Einfluss der Entlastungskraniektomie und des Kallikrein-Kinin Systems auf den sekundären Hirnschaden nach experimentellem Schädel-Hirntrauma

Etablierung eines Controlled Cortical Impact Modells für die Maus und Darstellung von ICP, CBF, MAP, histologische Kontusionsgrößen, Hirnödementwicklung und neurologischer Funktion nach experimentellem SHT. Anschließend Untersuchung therapeutischer Einflussnahme auf o.g. Parameter durch eine frühzeitige und um mehrere Stunden verzögerte Entlastungstrepanation. Schließlich Überprüfung der Rolle des kallikrein-Kinin Systems für die Ausbildung des sekundären Nekrosewachstums durch B1 und B2 knock out Mäusen und pharmakologische Hemmung des B2 Rezeptors. Eine Trepanation innerhalb der ersten 3 Stunden kann die Ausbildung des Sekundären Hinrschadens nahezu vollständig verhindern

Clinical review: Therapy for refractory intracranial hypertension in ischaemic stroke

The treatment of patients with large hemispheric ischaemic stroke accompanied by massive space-occupying oedema represents one of the major unsolved problems in neurocritical care medicine. Despite maximum intensive care, the prognosis of these patients is poor, with case fatality rates as high as 80%. Therefore, the term 'malignant brain infarction' was coined. Because conservative treatment strategies to limit brain tissue shift almost consistently fail, these massive infarctions often are regarded as an untreatable disease. The introduction of decompressive surgery (hemicraniectomy) has completely changed this point of view, suggesting that mortality rates may be reduced to approximately 20%. However, critics have always argued that the reduction in mortality may be outweighed by an accompanying increase in severe disability. Due to the lack of conclusive evidence of efficacy from randomised trials, controversy over the benefit of these treatment strategies remained, leading to large regional differences in the application of this procedure. Meanwhile, data from randomised trials confirm the results of former observational studies, demonstrating that hemicraniectomy not only significantly reduces mortality but also significantly improves clinical outcome without increasing the number of completely dependent patients. Hypothermia is another promising treatment option but still needs evidence of efficacy from randomised controlled trials before it may be recommended for clinical routine use. This review gives the reader an integrated view of the current status of treatment options in massive hemispheric brain infarction, based on the available data of clinical trials, including the most recent data from randomised trials published in 2007

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

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.</div

Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model

Objective: Disruption of the blood-spinal cord barrier (BSCB) with subsequent edema formation and further neuroinflammation contributes to aggravation of spinal cord injury (SCI). We aimed to observe the effect of antagonizing the binding of the neuropeptide Substance-P (SP) to its neurokinin-1 (NK1) receptor in a rodent SCI model. Methods: Female Wistar rats were subjected to a T9 laminectomy with or without (Sham) a T9 clip-contusion/compression SCI, followed by the implantation of an osmotic pump for the continuous, seven-day-long infusion of a NK1 receptor antagonist (NRA) or saline (vehicle) into the intrathecal space. The animals were assessed via MRI, and behavioral tests were performed during the experiment. 7 days after SCI, wet & dry weight and immunohistological analyses were conducted. Results: Substance-P inhibition via NRA showed limited effects on reducing edema. However, the invasion of T-lymphocytes and the number of apoptotic cells were significantly reduced with the NRA treatment. Moreover, a trend of reduced fibrinogen leakage, endothelial and microglial activation, CS-GAG deposition, and astrogliosis was found. Nevertheless, only insignificant general locomotion recovery could be observed in the BBB open field score and the Gridwalk test. In contrast, the CatWalk gait analysis showed an early onset of recovery in several parameters. Conclusion: Intrathecal administration of NRA might reinforce the integrity of the BSCB in the acute phase after SCI, potentially attenuating aspects of neurogenic inflammation, reducing edema formation, and improving functional recovery

Transplantation of Neural Precursor Cells Attenuates Chronic Immune Environment in Cervical Spinal Cord Injury

Inflammation after traumatic spinal cord injury (SCI) is non-resolving and thus still present in chronic injury stages. It plays a key role in the pathophysiology of SCI and has been associated with further neurodegeneration and development of neuropathic pain. Neural precursor cells (NPCs) have been shown to reduce the acute and sub-acute inflammatory response after SCI. In the present study, we examined effects of NPC transplantation on the immune environment in chronic stages of SCI. SCI was induced in rats by clip-compression of the cervical spinal cord at the level C6-C7. NPCs were transplanted 10 days post-injury. The functional outcome was assessed weekly for 8 weeks using the Basso, Beattie, and Bresnahan scale, the CatWalk system, and the grid walk test. Afterwards, the rats were sacrificed, and spinal cord sections were examined for M1/M2 macrophages, T lymphocytes, astrogliosis, and apoptosis using immunofluorescence staining. Rats treated with NPCs had compared to the control group significantly fewer pro-inflammatory M1 macrophages and reduced immunodensity for inducible nitric oxide synthase (iNOS), their marker enzyme. Anti-inflammatory M2 macrophages were rarely present 8 weeks after the SCI. In this model, the sub-acute transplantation of NPCs did not support survival and proliferation of M2 macrophages. Post-traumatic apoptosis, however, was significantly reduced in the NPC group, which might be explained by the altered microenvironment following NPC transplantation. Corresponding to these findings, reactive astrogliosis was significantly reduced in NPC-transplanted animals. Furthermore, we could observe a trend toward smaller cavity sizes and functional improvement following NPC transplantation. Our data suggest that transplantation of NPCs following SCI might attenuate inflammation even in chronic injury stages. This might prevent further neurodegeneration and could also set a stage for improved neuroregeneration after SCI

Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury: a CENTER-TBI study

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).MethodsUsing 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.ResultsLPRx 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.ConclusionsLPRx 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 registrationClinicalTrials.gov Identifier: NCT02210221. First submitted July 29, 2014. First posted August 6, 2014.</p

Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury: a CENTER-TBI study.

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

Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury: a CENTER-TBI study

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

The neuropsychological assessment battery (NAB) is a valuable tool for evaluating neuropsychological outcome after aneurysmatic subarachnoid hemorrhage

Background!#!Detecting and treating neuropsychological deficits after aneurysmatic subarachnoid hemorrhage (aSAH) play a key role in regaining independence; however, detecting deficits relevant to social and professional reintegration has been difficult and optimal timing of assessments remains unclear. Therefore, we evaluated the feasibility of administering the Neuropsychological Assessment Battery screening module (NAB-S) to patients with aSAH, assessed its value in predicting the ability to return to work and characterized clinical as well as neuropsychological recovery over the period of 24 months.!##!Methods!#!A total of 104 consecutive patients treated for aSAH were recruited. After acute treatment, follow up visits were conducted at 3, 12 and 24 months after the hemorrhage. NAB-S, Montreal Cognitive Assessment (MoCA) and physical examination were performed at each follow up visit.!##!Results!#!The NAB-S could be administered to 64.9, 75.9 and 88.9% of the patients at 3, 12 and 24 months, respectively. Moderate impairment of two or more neuropsychological domains (e.g speech, executive function, etc.) significantly correlated with inability to return to work at 12 and 24 months as well as poor outcome assessed by the extended Glasgow Outcome Scale (GOSE) at 3, 12 and 24 months. The number of patients with favorable outcomes significantly increased from 25.5% at discharge to 56.5 and 57.1% at 3 and 12 months, respectively, and further increased to 74.1% after 24 months.!##!Conclusion!#!The NAB-S can be administered to the majority of patients with aSAH and can effectively detect clinically relevant neuropsychological deficits. Clinical recovery after aSAH continues for at least 24 months after the hemorrhage which should be considered in the design of future clinical trials

Impact of decompressive laminectomy on the functional outcome of patients with metastatic spinal cord compression and neurological impairment

Metastatic spinal cord compression (MSCC) is a frequent phenomenon in advanced tumor diseases with often severe neurological impairments. Affected patients are often treated by decompressive laminectomy. To assess the impact of this procedure on Karnofsky Performance Index (KPI) and Frankel Grade (FG) at discharge, a single center retrospective cohort study of neurologically impaired MSCC-patients treated with decompressive laminectomy between 2004 and 2014 was performed. 101 patients (27 female/74 male; age 66.1 ± 11.5 years) were identified. Prostate was the most common primary tumor site (40%) and progressive disease was present in 74%. At admission, 80% of patients were non-ambulatory (FG A-C). Imaging revealed prevalently thoracic MSCC (78%). Emergency surgery (&amp;lt; 24 h) was performed in 71% and rates of complications and revision surgery were 6% and 4%, respectively. At discharge, FG had improved in 61% of cases, and 51% of patients had regained ambulation. Univariate predictors for not regaining the ability to walk were bowl dysfunction (p = 0.0015), KPI &amp;lt; 50% (p = 0.048) and FG &amp;lt; C (p = 0.001) prior to surgery. In conclusion, decompressive laminectomy showed beneficial effects on the functional outcome at discharge. A good neurological status prior to surgery was key predictor for a good functional outcome