Jamshid Ghajar

All Publications

• A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive care medicine Hawryluk, G. W., Aguilera, S., Buki, A., Bulger, E., Citerio, G., Cooper, D. J., Arrastia, R. D., Diringer, M., Figaji, A., Gao, G., Geocadin, R., Ghajar, J., Harris, O., Hoffer, A., Hutchinson, P., Joseph, M., Kitagawa, R., Manley, G., Mayer, S., Menon, D. K., Meyfroidt, G., Michael, D. B., Oddo, M., Okonkwo, D., Patel, M., Robertson, C., Rosenfeld, J. V., Rubiano, A. M., Sahuquillo, J., Servadei, F., Shutter, L., Stein, D., Stocchetti, N., Taccone, F. S., Timmons, S., Tsai, E., Ullman, J. S., Vespa, P., Videtta, W., Wright, D. W., Zammit, C., Chesnut, R. M. 2019

  Abstract

  BACKGROUND: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based.METHODS: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations.RESULTS: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination.CONCLUSIONS: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.

  View details for DOI 10.1007/s00134-019-05805-9

  View details for PubMedID 31659383

• Concussion Guidelines Step 2: Evidence for Subtype Classification. Neurosurgery Lumba-Brown, A., Teramoto, M., Bloom, O. J., Brody, D., Chesnutt, J., Clugston, J. R., Collins, M., Gioia, G., Kontos, A., Lal, A., Sills, A., Ghajar, J. 2019

  Abstract

  BACKGROUND: Concussion is a heterogeneous mild traumatic brain injury (mTBI) characterized by a variety of symptoms, clinical presentations, and recovery trajectories. By thematically classifying the most common concussive clinical presentations into concussion subtypes (cognitive, ocular-motor, headache/migraine, vestibular, and anxiety/mood) and associated conditions (cervical strain and sleep disturbance), we derive useful definitions amenable to future targeted treatments.OBJECTIVE: To use evidence-based methodology to characterize the 5 concussion subtypes and 2 associated conditions and report their prevalence in acute concussion patients as compared to baseline or controls within 3 d of injury.METHODS: A multidisciplinary expert workgroup was established to define the most common concussion subtypes and their associated conditions and select clinical questions related to prevalence and recovery. A literature search was conducted from January 1, 1990 to November 1, 2017. Two experts abstracted study characteristics and results independently for each article selected for inclusion. A third expert adjudicated disagreements. Separate meta-analyses were conducted to do the following: 1) examine the prevalence of each subtype/associated condition in concussion patients using a proportion, 2) assess subtype/associated conditions in concussion compared to baseline/uninjured controls using a prevalence ratio, and 3) compare the differences in symptom scores between concussion subtypes and uninjured/baseline controls using a standardized mean difference (SMD).RESULTS: The most prevalent concussion subtypes for pediatric and adult populations were headache/migraine (0.52; 95% CI=0.37, 0.67) and cognitive (0.40; 95% CI=0.25, 0.55), respectively. In pediatric patients, the prevalence of the vestibular subtype was also high (0.50; 95% CI=0.40, 0.60). Adult patients were 4.4, 2.9, and 1.7 times more likely to demonstrate cognitive, vestibular, and anxiety/mood subtypes, respectively, as compared with their controls (P<.05). Children and adults with concussion showed significantly more cognitive symptoms than their respective controls (SMD=0.66 and 0.24; P<.001). Furthermore, ocular-motor in adult patients (SMD=0.72; P<.001) and vestibular symptoms in both pediatric and adult patients (SMD=0.18 and 0.36; P<.05) were significantly worse in concussion patients than in controls.CONCLUSION: Five concussion subtypes with varying prevalence within 3 d following injury are commonly seen clinically and identifiable upon systematic literature review. Sleep disturbance, a concussion-associated condition, is also common. There was insufficient information available for analysis of cervical strain. A comprehensive acute concussion assessment defines and characterizes the injury and, therefore, should incorporate evaluations of all 5 subtypes and associated conditions.

  View details for DOI 10.1093/neuros/nyz332

  View details for PubMedID 31432081

• Disrupted White Matter Microstructure of the Cerebellar Peduncles in Scholastic Athletes After Concussion FRONTIERS IN NEUROLOGY Mallott, J. M., Palacios, E. M., Maruta, J., Ghajar, J., Mukherjee, P. 2019; 10

  View details for DOI 10.3389/fneur.2019.00518

  View details for Web of Science ID 000467976100002

• Hypertonic Saline is Superior to Mannitol for the Combined Effect on Intracranial Pressure and Cerebral Perfusion Pressure Burdens in Patients With Severe Traumatic Brain Injury. Neurosurgery Mangat, H. S., Wu, X., Gerber, L. M., Schwarz, J. T., Fakhar, M., Murthy, S. B., Stieg, P. E., Ghajar, J., Hartl, R. 2019

  Abstract

  BACKGROUND: Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect on the cerebral perfusion pressure (CPP) and ICP has not been studied rigorously.OBJECTIVE: To determine the difference in effects of HTS and mannitol on the combined burden of high ICP and low CPP in patients with severe TBI.METHODS: We performed a case-control study using prospectively collected data from the New York State TBI-trac database (Brain Trauma Foundation, New York, New York). Patients who received only 1 hyperosmotic agent, either mannitol or HTS for raised ICP, were included. Patients in the 2 groups were matched (1:1 and 1:2) for factors associated with 2-wk mortality: age, Glasgow Coma Scale score, pupillary reactivity, hypotension, abnormal computed tomography scans, and craniotomy. Primary endpoint was the combined burden of ICPhigh (>25 mm Hg) and CPPlow (<60 mm Hg).RESULTS: There were 25 matched pairs for 1:1 comparison and 24 HTS patients matched to 48 mannitol patients in 1:2 comparisons. Cumulative median osmolar doses in the 2 groups were similar. In patients treated with HTS compared to mannitol, total number of days (0.6±0.8 vs 2.4±2.3 d, P<.01), percentage of days with (8.8±10.6 vs 28.1±26.9%, P<.01), and the total duration of ICPhigh+CPPlow (11.12±14.11 vs 30.56±31.89 h, P=.01) were significantly lower. These results were replicated in the 1:2 match comparisons.CONCLUSION: HTS bolus therapy appears to be superior to mannitol in reduction of the combined burden of intracranial hypertension and associated hypoperfusion in severe TBI patients.

  View details for PubMedID 30877299

• Concussion Subtype Identification With the Rivermead Post-concussion Symptoms Questionnaire FRONTIERS IN NEUROLOGY Maruta, J., Lumba-Brown, A., Ghajar, J. 2018; 9

  View details for DOI 10.3389/fneur.2018.01034

  View details for Web of Science ID 000451953400001

• Association of Visual Tracking Metrics With Post-concussion Symptomatology FRONTIERS IN NEUROLOGY Maruta, J., Spielman, L. A., Rajashekar, U., Ghajar, J. 2018; 9

  View details for DOI 10.3389/fneur.2018.00611

  View details for Web of Science ID 000439875000001

• Establishing Evidence for Concussion Subtypes Lumba-Brown, A., Lal, A., Collins, M., Kontos, A., Gioia, G., Bloom, J., Chesnutt, J., Clugston, J., Sills, A., Brody, D., Ghajar, J. LIPPINCOTT WILLIAMS & WILKINS. 2018: E106

  View details for Web of Science ID 000435555500091

• Concussion Subtype Identification With the Rivermead Post-concussion Symptoms Questionnaire. Frontiers in neurology Maruta, J., Lumba-Brown, A., Ghajar, J. 2018; 9: 1034

  Abstract

  Classifying concussion in key subtypes according to presenting symptomatology at an early post-injury stage is an emerging approach that may allow prediction of clinical trajectories and delivery of targeted treatments. The Rivermead Post-concussion Symptoms Questionnaire (RPQ) is a simple, freely available, and widely used tool for assessment of the presence and severity of various post-concussion symptoms. We aimed to probe the prevalence among athletes of symptom classes associated with identified concussion phenotypes using the RPQ at baseline and acutely after a concussion. Participants of organized sports aged 12-30 years were baseline-assessed with the expectation that some would experience a concussion during the study period. Concussed athletes were re-assessed within 2 weeks of their injuries. The RPQ was supplemented with three specific questions and reworded for baseline assessment. A binomial test was used to contrast the prevalence of an attribute in the concussed cohort against the probability established by the baseline observation. Three thousand and eighty-eight athletes were baseline-assessed and eighty-nine were re-assessed post-concussion. All concussed athletes endorsed having some elevated symptoms in the RPQ, and such endorsements were more prevalent than those among normal athletes. Moderate-to-severe post-concussion symptoms of specific classes tended to be endorsed with few additional symptoms of other classes of similar intensities. Elevated symptoms detected with the RPQ within as short as 2 weeks after a concussion may help delineate patients' clinical subtypes and guide their treatment. Further refinement of symptom questionnaires and use of objective measures will be needed to properly populate the concussion subtype classification.

  View details for PubMedID 30559709

  View details for PubMedCentralID PMC6287109

• Mild traumatic brain injury and concussion: terminology and classification. Handbook of clinical neurology Sussman, E. S., Pendharkar, A. V., Ho, A. L., Ghajar, J. 2018; 158: 21–24

  Abstract

  Traumatic brain injury (TBI) is a major cause of morbidity and mortality throughout the world. Mild TBI, which is typically defined by Glasgow Coma Scale score ≥13, accounts for the vast majority of all TBIs, particularly in the setting of sports-related injuries. The terms concussion and TBI are often used interchangeably, both in the medical literature and in clinical care of this patient population. However, the lack of clearly defined definitions of these terms often leads to confusion, and this confusion may lead to delayed diagnosis and inconsistent management of affected patients. Here, we review the current terminology and classification of mild TBI and concussion. We will also discuss recent efforts to stratify these injuries into clinically relevant subtypes or profiles that are both diagnostic- and treatment-targeted.

  View details for PubMedID 30482349

• Association of Visual Tracking Metrics With Post-concussion Symptomatology. Frontiers in neurology Maruta, J., Spielman, L. A., Rajashekar, U., Ghajar, J. 2018; 9: 611

  Abstract

  Attention impairment may provide a cohesive neurobiological explanation for clusters of clinical symptoms that occur after a concussion; therefore, objective quantification of attention is needed. Visually tracking a moving target is an attention-dependent sensorimotor function, and eye movement can be recorded easily and objectively to quantify performance. Our previous work suggested the utility of gaze-target synchronization metrics of a predictive visual tracking task in concussion screening and recovery monitoring. Another objectively quantifiable performance measure frequently suggested for concussion screening is simple visuo-manual reaction time (simple reaction time, SRT). Here, we used visual tracking and SRT tasks to assess changes between pre- and within-2-week post-concussion performances and explore their relationships to post-concussion symptomatology. Athletes participating in organized competitive sports were recruited. Visual tracking and SRT records were collected from the recruited athlete pool as baseline measures over a 4-year period. When athletes experienced a concussion, they were re-assessed within 2 weeks of their injury. We present the data from a total of 29 concussed athletes. Post-concussion symptom burden was assessed with the Rivermead Post-Concussion Symptoms Questionnaire and subscales of the Brain Injury Screening Questionnaire. Post-concussion changes in visual tracking and SRT performance were examined using a paired t-test. Correlations of changes in visual tracking and SRT performance to symptom burden were examined using Pearson's coefficients. Post-concussion changes in visual tracking performance were not consistent among the athletes. However, changes in several visual tracking metrics had moderate to strong correlations to symptom scales (r up to 0.68). On the other hand, while post-concussion SRT performance was reduced (p < 0.01), the changes in the performance metrics were not meaningfully correlated to symptomatology (r ≤ 0.33). Results suggest that visual tracking performance metrics reflect clinical symptoms when assessed within 2 weeks of concussion. Evaluation of concussion requires assessments in multiple domains because the clinical profiles are heterogeneous. While most individuals show recovery within a week of injury, others experience prolonged recovery periods. Visual tracking performance metrics may serve as a biomarker of debilitating symptoms of concussion implicating attention as a root cause of such pathologies.

  View details for PubMedID 30093880

  View details for PubMedCentralID PMC6070608

• Visual Tracking in Development and Aging FRONTIERS IN NEUROLOGY Maruta, J., Spielman, L. A., Rajashekar, U., Ghajar, J. 2017; 8: 640

  Abstract

  A moving target is visually tracked with a combination of smooth pursuit and saccades. Human visual tracking eye movement develops through early childhood and adolescence, and declines in senescence. However, the knowledge regarding performance changes over the life course is based on data from distinct age groups in isolation using different procedures, and thus is fragmented. We sought to describe the age-dependence of visual tracking performance across a wide age range and compare it to that of simple visuo-manual reaction time. We studied a cross-sectional sample of 143 subjects aged 7-82 years old (37% male). Eye movements were recorded using video-oculography, while subjects viewed a computer screen and tracked a small target moving along a circular trajectory at a constant speed. For simple reaction time (SRT) measures, series of key presses that subjects made in reaction to cue presentation on a computer monitor were recorded using a standard software. The positional precision and smooth pursuit velocity gain of visual tracking followed a U-shaped trend over age, with best performances achieved between the ages of 20 and 50 years old. A U-shaped trend was also found for mean reaction time in agreement with the existing literature. Inter-individual variability was evident at any age in both visual tracking and reaction time metrics. Despite the similarity in the overall developmental and aging trend, correlations were not found between visual tracking and reaction time performances after subtracting the effects of age. Furthermore, while a statistically significant difference between the sexes was found for mean SRT in the sample, a similar difference was not found for any of the visual tracking metrics. Therefore, the cognitive constructs and their neural substrates supporting visual tracking and reaction time performances appear largely independent. In summary, age is an important covariate for visual tracking performance, especially for a pediatric population. Since visual tracking performance metrics may provide signatures of abnormal neurological or cognitive states independent of reaction time-based metrics, further understanding of age-dependent variations in normal visual tracking behavior is necessary.

  View details for PubMedID 29250026

• The Effect of Physical Exercise After a Concussion: A Systematic Review and Meta-analysis. American journal of sports medicine Lal, A., Kolakowsky-Hayner, S. A., Ghajar, J., Balamane, M. 2017: 363546517706137-?

  Abstract

  Data evaluating the role of exercise in patients with a concussion are contradictory. Studies have reported improvement in the Post-Concussion Symptom Scale (PCSS) score, whereas others showed no effect on the PCSS score.To conduct a systematic review and meta-analysis on the role of physical exercise on different outcomes in patients with a concussion.Systematic review and meta-analysis.A search of 5 databases from the earliest available date to September 30, 2016, and a hand search of a few articles were performed. Trial registries were reviewed, and authors of multiple studies were contacted to find additional published or unpublished studies. Randomized controlled trials (RCTs), cohort studies, and before and after (pre-post) studies evaluating the effect of physical exercise, compared with control, in patients with a concussion or mild traumatic brain injury were included.The search generated 1096 studies. Of these, 14 studies (5 RCTs, 1 propensity score matching study, 3 cohort studies, and 5 before and after studies) met our inclusion criteria. Exercise significantly decreased the PCSS score (mean difference, -13.06; 95% CI, -16.57 to -9.55; P < .00001; I(2) = 44%), percentage of patients with symptoms of a concussion (risk ratio, 0.74; 95% CI, 0.63 to 0.86; P = .0001; I(2) = 0%), and days off work (17.7 days vs 32.2 days, respectively; P < .05) compared with control. Exercise improved the reaction time (standard mean difference, -0.43; 95% CI, -0.80 to -0.06; P = .02) component of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) score without affecting the Balance Error Scoring System (BESS) score and neuropsychological parameters. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) scores were moderate for the PCSS, symptoms, ImPACT, BESS, and neuropsychological tests.Physical exercise appears to improve the PCSS score and symptoms in patients with a concussion. A high-quality RCT evaluating different intensities of exercise at different time points, for different durations after a concussion, for different races/ethnicities, and for sex needs to be conducted to evaluate a clear effect of exercise in patients with a concussion.

  View details for DOI 10.1177/0363546517706137

  View details for PubMedID 28570092

• In Reply: Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery Hawryluk, G. W., Ullman, J. S., Totten, A. M., Ghajar, J. 2017

  View details for DOI 10.1093/neuros/nyx087

  View details for PubMedID 28402563

• Frequency Responses to Visual Tracking Stimuli May Be Affected by Concussion MILITARY MEDICINE Maruta, J., Jaw, E., Modera, P., Rajashekar, U., Spielman, L. A., Ghajar, J. 2017; 182: 120-123

  Abstract

  Human visual tracking performance is known to be reduced with an increase of the target's speed and oscillation frequency, but changes in brain states following a concussion may alter these frequency responses. The goal of this study was to characterize and compare frequency-dependent smooth pursuit velocity degradation in normal subjects and patients who had chronic postconcussion symptoms, and also examine cases of acutely concussed patients. Eye movements were recorded while subjects tracked a target that moved along a circular trajectory of 10° radius at 0.33, 0.40, or 0.67 Hz. Performance was characterized by the gain of smooth pursuit velocity, with reduced gain indicating reduced performance. The difference between normal and chronic patient groups in the pattern of decrease in the gain of horizontal smooth pursuit velocity as a function of the stimulus frequency reflected patients performing more poorly than normal subjects at 0.4 Hz while both groups performing similarly at 0.33 or 0.67 Hz. The performance of acute patients may represent yet another type of frequency response. The findings suggest that there may be ranges of stimulus frequencies that differentiate the effects of concussion from normal individuals.

  View details for DOI 10.7205/MILMED-D-16-00093

  View details for Web of Science ID 000398947100020

  View details for PubMedID 28291462

• Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery Carney, N., Totten, A. M., O'Reilly, C., Ullman, J. S., Hawryluk, G. W., Bell, M. J., Bratton, S. L., Chesnut, R., Harris, O. A., Kissoon, N., Rubiano, A. M., Shutter, L., Tasker, R. C., Vavilala, M. S., Wilberger, J., Wright, D. W., Ghajar, J. 2016: -?

  Abstract

  The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.TBI, traumatic brain injuryRESCUEicp, Randomised Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of ICP.

  View details for PubMedID 27654000

• Degradation of Binocular Coordination during Sleep Deprivation FRONTIERS IN NEUROLOGY Tong, J., Maruta, J., Heaton, K. J., Maule, A. L., Rajashekar, U., Spielman, L. A., Ghajar, J. 2016; 7

  Abstract

  To aid a clear and unified visual perception while tracking a moving target, both eyes must be coordinated, so the image of the target falls on approximately corresponding areas of the fovea of each eye. The movements of the two eyes are decoupled during sleep, suggesting a role of arousal in regulating binocular coordination. While the absence of visual input during sleep may also contribute to binocular decoupling, sleepiness is a state of reduced arousal that still allows for visual input, providing a context within which the role of arousal in binocular coordination can be studied. We examined the effects of sleep deprivation on binocular coordination using a test paradigm that we previously showed to be sensitive to sleep deprivation. We quantified binocular coordination with the SD of the distance between left and right gaze positions on the screen. We also quantified the stability of conjugate gaze on the target, i.e., gaze-target synchronization, with the SD of the distance between the binocular average gaze and the target. Sleep deprivation degraded the stability of both binocular coordination and gaze-target synchronization, but between these two forms of gaze control the horizontal and vertical components were affected differently, suggesting that disconjugate and conjugate eye movements are under different regulation of attentional arousal. The prominent association found between sleep deprivation and degradation of binocular coordination in the horizontal direction may be used for a fit-for-duty assessment.

  View details for DOI 10.3389/fneur.2016.00090

  View details for Web of Science ID 000377585200002

  View details for PubMedID 27379009

  View details for PubMedCentralID PMC4904152

• Clinical evaluation of concussion: the evolving role of oculomotor assessments NEUROSURGICAL FOCUS Sussman, E. S., Ho, A. L., Pendharkar, A. V., Ghajar, J. 2016; 40 (4)

  Abstract

  Sports-related concussion is a change in brain function following a direct or an indirect force to the head, identified in awake individuals and accounting for a considerable proportion of mild traumatic brain injury. Although the neurological signs and symptoms of concussion can be subtle and transient, there can be persistent sequelae, such as impaired attention and balance, that make affected patients particularly vulnerable to further injury. Currently, there is no accepted definition or diagnostic criteria for concussion, and there is no single assessment that is accepted as capable of identifying all patients with concussion. In this paper, the authors review the available screening tools for concussion, with particular emphasis on the role of visual function testing. In particular, they discuss the oculomotor assessment tools that are being investigated in the setting of concussion screening.

  View details for DOI 10.3171/2016.1.FOCUS15610

  View details for Web of Science ID 000373476500006

  View details for PubMedID 27032924

• Executive summary of concussion guidelines step 1: systematic review of prevalent indicators. Neurosurgery Carney, N., Ghajar, J., Jagoda, A., Bedrick, S., Davis-O'Reilly, C., du Coudray, H., Hack, D., Helfand, N., Huddleston, A., Nettleton, T., Riggio, S. 2014; 75: S1-2

  View details for DOI 10.1227/NEU.0000000000000434

  View details for PubMedID 24867198

• Concussion guidelines step 1: systematic review of prevalent indicators. Neurosurgery Carney, N., Ghajar, J., Jagoda, A., Bedrick, S., Davis-O'Reilly, C., du Coudray, H., Hack, D., Helfand, N., Huddleston, A., Nettleton, T., Riggio, S. 2014; 75: S3-S15

  Abstract

  Currently, there is no evidence-based definition for concussion that is being uniformly applied in clinical and research settings.To conduct a systematic review of the highest-quality literature about concussion and to assemble evidence about the prevalence and associations of key indicators of concussion. The goal was to establish an evidence-based foundation from which to derive, in future work, a definition, diagnostic criteria, and prognostic indicators for concussion.Key questions were developed, and an electronic literature search from 1980 to 2012 was conducted to acquire evidence about the prevalence of and associations among signs, symptoms, and neurologic and cognitive deficits in samples of individuals exposed to potential concussive events. Included studies were assessed for potential for bias and confound and rated as high, medium, or low potential for bias and confound. Those rated as high were excluded from the analysis. Studies were further triaged on the basis of whether the definition of a case of concussion was exclusive or inclusive; only those with wide, inclusive case definitions were used in the analysis. Finally, only studies reporting data collected at fixed time points were used. For a study to be included in the conclusions, it was required that the presence of any particular sign, symptom, or deficit be reported in at least 2 independent samples.From 5437 abstracts, 1362 full-text publications were reviewed, of which 231 studies were included in the final library. Twenty-six met all criteria required to be used in the analysis, and of those, 11 independent samples from 8 publications directly contributed data to conclusions. Prevalent and consistent indicators of concussion are (1) observed and documented disorientation or confusion immediately after the event, (2) impaired balance within 1 day after injury, (3) slower reaction time within 2 days after injury, and/or (4) impaired verbal learning and memory within 2 days after injury.The results of this systematic review identify the consistent and prevalent indicators of concussion and their associations, derived from the strongest evidence in the published literature. The product is an evidence-based foundation from which to develop diagnostic criteria and prognostic indicators.GCS, Glasgow Coma ScaleLOC, loss of consciousnessPCE, potential concussive eventPTA, posttraumatic amnesiaSOT, Sensory Organization TestSSD, signs, symptoms, neurologic deficits, and cognitive deficits.

  View details for DOI 10.1227/NEU.0000000000000433

  View details for PubMedID 25006974

• Possible Medication-Resistant Deficits in Adult ADHD. Journal of attention disorders Maruta, J., Spielman, L. A., Tseretopoulos, I. D., Hezghia, A., Ghajar, J. 2014

  Abstract

  The nature of ADHD, especially in adulthood, is not well-understood. Therefore, we explored subcomponents of attention in adult ADHD.Twenty-three adults with ADHD were tested on neurocognitive and visual tracking performance both while on their regular prescription stimulant medication and while abstaining from the medication for 1 day. Pairwise comparisons to 46 two-for-one matched normal controls were made to detect medication-resistant effects of ADHD, and within-participant comparisons were made to detect medication-sensitive effects in patients.Even when on medication, patients performed more poorly than controls on a spatial working memory task, and on visual tracking and simple reaction time tasks immediately following other attention-demanding tasks. Patients' visual tracking performance degraded while off-medication in a manner consistent with reduced vigilance.There may be persistent cognitive impairments in adult ADHD despite medication. In addition, the benefit of stimulants seems reduced under cognitive fatigue.

  View details for PubMedID 24970719

• Predictive Visual Tracking: Specificity in Mild Traumatic Brain Injury and Sleep Deprivation MILITARY MEDICINE Maruta, J., Heaton, K. J., Mau, A. L., Ghajar, J. 2014; 179 (6): 619-625

  Abstract

  We tested whether reduced cognitive function associated with mild traumatic brain injury (mTBI) and sleep deprivation can be detected and distinguished using indices of predictive visual tracking. A circular visual tracking test was given to 13 patients with acute mTBI (recruited within 2 weeks of injury), 127 normal control subjects, and 43 healthy subjects who were fatigued by 26-hour sleep deprivation. Eye movement was monitored with video-oculography. In the mTBI-related portion of the study, visual tracking performance of acute mTBI patients was significantly worse than normal subjects (p < 0.001). In the sleep-deprivation-related portion of the study, no change was detected between the two baseline measures separated by 2 to 3 weeks, but the 26-hour sleep deprivation significantly degraded the visual tracking performance (p < 0.001). The mTBI subjects had substantially worse visual tracking than sleep-deprived subjects that could also be identified with different visual tracking indices, indicating possible different neurophysiological mechanisms. Results suggest that cognitive impairment associated with mTBI and fatigue may be triaged with the aid of visual tracking measures.

  View details for DOI 10.7205/MILMED-D-13-00420

  View details for Web of Science ID 000340806500006

  View details for PubMedID 24902128

• Detecting eye movement abnormalities from concussion. Progress in neurological surgery Maruta, J., Ghajar, J. 2014; 28: 226-233

  Abstract

  An attention-based biomarker may be useful for concussion screening. A key role of attention is to generate time-based expectancies of specific sensory information, and it is postulated that postconcussion cognitive impairments and symptoms may stem from a primary deficit in this predictive timing mechanism. There is a close relationship between gaze and attention, but in addressing predictive timing, there is a need for an appropriate testing paradigm and methods to quantify oculomotor anomalies. We have utilized a continuous predictive visual tracking paradigm because human visual tracking requires predicting the temporal course of a stimulus and dynamically synchronizing the required action with the stimulus. We have shown that concussion patients often show disrupted gaze-target synchronization characterized by large gaze position error variability and overall phase advancement. Various attention components interact with visual tracking, and thus there is a possibility that different neurological and physiological conditions produce identifiable visual tracking characteristics. Analyzing neuromotor functions, specifically oculomotor synchronization, can provide a fast, accurate, and reliable assessment of cognitive functions. © 2014 S. Karger AG, Basel.

  View details for DOI 10.1159/000358786

  View details for PubMedID 24923406

• Age-specific cerebral perfusion pressure thresholds and survival in children and adolescents with severe traumatic brain injury*. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Allen, B. B., Chiu, Y. L., Gerber, L. M., Ghajar, J., Greenfield, J. P. 2014; 15 (1): 62–70

  Abstract

  Evidence-based traumatic brain injury guidelines support cerebral perfusion pressure thresholds for adults at a class 2 level, but evidence is lacking in younger patients. The purpose of this study is to identify the impact of age-specific cerebral perfusion pressure thresholds on short-term survival among patients with severe traumatic brain injury.Institutional review board-approved, prospective, observational cohort study.Level I or II trauma centers in New York State.Data on all patients with a postresuscitation Glasgow Coma Score less than 9 were added in the Brain Trauma Foundation prospective New York State TBI-trac database.We calculated the survival rates and relative risks of mortality for patients with severe traumatic brain injury based on predefined age-specific cerebral perfusion pressure thresholds. A higher threshold and a lower threshold were defined for each age group: 60 and 50 mm Hg for 12 years old or older, 50 and 35 mm Hg for 6-11 years, and 40 and 30 mm Hg for 0-5 years. Patients were stratified into age groups of 0-11, 12-17, and 18 years old or older. Three exclusive groups of CPP-L (events below low cerebral perfusion pressure threshold), CPP-B (events between high and low cerebral perfusion pressure thresholds), and CPP-H (events above high cerebral perfusion pressure threshold) were defined. As an internal control, we evaluated the associations between cerebral perfusion pressure events and events of hypotension and elevated intracranial pressure. Survival was significantly higher in 0-11 and 18 years old or older age groups for patients with CPP-H events compared with those with CPP-L events. There was a significant decrease in survival with prolonged exposure to CPP-B events for the 0-11 and 18 years old and older age groups when compared with the patients with CPP-H events (p = 0.0001 and p = 0.042, respectively). There was also a significant decrease in survival with prolonged exposure to CPP-L events in all age groups compared with the patients with CPP-H events (p< 0.0001 for 0- to 11-yr olds, p = 0.0240 for 12- to 17-yr olds, and p < 0.0001 for 18-yr old and older age groups). The 12- to 17-year olds had a significantly higher likelihood of survival compared with adults with prolonged exposure to CPP-L events (< 50 mm Hg). CPP-L events were significantly related to systemic hypotension for the 12- to 17-year-old group (p = 0.004) and the 18-year-old and older group (p < 0.0001). CPP-B events were significantly related to systemic hypotension in the 0- to 11-year-old group (p = 0.014). CPP-B and CPP-L events were significantly related to elevated intracranial pressure in all age groups.Our data provide new evidence that cerebral perfusion pressure targets should be age specific. Furthermore, cerebral perfusion pressure goals above 50 or 60 mm Hg in adults, above 50 mm Hg in 6- to 17-year olds, and above 40 mm Hg in 0- to 5-year olds seem to be appropriate targets for treatment-based studies. Systemic hypotension had an inconsistent relationship to events of low cerebral perfusion pressure, whereas elevated intracranial pressure was significantly related to all low cerebral perfusion pressure events across all age groups. This may impart a clinically important difference in care, highlighting the necessity of controlling intracranial pressure at all times, while targeting systolic blood pressure in specific instances.

  View details for PubMedID 24196011

  View details for PubMedCentralID PMC4077612

• Individual Differences in Distinct Components of Attention are Linked to Anatomical Variations in Distinct White Matter Tracts. Frontiers in neuroanatomy Niogi, S., Mukherjee, P., Ghajar, J., McCandliss, B. D. 2010; 4: 2-?

  Abstract

  Inter-subject variations in white matter tract properties are known to correlate with individual differences in performance in cognitive domains such as attention. The specificity of such linkages, however, is largely unexplored at the level of specific component operations of attention associated with distinct anatomical networks. This study examines individual performance variation within three functional components of attention - alerting, orienting, and conflict processing - identified by the Attention Network Task (ANT), and relates each to inter-subject variation in a distinct set of white matter tract regions. Diffusion tensor imaging data collected at 3T was used to calculate average fractional anisotropy within a set of individualized a priori defined regions of interest using the Reproducible Objective Quantification Scheme (ROQS) (Niogi and McCandliss, 2006; Niogi et al., 2007). Results demonstrate three functionally distinct components of attention that each correlate distinctly with three white matter tract regions. Structure-function correlations were found between alerting and the anterior limb of the internal capsule, orienting and the splenium of the corpus callosum, and conflict and the anterior corona radiata. A multiple regression/dissociation analysis demonstrated a triple dissociation between these three structure-function relationships that provided evidence of three anatomically and functionally separable networks. These results extend previous findings from functional imaging and lesion studies that suggest these three components of attention are subserved by dissociable networks, and suggest that variations in white matter tract microstructure may modulate the efficiency of these cognitive processes in highly specific ways.

  View details for DOI 10.3389/neuro.05.002.2010

  View details for PubMedID 20204143

  View details for PubMedCentralID PMC2831631

• The predictive brain state: asynchrony in disorders of attention? The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry Ghajar, J., Ivry, R. B. 2009; 15 (3): 232–42

  Abstract

  It is postulated that a key function of attention in goal-oriented behavior is to reduce performance variability by generating anticipatory neural activity that can be synchronized with expected sensory information. A network encompassing the prefrontal cortex, parietal lobe, and cerebellum may be critical in the maintenance and timing of such predictive neural activity. Dysfunction of this temporal process may constitute a fundamental defect in attention, causing working memory problems, distractibility, and decreased awareness.

  View details for PubMedID 19074688

  View details for PubMedCentralID PMC4342364

• Structural dissociation of attentional control and memory in adults with and without mild traumatic brain injury BRAIN Niogi, S. N., Mukherjee, P., Ghajar, J., Johnson, C. E., Kolster, R., Lee, H., Suh, M., Zimmerman, R. D., Manley, G. T., McCandliss, B. D. 2008; 131: 3209-3221

  Abstract

  Memory and attentional control impairments are the two most common forms of dysfunction following mild traumatic brain injury (TBI) and lead to significant morbidity in patients, yet these functions are thought to be supported by different brain networks. This 3 T magnetic resonance diffusion tensor imaging (DTI) study investigates whether microstructural integrity of white matter, as measured by fractional anisotropy (FA) within a small set of individually localized regions of interest (ROIs), is associated with these cognitive domains in normal adults and adults with mild TBI. Results in a sample of 23 normal controls reveal a significant correlation between attentional control and FA within a ROI in the left hemisphere anterior corona radiata. Furthermore, the controls demonstrate a correlation between memory performance and FA in a ROI placed in the uncinate fasciculus. Next, to examine whether these relationships are found in the pathological ranges of attention, memory and microstructural white matter integrity associated with mild TBI, these analyses were applied to a group of 43 mild TBI patients. Results, which generally demonstrated a wider range of attention, memory and FA scores, replicated the correlation between attentional control and FA in left hemisphere anterior corona radiata, as well as the correlation between memory performance and FA in the uncinate fasciculus. These two sets of brain-behaviour relationships were highly specific, as shown by a lack of correlation between attention and uncinate fasciculus FA and the lack of correlation between memory performance and anterior corona radiata FA. Furthermore, a 'correlational double dissociation' was demonstrated to exist between two distinct frontal structures independently associated with attention and memory, respectively, via a series of multiple regression analyses in both normal controls and adults with mild TBI. The results of the multiple regression analyses provide direct evidence that tract-specific variation in microstructural white matter integrity among normal controls and among mild TBI patients can account for much of the variation in performance in specific cognitive domains. More generally, such findings suggest that diffusion anisotropy measurement can be used as a quantitative biomarker for neurocognitive function and dysfunction.

  View details for DOI 10.1093/brain/awn247

  View details for Web of Science ID 000261996700012

  View details for PubMedID 18952679

• Increased oculomotor deficits during target blanking as an indicator of mild traumatic brain injury. Neuroscience letters Suh, M., Basu, S., Kolster, R., Sarkar, R., McCandliss, B., Ghajar, J. 2006; 410 (3): 203–7

  Abstract

  Given the susceptibility of cerebellar-cortical tracts to shearing injury from traumatic brain injury (TBI), we investigated impairment in the generation of predictive eye movements and its relationship to cognitive deficits in mild TBI patients using a smooth pursuit target-blanking paradigm. Compared to a target-tracking paradigm without blanking, this paradigm more greatly necessitates the generation of predictive eye movements, which are subserved by brain regions involved in cognitive processing. Mild TBI patients showed impaired prediction of target trajectories during target blanking, demonstrated by generation of saccades at earlier and more variable time points, as well as greater and more variable oculomotor error compared to controls. In addition, California Verbal Learning Test (CVLT-II) scores related to working memory, learning, and executive function were more highly correlated with oculomotor variability during target blanking than during target tracking. Our results suggest that a disruption of cerebellar-cortical connections in TBI may account for both oculomotor and cognitive impairment, and that measures of predictive eye movements during target blanking may be a sensitive metric of cognitive deficits after mild TBI.

  View details for PubMedID 17055156

• Deficits in predictive smooth pursuit after mild traumatic brain injury. Neuroscience letters Suh, M., Kolster, R., Sarkar, R., McCandliss, B., Ghajar, J. 2006; 401 (1-2): 108–13

  Abstract

  Given that even mild traumatic brain injury (TBI) may produce extensive diffuse axonal injury (DAI), we hypothesized that mild TBI patients would show deficits in predictive smooth pursuit eye movements (SPEM), associated with impaired cognitive functions, as these processes are dependent on common white matter connectivity between multiple cerebral and cerebellar regions. The ability to predict target trajectories during SPEM was investigated in 21 mild TBI patients using a periodic sinusoidal paradigm. Compared to 26 control subjects, TBI patients demonstrated decreased target prediction. TBI patients also showed increased eye position error and variability of eye position, which correlated with decreased target prediction. In all subjects, average target prediction, eye position error and eye position variability correlated with scores related to attention and executive function on the California Verbal Learning Test (CVLT-II). However, there were no differences between TBI and control groups in average eye gain or intra-individual eye gain variability, or in performance on the Wechsler Abbreviated Scale of Intelligence (WASI), suggesting that the observed deficits did not result from general oculomotor impairment or reduced IQ. The correlation between SPEM performance and CVLT-II scores suggests that predictive SPEM may be a sensitive assay of cognitive functioning, including attention and executive function. This is the first report to our knowledge that TBI patients show impaired predictive SPEM and eye position variability, and that these impairments correlate with cognitive deficits.

  View details for PubMedID 16554121

• Increasing Adherence to Brain Trauma Foundation Guidelines for Hospital Care of Patients With Traumatic Brain Injury CRITICAL CARE NURSE Saherwala, A. A., Bader, M., Stutzman, S. E., Figueroa, S. A., Ghajar, J., Gorman, A. R., Minhajuddin, A., Olson, D. M. 2018; 38 (1): E11–E20

  Abstract

  The Brain Trauma Foundation has developed treatment guidelines for the care of patients with acute traumatic brain injury. The Adam Williams Initiative is a program established to provide education and resources to encourage hospitals across the United States to incorporate the guidelines into practice.To explore the relationship in hospitals between participation in the Adam Williams Initiative and adherence to the Brain Trauma Foundation guidelines for patients with acute traumatic brain injury.Hospitals that participated in the Adam Williams Initiative entered data into an online tracking system of patients with traumatic brain injury for at least 2 years after the initial site training. Data included baseline hospital records and daily records on hospital care of patients with traumatic brain injury, including blood pressure, intracranial pressure, cerebral perfusion pressure, oxygenation, and other data relevant to the 15 key metrics in the Brain Trauma Foundation guidelines.The 16 hospitals funded by the Adam Williams Initiative had good overall adherence to the 15 key metrics of the recommendations detailed in the Brain Trauma Foundation guidelines. Variability in results was primarily due to data collection methods and analysis.The Adam Williams Initiative helps promote adherence to the Brain Trauma Foundation guidelines for hospital care of patients with traumatic brain injury by providing a platform for developing and standardizing best practices. Participation in the initiative is associated with high adherence to clinical guidelines, a situation that may subsequently improve care and outcomes for patients with traumatic brain injury.

  View details for PubMedID 29437084

• Living Guideline Development in Traumatic Brain Injury: Opportunities to Link Quality of Care, Research, and Better Patient Outcomes to a Future Research Agenda Kolakowsky-Hayner, S. A., Totten, A. M., Assasnik, S., Balamane, M., Ghajar, J. LIPPINCOTT WILLIAMS & WILKINS. 2017: E85–E86

  View details for Web of Science ID 000418588100053

• Chronic Post-Concussion Neurocognitive Deficits. II. Relationship with Persistent Symptoms FRONTIERS IN HUMAN NEUROSCIENCE Maruta, J., Spielman, L. A., Yarusi, B. B., Wang, Y., Silver, J. M., Ghajar, J. 2016; 10

  Abstract

  Individuals who sustain a concussion may continue to experience problems long after their injury. However, it has been postulated in the literature that the relationship between a concussive injury and persistent complaints attributed to it is mediated largely by the development of symptoms associated with posttraumatic stress disorder (PTSD) and depression. We sought to characterize cognitive deficits of adult patients who had persistent symptoms after a concussion and determine whether the original injury retains associations with these deficits after accounting for the developed symptoms that overlap with PTSD and depression. We compared the results of neurocognitive testing from 33 patients of both genders aged 18-55 at 3 months to 5 years post-injury with those from 140 control subjects. Statistical comparisons revealed that patients generally produced accurate responses on reaction time-based tests, but with reduced efficiency. On visual tracking, patients increased gaze position error variability following an attention demanding task, an effect that may reflect greater fatigability. When neurocognitive performance was examined in the context of demographic- and symptom-related variables, the original injury retained associations with reduced performance at a statistically significant level. For some patients, reduced cognitive efficiency and fatigability may represent key elements of interference when interacting with the environment, leading to varied paths of recovery after a concussion. Poor recovery may be better understood when these deficits are taken into consideration.

  View details for DOI 10.3389/fnhum.2016.00045

  View details for Web of Science ID 000370120800001

  View details for PubMedID 26912999

• Chronic Post-Concussion Neurocognitive Deficits. I. Relationship with White Matter Integrity FRONTIERS IN HUMAN NEUROSCIENCE Maruta, J., Palacios, E. M., Zimmerman, R. D., Ghajar, J., Mukherjee, P. 2016; 10

  Abstract

  We previously identified visual tracking deficits and associated degradation of integrity in specific white matter tracts as characteristics of concussion. We re-explored these characteristics in adult patients with persistent post-concussive symptoms using independent new data acquired during 2009-2012. Thirty-two patients and 126 normal controls underwent cognitive assessments and MR-DTI. After data collection, a subset of control subjects was selected to be individually paired with patients based on gender and age. We identified patients' cognitive deficits through pairwise comparisons between patients and matched control subjects. Within the remaining 94 normal subjects, we identified white matter tracts whose integrity correlated with metrics that indicated performance degradation in patients. We then tested for reduced integrity in these white matter tracts in patients relative to matched controls. Most patients showed no abnormality in MR images unlike the previous study. Patients' visual tracking was generally normal. Patients' response times in an attention task were slowed, but could not be explained as reduced integrity of white matter tracts relating to normal response timing. In the present patient cohort, we did not observe behavioral or anatomical deficits that we previously identified as characteristic of concussion. The recent cohort likely represented those with milder injury compared to the earlier cohort. The discrepancy may be explained by a change in the patient recruitment pool circa 2007 associated with an increase in public awareness of concussion.

  View details for DOI 10.3389/fnhum.2016.00035

  View details for Web of Science ID 000369850900001

  View details for PubMedID 26903842

  View details for PubMedCentralID PMC4748060

• Filling in the gaps: Anticipatory control of eye movements in chronic mild traumatic brain injury NEUROIMAGE-CLINICAL Diwakar, M., Harrington, D. L., Maruta, J., Ghajar, J., El-Gabalawy, F., Muzzatti, L., Corbetta, M., Huang, M., Lee, R. R. 2015; 8: 210-223

  Abstract

  A barrier in the diagnosis of mild traumatic brain injury (mTBI) stems from the lack of measures that are adequately sensitive in detecting mild head injuries. MRI and CT are typically negative in mTBI patients with persistent symptoms of post-concussive syndrome (PCS), and characteristic difficulties in sustaining attention often go undetected on neuropsychological testing, which can be insensitive to momentary lapses in concentration. Conversely, visual tracking strongly depends on sustained attention over time and is impaired in chronic mTBI patients, especially when tracking an occluded target. This finding suggests deficient internal anticipatory control in mTBI, the neural underpinnings of which are poorly understood. The present study investigated the neuronal bases for deficient anticipatory control during visual tracking in 25 chronic mTBI patients with persistent PCS symptoms and 25 healthy control subjects. The task was performed while undergoing magnetoencephalography (MEG), which allowed us to examine whether neural dysfunction associated with anticipatory control deficits was due to altered alpha, beta, and/or gamma activity. Neuropsychological examinations characterized cognition in both groups. During MEG recordings, subjects tracked a predictably moving target that was either continuously visible or randomly occluded (gap condition). MEG source-imaging analyses tested for group differences in alpha, beta, and gamma frequency bands. The results showed executive functioning, information processing speed, and verbal memory deficits in the mTBI group. Visual tracking was impaired in the mTBI group only in the gap condition. Patients showed greater error than controls before and during target occlusion, and were slower to resynchronize with the target when it reappeared. Impaired tracking concurred with abnormal beta activity, which was suppressed in the parietal cortex, especially the right hemisphere, and enhanced in left caudate and frontal-temporal areas. Regional beta-amplitude demonstrated high classification accuracy (92%) compared to eye-tracking (65%) and neuropsychological variables (80%). These findings show that deficient internal anticipatory control in mTBI is associated with altered beta activity, which is remarkably sensitive given the heterogeneity of injuries.

  View details for DOI 10.1016/j.nicl.2015.04.011

  View details for Web of Science ID 000373187100022

  View details for PubMedCentralID PMC4473731

• Impact of falls on early mortality from severe traumatic brain injury. Journal of trauma management & outcomes Gerber, L. M., Ni, Q., Härtl, R., Ghajar, J. 2009; 3: 9-?

  Abstract

  The causes of severe traumatic brain injury (TBI) vary by age and other demographic characteristics. Mortality after trauma is higher for elderly than younger patients. This study is based on 2779 patients with severe TBI treated at 24 trauma centers enrolled in a New York State quality improvement program. The prospectively collected database includes information on age, sex, mechanism of injury, initial Glasgow Coma Scale score, blood pressure, pupillary assessment, and CT scan findings. This multi-center study was conducted to explore the impact of falls on early mortality from severe TBI among the elderly.After exclusion criteria were applied, a total of 2162 patients were eligible for analysis. Falls contributed to 21% of all severe TBI, 12% occurring from > 3 meters and 9% from < 3 meters. Two-week mortality ranged from 18% due to injuries other than falls to 31% due to falls from < 3 meters (p =< 0.0001). Mortality after a severe TBI is much greater among older people, reaching 58% for people 65 years and older sustaining a fall from < 3 meters.Among those 65 and older, falls contributed to 61% of all injuries and resulted in especially high mortality among individuals experiencing low falls. Preventive efforts directed toward older people to avoid falls from < 3 meters could have a significant impact on mortality.

  View details for DOI 10.1186/1752-2897-3-9

  View details for PubMedID 19643003

  View details for PubMedCentralID PMC2739840