Diffuse axonal injury after traumatic brain injury is a prognostic factor for functional outcome:A systematic review and meta-analysis

Objective: To determine the prognosis of adult patients with traumatic brain injury (TBI) and diffuse axonal injury (DAI).Methods: Online search (PubMed, Embase and Ovid Science Direct) of articles providing information about outcome in (1) patients with DAI in general, (2) DAI vs. non-DAI, (3) related to magnetic resonance imaging (MRI) classification and (4) related to lesion location/load. A reference check and quality assessment were performed.Results: A total of 32 articles were included. TBI patients with DAI had a favourable outcome in 62%. The risk of unfavourable outcome in TBI with DAI was three times higher than in TBI without DAI. Odds ratio (OR) for unfavourable outcome was 2.9 per increase of DAI grade on MRI. Lesions located in the corpus callosum were associated with an unfavourable outcome. Other specific lesion locations and lesions count showed inconsistent results regarding outcome. Lesion volume was predictive for outcome only on apparent diffusion coefficient and fluid attenuation inversion recovery MRI sequences.Conclusions: Presence of DAI on MRI in patients with TBI results in a higher chance of unfavourable outcome. With MRI grading, OR for unfavourable outcome increases threefold with every grade. Lesions in the corpus callosum in particular are associated with an unfavourable outcome

Patients with mild traumatic brain injury and acute neck pain at the emergency department are a distinct category within the mTBI spectrum:a prospective multicentre cohort study

Background: Acute neck pain (ANP) has recently been demonstrated to be a predictor of persistent posttraumatic complaints after mild traumatic brain injury (mTBI). The aim of this study was to determine specific characteristics of patients with ANP following mTBI, their posttraumatic complaints and relationship with functional outcome. Methods: Data from a prospective follow-up study of 922 mTBI patients admitted to the emergency department (ED) in three level-one trauma centres were analysed. Patients were divided into two groups: 156 ANP patients and 766 no acute neck pain (nANP) patients. Posttraumatic complaints were evaluated 2 weeks and 6 months post-injury using standardized questionnaires and functional outcome was evaluated at 6 months with the Glasgow Outcome Scale Extended (GOSE). Results: ANP patients were more often female (p < 0.01), younger (38 vs. 47 years, p < 0.01) with more associated acute symptoms at the ED (p < 0.05) compared to nANP patients. More motor vehicle accidents (12% vs. 6%, p = 0.01) and less head wounds (58% vs. 73%, p < 0.01) in ANP patients indicated 'high-energy low-impact' trauma mechanisms. ANP patients showed more posttraumatic complaints 2 weeks and 6 months post-injury (p < 0.05) and more often incomplete recovery (GOSE < 8) was present after 6 months (56% vs. 40%, p = 0.01). Conclusions: MTBI patients with acute neck pain at the ED constitute a distinct group within the mTBI spectrum with specific injury and demographic characteristics. Early identification of this at risk group already at the ED might allow specific and timely treatment to avoid development of incomplete recovery

Family History is Associated with Phenotype in Dementia with Lewy Bodies

It is currently unknown whether patients with dementia with Lewy bodies (DLB) with relatives with dementia or Parkinson's disease (familial DLB patients) have a different phenotype than sporadic DLB patients. In this study, we aimed to examine disease onset, rate of cognitive decline, survival, and Alzheimer's disease (AD) biomarkers in patients with familial DLB (n = 154) and sporadic DLB (n = 137), using linear mixed model analysis and Cox regression analysis, among others. Familial patients had a shorter survival (8.0 years) and more often elevated cerebrospinal fluid AD biomarkers (47%) than sporadic patients (9.0 years; p≤0.001; 30%, p = 0.037). Our findings suggest that genetic factors are important in DLB and that the identification of new genetic factors will probably improve the prediction of prognosis

The Pentagon Copying Test and the Clock Drawing Test as Prognostic Markers in Dementia with Lewy Bodies

Aims: To determine whether the pentagon copying test (PCT) and the clock drawing test (CDT) are associated with nursing home admission or survival in dementia with Lewy bodies (DLB). Methods: The PCT and/or the CDT were retrospectively collected from 103 clinically diagnosed probable DLB patients at a university medical center and general hospital. Patients with high versus low scores on these tests were compared. Results: Kaplan-Meier analysis showed that patients with a low score on the PCT had a shorter time to nursing home admission than patients with a high score (log-rank χ2 = 6.1, p = 0.01). Patients with a low score on the PCT or the CDT had a shorter survival than patients with a high score (log-rank χ2 = 5.4, p = 0.02, and log-rank χ2 = 11.2, p < 0.001, respectively). Cox regression analyses showed the same associations with an HR of 2.2 (95% CI 1.2–4.1) for the PCT and an HR of 2.9 (95% CI 1.6–5.4) for the CDT. Conclusion: The PCT and the CDT may function as prognostic markers in DLB. This finding is clinically relevant as these tests can be applied easily in the clinical setting and can provide valuable prognostic information. Furthermore, it may improve disease management and patient selection for research purposes

C-Terminal Proarginine Vasopressin is Associated with Disease Outcome and Mortality, but not with Delayed Cerebral Ischemia in Critically Ill Patients with an Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is an important indication for intensive care unit admission and may lead to significant morbidity and mortality. We assessed the ability of C-terminal proarginine vasopressin (CT-proAVP) to predict disease outcome, mortality, and delayed cerebral ischemia (DCI) in critically ill patients with aSAH compared with the World Federation of Neurological Surgeons (WFNS) score and Acute Physiological and Chronic Health Evaluation IV (APACHE IV) model. Methods: C-terminal proarginine vasopressin was collected on admission in this single-center, prospective, observational cohort study. The primary aim was to investigate the relationship between CT-proAVP and poor functional outcome at 1 year (Glasgow Outcome Scale score 1–3) in a multivariable logistic regression model adjusted for WFNS and APACHE IV scores. Secondary aims were mortality and DCI. The multivariable logistic regression model for DCI was also adjusted for the modified Fisher scale. Results: In 100 patients, the median CT-proAVP level was 24.9 pmol/L (interquartile range 11.5–53.8); 45 patients had a poor 1-year functional outcome, 19 patients died within 30 days, 25 patients died within 1 year, and DCI occurred in 28 patients. Receiver operating characteristics curves revealed high accuracy for CT-proAVP to identify patients with poor 1-year functional outcome (area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.77–0.92, p < 0.001), 30-day mortality (AUC 0.84, 95% CI 0.76–0.93, p < 0.001), and 1-year mortality (AUC 0.79, 95% CI 0.69–0.89, p < 0.001). CT-proAVP had a low AUC for identifying patients with DCI (AUC 0.67, 95% CI 0.55–0.79, p 0.008). CT-proAVP ≥ 24.9 pmo/L proved to be a significant predictor for poor 1-year functional outcome (odds ratio [OR] 8.04, 95% CI 2.97–21.75, p < 0.001), and CT-proAVP ≥ 29.1 pmol/L and ≥ 27.7 pmol/L were significant predictors for 30-day and 1-year mortality (OR 9.31, 95% CI 1.55–56.07, p 0.015 and OR 5.15, 95% CI 1.48–17.93, p 0.010) in multivariable models with WFNS and APACHE IV scores. CT-proAVP ≥ 29.5 pmol/L was not a significant predictor for DCI in a multivariable model adjusted for the modified Fisher scale (p = 0.061). Conclusions: C-terminal proarginine vasopressin was able to predict poor functional outcome and mortality in critically ill patients with aSAH. Its prognostic ability to predict DCI was low. Trial Registration: Nederlands Trial Register: NTR4118

A pilot study of rivastigmine in the treatment of delirium after stroke: A safe alternative

<p>Abstract</p> <p>Background</p> <p>Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine.</p> <p>Methods</p> <p>This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge.</p> <p>Results</p> <p>No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2–17).</p> <p>Conclusion</p> <p>Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke.</p> <p>Trial registration</p> <p>Nederlands Trial Register NTR1395</p

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage

The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH

Consensus guidelines for lumbar puncture in patients with neurological diseases

Introduction Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain. Methods We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III). Results Our consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the development of post-LP complications. Discussion When an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage

BACKGROUND AND OBJECTIVES: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. METHODS: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). RESULTS: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). DISCUSSION: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH

Dutch Prospective Observational Study on Prehospital Treatment of Severe Traumatic Brain Injury: The BRAIN-PROTECT Study Protocol

Background: Severe traumatic brain injury (TBI) is associated with a high mortality rate and those that survive commonly have permanent disability. While there is a broad consensus that appropriate prehospital treatment is crucial for a favorable neurological outcome, evidence to support currently applied treatment strategies is scarce. In particular, the relationship between prehospital treatments and patient outcomes is unclear. The BRAIN-PROTECT study therefore aims to identify prehospital treatment strategies associated with beneficial or detrimental outcomes. Here, we present the study protocol. Study Protocol: BRAIN-PROTECT is the acronym for BRAin INjury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma. It is a prospective observational study on the prehospital treatment of patients with suspected severe TBI in the Netherlands. Prehospital epidemiology, interventions, medication strategies, and nonmedical factors that may affect outcome are studied. Multivariable regression based modeling will be used to identify confounder-adjusted relationships between these factors and patient outcomes, including mortality at 30 days (primary outcome) or mortality and functional neurological outcome at 1 year (secondary outcomes). Patients in whom severe TBI is suspected during prehospital treatment (Glasgow Coma Scale score 8 in combination with a trauma mechanism or clinical findings suggestive of head injury) are identified by all four helicopter emergency medical services (HEMS) in the Netherlands. Patients are prospectively followed up in 9 participating trauma centers for up to one year. The manuscript reports in detail the objectives, setting, study design, patient inclusion, and data collection process. Ethical and juridical aspects, statistical considerations, as well as limitations of the study design are discussed. Discussion: Current prehospital treatment of patients with suspected severe TBI is based on marginal evidence, and optimal treatment is basically unknown. The BRAINPROTECT study provides an opportunity to evaluate and compare different treatment strategies with respect to patient outcomes. To our knowledge, this study project is the first large-scale prospective prehospital registry of patients with severe TBI that also collects long-term follow-up data and ma