure reactivity index (PRx), CPP, optimal CPP (CPPopt), and deviations from CPPopt (ΔCPPopt) in a series of children with TBI generally and regarding age relations, temporal changes, and the influence on outcome.METHODSIntracranial pressure (ICP) and mean arterial pressure (MAP) monitoring data were collected during neurointensive care in 57 children who sustained a TBI and were ≤ 17 years of age. CPP, PRx, CPPopt, and ΔCPPopt (actual CPP − CPPopt) were calculated. Clinical outcomes at 6 months postinjury were dichotomized into favorable outcomes (Glasgow Outcome Scale [GOS] score 4 or 5) and unfavorable outcomes (GOS scores 1–3).RESULTSThe median patient age was 15 (range 0.5–17) years, and the median Glasgow Coma Scale motor score at admission was 5 (range 2–5). Forty-nine (86%) of the 57 patients had favorable outcomes. For the entire group, lower PRx (better preserved CPA) was associated with a more favorable outcome (p = 0.023, ANCOVA adjusted for age). When the children were divided into age groups, this finding was statistically significant in children ≤ 15 years of age (p = 0.016), but not in children ≥ 16 years (p = 0.528). In children ≤ 15 years, a lower proportion of time with ΔCPPopt < −10% was significantly associated with a favorable outcome (p = 0.038), but not in the older age group. Temporal analysis indicated that PRx was higher (more impaired CPA) from day 4 and CPPopt was higher from day 6 in the unfavorable outcome group compared with the favorable outcome group, although those findings were not significant.CONCLUSIONSImpaired CPA is related to poor outcome, particularly in children ≤ 15 years of age. In that age group, actual CPP below the CPPopt level contributed significantly to unfavorable outcome, while levels close to or above the CPPopt were unrelated to outcome. CPPopt appears to be higher during the time period when CPA is most impaired.
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21.
  • Velle, Fartein, et al. (författare)
  • The effects of cerebral pressure autoregulation status and CPP levels on cerebral metabolism in pediatric traumatic brain injury
  • 2024
  • Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 166:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCerebral perfusion pressure (CPP) management in the developing child with traumatic brain injury (TBI) is challenging. The pressure reactivity index (PRx) may serve as marker of cerebral pressure autoregulation (CPA) and optimal CPP (CPPopt) may be assessed by identifying the CPP level with best (lowest) PRx. To evaluate the potential of CPPopt guided management in children with severe TBI, cerebral microdialysis (CMD) monitoring levels of lactate and the lactate/pyruvate ratio (LPR) (indicators of ischemia) were related to actual CPP levels, autoregulatory state (PRx) and deviations from CPPopt (ΔCPPopt).MethodsRetrospective study of 21 children ≤ 17 years with severe TBI who had both ICP and CMD monitoring were included. CPP, PRx, CPPopt and ΔCPPopt where calculated, dichotomized and compared with CMD lactate and lactate-pyruvate ratio.ResultsMedian age was 16 years (range 8–17) and median Glasgow coma scale motor score 5 (range 2–5). Both lactate (p = 0.010) and LPR (p =  < 0.001) were higher when CPP ≥ 70 mmHg than when CPP < 70. When PRx ≥ 0.1 both lactate and LPR were higher than when PRx < 0.1 (p =  < 0.001). LPR was lower (p = 0.012) when CPPopt ≥ 70 mmHg than when CPPopt < 70, but there were no differences in lactate levels. When ΔCPPopt > 10 both lactate (p = 0.026) and LPR (p = 0.002) were higher than when ΔCPPopt < –10.ConclusionsIncreased levels of CMD lactate and LPR in children with severe TBI appears to be related to disturbed CPA (PRx). Increased lactate and LPR also seems to be associated with actual CPP levels ≥ 70 mmHg. However, higher lactate and LPR values were also seen when actual CPP was above CPPopt. Higher CPP appears harmful when CPP is above the upper limit of pressure autoregulation. The findings indicate that CPPopt guided CPP management may have potential in pediatric TBI.
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22.
  • Abu Hamdeh, Sami, et al. (författare)
  • Intracranial pressure elevations in diffuse axonal injury : association with nonhemorrhagic MR lesions in central mesencephalic structures
  • 2019
  • Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 131:2, s. 604-611
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in patients with DAI.Methods: Fifty-two patients with severe TBI (median age 24 years, range 9–61 years), who had undergone ICP monitoring and had DAI on MRI, as determined using T2*-weighted gradient echo, susceptibility-weighted imaging, and diffusion-weighted imaging (DWI) sequences, were enrolled. The proportion of good monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression.Results: All patients had episodes of ICP > 20 mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95% CI 3%–13%, p = 0.004) and young age (−0.2% of GMT with ICP > 20 mm Hg, 95% CI −0.07% to −0.3%, p = 0.002) were associated with increased ICP.Conclusions: Increased ICP occurs in approximately one-third of patients with severe TBI who have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN-T) are associated with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in patients with DAI.Abbreviations: ADC = apparent diffusion coefficient; CPP = cerebral perfusion pressure; DAI = diffuse axonal injury; DWI = diffusion-weighted imaging; EVD = external ventricular drain; GCS = Glasgow Coma Scale; GMT = good monitoring time; GOSE = Glasgow Outcome Scale–Extended; ICC = intraclass correlation coefficient; ICP = intracranial pressure; MAP = mean arterial blood pressure; NICU = neurointensive care unit; SN-T = substantia nigra and mesencephalic tegmentum; SWI = susceptibility-weighted imaging; TBI = traumatic brain injury; T2*GRE = T2*-weighted gradient echo.
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23.
  • Abu Hamdeh, Sami, et al. (författare)
  • Intracranial pressure elevations in diffuse axonal injury are associated with non-hemorrhagic MR lesions in central mesencephalic structures
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: Increased intracranial pressure (ICP) in severe traumatic brain injury (TBI) patients with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in DAI patients.Methods: Fifty-two severe TBI patients (median 24, range 9-61 years), with ICP-monitoring and DAI on MRI, using T2*-weighted gradient echo, susceptibility-weighted and diffusion-weighted (DW) sequences, were enrolled. Proportion of good monitoring time (GMT) with ICP>20 mmHg during the first 120 hours post-injury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression. Results: All patients had episodes of ICP>20 mmHg. The mean proportion of GMT with ICP>20 mmHg was 5% and 27% of the patients (14/52) had more than 5% of GMT with ICP>20 mmHg. Glasgow Coma Scale motor score at admission (P=0.04) and lesions on DW images in the substantia nigra and mesencephalic tegmentum (SN-T, P=0.001) were associated with the proportion of GMT with ICP>20 mmHg. In multivariate linear regression, lesions on DW images in SN-T (8% of GMT with ICP>20 mmHg, 95% CI 3–13%, P=0.004) and young age (-0.2% of GMT with ICP>20 mmHg, 95% CI -0.07–-0.3%, P=0.0008) were associated with increased ICP.   Conclusions: Increased ICP occurs in ~1/3 of severe TBI patients with DAI. Age and lesions on DW images in the central mesencephalon (SN-T) associate with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in DAI patients.
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24.
  • Borota, Ljubisa, et al. (författare)
  • Dual lumen balloon catheter - An effective substitute for two single lumen catheters in treatment of vascular targets with challenging anatomy
  • 2018
  • Ingår i: Journal of clinical neuroscience. - : Elsevier BV. - 0967-5868 .- 1532-2653. ; 51, s. 91-99
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to describe our experience in the treatment of various pathological conditions of the cranial and spinal blood vessels and hypervascularized lesions using dual lumen balloon catheters. Twenty-five patients were treated with endovascular techniques: two with vasospasm of cerebral blood vessels caused by subarachnoid hemorrhage, one with a hypervascularized metastasis in the vertebral body, two with spinal dural fistula, four with cerebral dural fistula, three with cerebral arteriovenous malformations, and 13 with aneurysms. The dual lumen balloon catheters were used for remodeling of the coil mesh, injection of various liquid embolic agents, particles and nimodipine, for the prevention of reflux and deployment of coils and stents. The diameter of catheterized blood vessels varied from 0.7 mm to 4 mm. Two complications occurred: perforation of an aneurysm in one case and gluing of the tip of balloon catheter by embolic material in another case. All other interventions were uneventful, and therapeutic goals were achieved in all cases except in the case with gluing of the tip of balloon catheter. The balloons effectively prevented reflux regardless of the type of the embolic material and diameter of blood vessel. The results of our study show that dual lumen balloon catheters allow complex interventions in the narrow cerebral and spinal blood vessels where the safe use of two single lumen catheters is either limited or impossible.
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25.
  • Clausen, Fredrik, 1973-, et al. (författare)
  • The nitrone free radical scavenger NXY-059 is neuroprotective when administered after traumatic brain injury in the rat
  • 2008
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert, Inc.. - 0897-7151 .- 1557-9042. ; 25:12, s. 1449-1457
  • Tidskriftsartikel (refereegranskat)abstract
    • Reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumatic brain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimental TBI. NXY-059, a nitrone free radical trapping compound, has been shown to be neuroprotective in models of ischemic stroke but has not been evaluated in experimental TBI. In the present study, a continuous 24-h intravenous infusion of NXY-059 or vehicle was initiated 30min following a severe lateral fluid percussion brain injury (FPI) in adult rats (n=22), and histological and behavioral outcomes were evaluated. Sham-injured animals (n=22) receiving identical drug infusion were used as controls. Visuospatial learning was evaluated in the Morris water maze at post-injury days 11–14, followed by a probe trial (memory test) at day 18. The animals were sacrificed at day 18, and loss of hemispheric brain tissue was measured in microtubule-associated protein (MAP)–2stained sections. Brain-injured, NXY-059-treated animals showed a significant reduction of visuospatial learning deficits when compared to the brain-injured, vehicle-treated control animals (p<0.05). NXY-059-treated animals significantly reduced the loss of hemispheric tissue compared to brain-injured controls (43.0±11mm3 versus 74.4±19mm3, respectively; p<0.01). The results show that post-injury treatment with NXY-059 significantly attenuated the loss of injured brain tissue and improved cognitive outcome, suggesting a major role for ROS in the pathophysiology of TBI.
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26.
  • Dyhrfort, Philip, et al. (författare)
  • A Dedicated 21-Plex Proximity Extension Assay Panel for High-Sensitivity Protein Biomarker Detection Using Microdialysis in Severe Traumatic Brain Injury : The Next Step in Precision Medicine?
  • 2023
  • Ingår i: NEUROTRAUMA REPORTS. - : Mary Ann Liebert. - 2689-288X. ; 4:1, s. 25-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral protein profiling in traumatic brain injury (TBI) is needed to better comprehend secondary injury pathways. Cerebral microdialysis (CMD), in combination with the proximity extension assay (PEA) technique, has great potential in this field. By using PEA, we have previously screened >500 proteins from CMD samples collected from TBI patients. In this study, we customized a PEA panel prototype of 21 selected candidate protein biomarkers, involved in inflammation (13), neuroplasticity/-repair (six), and axonal injury (two). The aim was to study their temporal dynamics and relation to age, structural injury, and clinical outcome. Ten patients with severe TBI and CMD monitoring, who were treated in the Neurointensive Care Unit, Uppsala University Hospital, Sweden, were included. Hourly CMD samples were collected for up to 7 days after trauma and analyzed with the 21-plex PEA panel. Seventeen of the 21 proteins from the CMD sample analyses showed significantly different mean levels between days. Early peaks (within 48 h) were noted with interleukin (IL)-1 beta, IL-6, IL-8, granulocyte colony-stimulating factor, transforming growth factor alpha, brevican, junctional adhesion molecule B, and neurocan. C-X-C motif chemokine ligand 10 peaked after 3 days. Late peaks (>5 days) were noted with interleukin-1 receptor antagonist (IL-1ra), monocyte chemoattractant protein (MCP)-2, MCP-3, urokinase-type plasminogen activator, Dickkopf-related protein 1, and DRAXIN. IL-8, neurofilament heavy chain, and TAU were biphasic. Age (above/below 22 years) interacted with the temporal dynamics of IL-6, IL-1ra, vascular endothelial growth factor, MCP-3, and TAU. There was no association between radiological injury (Marshall grade) or clinical outcome (Extended Glasgow Outcome Scale) with the protein expression pattern. The PEA method is a highly sensitive molecular tool for protein profiling from cerebral tissue in TBI. The novel TBI dedicated 21-plex panel showed marked regulation of proteins belonging to the inflammation, plasticity/repair, and axonal injury families. The method may enable important insights into complex injury processes on a molecular level that may be of value in future efforts to tailor pharmacological TBI trials to better address specific disease processes and optimize timing of treatments.
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27.
  • Dyhrfort, Philip, et al. (författare)
  • Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care
  • 2019
  • Ingår i: Journal of Neurotrauma. - : MARY ANN LIEBERT, INC. - 0897-7151 .- 1557-9042. ; 36:20, s. 2872-2885
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) is followed by secondary injury mechanisms strongly involving neuroinflammation. To monitor the complex inflammatory cascade in human TBI, we used cerebral microdialysis (MD) and multiplex proximity extension assay (PEA) technology and simultaneously measured levels of 92 protein biomarkers of inflammation in MD samples every three hours for five days in 10 patients with severe TBI under neurointensive care. One mu L MD samples were incubated with paired oligonucleotide-conjugated antibodies binding to each protein, allowing quantification by real-time quantitative polymerase chain reaction. Sixty-nine proteins were suitable for statistical analysis. We found five different patterns with either early (<48 h; e.g., CCL20, IL6, LIF, CCL3), mid (48-96 h; e.g., CCL19, CXCL5, CXCL10, MMP1), late (>96 h; e.g., CD40, MCP2, MCP3), biphasic peaks (e.g., CXCL1, CXCL5, IL8) or stable (e.g., CCL4, DNER, VEGFA)/low trends. High protein levels were observed for e.g., CXCL1, CXCL10, MCP1, MCP2, IL8, while e.g., CCL28 and MCP4 were detected at low levels. Several proteins (CCL8, -19, -20, -23, CXCL1, -5, -6, -9, -11, CST5, DNER, Flt3L, and SIRT2) have not been studied previously in human TBI. Cross-correlation analysis revealed that LIF and CXCL5 may play a central role in the inflammatory cascade. This study provides a unique data set with individual temporal trends for potential inflammatory biomarkers in patients with TBI. We conclude that the combination of MD and PEA is a powerful tool to map the complex inflammatory cascade in the injured human brain. The technique offers new possibilities of protein profiling of complex secondary injury pathways.
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28.
  • Engquist, Henrik, et al. (författare)
  • CBF changes and cerebral energy metabolism during hypervolemia, hemodilution, and hypertension therapy in patients with poor-grade subarachnoid hemorrhage
  • 2021
  • Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 134:2, s. 555-564
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Despite the multifactorial pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), augmentation of cerebral blood flow (CBF) is still considered essential in the clinical management of DCI. The aim of this prospective observational study was to investigate cerebral metabolic changes in relation to CBF during therapeutic hypervolemia, hemodilution, and hypertension (HHH) therapy in poor-grade SAH patients with DCI.METHODS: CBF was assessed by bedside xenon-enhanced CT at days 0–3, 4–7, and 8–12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. CBF measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group.RESULTS: In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1–33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2–46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a lactate/pyruvate (L/P) ratio of 26.9 (IQR 22.9–48.5) at baseline and 31.6 (IQR 22.4–35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients.CONCLUSIONS: Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation.
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29.
  • Engquist, Henrik, 1964- (författare)
  • Clinical Bedside Studies of Cerebral Blood Flow in Severe Subarachnoid Hemorrhage Using Xenon CT
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aneurysmal subarachnoid hemorrhage (SAH) is frequently complicated by delayed cerebral ischemia (DCI), contributing to poor outcome. Particularly for patients in poor neurological state, prediction of the acute clinical course is difficult, as is the early detection of DCI. Repeated measurement of global and regional cerebral blood flow (CBF) could potentially identify patients at risk of deterioration and guide in the clinical management.The studies in this thesis are based on bedside measurements of CBF by xenon-enhanced CT with the aim to assess and characterize global and regional CBF disturbances at different phases in the acute course after severe SAH. Furthermore, the effects of hemodynamic augmentation by hypervolemia, hemodilution and hypertension (HHH-therapy) on CBF and cerebral energy metabolism in patients with DCI are addressed.In Paper I, CBF disturbances at the early phase (day 0–3) after SAH were found common and often heterogeneous with substantial regions of near ischemic CBF. Older age and more severe hemorrhage (graded according to Fisher from CT) were factors associated with more compromised CBF. In Paper II, exploring the temporal dynamics of CBF, low initial CBF was associated with a persistent low level of CBF at day 4–7. The association was more pronounced when patients receiving HHH-therapy were separated, and indicates that patients with low CBF, even without clinical signs of DCI, could benefit from careful surveillance and optimization of circulation. In Paper III, the effects on CBF from HHH-therapy in patients with DCI was assessed. Hematocrit decreased during treatment, while the increase in systemic blood pressure was modest. Global CBF and CBF of the worst perfused regions increased, and the proportion of regions with critically low flow decreased accordingly. In Paper IV, the effects of HHH was further assessed in patients also monitored with cerebral microdialysis (CMD). CBF improved during HHH-therapy, while the cerebral energy metabolic CMD parameters stayed statistically unchanged. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was common, possibly explained by mitochondrial dysfunction.
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30.
  • Engquist, Henrik, et al. (författare)
  • Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT
  • 2018
  • Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 28:2, s. 143-151
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is difficult and still carries controversies. In this study, the effect of therapeutic hypervolemia, hemodilution, and hypertension (HHH-therapy) on cerebral blood flow (CBF) was assessed by xenon-enhanced computerized tomography (XeCT) hypothesizing an increase in CBF in poorly perfused regions.METHODS:Bedside XeCT measurements of regional CBF in mechanically ventilated SAH patients were routinely scheduled for day 0-3, 4-7, and 8-12. At clinical suspicion of DCI, patients received 5-day HHH-therapy. For inclusion, XeCT was required at 0-48 h before start of HHH (baseline) and during therapy. Data from corresponding time-windows were also collected for non-DCI patients.RESULTS:Twenty patients who later developed DCI were included, and twenty-eight patients without DCI were identified for comparison. During HHH, there was a slight nonsignificant increase in systolic blood pressure (SBP) and a significant reduction in hematocrit. Median global cortical CBF for the DCI group increased from 29.5 (IQR 24.6-33.9) to 38.4 (IQR 27.0-41.2) ml/100 g/min (P = 0.001). There was a concomitant increase in regional CBF of the worst vascular territories, and the proportion of area with blood flow below 20 ml/100 g/min was significantly reduced. Non-DCI patients showed higher CBF at baseline, and no significant change over time.CONCLUSIONS:HHH-therapy appeared to increase global and regional CBF in DCI patients. The increase in SBP was small, while the decrease in hematocrit was more pronounced, which may suggest that intravascular volume status and rheological effects are of importance. XeCT may be potentially helpful in managing poor-grade SAH patients.
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31.
  • Engquist, Henrik, et al. (författare)
  • Hemodynamic Disturbances in the Early Phase After Subarachnoid Hemorrhage : Regional Cerebral Blood Flow Studied by Bedside Xenon-enhanced CT.
  • 2018
  • Ingår i: Journal of Neurosurgical Anesthesiology. - 0898-4921 .- 1537-1921. ; 30:1, s. 49-58
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The mechanisms leading to neurological deterioration and the devastating course of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) are still not well understood. Bedside xenon-enhanced computerized tomography (XeCT) enables measurements of regional cerebral blood flow (rCBF) during neurosurgical intensive care. In the present study, CBF characteristics in the early phase after severe SAH were explored and related to clinical characteristics and early clinical course outcome.MATERIALS AND METHODS: Patients diagnosed with SAH and requiring mechanical ventilation were prospectively enrolled in the study. Bedside XeCT was performed within day 0 to 3.RESULTS: Data from 64 patients were obtained. Median global CBF was 34.9 mL/100 g/min (interquartile range [IQR], 26.7 to 41.6). There was a difference in CBF related to age with higher global CBF in the younger patients (30 to 49 y). CBF was also related to the severity of SAH with lower CBF in Fisher grade 4 compared with grade 3. rCBF disturbances and hypoperfusion were common; in 43 of the 64 patients rCBF<20 mL/100 g/min was detected in more than 10% of the region-of-interest (ROI) area and in 17 patients such low-flow area exceeded 30%. rCBF was not related to the localization of the aneurysm; there was no difference in rCBF of ipsilateral compared with contralateral vascular territories. In patients who initially were in Hunt & Hess grade I to III, median global CBF day 0 to 3 was significantly lower for patients who were in poor neurological state at discharge compared with patients in good neurological state, 25.5 mL/100 g/min (IQR, 21.3 to 28.3) versus 37.8 mL/100 g/min (IQR, 30.5 to 47.6).CONCLUSIONS: CBF disturbances are common in the early phase after SAH. In many patients, CBF was heterogenic and substantial areas with low rCBF were detected. Age and CT Fisher grade were factors influencing global cortical CBF. Bedside XeCT may be a tool to identify patients at risk of deteriorating so they can receive intensified management, but this needs further exploration.
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32.
  • Fahlström, Markus, et al. (författare)
  • A mathematical model for temporal cerebral blood flow response to acetazolamide evaluated in patients with Moyamoya disease
  • 2024
  • Ingår i: Magnetic Resonance Imaging. - : Elsevier. - 0730-725X .- 1873-5894. ; 110, s. 35-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated.Methods: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations.Results: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions.Conclusions: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.
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33.
  • Fahlström, Markus, et al. (författare)
  • Evaluation of single-delay arterial spin labeling-based spatial coefficient of variation and histogram-based parameters in relation to cerebrovascular reserve in patients with Moyamoya disease.
  • 2023
  • Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoVCBF) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoVCBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATAvol), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoVCBF, skewness, kurtosis, and ATAvol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD.METHODS: Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVRmax was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography.RESULTS: Significant differences between affected and unaffected regions were found for CBF, CVRmax, and ATAvol. No association was found between CVRmax and any other parameter. High correlations were found between spatial CoVCBF, skewness and ATAvol.CONCLUSION: Spatial CoVCBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value.
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34.
  • Fahlström, Markus, et al. (författare)
  • High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease
  • 2020
  • Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 41:3, s. 430-436
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling–derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease.MATERIALS AND METHODS: Eight patients with Moyamoya disease were included before or after revascularization surgery. CBF maps were acquired using a 3D pseudocontinuous arterial spin-labeling sequence, before and 5, 15, and 25 minutes after an IV acetazolamide injection and were registered to each patient’s 3D-T1-weighted images. Vascular regions were defined by spatial normalization to a Montreal Neurological Institute–based vascular regional template. The arterial transit time artifacts were defined as voxels with high signal intensity corresponding to the right tail of the histogram for a given vascular region, with the cutoff selected by visual inspection. Arterial transit time artifact maps were created and applied as masks to exclude arterial transit time artifacts on CBF maps, to create corrected CBF maps. The cerebrovascular reserve capacity was calculated as CBF after acetazolamide injection relative to CBF at baseline for corrected and uncorrected CBF values, respectively.RESULTS: A total of 16 examinations were analyzed. Arterial transit time artifacts were present mostly in the MCA, whereas the posterior cerebral artery was generally unaffected. The largest differences between corrected and uncorrected CBF and cerebrovascular reserve capacity values, reported as patient group average ratio and percentage point difference, respectively, were 0.978 (95% CI, 0.968–0.988) and 1.8 percentage points (95% CI, 0.3–3.2 percentage points). Both were found in the left MCA, 15 and 5 minutes post-acetazolamide injection, respectively.CONCLUSIONS: Arterial transit time artifacts have negligible overestimation effects on calculated vascular region-based CBF and cerebrovascular reserve capacity values derived from single-delay 3D pseudocontinuous arterial spin-labeling.
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35.
  • Fahlström, Markus, et al. (författare)
  • Variable Temporal Cerebral Blood Flow Response to Acetazolamide in Moyamoya Patients Measured Using Arterial Spin Labeling
  • 2021
  • Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebrovascular reserve capacity (CVR), an important predictor of ischaemic events and a prognostic factor for patients with moyamoya disease (MMD), can be assessed by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Often, a single CBF measurement is performed between 5 and 20 min after ACZ injection. Assessment of the temporal response of the vasodilation secondary to ACZ administration using several repeated CBF measurements has not been studied extensively. Furthermore, the high standard deviations of the group-averaged CVRs reported in the current literature indicate a patient-specific dispersion of CVR values over a wide range. This study aimed to assess the temporal response of the CBF and derived CVR during ACZ challenge using arterial spin labeling in patients with MMD. Eleven patients with MMD were included before or after revascularisation surgery. CBF maps were acquired using pseudo-continuous arterial spin labeling before and 5, 15, and 25 min after an intravenous ACZ injection. A vascular territory template was spatially normalized to patient-specific space, including the bilateral anterior, middle, and posterior cerebral arteries. CBF increased significantly post-ACZ injection in all vascular territories and at all time points. Group-averaged CBF and CVR values remained constant throughout the ACZ challenge in most patients. The maximum increase in CBF occurred most frequently at 5 min post-ACZ injection. However, peaks at 15 or 25 min were also present in some patients. In 68% of the affected vascular territories, the maximum increase in CBF did not occur at 15 min. In individual cases, the difference in CVR between different time points was between 1 and 30% points (mean difference 8% points). In conclusion, there is a substantial variation in CVR between different time points after the ACZ challenge in patients with MMD. Thus, there is a risk that the use of a single post-ACZ measurement time point overestimates disease progression, which could have wide implications for decision-making regarding revascularisation surgery and the interpretation of the outcome thereof. Further studies with larger sample sizes using multiple CBF measurements post-ACZ injection in patients with MMD are encouraged.
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36.
  • Fletcher-Sandersjöö, Alexander, et al. (författare)
  • Absolute Contusion Expansion Is Superior to Relative Expansion in Predicting Traumatic Brain Injury Outcomes : A Multi-Center Observational Cohort Study
  • 2024
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 41:5-6, s. 705-713
  • Tidskriftsartikel (refereegranskat)abstract
    • Contusion expansion (CE) is a potentially treatable outcome predictor in traumatic brain injury (TBI), and a suitable end-point for hemostatic therapy trials. However, there is no consensus on the definition of clinically relevant CE, both in terms of measurement criteria (absolute vs. relative volume increase) and cutoff values. In light of this, the aim of this study was to assess the predictive abilities of different CE definitions on outcome. We performed a multi-center observational cohort study of adults with moderate-to-severe TBI treated in an intensive care unit. The exposure of interest was CE, defined as the absolute and relative volume change between the first and second computed tomography scan. The primary outcome was the Glasgow Outcome Scale (GOS) at 6–12 months post-injury, dichotomized into unfavorable (GOS ≤3) or favorable (GOS ≥4). The secondary outcome was all-cause mortality. In total, 798 patients were included, with a median duration of 7.0 h between the first and second CT scan. The median absolute and relative CE was 1.5 mL (interquartile range [IQR] 0.1–8.3 mL) and 100% (IQR 10–530%), respectively. Both CE forms were independently associated with unfavorable GOS. Absolute CE outperformed relative CE in predicting both unfavorable GOS (area under the curve [AUC]: 0.65 vs. 0.60, p = 0.002) and all-cause mortality (AUC: 0.66 vs. 0.60, p = 0.003). For dichotomized CE, absolute cutoffs of 1–10 mL yielded the best results. We conclude that absolute CE demonstrates stronger outcome correlation than relative CE. In studies focusing on lesion progression in TBI, it may be advantageous to use absolute CE as the primary outcome metric. For dichotomized outcomes, cutoffs between 1 and 10 mL are suggested, depending on the desired sensitivity-specificity balance.
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37.
  • Johnson, Ulf, et al. (författare)
  • Increased risk of critical CBF levels in SAH patients with actual CPP below calculated optimal CPP
  • 2017
  • Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 159:6, s. 1065-1071
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Cerebral pressure autoregulation can be quantified with the pressure reactivity index (PRx), based on the correlation between blood pressure and intracranial pressure. Using PRx optimal cerebral perfusion pressure (CPPopt) can be calculated, i.e., the level of CPP where autoregulation functions best. The relation between cerebral blood flow (CBF) and CPPopt has not been examined. The objective was to assess to which extent CPPopt can be calculated in SAH patients and to investigate CPPopt in relation to CBF.Methods Retrospective study of prospectively collected data. CBF was measured bedside with Xenon-enhanced CT (Xe-CT). The difference between actual CPP and CPPopt was calculated (CPPa dagger). Correlations between CPPa dagger and CBF parameters were calculated with Spearman's rank order correlation coefficient (rho). Separate calculations were done using all patients (day 0-14 after onset) as well as in two subgroups (day 0-3 and day 4-14).Results Eighty-two patients with 145 Xe-CT scans were studied. Automated calculation of CPPopt was possible in adjunct to 60% of the Xe-CT scans. Actual CPP < CPPopt was associated with higher numbers of low-flow regions (CBF < 10 ml/100 g/min) in both the early phase (day 0-3, n = 39, Spearman's rho = -0.38, p = 0.02) and late acute phase of the disease (day 4-14, n = 35, Spearman's rho = -0.39, p = 0.02). CPP level per se was not associated with CBF.Conclusions Calculation of CPPopt is possible in a majority of patients with severe SAH. Actual CPP below CPPopt is associated with low CBF.
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38.
  • Kevci, Rozerin, et al. (författare)
  • Lumbar puncture-verified subarachnoid hemorrhage : bleeding sources, need of radiological examination, and functional recovery
  • 2023
  • Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 165:7, s. 1847-1854
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The primary aim was to determine the diagnostic yield of vascular work-up, the clinical course during neurointensive care (NIC), and rate of functional recovery for patients with computed tomography (CT)-negative, lumbar puncture (LP)-verified SAH.Methods In this retrospective study, 1280 patients with spontaneous SAH, treated at our NIC unit, Uppsala University Hospital, Sweden, between 2008 and 2018, were included. Demography, admission status, radiological examinations (CT angiography (CTA) and digital subtraction angiography (DSA)), treatments, and functional outcome (GOS-E) at 12 months were evaluated.Results Eighty (6%) out of 1280 SAH patients were computed tomography (CT)-negative, LP-verified cases. Time between ictus and diagnosis was longer for the LP-verified SAH cohort in comparison to the CT-positive patients (median 3 vs 0 days, p < 0.001). One fifth of the LP-verified SAH patients exhibited an underlying vascular pathology (aneurysm/AVM), which was significantly less common than for the CT-verified SAH cohort (19% vs. 76%, p < 0.001). The CTA- and DSA-findings were consistent in all of the LP-verified cases. The LP-verified SAH patients exhibited a lower rate of delayed ischemic neurological deficits, but no difference in rebleeding rate, compared to the CT-verified cohort. At 1-year post-ictus, 89% of the LP-verified SAH patients had recovered favorably, but 45% of the cases did not reach good recovery. Having an underlying vascular pathology and an external ventricular drainage were associated with worse functional recovery (p = 0.02) in this cohort.Conclusions LP-verified SAH constituted a small proportion of the entire SAH population. Having an underlying vascular pathology was less frequent in this cohort, but still occurred in one out of five patients. Despite the small initial bleeding in the LP-verified cohort, many of these patients did not reach good recovery at 1 year, this calls for more attentive follow-up and rehabilitation in this cohort.
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39.
  • Kultanen, Hanna, et al. (författare)
  • Antithrombotic agent usage before ictus in aneurysmal subarachnoid hemorrhage : relation to hemorrhage severity, clinical course, and outcome
  • 2023
  • Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 165:5, s. 1241-1250
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe number of patients with aneurysmal subarachnoid hemorrhage (aSAH) who are on antithrombotic agents before ictus is rising. However, their effect on early brain injury and disease development remains unclear. The primary aim of this study was to determine if antithrombotic agents (antiplatelets and anticoagulants) were associated with a worse initial hemorrhage severity, rebleeding rate, clinical course, and functional recovery after aSAH.MethodsIn this observational study, those 888 patients with aSAH, treated at the neurosurgical department, Uppsala University Hospital, between 2008 and 2018 were included. Demographic, clinical, radiological (Fisher and Hijdra score), and outcome (Extended Glasgow Outcome Scale one year post-ictus) variables were assessed.ResultsOut of 888 aSAH patients, 14% were treated with antithrombotic agents before ictus. Seventy-five percent of these were on single therapy of antiplatelets, 23% on single therapy of anticoagulants, and 3% on a combination of antithrombotic agents. Those with antithrombotic agents pre-ictus were significantly older and exhibited more co-morbidities and a worse coagulation status according to lab tests. Antithrombotic agents, both as one group and as subtypes (antiplatelets and anticoagulants), were not associated with hemorrhage severity (Hijdra score/Fisher) nor rebleeding rate. The clinical course did not differ in terms of delayed ischemic neurological deficits or last-tier treatment with thiopental and decompressive craniectomy. These patients experienced a higher mortality and lower rate of favorable outcome in univariate analyses, but this did not hold true in multiple logistic regression analyses after adjustment for age and co-morbidities.ConclusionsAfter adjustment for age and co-morbidities, antithrombotic agents before aSAH ictus were not associated with worse hemorrhage severity, rebleeding rate, clinical course, or long-term functional recovery.
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40.
  • Lenell, Samuel, et al. (författare)
  • Clinical outcome and prognostic factors in elderly traumatic brain injury patients receiving neurointensive care
  • 2019
  • Ingår i: Acta Neurochirurgica. - : SPRINGER WIEN. - 0001-6268 .- 0942-0940. ; 161:6, s. 1243-1254
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The probability of favorable outcome after traumatic brain injury (TBI) decreases with age. Elderly,≥60 years, are an increasing part of our population. Recent studies have shown an increase of favorable outcome in elderly over time. However,the optimal patient selection and neurointensive care (NIC) treatments may differ in the elderly and the young. The aims of this study were to examine outcome in a larger group of elderly TBI patients receiving NIC and to identify demographic and treatmentrelated prognostic factors.Methods: Patients with TBI≥60 years receiving NIC at our department between 2008 and 2014 were included. Demographics, co-morbidity, admission characteristics, and type of treatments were collected. Clinical outcome at around 6 months was assessed. Potential prognostic factors were included in univariate and multivariate regression analysis with favorable outcomeas dependent variable.Results: Two hundred twenty patients with mean age 70 years (median 69; range 60–87) were studied. Overall, favorable outcome was 46% (Extended Glasgow Outcome Scale (GOSE) 5–8), unfavorable outcome 27% (GOSE 2–4), and mortality 27% (GOSE 1). Significant independent negative prognostic variables were high age (p< 0.05), multiple injuries (p<0.05),GCSM≤3 on admission (p< 0.05), and mechanical ventilation (p<0.001).Conclusions: Overall, the elderly TBI patients> 60 years receiving modern NIC in this study had a fair chance of favorable outcome without large risks for severe deficits and vegetative state, also in patients over 75 years of age. High age, multiple injuries, GCS M≤3 on admission, and mechanical ventilation proved to be independent negative prognostic factors. The results underline that a selected group of elderly with TBI should have access to NIC
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41.
  • Lenell, Samuel, et al. (författare)
  • Neurointensive care of traumatic brain injury in the elderly : age-specific secondary insult levels and optimal physiological levels to target need to be defined
  • 2022
  • Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:1, s. 117-128
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundElderly patients with traumatic brain injury increase. Current targets and secondary insult definitions during neurointensive care (NIC) are mostly based on younger patients. The aim was therefore to study the occurrence of predefined secondary insults and the impact on outcome in different ages with particular focus on elderly.MethodsPatients admitted to Uppsala 2008–2014 were included. Patient characteristics, NIC management, monitoring data, and outcome were analyzed. The percentage of monitoring time for ICP, CPP, MAP, and SBP above-/below-predefined thresholds was calculated.ResultsFive hundred seventy patients were included, 151 elderly ≥ 65 years and 419 younger 16–64 years. Age ≥ 65 had significantly higher percentage of CPP > 100, MAP > 120, and SBP > 180 and age 16–64 had higher percentage of ICP ≥ 20, CPP ≤ 60, and MAP ≤ 80. Age ≥ 65 contributed independently to the different secondary insult patterens. When patients in all ages were analyzed, low percentage of CPP > 100 and SBP > 180, respectively, was significant predictors of favorable outcome and high percentage of ICP ≥ 20, CPP > 100, SBP ≤ 100, and SBP > 180, respectively, was predictors of death. Analysis of age interaction showed that patients ≥ 65 differed and had a higher odds for favorable outcome with large proportion of good monitoring time with SBP > 180.ConclusionsElderly ≥ 65 have different patterns of secondary insults/physiological variables, which is independently associated to age. The finding that SBP > 180 increased the odds of favorable outcome in the elderly but decreased the odds in younger patients may indicate that blood pressure should be treated differently depending on age.
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42.
  • Lenell, Samuel, 1983- (författare)
  • Traumatic brain injury in elderly patients
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The increase of elderly traumatic brain injury (TBI) patients constitutes a considerable challenge. The aim was therefore to specifically study elderly TBI patients with respect to patient characteristics, neurointensive care (NIC) and outcome, and to identify age specific features, which may be important for selection of patients and optimization of NIC in the elderly. Data from the Uppsala TBI-registry and collected physiological monitoring data from the NIC unit were analysed.Between 1996–1997 and 2008–2009, patients ≥60 years had doubled from 16% to 30%. Despite the increase of elderly an overall favorable outcome was maintained at around 75% between the two periods and the elderly showed favorable outcome in slightly more than 50%.Analysis of characteristics and outcome between 2008–2010 showed that fall accidents and acute subdural hematoma were more common in the elderly ≥65 years. Admission status and NIC treatment did not differ depending on age, except that a larger proportion of the elderly had surgery. Elderly ≥65 years showed a favorable outcome in 51% compared to 72% in the young.Studies of patients ≥60 years treated 2008–2014 showed that high age, multiple injuries, low Glasgow coma motor score on admission and the use of mechanical ventilation were negative prognostic factors.Elderly had different secondary insult patterns with a higher percentage of good monitoring time (%GMT) with high cerebral perfusion pressure (CPP), high mean arteria blood pressure (MAP) and high systolic blood pressure (SBP) and less %GMT with high intracranial pressure (ICP), low CPP and low MAP. On the contrary to the young, high %GMT with SBP>180 was associated with favorable outcome in the elderly, indicating that blood pressure probably should be treated differently in the elderly.Elderly had worse pressure autoregulation (higher values of PRx) and spent longer time with higher PRx. Elderly also had higher optimal CPP and spent lower %GMT with CPP close to optimal CPP. High PRx correlated with mortality in elderly but pressure autoregulation influenced outcome less in the elderly.Overall, the results show that elderly TBI patients differ in many aspects and more studies are warranted to increase knowledge and optimize NIC.
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43.
  •  
44.
  • Lewén, Anders, 1965-, et al. (författare)
  • ASL-MRI-guided evaluation of multiple burr hole revascularization surgery in Moyamoya disease
  • 2023
  • Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 165:8, s. 2057-2069
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Moyamoya (MM) disease is characterized by progressive intracranial arterial stenosis. Patients commonly need revascularization surgery to optimize cerebral blood flow (CBF). Estimation of CBF and cerebrovascular reserve (CVR) is therefore necessary before and after surgery. However, assessment of CBF before and after indirect revascularization surgery with the multiple burr hole (MBH) technique in MM has not been studied extensively. In this study, we describe our initial experience using arterial spin labeling magnetic resonance perfusion imaging (ASL-MRI) for CBF and CVR assessment before and after indirect MBH revascularization surgery in MM patients.METHODS: Eleven MM patients (initial age 6-50 years, 1 male/10 female) with 19 affected hemispheres were included. A total of 35 ASL-MRI examinations were performed using a 3D-pCASL acquisition before and after i.v. acetazolamide challenge (1000 mg in adults and 10 mg/kg in children). Twelve MBH procedures were performed in seven patients. The first follow-up ASL-MRI was performed 7-21 (mean 12) months after surgery.RESULTS: Before surgery, CBF was 46 ± 16 (mean ± SD) ml/100 g/min and CVR after acetazolamide challenge was 38.5 ± 9.9 (mean ± SD)% in the most affected territory (middle cerebral artery). In cases in which surgery was not performed, CVR was 56 ± 12 (mean ± SD)% in affected hemispheres. After MBH surgery, there was a relative change in CVR compared to baseline (preop) of + 23.5 ± 23.3% (mean ± SD). There were no new ischemic events.CONCLUSION: Using ASL-MRI we followed changes in CBF and CVR in patients with MM. The technique was encouraging for assessments before and after revascularization surgery.
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45.
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46.
  • Nyholm, Lena, 1973-, et al. (författare)
  • The influence of hyperthermia on intracranial pressure, cerebral oximetry and cerebral metabolism in traumatic brain injury
  • 2017
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 122:3, s. 177-184
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hyperthermia is a common secondary insult in traumatic brain injury (TBI). The aim was to evaluate the relationship between hyperthermia and intracranial pressure (ICP), and if intracranial compliance and cerebral blood flow (CBF) pressure autoregulation affected that relationship. The relationships between hyperthermia and cerebral oximetry (B(ti)pO(2)) and cerebral metabolism were also studied. Methods: A computerized multimodality monitoring system was used for data collection at the neurointensive care unit. Demographic and monitoring data (temperature, ICP, blood pressure, microdialysis, B(ti)pO(2)) were analyzed from 87 consecutive TBI patients. ICP amplitude was used as measure of compliance, and CBF pressure autoregulation status was calculated using collected blood pressure and ICP values. Mixed models and comparison between groups were used. Results: The influence of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and B(ti)pO(2)) was small, but individual differences were seen. Linear mixed models showed that hyperthermia raises ICP slightly more when temperature increases in the groups with low compliance and impaired CBF pressure autoregulation. There was also a tendency (not statistically significant) for increased B(ti)pO(2), and for increased pyruvate and lactate, with higher temperature, while the lactate/pyruvate ratio and glucose were stable. Conclusions: The major finding was that the effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and B(ti)pO(2)) were not extensive in general, but there were exceptional cases. Hyperthermia treatment has many side effects, so it is desirable to identify cases in which hyperthermia is dangerous. Information from multimodality monitoring may be used to guide treatment in individual patients.
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47.
  • Perez, Mauricio D., et al. (författare)
  • Phantom-based evaluation of a planar microwave sensor for non-invasive intracranial pressure monitoring
  • 2023
  • Ingår i: 2023 IEEE MTT-S International Microwave Biomedical Conference, IMBioC. - : IEEE. - 9781665492171 - 9781665492188 ; , s. 1-3
  • Konferensbidrag (refereegranskat)abstract
    • Intracranial pressure (ICP) measurements are essential to improve current clinical decision schemes in different scenarios: hospital, home, sports field, military field, etc. ICP is fundamental for understanding cerebrospinal fluid (CSF) mechanics and modelling better physiological conditions. Nowadays, several studies have focused on developing non-invasive ICP monitoring methods (nICP) based on different sensing modalities with advantages and disadvantages. Some works have focused on microwave-based sensing; among them is the application of NASA SansEC spectroscopy technology. This work extends previous results on this technology to nICP. Notably, in a simple phantom-based experiment and with a square spiral planar resonator sensor, pressure values up to 48 mmHg could be achievable. The phantom-based experiment consists of a large column tank gradually filled with a liquid that mimics the cerebrospinal fluid (CSF) based on data from the Italian database IFAC. Microwave-based methods for non-invasive intracranial pressure monitoring could be instrumental as tools that can be easily embedded and worn and give indications of brain health to trigger proper care in the future.
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48.
  • Redzwan, Syaiful, et al. (författare)
  • Initial in-vitro trial for intra-cranial pressure monitoring using subdermal proximity-coupled split-ring resonator
  • 2018
  • Ingår i: IMBioc 2018 - 2018 IEEE/MTT-S International Microwave Biomedical Conference. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538659182 ; , s. 73-75
  • Konferensbidrag (refereegranskat)abstract
    • Intra cranial pressure (ICP) monitoring is used in treating severe traumatic brain injury (TBI) patients. All current clinical available measurement methods are invasive presenting considerable social costs. This paper presents a preliminary investigation of the feasibility of ICP monitoring using an innovative microwave-based non-invasive approach. A phantom mimicking the dielectric characteristics of human tissues of the upper part of the head at low microwave frequencies is employed together to a proof-of-concept prototype based on the proposed approach consisting in a readout system and a sub-dermally implanted passive device, both based in split ring resonator techniques. This study shows the potential of our approach to detect two opposite pressure variation stages inside the skull. The employed phantom model needs to be improved to support finer variations in the pressure and better phantom parts, principally for the skull mimic and the loss tangent of all mimics.
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49.
  • Ronne-Engström, Elisabeth, et al. (författare)
  • Trends in incidence and treatments of spontaneous subarachnoid hemorrhage : a 10 year hospital based study
  • 2024
  • Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 166:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundImproved endovascular methods make it possible to treat complex ruptured aneurysms, but surgery is still needed in certain cases. We evaluated the effects on the clinical results of the changes in aneurysm treatment.MethodsThe study cohort was 837 patients with spontaneous subarachnoid hemorrhage (SAH) and one or multiple aneurysms, admitted to Dept of Neurosurgery, Uppsala University Hospital from 2012 to 2021. Demography, location and treatment of aneurysms, neurologic condition at admission and discharge, mortality and last tier treatment of high intracranial pressure (ICP) was evaluated. Functional outcome was measured using the Extended Glasgow Outcome Scale (GOSE) Data concerning national incidences of stroke diseases was collected from open Swedish databases.ResultsEndovascular methods were used in 666 cases (79.6%). In 111 (13.3%) with stents. Surgery was performed in 115 cases (13.7%) and 56 patients (6.7%) had no aneurysm treatment. The indications for surgery were a hematoma (51 cases, 44.3%), endovascular treatment not considered safe (47 cases, 40.9%), or had been attempted without success (13 cases, 11.3%). Treatment with stent devices increased, and with surgery decreased over time. There was a trend in decrease in hemicraniectomias over time. Both the patient group admitted awake (n = 681) and unconscious (n = 156) improved significantly in consciousness between admission and discharge. Favorable outcome (GOSE 5–8) was seen in 69% for patients admitted in Hunt & Hess I-II and 25% for Hunt & Hess III-V. Mortality at one year was 10.9% and 42.7% for those admitted awake and unconscious, respectively.The number of cases decreased during the study period, which was in line with Swedish national data.ConclusionsThe incidence of patients with SAH gradually decreased in our material, in line with national data. The treatment policy in our unit has been shifting to more use of endovascular methods. During the study period the use of hemicraniectomies decreased.
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50.
  • Rostami, Elham, 1979-, et al. (författare)
  • Early low cerebral blood flow and high cerebral lactate : prediction of delayed cerebral ischemia in subarachnoid hemorrhage
  • 2018
  • Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 128:6, s. 1762-1770
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE Delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is one of the major contributors to poor outcome. It is crucial to be able to detect early signs of DCI to prevent its occurrence. The objective of this study was to determine if low cerebral blood flow (CBF) measurements and pathological microdialysis parameters measured at the bedside can be observed early in patients with SAH who later developed DCI. METHODS The authors included 30 patients with severe SAH. The CBF measurements were performed at Day 0-3 after disease onset, using bedside xenon-CT. Interstitial glucose, lactate, pyruvate, glycerol, and glutamate were measured using microdialysis. RESULTS Nine of 30 patients developed DCI. Patients with DCI showed significantly lower global and regional CBF, and lactate was significantly increased in these patients. A high lactate/pyruvate ratio was also detected in patients with DCI. CONCLUSIONS Early low CBF measurements and a high lactate and lactate/pyruvate ratio may be early warning signs of the risk of developing DCI. The clinical value of these findings needs to be confirmed in larger studies.
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