Relationship between psychosocial and psychiatric risk factors and poor long-term outcome following mild traumatic brain injury: A systematic review.

BACKGROUND AND PURPOSE: Mild traumatic brain injury (mTBI) has an estimated worldwide incidence of >60 million per year, and long-term persistent postconcussion symptoms (PPCS) are increasingly recognized as being predicted by psychosocial variables. Patients at risk for PPCS may be amenable to closer follow-up to treat modifiable symptoms and prevent chronicity. In this regard, similarities seem to exist with psychosocial risk factors for chronicity in other health-related conditions. However, as opposed to other conditions, no screening instruments exist for mTBI. METHODS: A systematic search of the literature on psychological and psychiatric predictors of long-term symptoms in mTBI was performed by two independent reviewers using PubMed, Embase, and Web of Science. RESULTS: Fifty papers were included in the systematic analysis. Anxiety, depressive symptoms, and emotional distress early after injury predict PPCS burden and functional outcome up to 1 year after injury. In addition, coping styles and preinjury psychiatric disorders and mental health also correlate with PPCS burden and functional outcome. Associations between PPCS and personality and beliefs were reported, but either these effects were small or evidence was limited. CONCLUSIONS: Early psychological and psychiatric factors may negatively interact with recovery potential to increase the risk of chronicity of PPCS burden after mTBI. This opens opportunities for research on screening tools and early intervention in patients at risk.

Beyond intracranial pressure: monitoring cerebral perfusion and autoregulation in severe traumatic brain injury.

PURPOSE OF REVIEW: Severe traumatic brain injury (TBI) remains the most prevalent neurological condition worldwide. Observational and interventional studies provide evidence to recommend monitoring of intracranial pressure (ICP) in all severe TBI patients. Existing guidelines focus on treating elevated ICP and optimizing cerebral perfusion pressure (CPP), according to fixed universal thresholds. However, both ICP and CPP, their target thresholds, and their interaction, need to be interpreted in a broader picture of cerebral autoregulation, the natural capacity to adjust cerebrovascular resistance to preserve cerebral blood flow in response to external stimuli. RECENT FINDINGS: Cerebral autoregulation is often impaired in TBI patients, and monitoring cerebral autoregulation might be useful to develop personalized therapy rather than treatment of one size fits all thresholds and guidelines based on unidimensional static relationships. SUMMARY: Today, there is no gold standard available to estimate cerebral autoregulation. Cerebral autoregulation can be triggered by performing a mean arterial pressure (MAP) challenge, in which MAP is increased by 10% for 20 min. The response of ICP (increase or decrease) will estimate the status of cerebral autoregulation and can steer therapy mainly concerning optimizing patient-specific CPP. The role of cerebral metabolic changes and its relationship to cerebral autoregulation is still unclear and awaits further investigation.

Long-term outcomes after traumatic brain injury in elderly patients on antithrombotic therapy.

INTRODUCTION: Elderly patients receiving antithrombotic treatment have a significantly higher risk of developing an intracranial hemorrhage when suffering traumatic brain injury (TBI), potentially contributing to higher mortality rates and worse functional outcomes. It is unclear whether different antithrombotic drugs carry a similar risk. OBJECTIVE: This study aims to investigate injury patterns and long-term outcomes after TBI in elderly patients treated with antithrombotic drugs. METHODS: The clinical records of 2999 patients ≥ 65 years old admitted to the University Hospitals Leuven (Belgium) between 1999 and 2019 with a diagnosis of TBI, spanning all injury severities, were manually screened. RESULTS: A total of 1443 patients who had not experienced a cerebrovascular accident prior to TBI nor presented with a chronic subdural hematoma at admission were included in the analysis. Relevant clinical information, including medication use and coagulation lab tests, was manually registered and statistically analyzed using Python and R. In the overall cohort, 418 (29.0%) of the patients were treated with acetylsalicylic acid before TBI, 58 (4.0%) with vitamin K antagonists (VKA), 14 (1.0%) with a different antithrombotic drug, and 953 (66.0%) did not receive any antithrombotic treatment. The median age was 81 years (IQR = 11). The most common cause of TBI was a fall accident (79.4% of the cases), and 35.7% of the cases were classified as mild TBI. Patients treated with vitamin K antagonists had the highest rate of subdural hematomas (44.8%) (p = 0.02), hospitalization (98.3%, p = 0.03), intensive care unit admissions (41.4%, p < 0.01), and mortality within 30 days post-TBI (22.4%, p < 0.01). The number of patients treated with adenosine diphosphate (ADP) receptor antagonists and direct oral anticoagulants (DOACs) was too low to draw conclusions about the risks associated with these antithrombotic drugs. CONCLUSION: In a large cohort of elderly patients, treatment with VKA prior to TBI was associated with a higher rate of acute subdural hematoma and a worse outcome, compared with other patients. However, intake of low dose aspirin prior to TBI did not have such effects. Therefore, the choice of antithrombotic treatment in elderly patients is of utmost importance with respect to risks associated with TBI, and patients should be counselled accordingly. Future studies will determine whether the shift towards DOACs is mitigating the poor outcomes associated with VKA after TBI.

Profound prospective assessment of radiological and functional outcome 6 months after TBI in elderly.

BACKGROUND: Recovery after traumatic brain injury (TBI) in older adults is usually affected by the presence of comorbidities, leading to more severe sequelae in this age group than in younger patients. However, there are only few reports that prospectively perform in-depth assessment of outcome following TBI in elderly. OBJECTIVE: This study aims at documenting structural brain characteristics and functional outcome and quality of life in elderly patients 6 months after TBI and comparing these data with healthy volunteers undergoing the same assessments. METHODS: Thirteen TBI patients ≥ 65 years old, admitted to the University Hospitals Leuven (Belgium), between 2019 and 2022 due to TBI, including all injury severities, and a group of 13 healthy volunteers with similar demographic characteristics were prospectively included in the study. At admission, demographic, injury, and CT scan data were collected in our database. Six months after the accident, a brain MRI scan and standardized assessments of frailty, sleep quality, cognitive function, motor function, and quality of life were conducted. RESULTS: A total of 13 patients and 13 volunteers were included in the study, with a median age of 74 and 73 years, respectively. Nine out of the 13 patients presented with a mild TBI. The patient group had a significantly higher level of frailty than the control group, presenting a mean Reported Edmonton Frailty Scale score of 5.8 (SD 2.7) vs 0.7 (SD 1.1) (p < 0.01). No statistically significant differences were found between patient and control brain volumes, fluid attenuated inversion recovery white matter hyperintensity volumes, number of lesions and blackholes, and fractional anisotropy values. Patients demonstrated a significantly higher median reaction time in the One Touch Stockings of Cambridge (22.3 s vs 17.6, p = 0.03) and Reaction Time (0.5 s vs 0.4 s, p < 0.01) subtests in the Cambridge Neuropsychological Test Automated Battery. Furthermore, patients had a lower mean score on the first Box and Blocks test with the right hand (46.6 vs 61.7, p < 0.01) and a significantly higher mean score in the Timed-Up & Go test (13.1 s vs 6.2 s, p = 0.02) and Timed Up & Go with cognitive dual task (16.0 s vs 10.2 s, p < 0.01). Substantially lower QOLIBRI total score (60.4 vs 85.4, p < 0.01) and QOLIBRI-OS total score (53.8 vs 88.5, p < 0.01) were also observed in the patients' group. CONCLUSION: In this prospective study, TBI patients ≥ 65 years old when compared with elder controls showed slightly worse cognitive performance and poorer motor function, higher fall risk, but a substantially reduced QoL at 6 months FU, as well as significantly higher frailty, even when the TBI is classified as mild. No statistically significant differences were found in structural brain characteristics on MRI. Future studies with larger sample sizes are needed to refine the impact of TBI versus frailty on function and QoL in elderly.

Early surgery versus conservative treatment in patients with traumatic intracerebral hematoma: a CENTER-TBI study.

PURPOSE: Evidence regarding the effect of surgery in traumatic intracerebral hematoma (t-ICH) is limited and relies on the STITCH(Trauma) trial. This study is aimed at comparing the effectiveness of early surgery to conservative treatment in patients with a t-ICH. METHODS: In a prospective cohort, we included patients with a large t-ICH (< 48 h of injury). Primary outcome was the Glasgow Outcome Scale Extended (GOSE) at 6 months, analyzed with multivariable proportional odds logistic regression. Subgroups included injury severity and isolated vs. non-isolated t-ICH. RESULTS: A total of 367 patients with a large t-ICH were included, of whom 160 received early surgery and 207 received conservative treatment. Patients receiving early surgery were younger (median age 54 vs. 58 years) and more severely injured (median Glasgow Coma Scale 7 vs. 10) compared to those treated conservatively. In the overall cohort, early surgery was not associated with better functional outcome (adjusted odds ratio (AOR) 1.1, (95% CI, 0.6-1.7)) compared to conservative treatment. Early surgery was associated with better outcome for patients with moderate TBI and isolated t-ICH (AOR 1.5 (95% CI, 1.1-2.0); P value for interaction 0.71, and AOR 1.8 (95% CI, 1.3-2.5); P value for interaction 0.004). Conversely, in mild TBI and those with a smaller t-ICH (< 33 cc), conservative treatment was associated with better outcome (AOR 0.6 (95% CI, 0.4-0.9); P value for interaction 0.71, and AOR 0.8 (95% CI, 0.5-1.0); P value for interaction 0.32). CONCLUSIONS: Early surgery in t-ICH might benefit those with moderate TBI and isolated t-ICH, comparable with results of the STITCH(Trauma) trial.

Rehabilitation to improve outcomes of lumbar fusion surgery: a systematic review with meta-analysis.

PURPOSE: To evaluate the effectiveness of rehabilitation strategies on disability, pain, pain-related fear, and return-to-work in patients undergoing lumbar fusion surgery for degenerative conditions or adult isthmic spondylolisthesis. METHODS: Six electronic databases were systematically searched for randomized controlled trials (RCTs) evaluating the effect of rehabilitation (unimodal or multimodal). The estimated effect size was calculated for interventions with homogeneous content using a random-effects model. Certainty of evidence was assessed by GRADE. RESULTS: In total, 18 RCTs, including 1402 unique patients, compared specific rehabilitation to other rehabilitation strategies or usual care. Most described indications were degenerative disc disease and spondylolisthesis. All rehabilitation interventions were delivered in the postoperative period, and six of them also included a preoperative component. Intervention dose and intensity varied between studies (ranging from one session to daily sessions for one month). Usual care consisted mostly of information and postoperative mobilization. At short term, low quality of evidence shows that exercise therapy was more effective for reducing disability and pain than usual care (standardized mean difference [95% CI]: -0.41 [-0.71; -0.10] and -0.36 [-0.65; -0.08], four and five studies, respectively). Multimodal rehabilitation consisted mostly of exercise therapy combined with cognitive behavioral training, and was more effective in reducing disability and pain-related fear than exercise therapy alone (-0.31 [-0.49; -0.13] and -0.64 [-1.11; -0.17], six and four studies, respectively). Effects disappeared beyond one year. Rehabilitation showed a positive tendency towards a higher return-to-work rate (pooled relative risk [95% CI]: 1.30 [0.99; 1.69], four studies). CONCLUSION: There is low-quality evidence showing that both exercise therapy and multimodal rehabilitation are effective for improving outcomes up to six months after lumbar fusion, with multimodal rehabilitation providing additional benefits over exercise alone in reducing disability and pain-related fear. Additional high-quality studies are needed to demonstrate the effectiveness of rehabilitation strategies in the long term and for work-related outcomes.

Traumatic brain injury in the elderly population: a 20-year experience in a tertiary neurosurgery center in Belgium.

PURPOSE: Traumatic brain injury (TBI) rates in the elderly population are rapidly increasing worldwide. However, there are no clinical guidelines for the treatment of elderly TBI to date. This study aims at describing injury patterns and severity, clinical management, and outcomes in elderly TBI patients, which may contribute to specific prognostic tools and clinical guidelines in the future. METHODS: Clinical records of 2999 TBI patients ≥ 65 years old admitted in the University Hospital Leuven (Belgium) between 1999 and 2019 were manually screened and 1480 cases could be included. Records were scrutinized for relevant clinical data. RESULTS: The median age in the cohort was 78.0 years (IQR = 12). Falls represented the main accident mechanism (79.7%). The median Glasgow Coma Score on admission was 15 (range 3-15). Subdural hematomas were the most common lesion (28.4%). 90.1% of all patients were hospitalized and 27.0% were admitted to intensive care. 16.4% underwent a neurosurgical intervention. 11.0% of all patients died within 30 days post-TBI. Among the 521 patients with mild TBI, 28.6% were admitted to ICU and 13.1% had a neurosurgical intervention and 30-day mortality was 6.9%. CONCLUSION: Over the 20-year study period, an increase of age and comorbidities and a reduction in neurosurgical interventions and ICU admissions were observed, along with a trend to less severe injuries but a higher proportion of treatment withdrawals, while at the same time mortality rates decreased. TBI is a life-changing event, leading to severe consequences in the elderly population, especially at higher ages. Even mild TBI is associated with substantial rates of hospitalization, surgery, and mortality in elderly. The characteristics of the elderly population with TBI are subject to changes over time.

International comparative study of low back pain care pathways and analysis of key interventions.

PURPOSE: Low back pain (LBP) is a major public health problem worldwide. Significant practice variation exists despite guidelines, including strong interventionist focus by some practitioners. Translation of guidelines into pathways as integrated treatment plans is a next step to improve implementation. The goal of the present study was to analyze international examples of LBP pathways in order to identify key interventions as building elements for care pathway for LBP and radicular pain. METHODS: International examples of LBP pathways were searched in literature and grey literature. Authors of pathways were invited to fill a questionnaire and to participate in an in-depth telephone interview. Pathways were quantitatively and qualitatively analyzed, to enable the identification of key interventions to serve as pathway building elements. RESULTS: Eleven international LBP care pathways were identified. Regional pathways were strongly organized and included significant training efforts for primary care providers and an intermediate level of caregivers in between general practitioners and hospital specialists. Hospital pathways had a focus on multidisciplinary collaboration and stepwise approach trajectories. Key elements common to all pathways included the consecutive screening for red flags, radicular pain and psychosocial risk factors, the emphasis on patient empowerment and self-management, the development of evidence-based consultable protocols, the focus on a multidisciplinary work mode and the monitoring of patient-reported outcome measures. CONCLUSION: Essential building elements for the construction of LBP care pathways were identified from a transversal analysis of key interventions in a study of 11 international examples of LBP pathways.

An Update on the COGiTATE Phase II Study: Feasibility and Safety of Targeting an Optimal Cerebral Perfusion Pressure as a Patient-Tailored Therapy in Severe Traumatic Brain Injury.

INTRODUCTION: Monitoring of cerebral autoregulation (CA) in patients with a traumatic brain injury (TBI) can provide an individual 'optimal' cerebral perfusion pressure (CPP) target (CPPopt) at which CA is best preserved. This potentially offers an individualized precision medicine approach. Retrospective data suggest that deviation of CPP from CPPopt is associated with poor outcomes. We are prospectively assessing the feasibility and safety of this approach in the COGiTATE [CPPopt Guided Therapy: Assessment of Target Effectiveness] study. Its primary objective is to demonstrate the feasibility of individualizing CPP at CPPopt in TBI patients. The secondary objectives are to investigate the safety and physiological effects of this strategy. METHODS: The COGiTATE study has included patients in four European hospitals in Cambridge, Leuven, Nijmegen, and Maastricht (coordinating centre). Patients with severe TBI requiring intracranial pressure (ICP)-directed therapy are allocated into one of two groups. In the intervention group, CPPopt is calculated using a published (modified) algorithm. In the control group, the CPP target recommended in the Brain Trauma Foundation guidelines (CPP 60-70 mmHg) is used. RESULTS: Patient recruitment started in February 2018 and will continue until 60 patients have been studied. Fifty-one patients (85% of the intended total) have been recruited in October 2019. The first results are expected early 2021. CONCLUSION: This prospective evaluation of the feasibility, safety and physiological implications of autoregulation-guided CPP management is providing evidence that will be useful in the design of a future phase III study in severe TBI patients.

Association of Dose of Intracranial Hypertension with Outcome in Subarachnoid Hemorrhage.

BACKGROUND: In patients with aneurysmal subarachnoid hemorrhage (aSAH) the burden of intracranial pressure (ICP) and its contribution to outcomes remains unclear. In this multicenter study, the independent association between intensity and duration, or "dose," of episodes of intracranial hypertension and 12-month neurological outcomes was investigated. METHODS: This was a retrospective analysis of multicenter prospectively collected data of 98 adult patients with aSAH amendable to treatment. Patients were admitted to the intensive care unit of two European centers (Medical University of Innsbruck [Austria] and San Gerardo University Hospital of Monza [Italy]) from 2009 to 2013. The dose of intracranial hypertension was visualized. The obtained visualizations allowed us to investigate the association between intensity and duration of episodes of intracranial hypertension and the 12-month neurological outcomes of the patients, assessed with the Glasgow Outcome Score. The independent association between the cumulative dose of intracranial hypertension and outcome for each patient was investigated by using multivariable logistic regression models corrected for age, occurrence of delayed cerebral ischemia, and the Glasgow Coma Scale score at admission. RESULTS: The combination of duration and intensity defined the tolerance to intracranial hypertension for the two cohorts of patients. A semiexponential transition divided ICP doses that were associated with better outcomes (in blue) with ICP doses associated with worse outcomes (in red). In addition, in both cohorts, an independent association was found between the cumulative time that the patient experienced ICP doses in the red area and long-term neurological outcomes. The ICP pressure-time burden was a stronger predictor of outcomes than the cumulative time spent by the patients with an ICP greater than 20 mmHg. CONCLUSIONS: In two cohorts of patients with aSAH, an association between duration and intensity of episodes of elevated ICP and 12-month neurological outcomes could be demonstrated and was visualized in a color-coded plot.

Guidelines for Rehabilitation and Return to Play After Cervical Surgery in a General Athletic Population: A Delphi Analysis.

OBJECTIVE: Decisions concerning the rehabilitation process and return to play (RTP) after cervical spine surgery in a general sporting population can be difficult and may be influenced by several factors. Moreover, no clear guidelines for this are currently available. The aim of this study was to create tentative guidelines for rehabilitation and RTP after cervical surgery in a general sporting population. DESIGN: Five-step Delphi analysis. SETTINGS: Primary, secondary, and tertiary medical practitioners. PARTICIPANTS: Panel of Belgian neurosurgeons, orthopedic surgeons, physiotherapists, and physical and rehabilitation medicine practitioners. ASSESSMENT: Round 1 (R1) was a brainstorm phase. A comprehensive list of answers from R1 was validated in round 2 (R2). In round 3 (R3), experts ranked these items in a chronological order. Contraindications and criteria to start each rehabilitation step were linked in round 4 (R4). In round 5 (R5), panelists ranked theses about contraindications and criteria on a 5-point Likert scale. MAIN OUTCOME MEASURES: Theses scoring ≥10% "oppose" or "strongly oppose" were rejected. RESULTS: The response rate was 100% (n = 15) for R1, 93% (n = 14) for R2, 73% (n = 11) for R3, 53% (n = 8) for R4, and 67% (n = 10) for R5. In R5, 25 theses on absolute and relative contraindications and criteria were endorsed. CONCLUSIONS: This Delphi analysis resulted in contraindications and criteria for the rehabilitation process and RTP after cervical surgery in a general athletic population. Tentative guidelines and timetable are proposed. Key messages from these guidelines are (1) Rehabilitation should start before surgery with education; (2) Rehabilitation should be patient-tailored; and (3) An unstable arthrodesis is an absolute contraindication for RTP.

How good are the outcomes of instrumented debulking operations for symptomatic spinal metastases and how long do they stand? A subgroup analysis in the global spine tumor study group database.

BACKGROUND: The benefits of surgery for symptomatic spinal metastases have been demonstrated, largely based on series of patients undergoing debulking and instrumentation operations. However, as cancer treatments improve and overall survival lengths increase, the incidence of recurrent spinal cord compression after debulking may increase. The aim of the current paper is to document the postoperative evolution of neurological function, pain, and quality of life following debulking and instrumentation in the Global Spine Tumor Study Group (GSTSG) database. METHODS: The GSTSG database is a prospective multicenter data repository of consecutive patients that underwent surgery for a symptomatic spinal metastasis. For the present analysis, patients were selected from the database that underwent decompressive debulking surgery with instrumentation. Preoperative tumor type, Tomita and Tokuhashi scores, EQ-5D, Frankel, Karnofsky, and postoperative complications, survival, EQ-5D, Frankel, Karnofsky, and pain numeric rating scores (NRS) at 3, 6, 12, and 24 months were analyzed. RESULTS: A total of 914 patients underwent decompressive debulking surgery with instrumentation and had documented follow-up until death or until 2 years post surgery. Median preoperative Karnofsky performance index was 70. A total of 656 patients (71.8%) had visceral metastases and 490 (53.6%) had extraspinal bone metastases. Tomita scores were evenly distributed above (49.1%) and below or equal to 5 (50.9%), and Tokuhashi scores almost evenly distributed below or equal to 8 (46.3%) and above 8 (53.7%). Overall, 12-month survival after surgery was 56.3%. The surgery resulted in EQ-5D health status improvement and NRS pain reduction that was maintained throughout follow-up. Frankel scores improved at first follow-up in 25.0% of patients, but by 12 months neurological deterioration was observed in 18.8%. CONCLUSION: We found that palliative debulking and instrumentation surgeries were performed throughout all Tomita and Tokuhashi categories. These surgeries reduced pain scores and improved quality of life up to 2 years after surgery. After initial improvement, a proportion of patients experienced neurological deterioration by 1 year, but the majority of patients remained stable.

Postoperative bracing after lumbar surgery: a survey amongst spinal surgeons in Belgium.

PURPOSE: Bracing is frequently prescribed following lumbar surgery for degenerative conditions. However, previous studies failed to demonstrate the advantage of postoperative lumbar bracing in both short- and long-term outcome in terms of pain, quality of life and fusion rate. The purpose of this study was to assess the prescription patterns and rationale for postoperative bracing amongst spinal surgeons in Belgium. METHODS: A 16-item online survey was distributed by email to spinal surgeons affiliated to the Spine Society of Belgium (N = 252). RESULTS: A total of 105 surgeons (42%) completed the survey. The overall bracing frequency following lumbar surgery was 38%. A brace was more often prescribed following the fusion procedures (52%) than after the non-fusion procedures (21%) (p < 0.0001). The majority of surgeons (59%) considered bracing after at least one type of lumbar surgery. Orthopaedic surgeons (73%) reported a significantly higher rate of prescribing postoperative bracing compared to neurosurgeons (44%) (p = 0.003). Pain alleviation (67%) was the main goal for prescribing a postoperative brace. A total of 42% of the surgeons aimed to improve fusion rate by bracing after lumbar fusion procedures. A quasi-equal level of the scientific literature (29%), personal experience (35%) and teaching from peers (36%) was reported to contribute on the attitudes towards prescribing bracing. CONCLUSIONS: Postoperative bracing was prescribed by Belgian spinal surgeons following more than one-third of lumbar procedures. This was underpinned by beliefs regarding pain alleviation and higher fusion rate. Interestingly, based on the scientific literature these beliefs have been demonstrated to be false. These slides can be retrieved under Electronic Supplementary Material.

What Determines Outcome in Patients That Suffer Raised Intracranial Pressure After Traumatic Brain Injury?

INTRODUCTION: Episodes of raised intracranial pressure (ICP) after traumatic brain injury (TBI) are responsible for the majority of secondary brain injury events and thereby strongly affect long-term outcome. However, not all patients with major episodes of raised ICP suffer a poor outcome. The aim of the current analysis was to identify variables contributing to good outcome in patients suffering episodes of high ICP. METHODS: Retrospective analysis of 20 severe TBI patients admitted to the University Hospitals Leuven between 2010 and 2014. All patients had at least one episode of ICP > 30 mmHg for more than 3 min in succession. Outcome was assessed by the extended Glasgow Outcome Scale at 6 months. Partial least squares (PLS) regression was used to derive factors determining outcome. Pressure reactivity index (PRx) was calculated as an index for cerebrovascular autoregulation capacity. RESULTS: Both outcome groups did not differ for age, Glasgow Coma Score, pupil reactivity, computed tomography Marshall classification, glycaemia, haemoglobin and CRASH and IMPACT scores on admission. Significant differences were found for mean ICP, number of episodes of ICP > 30 mmHg, number and duration of longest PRx episodes. The number of episodes of ICP > 30 mmHg correlated significantly with the number and duration of longest PRx episodes. PLS regression indicates that episodes of impaired autoregulation contributed equally to explaining outcome compared to episodes of raised ICP. CONCLUSIONS: Prolonged episodes of disturbed dynamic cerebral autoregulation contribute to detrimental outcome in patients with increased ICP. Autoregulation seems to have an important protective role in tolerating episodes of raised ICP.

What Do We Mean by Cerebral Perfusion Pressure?

INTRODUCTION: No consensus exists on the exact method for measuring mean arterial blood pressure (MAP) in the definition of cerebral perfusion pressure (CPP). The aim of the current study is to investigate how different MAP measurement methods have influenced the CPP recommendations in the Brain Trauma Foundation (BTF) guidelines. METHODS: All papers on which the chapter on CPP thresholds in the 2007 version of the BTF guidelines is based, were reviewed. If accurate descriptions of head of bed elevation and arterial pressure transducer height were lacking, the authors were emailed for clarification. Additionally, the effect of choosing the radial artery for MAP measurement and the potential effect of gravity were studied in the literature. RESULTS: Thresholds of CPP in the BTF guidelines are based on 11 studies. Head of bed elevation at 30° was part of the protocol in 5 studies, patients were nursed flat in 1 study, and this variable remained unknown for 5 studies. The arterial pressure transducer was at heart level in 5 studies, at ear level in 3 studies, and height was unknown in 3 studies. Measuring MAP in the radial artery underestimates carotid artery MAP by approximately 10 mmHg in the flat position, and in a nonflat position gravity influences MAP of the internal carotid artery. CONCLUSION: There is no uniform definition for CPP, which may affect conclusions on proposed CPP targets in severe traumatic brain injury by ±10 mmHg.

Comparison of Intracranial Pressure and Pressure Reactivity Index Obtained Through Pressure Measurements in the Ventricle and in the Parenchyma During and Outside Cerebrospinal Fluid Drainage Episodes in a Manipulation-Free Patient Setting.

OBJECTIVE: We investigated the effect of cerebrospinal fluid (CSF) drainage on the intracranial pressure (ICP) signal measured in the parenchyma and the ventricle as well as the effect on the pressure reactivity index (PRx) calculated from both signals. METHODS: Ten patients were included in this prospective study. All patients received a parenchymal ICP sensor and an external ventricular drain (EVD) for CSF drainage. ICP signals (ICP-p and ICP-evd) were captured. Part of the study was a period of 90 min during which the patient was free from any manipulation, consisting of 30 min of drainage (O1), 30 min EVD closed (C) and 30 min of drainage (O2). RESULTS: Mean ICP-evd and mean AMP-evd increased (3.03 and 0.46 mmHg) from O1 to C and decreased (2.12 and 0.43 mmHg) from C to O2. ICP-p and AMP-p changes were less pronounced (closing EVD: +0.81 mmHg/+0.22 mmHg; opening EVD: -0.22 mmHg/-0.05 mmHg). Mean difference between PRx-evd and PRx-p was 0.12 for O1, 0.02 for C and -0.02 for O2. The intraclass correlation coefficient for absolute agreement of single measures was 0.66 for O1, 0.77 for C and 0.69 for O2. Mean PRx differences demonstrated a significant difference between O1 versus C and O1 versus O2 but not between C versus O2. CONCLUSION: Drainage of CSF reduces ICP magnitude and amplitude through the EVD. This effect was only marginal in parenchymal ICP measurements. In manipulation-free circumstances, agreement of PRx obtained through parenchymal and ventricular measurements was moderate to good, depending on the statistical method, and was not necessarily influenced by drainage.

Cerebral Perfusion Pressure Variability Between Patients and Between Centres.

INTRODUCTION: The aim of this analysis was to investigate to what extent median cerebral perfusion pressure (CPP) differs between severe traumatic brain injury (TBI) patients and between centres, and whether the 2007 change in CPP threshold in the Brain Trauma Foundation guidelines is reflected in patient data collected at several centres over different time periods. METHODS: Data were collected from the Brain-IT database, a multi-centre project between 2003 and 2005, and from a recent project in four centres between 2009 and 2013. For patients nursed with their head up at 30° and with the blood pressure transducer at atrium level, CPP was corrected by 10 mmHg. Median CPP, interquartile ranges and total CPP ranges over the monitoring time were calculated per patient and per centre. RESULTS: Per-centre medians pre-2007 were situated between 50 and 70 mmHg in 6 out of 16 centres, while 10 centres had medians above 70 mmHg and 4 above 80 mmHg. Post-2007, three out of four centres had medians between 60 and 70 mmHg and one above 80 mmHg. One out of two centres with data pre- and post-2007 shifted from a median CPP of 76 mmHg to 60 mmHg, while the other remained at 68-67 mmHg. CONCLUSIONS: CPP data are characterised by a high inter-individual variability, but the data also suggest differences in CPP policies between centres. The 2007 guideline change may have affected policies towards lower CPP in some centres. Deviations from the guidelines occur in the direction of CPP > 70 mmHg.

Visualizing Cerebrovascular Autoregulation Insults and Their Association with Outcome in Adult and Paediatric Traumatic Brain Injury.

OBJECTIVE: The aim of this study is to assess visually the impact of duration and intensity of cerebrovascular autoregulation insults on 6-month neurological outcome in severe traumatic brain injury. MATERIAL AND METHODS: Retrospective analysis of prospectively collected minute-by-minute intracranial pressure (ICP) and mean arterial blood pressure data of 259 adult and 99 paediatric traumatic brain injury (TBI) patients from multiple European centres. The relationship of the 6-month Glasgow Outcome Scale with cerebrovascular autoregulation insults (defined as the low-frequency autoregulation index above a certain threshold during a certain time) was visualized in a colour-coded plot. The analysis was performed separately for autoregulation insults occurring with cerebral perfusion pressure (CPP) below 50 mmHg, with ICP above 25 mmHg and for the subset of adult patients that did not undergo decompressive craniectomy. RESULTS: The colour-coded plots showed a time-intensity-dependent association with outcome for cerebrovascular autoregulation insults in adult and paediatric TBI patients. Insults with a low-frequency autoregulation index above 0.2 were associated with worse outcomes and below -0.6 with better outcomes, with and approximately exponentially decreasing transition curve between the two intensity thresholds. All insults were associated with worse outcomes when CPP was below 50 mmHg or ICP was above 25 mmHg. CONCLUSIONS: The colour-coded plots indicate that cerebrovascular autoregulation is disturbed in a dynamic manner, such that duration and intensity play a role in the determination of a zone associated with better neurological outcome.

Early Detection of Increased Intracranial Pressure Episodes in Traumatic Brain Injury: External Validation in an Adult and in a Pediatric Cohort.

OBJECTIVE: A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. DESIGN: Prognostic modeling. Noninterventional, observational, retrospective study. SETTING AND PATIENTS: The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The model's performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. CONCLUSIONS: The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.