Approaches for Monitoring Warfighter Blast-related Exposures in Training to Develop Effective Safety Standards.

INTRODUCTION: Traumatic brain injuries are of concern to the sports and military communities because of the age of the participants and costly burden to society. To markedly reduce the impact of traumatic brain injury and its sequela (TBI-S), it is necessary to determine the initial vulnerability of individuals as well as identify new technologies that indicate early signs of TBI-S. MATERIALS AND METHODS: Currently, diverse methods have been used by the authors and others in laboratory settings to reveal early signs of persistent TBI-S including simulation modeling of the effect of rapid deceleration on the deviatoric strain (shear force) imposed on specific brain regions, auditory evoked potential (AEP) measurements to determine injury to the auditory cortex optokinetic nystagmus (OKN) measures sensitive to vestibular trauma, and optical coherence tomography (OCT) measures that reveal changes in central visual function obtained noninvasively by examination of the retina. RESULTS: Simulation studies provided technical information on maximal deviatoric strain at the base of the sulci and interface of gray and white matter consistent with results from neuropathology and from magnetic resonance imaging. The AEP and OKN reveal measurable injury to similar regions below the Sylvian fissure including auditory cortex and midbrain, and the OCT reveals changes to the retina consistent with forceful deceleration effects. CONCLUSIONS: The studies and results are consistent with prior work demonstrating that noninvasive tests may be sensitive to the presence of TBI-S, potentially in the training field as advances in the portability of test instruments are underway. When combined with baseline data gathered from individuals in quantitative form, key variances can emerge. Therefore, it is hypothesized that AEP, OKN, and OCT, taken together, may yield faster objective and quantitative neurophysiological measures serving as a "signature" of neural injury and more indicative of potentially persistent TBI-S-recommending larger scale longitudinal studies.

Simulation of the Strain Amplification in Sulci Due to Blunt Impact to the Head.

Traumatic brain injury (TBI) has become a concern in sports, automobile accidents and combat operations. A better understanding of the mechanics leading to a TBI is required to cope with both the short-term life-threatening effects and long-term effects of TBIs, such as the development chronic traumatic encephalopathy (CTE). Kornguth et al. (1) proposed that an inflammatory and autoimmune process initiated by a water hammer effect at the bases of the sulci of the brain is a mechanism of TBI leading to CTE. A major objective of this study is to investigate whether the water hammer effect is present due to blunt impacts through the use of computational models. Frontal blunt impacts were simulated with 2D finite element models developed to capture the biofidelic geometry of a human head. The models utilized the Arbitrary Lagrangian Eulerian (ALE) method to model a layer of cerebrospinal fluid (CSF) as a deforming fluid allowing for CSF to move in and out of sulci. During the simulated impacts, CSF was not observed to be driven into the sulci during the transient response. However, elevated shear strain levels near the base of the sulci were exhibited. Further, increased shear strain was present when differentiation between white and gray matter was taken into account. Both of the results support clinical observations of (1).

Effect of catheter ablation and periprocedural anticoagulation regimen on the clinical course of migraine in atrial fibrillation patients with or without pre-existent migraine: results from a prospective study.

BACKGROUND: We examined the influence of catheter ablation and periprocedural anticoagulation regimen on trajectory of migraine in atrial fibrillation patients with or without migraine history. METHODS AND RESULTS: Forty patients with (group 1: 64 ± 8 years; men 78%) and 85 (group 2: 61 ± 10 years; men 73%) without migraine history undergoing atrial fibrillation-ablation were enrolled. Migraine status and quality of life were evaluated using standardized questionnaires. Diffusion magnetic resonance imaging of brain was performed for all at pre and 24 hours post procedure. Catheter ablation was performed with (88, 70%) or without (37, 30%) continuous warfarin treatment. Fifty-four patients (11 and 43 from groups 1 and 2, respectively) had subtherapeutic international normalized ratio on procedure day. At 17 ± 5 months follow-up, from group 1, 25 (63%) reported no migraine, 10 (25%) had < 1, and 3 (8%) had 2 to 3 monthly symptoms. Intensity of pain decreased from baseline 7 (Q1-Q3, 4-8) to 2 (0-4) scale points at follow-up (P < 0.001) and duration of headache from median 8 (Q1-Q3, 4-15) to 0.5 (Q1-Q3, 0-2) hours (P < 0.001). Two patients from group 1 reported increased migraine severity and 2 from group 2 had new-onset migraine. Follow-up diffusion magnetic resonance imaging revealed new infarcts in 9.6% (12/125) patients; of which 11 had subtherapeutic preprocedural international normalized ratio on or off continuous warfarin. Quality of life improved significantly in patients with successful ablation, being more pronounced in group 1. CONCLUSIONS: In most patients, migraine symptoms improved substantially after catheter ablation. Interestingly, the only cases of new migraine and aggravation of pre-existent headache had subtherapeutic international normalized ratio during the procedure and new cerebral infarcts.

Importance of proper patient selection and endpoint selection in evaluation of new therapies in acute stroke: further analysis of the SENTIS trial.

BACKGROUND: The magnitude of treatment effect in acute stroke depends on several factors, including time from symptom onset (TFSO) to treatment and severity of the initial insult. OBJECTIVE: To report further evaluation of NeuroFlo therapy, focusing on the effect of time and stroke severity. METHODS: SENTIS was a prospective randomized trial (N=515) comparing standard medical therapy with/without NeuroFlo therapy. For this analysis, we evaluated outcomes in groups of patients based on TFSO and stroke severity: patients randomized <6 h, 6-10 h, and >10 h with mild (NIHSS<8), moderate (8-14), and severe (>14) symptoms at randomization. 90-Day mRS (modified Rankin Scale) scores and stroke-related death rates were compared between treatment groups. RESULTS: For patients randomized <6 h TFSO (n=128), the OR for mRS 0-2 was 3.11 (CI 1.30 to 7.46, p=0.011) for treated versus non-treated patients. In patients with disease of moderate severity (NIHSS 8-14, n=214), NeuroFlo-treated patients were more likely to have a good outcome (mRS 0-2; OR=1.84, CI 1.02 to 3.33, p=0.043). The stroke-related death rate was better in the treated group with TFSO >10 h and NIHSS >14 (n=42) (OR=7.10, CI 1.13 to 44.55, p=0.036). CONCLUSIONS: The results of our analysis support the importance of careful selection of outcome measures and the impact that rapid treatment and initial stroke severity have on outcome.

Partial aortic occlusion for cerebral perfusion augmentation: safety and efficacy of NeuroFlo in Acute Ischemic Stroke trial.

BACKGROUND AND PURPOSE: Fewer than 5% of patients with acute ischemic stroke are currently treated, and there is need for additional treatment options. A novel catheter treatment (NeuroFlo) that increases cerebral blood flow was tested to 14 hours. METHODS: The Safety and Efficacy of NeuroFlo in Acute Ischemic Stroke trial is a randomized trial of the safety and efficacy of NeuroFlo treatment in improving neurological outcome versus standard medical management. The primary safety end point was the incidence of serious adverse events through 90 days. The primary efficacy end point on a modified intent-to-treat population was a global disability end point at 90 days. Secondary end points included mortality, intracranial hemorrhage, modified Rankin scale score outcome of 0 to 2, and modified Rankin scale shift analysis. RESULTS: Between October 2005 and January 2010, 515 patients were enrolled at 68 centers in 9 countries. The primary efficacy end point did not reach statistical significance (OR, 1.17; CI, 0.81-1.67; P=0.407). The primary safety end point did not show a difference in serious adverse events (P=0.923). Ninety-day mortality was 11.3% (26/230) in treatment and 16.3% (42/257) in control (P=0.087). Post hoc analyses showed that patients presenting within 5 hours (OR, 3.33; CI, 1.31-8.48), with NIHSS score 8 to 14 (OR, 1.80; CI, 0.99-3.30), or older than age 70 years (OR, 2.02; CI, 1.02-4.03) had better modified Rankin scale score outcomes of 0 to 2; additionally, there were fewer stroke-related deaths in treatment compared to control groups (7.4% = 17/230; 14.4% = 37/257). CONCLUSIONS: The trial met its primary safety end point but not its primary efficacy end point. Signals of treatment effect were suggested on all-cause mortality, in patients presenting early, older than age 70 years, or with moderate strokes, but these require confirmation. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00119717.