Abdullah Bin Zahid

Eye tracking a biomarker for concussion in the paediatricpediatric population

Objective The study aims to validate eye movement tracking performed without a baseline study as a biomarker for concussion in a paediatric population. Design This is a cross-sectional case control study of patients diagnosed with concussion in a referral centre compared to non-concussed controls. Methods Eye movements were recorded with an SR Research Eyelink 1000 eye tracker while a 220-second video was played. Eye tracking metrics were compared to Acute Concussion Evaluation (ACE) scores and clinical assessments of convergence and accommodation. Results 56 children with concussions (mean age of 13 years), as defined by symptom presence following an impulsive injury to the brain were evaluated at a mean of 22 weeks post-injury. Twelve eye tracking metrics were significantly different between concussed children and 83 uninjured controls. A model built on a balanced sub-sample to classify concussion based on eye tracking achieved an AUC of 0.854 (sensitivity 71.9%; specificity 84.4%). Two metrics were significant predictors of abnormal near point convergence (NPC) and accommodation. The model built to classify concussion based on NPC status achieved a specificity of 95.8% and a sensitivity of 57.1%. Reduced binocular amplitude of accommodation had a spearman correlation of 0.752 (p-value<0.001) with NPC. Seven eye tracking metrics were found to have a strong correlation (R=0.781) with binocular amplitude of accommodation. Conclusions Eye tracking reliably detected concussion and convergence and accommodative abnormalities in the paediatric population. We propose that eye tracking without baseline assessment may serve as an objective measure of concussion in paediatric patients. Competing interests Uzma Samadani has submitted intellectual property describing the technology utilised in this paper. These patents are owned by NYU, the VA and HCMC and licensed to Oculogica Inc., a company in which all of the above parties have an equity interest

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/y2 (95% confidence interval [CI], 0.64–1.08 mL/y2) and 1.5× faster, that is, 1.32 mL/y2 (95% CI, 1.09–1.56 mL/y2) 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%/y2 (95% CI, 0.0389%/y2 to 0.0767%/y2), again 1.5× faster, that is, 0.0919%/y2 (95% CI, 0.0716%/y2 to 0.1122%/y2) 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.

Calculation of brain atrophy using computed tomography and a new atrophy measurement tool

Purpose: To determine if brain atrophy can be calculated by performing volumetric analysis on conventional computed tomography (CT) scans in spite of relatively low contrast for this modality. Materials & Method: CTs for 73 patients from the local Veteran Affairs database were selected. Exclusion criteria: AD, NPH, tumor, and alcohol abuse. Protocol: conventional clinical acquisition (Toshiba; helical, 120 kVp, X-ray tube current 300mA, slice thickness 3-5mm). Locally developed, automatic algorithm was used to segment intracranial cavity (ICC) using (a) white matter seed (b) constrained growth, limited by inner skull layer and (c) topological connectivity. ICC was further segmented into CSF and brain parenchyma using a threshold of 16 Hu. Results: Age distribution: 25–95yrs; (Mean 67±17.5yrs.). Significant correlation was found between age and CSF/ICC(r=0.695, p<0.01 2-tailed). A quadratic model (y=0.06–0.001x+2.56x10-5x2 ; where y=CSF/ICC and x=age) was a better fit to data (r=0.716, p < 0.01). This is in agreement with MRI literature. For example, Smith et al. found annual CSF/ICC increase in 58 – 94.5 y.o. individuals to be 0.2%/year, whereas our data, restricted to the same age group yield 0.3%/year(0.2–0.4%/yrs. 95%C.I.). Slightly increased atrophy among elderly VA patients is attributable to the presence of other comorbidities. Conclusion: Brain atrophy can be reliably calculated using automated software and conventional CT. Compared to MRI, CT is more widely available, cheaper, and less affected by head motion due to ~100 times shorter scan time. Work is in progress to improve the precision of the measurements, possibly leading to assessment of longitudinal changes within the patient.

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.

Naturally Occurring Canine Glioma as a Model for Novel Therapeutics

Abstract 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.

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

ABSTRACT 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.

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.