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- Abu Hamdeh, Sami, 1982-
(författare)
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Clinical Consequences of Axonal Injury in Traumatic Brain Injury
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injury (TBI), mainly caused by road-traffic accidents and falls, is a leading cause of mortality. Survivors often display debilitating motor, sensory and cognitive symptoms, leading to reduced quality of life and a profound economic burden to society. Additionally, TBI is a risk factor for future neurodegenerative disorders including Alzheimer’s disease (AD). Commonly, TBI is categorized into focal and diffuse injuries, and based on symptom severity into mild, moderate and severe TBI. Diffuse axonal injury (DAI), biomechanically caused by rotational acceleration-deceleration forces at impact, is characterized by widespread axonal injury in superficial and deep white substance. DAI comprises a clinical challenge due to its variable course and unreliable prognostic methods. Furthermore, axonal injury may convey the link to neurodegeneration since molecules associated with neurodegenerative events aggregate in injured axons.The aim of this thesis was to study clinical consequences of axonal injury, its detection and pathological features, and potential link to neurodegeneration in severe TBI patients treated at the neurointensive care unit at Uppsala University Hospital. In paper I and IV DAI patients were studied for the relation of elevated intracranial pressure (ICP) and poor outcome to axonal injury on magnetic resonance imaging. In paper II, soluble amyloid-beta aggregates (oligomers and protofibrils), characteristic of AD pathology, were investigated in surgically resected brain tissue from severe TBI patients, using highly-selective Enzyme-Linked ImmunoSorbent Assays. In paper III, brain tissue biopsy samples from TBI patients with either focal injury or DAI were examined for differential proteome profiles using mass spectrometry-based proteomics.The results provide evidence that axonal injury, located in the central brain stem, in substantia nigra and the mesencephalic tegmentum, is particularly related to poor outcome and increased ICP during neurointensive care of DAI patients. A novel classification system for prognostication after DAI is proposed. Furthermore, the thesis shows that severe TBI induces rapid accumulation of neurotoxic soluble amyloid-beta oligomers and protofibrils. In addition, DAI initiates unique proteome profiles different from that of focal TBI in structurally normal-appearing brain. These findings have implication for the clinical management of DAI patients, and provide new insight in the neuropathological consequences of axonal injury.
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- Riemann, Lennart, et al.
(författare)
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Computed tomography lesions and their association with global outcome in young people with mild traumatic brain injury
- 2023
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:11-12, s. 1243-1254
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Tidskriftsartikel (refereegranskat)abstract
- Mild traumatic brain injury (mTBI) can be accompanied by structural damage to the brain. Here, we investigated how the presence of intracranial traumatic computed tomography (CT) pathologies relates to the global functional outcome in young patients one year after mTBI. All patients with mTBI (Glasgow Coma Scale: 13-15) ≤24 years in the multi-center, prospective, observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study were included. Patient demographics and CT findings were assessed at admission, and the Glasgow Outcome Scale Extended (GOSE) was evaluated at 12 months follow-up. The association between a "positive CT" (at least one of the following: epidural hematoma, subdural hematoma, traumatic subarachnoid hemorrhage (tSAH), intraventricular hemorrhage, subdural collection mixed density, contusion, traumatic axonal injury) and functional outcome (GOSE) was assessed using multi-variable mixed ordinal and logistic regression models. A total of 462 patients with mTBI and initial brain CT from 46 study centers were included. The median age was 19 (17-22) years, and 322 (70%) were males. CT imaging showed a traumatic intracranial pathology in 171 patients (37%), most commonly tSAH (48%), contusions (40%), and epidural hematomas (37%). Patients with a positive CT scan were less likely to achieve a complete recovery 12 months post-injury. The presence of any CT abnormality was associated with both lower GOSE scores (odds ratio [OR]: 0.39 [0.24-0.63]) and incomplete recovery (GOSE <8; OR: 0.41 [0.25-0.68]), also when adjusted for demographical and clinical baseline factors. The presence of intracranial traumatic CT pathologies was predictive of outcome 12 months after mTBI in young patients, which might help to identify candidates for early follow-up and additional care.
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- Riemann, Lennart, et al.
(författare)
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Concomitant spine trauma in patients with traumatic brain injury : Patient characteristics and outcomes
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Spine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).METHODS: Data from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7-8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.RESULTS: A total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37-66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.CONCLUSION: Rates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.
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- Riemann, Lennart, et al.
(författare)
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Injury Causes and Severity in Pediatric Traumatic Brain Injury Patients Admitted to the Ward or Intensive Care Unit : A Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study
- 2020
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Traumatic brain injury (TBI) is the leading cause of death and disability in children. It includes a range of different pathologies that differ considerably from adult TBI. Analyzing and understanding injury patterns of pediatric TBI is essential to establishing new preventive efforts as well as to improve clinical management.Methods: The multi-center, prospectively collected CENTER-TBI core and registry databases were screened and patients were included when younger than 18 years at enrollment and admitted to the regular ward (admission stratum) or intensive care unit (ICU stratum) following TBI. Patient demographics, injury causes, clinical findings, brain CT imaging details, and outcome (GOSE at 6 months follow-up) were retrieved and analyzed. Injury characteristics were compared between patients admitted to the regular ward and ICU and multivariate analysis of factors predicting an unfavorable outcome (GOSE 1-4) was performed.Results: from the core study were compared to the registry dataset which includes larger patient numbers but no follow-up data. Results: Two hundred and twenty seven patients in the core dataset and 687 patients in the registry dataset were included in this study. In the core dataset, road-traffic incidents were the most common cause of injury overall and in the ICU stratum, while incidental falls were most common in the admission stratum. Brain injury was considered serious to severe in the majority of patients and concurrent injuries in other body parts were very common. Intracranial abnormalities were detected in 60% of initial brain CTs. Intra- and extracranial surgical interventions were performed in one-fifth of patients. The overall mortality rate was 3% and the rate of unfavorable outcome 10%, with those numbers being considerably higher among ICU patients. GCS and the occurrence of secondary insults could be identified as independent predictors for an unfavorable outcome. Injury characteristics from the core study could be confirmed in the registry dataset.Conclusion: Our study displays the most common injury causes and characteristics of pediatric TBI patients that are treated in the regular ward or ICU in Europe. Road-traffic incidents were especially common in ICU patients, indicating that preventive efforts could be effective in decreasing the incidence of severe TBI in children.
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- Riemann, Lennart, et al.
(författare)
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Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury : a CENTER-TBI study
- 2020
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Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: After traumatic brain injury (TBI), brain tissue can be further damaged when cerebral autoregulation is impaired. Managing cerebral perfusion pressure (CPP) according to computed "optimal CPP" values based on cerebrovascular reactivity indices might contribute to preventing such secondary injuries. In this study, we examined the discriminative value of a low-resolution long pressure reactivity index (LPRx) and its derived "optimal CPP" in comparison to the well-established high-resolution pressure reactivity index (PRx).Methods: Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset, the association of LPRx (correlation between 1-min averages of intracranial pressure and arterial blood pressure over a moving time frame of 20 min) and PRx (correlation between 10-s averages of intracranial pressure and arterial blood pressure over a moving time frame of 5 min) to outcome was assessed and compared using univariate and multivariate regression analysis. "Optimal CPP" values were calculated using a multi-window algorithm that was based on either LPRx or PRx, and their discriminative ability was compared.Results: LPRx and PRx were both significant predictors of mortality in univariate and multivariate regression analysis, but PRx displayed a higher discriminative ability. Similarly, deviations of actual CPP from "optimal CPP" values calculated from each index were significantly associated with outcome in univariate and multivariate analysis. "Optimal CPP" based on PRx, however, trended towards more precise predictions.Conclusions: LPRx and its derived "optimal CPP" which are based on low-resolution data were significantly associated with outcome after TBI. However, they did not reach the discriminative ability of the high-resolution PRx and its derived "optimal CPP." Nevertheless, LPRx might still be an interesting tool to assess cerebrovascular reactivity in centers without high-resolution signal monitoring.Trial registration: ClinicalTrials.gov Identifier: NCT02210221. First submitted July 29, 2014. First posted August 6, 2014.
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- Riemann, Lennart, et al.
(författare)
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Persistent postconcussive symptoms in children and adolescents with mild traumatic brain injury receiving initial head computed tomography
- 2021
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 1933-0707 .- 1933-0715. ; 27:5, s. 538-547
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment.METHODS: Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13-15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire.RESULTS: A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001).CONCLUSIONS: Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL.
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- Steiner, Thorsten, et al.
(författare)
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European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage
- 2014
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 9:7, s. 840-855
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIntracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH. MethodA multidisciplinary writing committee of 24 researchers from 11 European countries identified 20 questions relating to ICH management and created recommendations based on the evidence in RCTs using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ResultsWe found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to <140mmHg within six-hours of ICH onset, early surgery for patients with a Glasgow Coma Scale score 9-12, and avoidance of corticosteroids. ConclusionThese guidelines inform the management of ICH based on evidence for the effects of treatments in RCTs. Outcome after ICH remains poor, prioritizing further RCTs of interventions to improve outcome.
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