Eye Tracking as a Biomarker for Concussion in Children.

OBJECTIVE: Concussion is the most common type of brain injury in both pediatric and adult populations and can potentially result in persistent postconcussion symptoms. Objective assessment of physiologic "mild" traumatic brain injury in concussion patients remains challenging. This study evaluates an automated eye-tracking algorithm as a biomarker for concussion as defined by its symptoms and the clinical signs of convergence insufficiency and accommodation dysfunction in a pediatric population. DESIGN: Cross-sectional case-control study. SETTING: Primary care. PATIENTS: Concussed children (N = 56; mean age = 13 years), evaluated at a mean of 22-week post-injury, compared with 83 uninjured controls. INDEPENDENT VARIABLES: Metrics comparing velocity and conjugacy of eye movements over time were obtained and were compared with the correlation between Acute Concussion Evaluation (ACE) scores, convergence, and accommodation dysfunction. MAIN OUTCOME MEASURES: Subjects' eye movements recorded with an automated eye tracker while they watched a 220-second cartoon film clip played continuously while moving within an aperture. RESULTS: Twelve eye-tracking metrics were significantly different between concussed and nonconcussed children. A model to classify concussion as diagnosed by its symptoms assessed using the ACE achieved an area under the curve (AUC) = 0.854 (71.9% sensitivity, 84.4% specificity, a cross-validated AUC = 0.789). An eye-tracking model built to identify near point of convergence (NPC) disability achieved 95.8% specificity and 57.1% sensitivity for an AUC = 0.810. Reduced binocular amplitude of accommodation had a Spearman correlation of 0.752(P value <0.001) with NPC. CONCLUSION: Eye tracking correlated with concussion symptoms and detected convergence and accommodative abnormalities associated with concussion in the pediatric population. It demonstrates utility as a rapid, objective, noninvasive aid in the diagnosis of concussion.

Prediction of discharge destination after traumatic brain injury in children using the head abbreviated injury scale.

INTRODUCTION: Traumatic brain injury (TBI) is a major public health problem, particularly in children. Prognostication of injury severity at the time of presentation is difficult. The Abbreviated Injury Scale (AIS) is a commonly used anatomical-based coding system created to classify and describe injury severity after initial presentation, once test results are able to better define the anatomical characteristics of the injury. We hypothesize that the Head AIS can predict discharge destination in children after TBI. METHODS: The trauma registry database for a Pediatric Level 1 Trauma center was queried for patients age ≤14 years from 2006 to 2015 with a Head AIS>2. All diagnoses with head AIS>2 were retrieved. Since one patient can have multiple diagnoses with an AIS>2, we selected the diagnosis with highest Head AIS associated with each patient. The demographics, length of stay, and the discharge disposition of patients were retrieved. Descriptive statistics were performed and association of Head AIS with the length of stay and discharge disposition was determined using logistic regression. RESULTS: 393 pediatric patients (age≤14 years) with an Head AIS ≥3, (64.0% males, mean age = 6.2 S.D. 4.58) presented over 10 years. Head AIS was strongly associated with mortality; with 0.8%, 1.1% and 42.0% of patients with Head AIS of 3, 4 and 5, respectively, dying - odds ratio for Head AIS 5 over Head AIS 3 = 89 (logistic regression, p-value<0.001). 80.0% of deaths (23 patients) in this cohort occurred within 24-h of presentation. Head AIS was associated with an increase likelihood of discharge to rehabilitation with 1.2%, 7.7% and 47.0% of survivors discharging to rehabilitation for Head AIS of 3, 4 and 5. CONCLUSION: Head AIS can reliably predict discharge disposition to home, rehab or death. Calculation of Head AIS prior to discharge could lead to accurate prediction of discharge destination.

Naturally Occurring Canine Glioma as a Model for Novel Therapeutics.

BACKGROUND: Current animal models of glioma are limited to small animal models, which are less predictive of treatment of human disease. Canines often develop gliomas de novo, but the natural history of the disease is not well described. OBJECTIVE: We provide data for naturally occurring canine gliomas; evaluating medical and surgical therapies. METHODS: We reviewed medical records of pet dogs with a presumptive diagnosis of glioma from MRI imaging that underwent surgery as part of the Canine Brain Tumor Clinical Trials Program. Breed, age, sex, median progression-free, and overall survival times and cause of death were recorded for multivariate analysis. RESULTS: Ninety five dogs (56 male; mean age = 8.3 years) were included, but nine were excluded as final pathology was non-neoplastic. Gross total resection was reported in 81 cases based on postoperative MRI. Seventy had high-grade tumors (grade III or IV). Eighty three dogs presented with seizures, being the most common presenting clinical sign. Median survival after surgery was 723 days (95% CI 343-1103) for grade II tumors, 301 days (197-404) for grade III and 200 days (126-274) for grade IV (p = .009 Kaplan-Meier survival analysis; Log Rank test). Age (cox regression, p = .14) or sex (Kaplan-Meier test, p = .22) did not predict survival. CONCLUSIONS: This study establishes normative data for a model exploiting dogs with naturally occurring glioma, which can be used to test novel therapies prior to translation to human trials. Further work will focus on the effects of different therapies, including chemotherapy, radiation therapy, and immunotherapy.

Accelerated Brain Atrophy on Serial Computed Tomography: Potential Marker of the Progression of Alzheimer Disease.

OBJECTIVE: The aim of this study was to validate computed tomography (CT)-based longitudinal markers of the progression of Alzheimer disease (AD). MATERIALS AND METHODS: We retrospectively studied 33 AD patients and 39 nondemented patients with other neurological illnesses (non-AD) having 4 to 12 CT examinations of the head, with over a mean (SD) of 3.9 (1.7) years. At each time point, we applied an automatic software to measure whole brain, cerebrospinal fluid, and intracranial space volumes. Longitudinal measures were then related to disease status and time since the first scan using hierarchical models. RESULTS: Absolute brain volume loss accelerated for non-AD patients by 0.86 mL/y (95% confidence interval [CI], 0.64-1.08 mL/y) and 1.5× faster, that is, 1.32 mL/y (95% CI, 1.09-1.56 mL/y) for AD patients (P = 0.006). In terms of brain volume normalized to intracranial space, the acceleration in atrophy rate for non-AD patients was 0.0578%/y (95% CI, 0.0389%/y to 0.0767%/y), again 1.5× faster, that is, 0.0919%/y (95% CI, 0.0716%/y to 0.1122%/y) for AD patients (P = 0.017). This translates to an increase in atrophy rate from 0.5% to 1.4% in AD versus to 1.1% in non-AD group after 10 years. CONCLUSIONS: Brain volumetry on CT reliably detected accelerated volume loss in AD and significantly lower acceleration factor in age-matched non-AD patients, leading to the possibility of its use to monitor the progression of cognitive decline and dementia.

Factors associated with the presence of cerebral microbleeds and its influence on outcomes of stroke not treated with alteplase.

OBJECTIVES: Cerebral microbleeds (CMB) are associated with increased risk of hemorrhagic transformation (HT) of ischemic stroke with alteplase. Whether the presence of CMB influences the risk of HT and discharge outcomes of stroke patients not receiving alteplase is unclear. We evaluated the factors associated with the presence of CMB, and if the rates of HT and discharge outcomes were modified by the presence of CMB among stroke patients not treated with alteplase. METHODS: Ischemic stroke patients who had MRI and did not receive alteplase were included in the study. CMB, HT and white matter hyperintensity (WMH) were evaluated using Microbleed Anatomical Rating Scale, Heidelberg bleeding classification, and Fazekas scales, respectively. Multivariate regression analysis was performed to evaluate factors associated with the presence of CMB. RESULTS: Among 196 patients in the study, 58 (30%) patients had CMB. Nine patients had ≥ 10 CMBs. Median National Institutes of Health stroke scale score was 4. In multivariate analysis, age (OR=1.07;95%CI=1.01-1.12), history of stroke (OR=3.10;95%CI=1.08-8.92), congestive heart failure (OR=7.26;95%CI=1.58-33.42), admission diastolic blood pressure (OR=1.03;95%CI=1.003-1.06) and severe WMH defined as Fazekas score 4-6 (OR=4.69;95%CI=1.80-12.23) were significantly associated with the presence of CMB. There was no difference in HT (10% vs 12%, p = 0.80) or discharge outcomes (modified Rankin Scale 0-2: 53% vs 57%, p = 0.62) of patients with CMB compared to those without CMB. CONCLUSION: CMB are associated with severe WMH and higher diastolic blood pressure. CMB are not associated with the HT occurrence or discharge outcome of mild ischemic stroke in the absence of alteplase.

Increase in brain atrophy after subdural hematoma to rates greater than associated with dementia.

OBJECTIVEChronic subdural hematoma (cSDH) is a highly morbid condition associated with brain atrophy in the elderly. It has a reported 30% 1-year mortality rate. Approximately half of afflicted individuals report either no or relatively unremarkable trauma preceding their diagnosis, raising the possibility that cSDH is a manifestation of degenerative or inflammatory disease rather than trauma. The purpose of this study was to compare the rates of cerebral atrophy before and after cSDH to determine whether it is more likely that cSDH causes atrophy or that atrophy causes cSDH. The authors also compared atrophy rates in patients with cSDH to the rates in patients with and without dementia.METHODSThe authors developed algorithmic segmentation analysis software to measure whole-brain, CSF, and intracranial space volumes. They then identified military veterans who had undergone at least 4 brain CT scans over a period of 10 years. Within this database, the authors identified 146 patients with 962 head CT scans who had received diagnoses of either cSDH, dementia, or no known dementia condition. Volumetric analyses of brains in 45 patients with dementia (dementia group) and 73 patients without dementia (nondementia group), in whom 262 and 519 head CT scans were obtained, respectively, were compared with 11 patients in whom 81 CT scans were obtained a mean of 4.21 years before a cSDH diagnosis and 17 patients in whom 100 scans were obtained a mean of 4.24 years after SDH. Longitudinal measures were then related to disease status and the time since first scan by using hierarchical models, and atrophy rates between the groups were compared.RESULTSHead CT scans from patients were obtained for an average time period of 4.21 years (SD 1.69) starting at a mean patient age of 74 years. Absolute brain volume loss for the 17 patients in the post-SDH group (13 were treated surgically) was significantly greater, at 16.32 ml/year, compared with 6.61 ml/year in patients with dementia, 5.33 ml/year in patients without dementia, and 3.57 ml/year in pre-SDH patients. The atrophy rate for these individuals prior to enrollment in the study was 2.32 ml/year (p = 0.001). In terms of brain volume normalized to cranial cavity size, the post-SDH group had an atrophy rate of 0.7801%/year, compared with 0.4467%/year in patients with dementia, 0.3474%/year in patients without dementia, and 0.2135%/year in the pre-SDH group.CONCLUSIONSPrior to development of a cSDH, the atrophy rates in patients who ultimately develop cSDH are similar to those of patients without dementia. After development of a cSDH, the atrophy rates increase to more than twice those of patients with dementia. Chronic subdural hematoma is thus associated with a significant increase in brain atrophy rate. These findings suggest the neurotoxic consequences of cSDH and may have implications for better understanding of the pathophysiology of cerebral atrophy and dementia.

Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip.

OBJECTIVE The precise threshold differentiating normal and elevated intracranial pressure (ICP) is variable among individuals. In the context of several pathophysiological conditions, elevated ICP leads to abnormalities in global cerebral functioning and impacts the function of cranial nerves (CNs), either or both of which may contribute to ocular dysmotility. The purpose of this study was to assess the impact of elevated ICP on eye-tracking performed while patients were watching a short film clip. METHODS Awake patients requiring placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video moving around the perimeter of a viewing monitor. Pupil position was recorded at 500 Hz and metrics associated with each eye individually and both eyes together were calculated. Linear regression with generalized estimating equations was performed to test the association of eye-tracking metrics with changes in ICP. RESULTS Eye tracking was performed at ICP levels ranging from -3 to 30 mm Hg in 23 patients (12 women, 11 men, mean age 46.8 years) on 55 separate occasions. Eye-tracking measures correlating with CN function linearly decreased with increasing ICP (p < 0.001). Measures for CN VI were most prominently affected. The area under the curve (AUC) for eye-tracking metrics to discriminate between ICP < 12 and ≥ 12 mm Hg was 0.798. To discriminate an ICP < 15 from ≥ 15 mm Hg the AUC was 0.833, and to discriminate ICP < 20 from ≥ 20 mm Hg the AUC was 0.889. CONCLUSIONS Increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching a short film clip. These results suggest that eye tracking may be used as a noninvasive, automatable means to quantitate the physiological impact of elevated ICP, which has clinical application for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome.

Assessment of acute head injury in an emergency department population using sport concussion assessment tool - 3rd edition.

Sport Concussion Assessment Tool version 3 (SCAT-3) is one of the most widely researched concussion assessment tools in athletes. Here normative data for SCAT3 in nonathletes are presented. The SCAT3 was administered to 98 nonathlete healthy controls, as well as 118 participants with head-injury and 46 participants with other body trauma (OI) presenting to the ED. Reference values were derived and classifier functions were built to assess the accuracy of SCAT3. The control population had a mean of 2.30 (SD = 3.62) symptoms, 4.38 (SD = 8.73) symptom severity score (SSS), and 26.02 (SD = 2.52) standardized assessment of concussion score (SAC). Participants were more likely to be diagnosed with a concussion (from among healthy controls) if the SSS > 7; or SSS ≤ 7 and SAC ≤22 (sensitivity = 96%, specificity = 77%). Identification of head injury patients from among both, healthy controls and body trauma was possible using rule SSS > 7 and headache or pressure in head present, or SSS ≤ 7 and SAC ≤ 22 (sensitivity = 87%, specificity = 80%). In this current study, the SCAT-3 provided high sensitivity to discriminate acute symptoms of TBI in the ED setting. Individuals with a SSS > 7 and headache or pressure in head, or SSS ≤ 7 but with a SAC ≤ 22 within 48-hours of an injury should undergo further testing.