scholarly journals Levels of caspase-1 in cerebrospinal fluid of patients with traumatic brain injury: correlation with intracranial pressure and outcome

2020 ◽  
pp. 1-6 ◽  
Author(s):  
Jon Pérez-Bárcena ◽  
Catalina Crespí ◽  
Guillem Frontera ◽  
Juan Antonio Llompart-Pou ◽  
Osman Salazar ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
External Ventricular Drain ◽  
Area Under The Curve ◽  
Protein Levels ◽  
Poor Outcome ◽  
Caspase 1 ◽  
Auc Value ◽  
Poor Outcomes

OBJECTIVEThe objectives of this study were to evaluate levels of inflammasome-signaling proteins in serum and CSF of patients with traumatic brain injury (TBI), and to correlate these protein levels with intracranial pressure (ICP) and clinical outcomes at 6 months after injury.METHODSThis is a prospective and observational study in patients with moderate and severe TBI who required an external ventricular drain as part of their treatment. Serum and CSF samples were collected 3 times a day for the first 5 days after TBI. The authors have determined the protein concentration of caspase-1 in the CSF and serum of patients with TBI by using commercially available enzyme-linked immunosorbent assays. The ICP value was recorded hourly. The 6-month outcome was assessed using the Glasgow Outcome Scale–Extended.RESULTSA total of 21 patients were included in this study, and a total of 234 paired serum-CSF samples were analyzed. The area under the curve (AUC) value of caspase-1 in CSF during the 5-day period was 2452.9 pg/mL·hr in the group of patients with high ICP vs 617.6 pg/mL·hr in the patients with low ICP. The differences were mainly on day 2 (19.7 pg/mL vs 1.8 pg/mL; p = 0.06) and day 3 (13.9 pg/mL vs 1 pg/mL; p = 0.05). The AUC value of caspase in CSF during the 5-day period was 1918.9 pg/mL·hr in the group of patients with poor outcome versus 924.5 pg/mL·hr in the patients with good outcome. The protein levels of caspase-1 in CSF were higher in patients with unfavorable outcomes during the first 96 hours after TBI.CONCLUSIONSIn this cohort of patients with TBI who were admitted to the neurosurgical ICU, the inflammasome protein caspase-1 is increased in the CSF of patients with high ICP, especially on days 2 and 3 after TBI. Also the protein levels of caspase-1 in CSF were higher in patients with poor outcome during the first 96 hours after TBI. Moreover, not only the absolute value of caspase-1 in CSF but also its trend is associated with poor outcomes.

Abstract TMP23: Inflammasome-derived Caspase-1 is Elevated in the Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients and Correlated to Outcome

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yonatan Hirsch ◽  
Joseph R Geraghty ◽  
Eitan A Katz ◽  
Jeffrey A Loeb ◽  
Fernando Testai
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Analysis Of Covariance ◽  
Control Group ◽  
Normal Brain ◽  
Poor Outcome ◽  
Caspase 1 ◽  
Initial Severity ◽  
Poor Outcomes

Introduction: The role of neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) and its relationship to outcome is the subject of many ongoing studies. The proteolytic enzyme, caspase-1, activated by the inflammasome complex, is known to contribute to numerous downstream pro-inflammatory effects. In this study, we investigated caspase-1 activity in the cerebrospinal fluid (CSF) of SAH patients and its association to outcome. Methods: SAH patients were recruited from a regional stroke referral center. CSF samples from 18 SAH subjects were collected via an external ventricular drain and obtained within 72 hours of the onset of symptoms. For control subjects, we collected the CSF from 9 patients undergoing lumbar puncture with normal CSF and normal brain MRI. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3). The levels of caspase-1 activity in various groups were analyzed using Mann-Whitney and Pearson correlation tests. Caspase-1 activity was also adjusted by initial severity of bleed using analysis of covariance (ANCOVA). Results: Caspase-1 levels from SAH patients were significantly higher than that measured from the control group (mean 1.06x10-2 vs 1.90x10-3 counts per second (CPS)/μl*min), p = 0.0002). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Caspase-1 activity was significantly higher in the poor outcome group (mean 1.54x10-2 vs 1.60x10-3 CPS/μl*min), p = 0.0012). Additionally, caspase-1 activity had a statistically significant correlation with GOS score (r = -0.60; p = 0.0100). When adjusted for initial severity of bleed, the difference in caspase-1 activity in good vs. poor outcome remained significant (adjusted mean 7.10x10-3 vs. 2.54x10-2 CPS/μl*min, p=0.004). Conclusions: The inflammasome-dependent protein caspase-1 is elevated in CSF early after SAH and higher in those with poor functional outcome. Inflammasome activity therefore may serve as a novel biomarker to predict outcome shortly after aneurysm rupture.

Management of traumatic brain injury

2016 ◽  
Author(s):  
Alistair A. Gibson ◽  
Peter J. D. Andrews
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
External Ventricular Drain ◽  
Young Male ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Moderate Hypothermia ◽  
High Dose ◽  
Thromboembolism Prophylaxis

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and although young male adults are at particular risk, it affects all ages. TBI often occurs in the presence of significant extracranial injuries and immediate management focuses on the ABCs—airway with cervical spine control, breathing, and circulation. Best outcomes are achieved by management in centres that can offer comprehensive neurological critical care and appropriate management for extracranial injuries. If patients require transfer from an admitting hospital to a specialist centre, the transfer must be carried out by an appropriately skilled and equipped transport team. The focus of specific TBI management is on the avoidance of secondary injury to the brain. The principles of management are to avoid hypotension and hypoxia, control intracranial pressure and maintain cerebral perfusion pressure above 60 mmHg. Management of increased intracranial pressure is generally by a stepwise approach starting with sedation and analgesia, lung protective mechanical ventilation to normocarbia in a 30° head-up position, maintenance of oxygenation, and blood pressure. Additional measures include paralysis with a neuromuscular blocking agent, CSF drainage via an external ventricular drain, osmolar therapy with mannitol or hypertonic saline, and moderate hypothermia. Refractory intracranial hypertension may be treated surgically with decompressive craniectomy or medically with high dose barbiturate sedation. General supportive measures include provision of adequate nutrition preferably by the enteral route, thromboembolism prophylaxis, skin and bowel care, and management of all extracranial injuries.

Surgical intervention and patient factors associated with poor outcomes in patients with traumatic brain injury at a tertiary care hospital in Uganda

2021 ◽  
pp. 1-10
Author(s):  
Charis A. Spears ◽  
Syed M. Adil ◽  
Brad J. Kolls ◽  
Michael E. Muhumza ◽  
Michael M. Haglund ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Low Income ◽  
Surgical Intervention ◽  
Tertiary Care ◽  
Care Hospital ◽  
Treatment Variable ◽  
Patient Factors ◽  
Poor Outcome ◽  
Poor Outcomes

OBJECTIVE The purpose of this study was to investigate whether neurosurgical intervention for traumatic brain injury (TBI) is associated with reduced risks of death and clinical deterioration in a low-income country with a relatively high neurosurgical capacity. The authors further aimed to assess whether the association between surgical intervention and acute poor outcomes differs according to TBI severity and various patient factors. METHODS Using TBI registry data collected from a national referral hospital in Uganda between July 2016 and April 2020, the authors performed Cox regression analyses of poor outcomes in admitted patients who did and did not undergo surgery for TBI, with surgery as a time-varying treatment variable. Patients were further stratified by TBI severity using the admission Glasgow Coma Scale (GCS) score: mild TBI (mTBI; GCS scores 13–15), moderate TBI (moTBI; GCS scores 9–12), and severe TBI (sTBI; GCS scores 3–8). Poor outcomes constituted Glasgow Outcome Scale scores 2–3, deterioration in TBI severity between admission and discharge (e.g., mTBI to sTBI), and death. Several clinical and demographic variables were included as covariates. Patients were observed for outcomes from admission through hospital day 10. RESULTS Of 1544 patients included in the cohort, 369 (24%) had undergone surgery. Rates of poor outcomes were 4% (n = 13) for surgical patients and 12% (n = 144) among nonsurgical patients (n = 1175). Surgery was associated with a 59% reduction in the hazard for a poor outcome (HR 0.41, 95% CI 0.23–0.72). Age, pupillary nonreactivity, fall injury, and TBI severity at admission were significant covariates. In models stratifying by TBI severity at admission, patients with mTBI had an 80% reduction in the hazard for a poor outcome with surgery (HR 0.20, 95% CI 0.04–0.90), whereas those with sTBI had a 65% reduction (HR 0.35, 95% CI 0.14–0.89). Patients with moTBI had a statistically nonsignificant 56% reduction in hazard (HR 0.44, 95% CI 0.17–1.17). CONCLUSIONS In this setting, the association between surgery and rates of poor outcomes varied with TBI severity and was influenced by several factors. Patients presenting with mTBI had the greatest reduction in the hazard for a poor outcome, followed by those presenting with sTBI. However, patients with moTBI had a nonsignificant reduction in the hazard, indicating greater variability in outcomes and underscoring the need for closer monitoring of this population. These results highlight the importance of accurate, timely clinical evaluation throughout a patient’s admission and can inform decisions about whether and when to perform surgery for TBI when resources are limited.

Patient-specific thresholds of intracranial pressure in severe traumatic brain injury

2014 ◽  
Vol 120 (4) ◽  
pp. 893-900 ◽  
Author(s):  
Christos Lazaridis ◽  
Stacia M. DeSantis ◽  
Peter Smielewski ◽  
David K. Menon ◽  
Peter Hutchinson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Severe Traumatic Brain Injury ◽  
Continuous Monitoring ◽  
Cross Validation ◽  
Area Under The Curve ◽  
Reactivity Index ◽  
Patient Specific ◽  
Pressure Reactivity

Object Based on continuous monitoring of the pressure reactivity index (PRx), the authors defined individualized intracranial pressure (ICP) thresholds by graphing the relationship between ICP and PRx. These investigators hypothesized that an “ICP dose” based on individually assessed ICP thresholds would correlate more closely with the 6-month outcome when compared with ICP doses derived by the recommended universal thresholds of 20 and 25 mm Hg. Methods This study was a retrospective analysis of prospectively collected data from 327 patients with severe traumatic brain injury. Results Individualized thresholds were visually identified from graphs of PRx versus ICP; PRx > 0.2 was the cutoff. Intracranial pressure doses were then computed as the cumulative area under the curve above the defined thresholds in graphing ICP versus time. The term “Dose 20” (D20) was used to refer to an ICP threshold of 20 mm Hg; the markers D25 and DPRx were calculated similarly. Separate logistic regression models were fit with death as the outcome and each dose as the predictor, both alone and adjusted for covariates. The discriminative ability of each dose for mortality was assessed by receiver operating characteristic AUC analysis in which 5-fold cross-validation was used. A clearly identifiable PRx-based threshold was possible in 224 patients (68%). The DPRx (AUC 0.81, 95% CI 0.74–0.87) was found to have the highest area under the curve (AUC) over both D20 (0.75, 95% CI 0.68–0.81) and D25 (0.77, 95% CI 0.70–0.83); in the cross-validation model, DPRx remained the best discriminator of mortality (DPRx: AUC 0.77 [95% CI 0.68–0.89]; D20: 0.72 [95% CI 0.66–0.81]; and D25: 0.65 [95% CI 0.56–0.73]). Conclusions The authors explored the importance of different ICP thresholds for outcome by calculating patient-specific ICP doses based on the continuous monitoring of cerebrovascular pressure reactivity. They found that these individualized doses of intracranial hypertension were stronger predictors of death than doses derived from the universal thresholds of 20 and 25 mm Hg. The PRx could offer a method that can be directed toward individualizing the ICP threshold.

scholarly journals Facial Fractures: Independent Prediction of Neurosurgical Intervention

2021 ◽  
Author(s):  
Brandon Lucke-Wold ◽  
Kevin Pierre ◽  
Sina Aghili-Mehrizi ◽  
Gregory Murad
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
External Ventricular Drain ◽  
Intervention Group ◽  
Facial Fracture ◽  
Pressure Monitor ◽  
Significant Difference ◽  
Neurosurgical Intervention

Abstract Background:Over half of patients with facial fractures have associated traumatic brain injury. Based on previous force dynamic cadaveric studies, Lefort type 2 and 3 fractures are more associated with severe injury. Whether this correlates to neurosurgical intervention have not been well characterized. The purpose of this retrospective data analysis is to characterize fracture pattern types in patients requiring neurosurgical intervention and to see if this is different from those not requiring intervention. Methods:Retrospective data was collected from the trauma registry from 2010-2019. Inclusion criteria: adults over 18, confirmed facial fracture with available neuroimaging, reported traumatic brain injury, and admission to ICU or floor bed. Exclusion criteria: patients less than 18 years old, patients with no neuroimaging, and patients that were deceased prior to initiation of neurosurgical intervention. Data included: basic demographic data, presenting Glasgow Coma Scale (GCS) score, mechanism of injury, type of traumatic brain injury, neurosurgical intervention, and facial fracture type. Retrospective Contingency Analysis with Fraction of Total Comparison was used with Chi-Square analysis for demographic and injury characteristic data.Results:1172 patients met inclusion criteria. 1001 required no neurosurgical intervention and 171 required intervention. No significant difference was seen between the non-intervention group and intervention group in terms of demographic data or baseline injury characteristics except for presenting GCS. A significant difference was seen between groups for presenting Glasgow Coma Scale (c2=67.71, p<0.001). The intervention group had greater number of patients with GCS<8 compared to the non-intervention group. Fracture patterns were overall similar between the non-intervention group compared to intervention group (c2=4.518, p=0.92), however subset analysis did reveal a 2 fold increase in Lefort type 2 fractures and notable increase in Lefort type 3 and panfacial fractures in the intervention group. The intervention group was further divided into those requiring external ventricular drain or intracranial pressure monitor only vs. patients requiring craniectomy, craniotomy, or burr holes with or with external ventricular drain or intracranial pressure monitor. A significant difference was seen between groups (c2=20.02, p=0.03). The craniectomy, craniotomy, or burr hole group was much more likely to have Lefort type 2 or 3 fractures compared to the external ventricular drain or intracranial pressure monitor group only. Conclusions:Lefort type 2 and type 3 fractures are significantly associated with requiring neurosurgical intervention. An improved algorithm for managing these patients has been proposed in the discussion. Ongoing work will focus on validating and refining the algorithm in order to improve patient care for trauma patients with facial fracture and traumatic brain injury.

scholarly journals Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain–associated ventriculitis in patients with severe traumatic brain injury

2019 ◽  
Vol 47 (5) ◽  
pp. E15 ◽  
Author(s):  
Markus Lenski ◽  
Annamaria Biczok ◽  
Katrin Neufischer ◽  
Jörg-Christian Tonn ◽  
Josef Briegel ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Markers ◽  
Early Stage ◽  
External Ventricular Drain ◽  
Area Under The Curve ◽  
Positive Likelihood Ratio ◽  
Diagnostic Value ◽  
Total Leukocyte Count ◽  
Diagnostic Potential

ObjectiveThe aim of this study was to investigate the diagnostic potential of the inflammatory markers interleukin-6 (IL-6), total leukocyte count (TLC), and protein in the CSF and IL-6, C-reactive protein, and white blood cell count in the serum for the early diagnosis of ventriculitis in patients with traumatic brain injury (TBI) and an external ventricular drain compared with patients without ventriculitis.MethodsRetrospective data from 40 consecutive patients with TBI and an external ventricular drain treated in the authors’ intensive care unit between 2013 and 2017 were analyzed. For all markers, arithmetical means and standard deviations, area under the curve (AUC), cutoff values, sensitivity, specificity, positive likelihood ratio (LR), and negative LR were calculated and correlated with presence or absence of ventriculitis.ResultsThere were 35 patients without ventriculitis and 5 patients with ventriculitis. The mean ± SD IL-6 concentration in CSF was significantly increased, with 6519 ± 4268 pg/mL at onset of ventriculitis compared with 1065 ± 1705 pg/mL in patients without ventriculitis (p = 0.04). Regarding inflammatory markers in CSF, IL-6 showed the highest diagnostic potential for differentiation between the presence and absence of ventriculitis (AUC 0.938, cutoff 4064 pg/mL, sensitivity 100%, specificity 92.3%, positive LR 13, and negative LR 0), followed by TLC (AUC 0.900, cutoff 64.5 /µL, sensitivity 100%, specificity 80%, positive LR 5.0, and negative LR 0) and protein (AUC 0.876, cutoff 31.5 mg/dL, sensitivity 100%, specificity 62.5%, positive LR 2.7, and negative LR 0).ConclusionsThe level of IL-6 in CSF has the highest diagnostic value of all investigated inflammatory markers for detecting ventriculitis in TBI patients at an early stage. In particular, CSF IL-6 levels higher than the threshold of 4064 pg/mL were significantly associated with the probability of ventriculitis.

DOES ADHERENCE TO TREATMENT TARGETS IN CHILDREN WITH SEVERE TRAUMATIC BRAIN INJURY AVOID BRAIN HYPOXIA? A BRAIN TISSUE OXYGENATION STUDY

Neurosurgery ◽  
2008 ◽  
Vol 63 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Anthony A. Figaji ◽  
A. Graham Fieggen ◽  
Andrew C. Argent ◽  
Peter D. LeRoux ◽  
Jonathan C. Peter
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Brain Tissue ◽  
Cerebral Perfusion Pressure ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Treatment Targets ◽  
Poor Outcome ◽  
Severe Tbi

ABSTRACT OBJECTIVE Most physicians rely on conventional treatment targets for intracranial pressure, cerebral perfusion pressure, systemic oxygenation, and hemoglobin to direct management of traumatic brain injury (TBI) in children. In this study, we used brain tissue oxygen tension (PbtO2) monitoring to examine the association between PbtO2 values and outcome in pediatric severe TBI and to determine the incidence of compromised PbtO2 in patients for whom acceptable treatment targets had been achieved. METHODS In this prospective observational study, 26 children with severe TBI and a median postresuscitation Glasgow Coma Scale score of 5 were managed with continuous PbtO2 monitoring. The relationships between outcome and the 6-hour period of lowest PbtO2 values and the length of time that PbtO2 was less than 20, 15, 10, and 5 mmHg were examined. The incidence of reduced PbtO2 for each threshold was evaluated where the following targets were met: intracranial pressure less than 20 mmHg, cerebral perfusion pressure greater than 50 mmHg, arterial oxygen tension greater than 60 mmHg (and peripheral oxygen saturation &gt; 90%), and hemoglobin greater than 8 g/dl. RESULTS There was a significant association between poor outcome and the 6-hour period of lowest PbtO2 and length of time that PbtO2 was less than 15 and 10 mmHg. Multiple logistic regression analysis showed that low PbtO2 had an independent association with poor outcome. Despite achieving the management targets described above, 80% of patients experienced one or more episodes of compromised PbtO2 (&lt; 20 mmHg), and almost one-third experienced episodes of brain hypoxia (PbtO2 &lt; 10 mmHg). CONCLUSION Reduced PbtO2 is associated with poor outcome in pediatric severe TBI. In addition, many patients experience episodes of compromised PbtO2 despite achieving acceptable treatment targets.

scholarly journals Management of raised intracranial pressure in aneurysmal subarachnoid hemorrhage: time for a consensus?

2017 ◽  
Vol 43 (5) ◽  
pp. E13 ◽  
Author(s):  
Naif M. Alotaibi ◽  
Justin Z. Wang ◽  
Christopher R. Pasarikovski ◽  
Daipayan Guha ◽  
Fawaz Al-Mufti ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Management Strategies ◽  
Future Research ◽  
Treatment Algorithms ◽  
Controversial Topic ◽  
Poor Outcomes

Elevated intracranial pressure (ICP) is a well-recognized phenomenon in aneurysmal subarachnoid hemorrhage (aSAH) that has been demonstrated to lead to poor outcomes. Despite significant advances in clinical research into aSAH, there are no consensus guidelines devoted specifically to the management of elevated ICP in the setting of aSAH. To treat high ICP in aSAH, most centers extrapolate their treatment algorithms from studies and published guidelines for traumatic brain injury. Herein, the authors review the current management strategies for treating raised ICP within the aSAH population, emphasize key differences from the traumatic brain injury population, and highlight potential directions for future research in this controversial topic.

Sign in / Sign up

Export Citation Format

Share Document