Ramon Diaz-Arrastia - Academia.edu (original) (raw)

Papers by Ramon Diaz-Arrastia

JAMA network open, Mar 20, 2023

IMPORTANCE Many level I trauma center patients experience clinical sequelae at 1 year following t... more IMPORTANCE Many level I trauma center patients experience clinical sequelae at 1 year following traumatic brain injury (TBI). Longer-term outcome data are needed to develop better monitoring and rehabilitation services. OBJECTIVE To examine functional recovery, TBI-related symptoms, and quality of life from 1 to 5 years postinjury. DESIGN, SETTING, AND PARTICIPANTS This cohort study enrolled trauma patients across 18 US level I trauma centers between 2014 and 2018. Eligible participants were enrolled within 24 hours of injury and followed up to 5 years postinjury. Data were analyzed January 2023. EXPOSURES Mild TBI (mTBI), moderate-severe TBI (msTBI), or orthopedic traumatic controls (OTC). MAIN OUTCOMES AND MEASURES Functional independence (Glasgow Outcome Scale-Extended [GOSE] score 5 or higher), complete functional recovery (GOSE score, 8), better (ie, lower) TBI-related symptom burden (Rivermead Post Concussion Symptoms Questionnaire score of 15 or lower), and better (ie, higher) health-related quality of life (Quality of Life After Brain Injury Scale-Overall Scale score 52 or higher); mortality was analyzed as a secondary outcome. RESULTS A total 1196 patients were included in analysis (mean [SD] age, 40.8 [16.9] years; 781 [65%] male; 158 [13%] Black, 965 [81%] White). mTBI and OTC groups demonstrated stable, high rates of functional independence (98% to 100% across time). While odds of independence were lower among msTBI survivors, the majority were independent at 1 year (72%), and this proportion increased over time (80% at 5 years; group × year, P = .005; independence per year: odds ratio [OR] for msTBI, 1.28; 95% CI, 1.03-1.58; OR for mTBI, 0.81; 95% CI, 0.64-1.03). For other outcomes, group differences at 1 year remained stable over time (group × year, P Ն .44). Odds of complete functional recovery remained lower for persons with mTBI vs OTC (OR, 0.39; 95% CI, 0.28-0.56) and lower for msTBI vs mTBI (OR, 0.34; 95% CI, 0.24-0.48). Odds of better TBI-related symptom burden and quality of life were similar for both TBI subgroups and lower than OTCs. Mortality between 1 and 5 years was higher for msTBI (5.5%) than mTBI (1.5%) and OTC (0.7%; P = .02). CONCLUSIONS AND RELEVANCE In this cohort study, patients with previous msTBI displayed increased independence over 5 years; msTBI was also associated with increased mortality. These findings, in combination with the persistently elevated rates of unfavorable outcomes in mTBI vs controls imply that more monitoring and rehabilitation are needed for TBI.

Journal of Head Trauma Rehabilitation, Nov 1, 2016

Objectives-Examine the effects of post-traumatic amnesia (PTA) duration on neuropsychological and... more Objectives-Examine the effects of post-traumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI). Participants-330 persons with cmTBI defined as Glasgow Coma Scale score of 13-15 in Emergency Department, with well-defined abnormalities on neuroimaging. Methods-Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months. Measures-Glasgow Outcome Scale-Extended, California Verbal Learning Test II, Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days post injury. Results-Despite all having a Glasgow Coma Score of 13-15, a quarter of the sample had a PTA duration of greater than 7 days; half had PTA of 1-7 days. Both cognitive performance and GOS-E outcomes were strongly associated with time since injury and PTA duration, with those with PTA> 1 week showing residual moderate disability at 6-month assessment. Conclusions-Findings reinforce importance of careful measurement of duration of PTA to refine outcome prediction and allocation of resources to those with cmTBI. Future research would benefit from standardization in CT criteria and use of severity indices beyond GCS to characterize cmTBI.

Neurogenetics, Nov 17, 2015

Compliance with ethical standards Conflicts of interest The authors declare that they have no con... more Compliance with ethical standards Conflicts of interest The authors declare that they have no conflicts of interest. Research involving human participants All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

Psychiatry Research: Neuroimaging, Mar 1, 2011

Science Advances, Aug 7, 2020

Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain in... more Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Crosssectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.

Journal of Clinical Neuroscience, 2017

Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The so... more Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence *

Frontiers in Neurology, Nov 3, 2021

The guiding principle for data stewardship dictates that data be FAIR: findable, accessible, inte... more The guiding principle for data stewardship dictates that data be FAIR: findable, accessible, interoperable, and reusable. Data reuse allows researchers to probe data that may have been originally collected for other scientific purposes in order to gain novel insights. The current study reuses the Transforming Research and Clinical Knowledge for Traumatic Brain Injury (TRACK-TBI) Pilot dataset to build upon prior findings and ask new scientific questions. Specifically, we have previously used a multivariate analytics approach to multianalyte serum protein data from the TRACK-TBI Pilot dataset to show that an inflammatory ensemble of biomarkers can predict functional outcome at 3 and 6 months post-TBI. We and others have shown that there are quantitative and qualitative changes in inflammation that come with age, but little is known about how this interaction affects recovery from TBI. Here we replicate the prior proteomics findings with improved missing value analyses and non-linear principal component analysis and then expand upon this work to determine whether age moderates the effect of inflammation on recovery. We show that increased age correlates with worse functional recovery on the Glasgow Outcome Scale-Extended (GOS-E) as well as increased inflammatory signature. We then explore the interaction between age and inflammation on recovery, which suggests that inflammation has a more detrimental effect on recovery for older TBI patients.

Journal of Neurotrauma, Apr 15, 2019

Accurate diagnosis of traumatic brain injury (TBI) is critical to ensure that patients receive ap... more Accurate diagnosis of traumatic brain injury (TBI) is critical to ensure that patients receive appropriate follow-up care, avoid risk of subsequent injury, and are aware of possible long-term consequences. However, diagnosis of TBI, particularly in the emergency department (ED), can be difficult because the symptoms of TBI are vague and nonspecific, and patients with suspected TBI may present with additional injuries that require immediate medical attention. We performed a retrospective chart review to evaluate accuracy of TBI diagnosis in the ED. Records of 1641 patients presenting to the ED with suspected TBI and a head computed tomography (CT) were reviewed. We found only 47% of patients meeting the American Congress of Rehabilitation Medicine criteria for TBI received a documented ED diagnosis of TBI in medical records. After controlling for demographic and clinical factors, patients presenting at a level I trauma center, with cause of injury other than fall, without CT findings of TBI, and without loss of consciousness were more likely to lack documented diagnosis despite meeting diagnostic criteria for TBI. A greater proportion of patients without documented ED diagnosis of TBI were discharged home compared to those with a documented diagnosis of TBI (58% vs. 40%; p < 0.001). Together, these data suggest that many patients who have sustained a TBI are discharged home from the ED without a documented diagnosis of TBI, and that improved awareness and implementation of diagnostic criteria for TBI is important in the ED and for in-and outpatient providers.

Sleep, 2020

Study Objectives Sleep disorders affect over half of mild traumatic brain injury (mTBI) patients.... more Study Objectives Sleep disorders affect over half of mild traumatic brain injury (mTBI) patients. Despite evidence linking sleep and neurodegeneration, longitudinal TBI-related dementia studies have not considered sleep. We hypothesized that poor sleepers with mTBI would have elevated markers of neurodegeneration and lower cognitive function compared to mTBI good sleepers and controls. Our objective was to compare biomarkers of neurodegeneration and cognitive function with sleep quality in warfighters with chronic mTBI. Methods In an observational warfighters cohort (n = 138 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with plasma biomarkers of neurodegeneration and cognitive scores collected an average of 8 years after injury. Results In the mTBI cohort, poor sleepers (PSQI ≥ 10, n = 86) had elevated plasma neurofilament light (NfL, x̅ = 11.86 vs 7.91 pg/mL, p = 0.0007, d = 0.63) and lower executive function scores by the categorical fluency (x̅ = 18.0...

Frontiers in Physiology, 2021

ObjectiveTo characterize the relationship between persistent post-traumatic headache (pPTH) and t... more ObjectiveTo characterize the relationship between persistent post-traumatic headache (pPTH) and traumatic cerebrovascular injury (TCVI) in chronic traumatic brain injury (TBI). Cerebrovascular reactivity (CVR), a measure of the cerebral microvasculature and endothelial cell function, is altered both in individuals with chronic TBI and migraine headache disorder (Amyot et al., 2017; Lee et al., 2019b). The pathophysiologies of pPTH and migraine are believed to be associated with chronic microvascular dysfunction. We therefore hypothesize that TCVI may contribute to the underlying migraine-like mechanism(s) of pPTH.Materials and Methods22 moderate/severe TBI participants in the chronic stage (>6 months) underwent anatomic and functional magnetic resonance imaging (fMRI) scanning with hypercapnia gas challenge to measure CVR as well as the change in CVR (ΔCVR) after single-dose treatment of a specific phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, which potentiates vasodilation ...

Acta Neuropathologica Communications, 2021

Efforts to characterize the late effects of traumatic brain injury (TBI) have been in progress fo... more Efforts to characterize the late effects of traumatic brain injury (TBI) have been in progress for some time. In recent years much of this activity has been directed towards reporting of chronic traumatic encephalopathy (CTE) in former contact sports athletes and others exposed to repetitive head impacts. However, the association between TBI and dementia risk has long been acknowledged outside of contact sports. Further, growing experience suggests a complex of neurodegenerative pathologies in those surviving TBI, which extends beyond CTE. Nevertheless, despite extensive research, we have scant knowledge of the mechanisms underlying TBI-related neurodegeneration (TReND) and its link to dementia. In part, this is due to the limited number of human brain samples linked to robust demographic and clinical information available for research. Here we detail a National Institutes for Neurological Disease and Stroke Center Without Walls project, the COllaborative Neuropathology NEtwork Char...

Frontiers in Endocrinology, 2018

NeuroImage: Clinical, 2019

Traumatic cerebral vascular injury (TCVI) is a frequent, but under-recognized, endophenotype of t... more Traumatic cerebral vascular injury (TCVI) is a frequent, but under-recognized, endophenotype of traumatic brain injury (TBI). It likely contributes to functional deficits after TBI and TBI-related chronic disability, and represents an attractive target for targeted therapeutic interventions. The aim of this prospective study is to assess microvascular injury/dysfunction in chronic TBI by measuring cerebral vascular reactivity (CVR) by 2 methods, functional magnetic resonance imaging (fMRI) and functional Near InfraRed Spectroscopy (fNIRS) imaging, as each has attractive features relevant to clinical utility. 42 subjects (27 chronic TBI, 15 age-and gender-matched non-TBI volunteers) were enrolled and underwent outpatient CVR testing by 2 methods, MRI-BOLD and fNIRS, each with hypercapnia challenge, a neuropsychological testing battery, and symptom survey questionnaires. Chronic TBI subjects showed a significant reduction in global CVR compared to HC (p < 0.0001). Mean CVR measures by fMRI were 0.225 ± 0.014 and 0.183 ± 0.026 %BOLD/mmHg for non-TBI and TBI subjects respectively and 12.3 ± 1.8 and 9.2 ± 1.7 mM/mmHg by fNIRS for non-TBI versus TBI subjects respectively. Global CVR measured by fNIRS imaging correlates with results by MRI-BOLD (R = 0.5). Focal CVR deficits seen on CVR maps by fMRI are also observed in the same areas by fNIRS in the frontal regions. Global CVR is significantly lower in chronic TBI patients and is reliably measured by both fMRI and fNIRS, the former with better spatial and the latter with better temporal resolution. Both methods show promise as noninvasive measures of CVR function and microvascular integrity after TBI.

Journal of Neurosurgery, 2018

OBJECTIVEFollowing traumatic brain injury (TBI), midline shift of the brain at the level of the s... more OBJECTIVEFollowing traumatic brain injury (TBI), midline shift of the brain at the level of the septum pellucidum is often caused by unilateral space-occupying lesions and is associated with increased intracranial pressure and worsened morbidity and mortality. While outcome has been studied in this population, the recovery trajectory has not been reported in a large cohort of patients with TBI. The authors sought to utilize the Citicoline Brain Injury Treatment (COBRIT) trial to analyze patient recovery over time depending on degree of midline shift at presentation.METHODSPatient data from the COBRIT trial were stratified into 4 groups of midline shift, and outcome measures were analyzed at 30, 90, and 180 days postinjury. A recovery trajectory analysis was performed identifying patients with outcome measures at all 3 time points to analyze the degree of recovery based on midline shift at presentation.RESULTSThere were 892, 1169, and 895 patients with adequate outcome data at 30, 90...

Annals of clinical and translational neurology, 2018

Traumatic cerebrovascular injury (TCVI), a common consequence of traumatic brain injury (TBI), pr... more Traumatic cerebrovascular injury (TCVI), a common consequence of traumatic brain injury (TBI), presents an attractive therapeutic target. Because phosphodiesterase-5 (PDE5) inhibitors potentiate the action of nitric oxide (NO) produced by endothelial cells, they are candidate therapies for TCVI. This study aims to: (1) measure cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and change in CVR after a single dose of sildenafil (ΔCVR) in chronic TBI compared to uninjured controls; (2) examine the safety and tolerability of 8-week sildenafil administration in chronic symptomatic moderate/severe TBI patients; and as an exploratory aim, (3) assess the effect of an 8-week course of sildenafil on chronic TBI symptoms. Forty-six subjects (31 chronic TBI, 15 matched healthy volunteers) were enrolled. Baseline CBF and CVR before and after administration of sildenafil were measured. Symptomatic TBI subjects then completed an 8-week double-blind, placebo-controlled, crossover trial ...

Journal of neurotrauma, Jan 25, 2017

Traumatic cerebrovascular injury (TCVI) is a common pathologic mechanism of traumatic brain injur... more Traumatic cerebrovascular injury (TCVI) is a common pathologic mechanism of traumatic brain injury (TBI) and presents an attractive target for intervention. The aims of this study were to assess cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI), to assess their value as biomarkers of TCVI in chronic TBI, characterize the spatial distribution of TCVI, and assess the relationships between each biomarker and neuropsychological and clinical assessments. 42 subjects (27 chronic TBI, 15 age and gender-matched healthy volunteers) were studied cross-sectionally. CBF was measured by arterial spin labeling (ASL), and CVR by assessing the MRI-Blood Oxygen Level Dependent (BOLD) signal with hypercapnia challenge. A focused neuropsychological battery adapted from the TBI Common Data Elements, and neurobehavioral symptom questionnaires were administered at the time of the imaging session. Chronic TBI subjects showed a significant reduction in me...

Critical care medicine, 2017

A relationship between reduced brain tissue oxygenation and poor outcome following severe traumat... more A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study. Randomized prospective clinical trial. Ten ICUs in the United States. One hundred nineteen severe traumatic brain injury patients. Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 ...

eneuro, 2017

Diffuse axonal injury (DAI) is a hallmark of traumatic brain injury (TBI) pathology. Recently, th... more Diffuse axonal injury (DAI) is a hallmark of traumatic brain injury (TBI) pathology. Recently, the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) was developed to generate an experimental model of DAI in a mouse. The characterization of DAI using diffusion tensor magnetic resonance imaging (MRI; diffusion tensor imaging, DTI) may provide a useful set of outcome measures for preclinical and clinical studies. The objective of this study was to identify the complex neurobiological underpinnings of DTI features following DAI using a comprehensive and quantitative evaluation of DTI and histopathology in the CHIMERA mouse model. A consistent neuroanatomical pattern of pathology in specific white matter tracts was identified acrossex vivoDTI maps and photomicrographs of histology. These observations were confirmed by voxelwise and regional analysis of DTI maps, demonstrating reduced fractional anisotropy (FA) in distinct regions such as the optic tract. Similar re...

Acta neuropathologica, Jan 24, 2016

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive ... more Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques. In this study, we analyzed postmortem brain tissues from five institutionalized patients with schizophrenia and history of surgical leucotomy with subsequent survival of at least another 40 years. Because leucotomy involves severing axons bilaterally in prefrontal cortex, this surgical procedure represents a human model of single traumatic brain injury with severe axonal damage and no external impact. We examined c...

Journal of Head Trauma Rehabilitation, 2017

Objective: While traumatic brain injury (TBI) is common across the life span, the detailed neurob... more Objective: While traumatic brain injury (TBI) is common across the life span, the detailed neurobehavioral characteristics of older adults with prior TBI remain unclear. Our goal was to compare the clinical profile of older independently living veterans with and without prior TBI. Setting: Two veterans' retirement communities. Participants: Seventy-five participants with TBI and 71 without (mean age = 78 years). Design: Cross-sectional. Main Measures: TBI history was determined by the Ohio State University TBI Questionnaire. We assessed psychiatric and medical history via interviews and chart review and conducted measures assessing functional/lifestyle, psychiatric, and cognitive outcomes. Regression analyses (adjusted for demographics, diabetes, prior depression, substance abuse, and site) were performed to compare between TBI and non-TBI participants. Results: Compared with veterans without TBI, those with TBI had greater functional impairment (adjusted P = .05), endorsed more...