Bhanu Sharma

The role of apolipoprotein E episilon (ɛ)-4 allele on outcome following traumatic brain injury: A systematic review

Abstract Background: The apolipoprotein E gene (APOE) has emerged as a candidate for prognosticating traumatic brain injury (TBI) recovery, with APOEɛ4 identified as a susceptibility marker for poor outcome, despite large discrepancy in its reported influence post-TBI. Methods: A systematic review was conducted, including all primary articles investigating the role of APOEɛ4 on TBI outcome. A total of 65 studies were included, including 24 predominantly investigating mild (mTBI), seven moderate (modTBI) and 33 severe (sTBI); severity was not reported in one study. Results: In mTBI studies, the association between APOEɛ4 and post-TBI outcome was concluded as non-contributory in 14 studies (58.3%), hazardous in nine (37.5%) and protective in one (4.2%). In sTBI studies, the role of APOEɛ4 was hazardous in 21 (63.6%), non-contributory in nine (27.3%) and protective in three (9.1%). Of the seven studies investigating dementia outcomes, four observed a hazardous association with APOEɛ4, while three reported no association. Six studies examined Alzheimer’s dementia pathology, of which three reported a hazardous influence of APOEɛ4. Conclusions: The influence of APOEɛ4 on neuropsychological testing, functional outcome and in paediatric populations was incongruous. This review supports the majority of research indicating APOEɛ4 adversely influences recovery following TBI, particularly with respect to dementia-related outcomes and outcomes following sTBI.

Missed diagnosis of traumatic brain injury in patients with traumatic spinal cord injury.

OBJECTIVE To determine the frequency of missed acute care traumatic brain injury diagnoses in patients with traumatic spinal cord injury, and to examine risk factors for missed traumatic brain injury diagnosis. DESIGN Prospective magnetic resonance imaging and neuro-psychological assessment plus retrospective medical record review, including computed tomography. SUBJECTS Ninety-two adults with traumatic spinal cord injury recruited from a large, tertiary spinal cord injury program, initially referred from urban teaching hospitals with neurotrauma facilities. METHODS Diagnosis of traumatic brain injury made with clinical neurological indices (i.e., Glasgow Coma Scale, post-traumatic amnesia, and loss of consciousness), neuroimaging (computed tomography and structural magnetic resonance imaging), and neuropsychological tests of attention and speed of processing, memory, and executive function; all measures were validated on a case-by-case basis to rule out confounds. Missed traumatic brain injury diagnoses were made via acute care medical record review and were corroborated by patient/family report where possible. RESULTS The frequency of missed traumatic brain injury diagnoses in our sample was 58.5%. Missed traumatic brain injury diagnoses were more frequent in injuries sustained outside of a motor vehicle collision (MVC), with 75.0% of acute care traumatic brain injury diagnoses missed in non-MVC patients vs. 42.9% missed in MVC patients. Among patients with non-MVC injuries, a comparable percentage of missed traumatic brain injury diagnoses were observed in patients with cervical (79%) and sub-cervical injuries (80%). CONCLUSION In more than half of the traumatic spinal cord injury patients referred for in-patient rehabilitation, acute care diagnoses of traumatic brain injury were missed. A risk factor for missed diagnosis was an injury caused by a mechanism other than an MVC (e.g., falls, assaults), perhaps due to reduced expectations of traumatic brain injury in non-MVC patients. In our research study, we employed multiple assessments to aid diagnosis, which is particularly important for detecting the milder traumatic brain injuries often associated with spinal cord injury; unfortunately, limited resources may preclude a comprehensive diagnostic approach in clinical settings. Our findings point to the need to examine current acute care diagnostic protocols, and to increase vigilance in patients with traumatic injuries sustained outside of an MVC setting.

A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion

Abstract Background: Nutritional interventions are promising treatment adjuncts in the management of concussion. Vitamin D (VDH) supplementation has demonstrated neuroprotective properties in multiple models of acquired brain injury. Objective: Review the neuroprotective role of VDH supplementation following traumatic brain injury (TBI). Methods: A Medline search was conducted to review manuscripts investigating the influence of VDH status or supplementation on TBI outcomes. Results: The search identified 165 studies, of which five were included. Four manuscripts studied a rodent model of TBI, while one studied a clinical sample. Vitamin D monotherapy independently reduced inflammation and neuronal injury following TBI, with a more robust effect observed in combination with progesterone (PROG). One study demonstrated VDH deficiency exacerbates post-TBI inflammatory response. One study in a clinical sample found combination therapy superior to PROG alone or placebo in improving outcomes after severe TBI. One study observed a more robust response to low-dose VDH compared to high-dose VDH when given in combination with PROG. Conclusion: A protective role for VDH and a vitamin D sufficient status was identified for numerous outcomes following TBI. However, VDH supplementation cannot be recommended at this time to improve outcomes following TBI.

Traumatic Brain Injury in Spinal Cord Injury: Frequency and Risk Factors.

Background:The frequency of traumatic brain injury (TBI) co-occurring with traumatic spinal cord injury (tSCI) is unclear despite a number of past studies; as well, limited research has examined predictors of co-morbid TBI in tSCI patients. Objectives:(1a) To summarize past literature on comorbid diagnosis of TBI in tSCI in order to reexamine the frequency of dual diagnosis in a study designed to obviate past methodological limitations; (1b) to compare dual-diagnosis frequency with vs without the inclusion of diagnostically ambiguous cases; and (2) to measure risk factors for tSCI and comorbid TBI. Methods:Ninety-one of 135 eligible adults with tSCI, 3 to 6 months postinjury, were prospectively recruited from a tertiary inpatient tSCI rehabilitation program. TBI diagnosis was based on comprehensive, validated clinical neurological and neuroimaging measures. Results:Objective 1: 39.6% of the tSCI patients sustained a concomitant TBI, but when ambiguous cases were removed from analysis, frequency rose to 58.1%. Objective 2: Motor vehicle collisions were most likely to yield a comorbid TBI diagnosis, but 31.6% of falls also resulted in TBI. Patients with cervical and thoracic injuries showed a very similar frequency of comorbid TBI. Conclusions:Varied methodological approaches, particularly the decision to include/exclude ambiguous cases, likely explain disparate past estimates of TBI in tSCI. However, even this studys lower frequency estimate, at nearly 40%, is clinically important. The prevailing assumption that dual diagnosis is less common in thoracic than cervical spine injuries was not supported. Finally, while comorbid TBI most frequently occurred in motor vehicle collisions, nearly a third of tSCIs sustained in falls resulted in comorbid TBI in our sample.

A qualitative exploration of work-related head injury: vulnerability at the intersection of workers’ decision making and organizational values

BackgroundWork-related head injury is a critical public health issue due to its rising prevalence; the association with profound disruption of workers’ lives; and significant economic burdens in terms of medical costs and lost wages. Efforts to understand and prevent these types of injuries have largely been dominated by epidemiological research and safety science, which has focused on identifying risk at the level of the individual worker, population group, or organizational sector. Limited research has focused on the perspectives of the workers, a key stakeholder group for informing understanding of vulnerability to work-related head injury. This study explored workers’ perspectives to better understand their decision-making and how and why their injuries occurred.MethodsWe conducted a qualitative study using in-depth semi-structured interviews with thirty-two adult workers who had sustained a work-related head injury. Workers were recruited from an urban clinic in central Ontario, Canada. Labour Process Theory informed the thematic analysis.ResultsThree hazardous work conditions were identified: insufficient training; inadequate staffing; and inattention to the physical environment. In addition, professional and organizational norms were implicated in vulnerability to head injury including putting the client before the worker and the pressure to work unsafely. The findings also highlight a complex interrelationship between workers’ decision-making and professional and organizational norms that produces vulnerability to head injury, a vulnerability which oftentimes is reproduced by workers’ decisions to work despite hazardous conditions.ConclusionsOur findings suggest that, beyond the need to redress the inattention to hazards in the physical environment, there is a need to address norms that influence worker decision-making to improve the safety of workers. Using Labour Process Theory highlights an important social dynamic within workplace sectors that could inform future development and implementation of multi-level and integrated public health strategies to reduce work-related head injury.

Construction fatality due to electrical contact in Ontario, Canada, 1997–2007

BACKGROUND Electrical contact is a leading cause of occupational fatality in the construction industry. However, research on the factors that contribute to electricity-related fatality in construction is limited. OBJECTIVES To characterize, using an adapted Haddons Matrix, the factors that contribute to electricity-related occupational fatalities in the construction industry in Ontario, Canada. METHODS Coroners data on occupational electricity-related fatalities between 1997-2007 in the construction industry were acquired from the Ontario Ministry of Labour. Using an adapted Haddons Matrix, we characterized worker, agent, and environmental characteristics of electricity-related occupational fatalities in the province through a narrative text analysis. RESULTS Electrical contact was responsible for 15% of all occupational fatalities among construction workers in Ontario. Factors associated with said occupational fatalities included direct contact with electrical sources, lower voltage sources, and working outdoors. CONCLUSIONS This study provides a profile of electricity-related occupational fatalities among construction workers in Ontario, and can be used to inform safety regulations.

Longitudinal Recovery of Executive Control Functions After Moderate-Severe Traumatic Brain Injury: Examining Trajectories of Variability and Ex-Gaussian Parameters:

Background. Executive control deficits are deleterious and enduring consequences of moderate-severe traumatic brain injury (TBI) that disrupt everyday functioning. Clinically, such impairments can manifest as behavioural inconsistency, measurable experimentally by the degree of variability across trials of a reaction time (RT) task (also known as intraindividual variability [IIV]). Growing research on cognition after TBI points to cognitive deterioration in the chronic stages postinjury. Objective. To examine the longitudinal recovery of RT characteristics (IIV and more detailed ex-Gaussian components, as well as the number of impulsively quick responses) following moderate-severe TBI. Methods. Seventy moderate-severe TBI patients were assessed at 2, 5, 12, and 24+ months postinjury on a go/no-go RT task. RT indices (ex-Gaussian parameters mu and sigma [mean and variability of the normal distribution component], and tau [extremely slow responses]; mean, intraindividual coefficient of variation [ICV], and intraindividual standard deviation [ISD]) were analyzed with repeated-measures multivariate analysis of variance. Results. ICV, ISD, and ex-Gaussian tau significantly decreased (ie, improved) over time in the first year of injury, but worsened from 1 to 2+ years, as did the frequency of extremely fast responses. These quadratic patterns were accentuated by age and shown primarily in tau (extremely slow) and extremely fast (impulsive) responses. Conclusions. The pattern of early recovery followed by decline in executive control function is consistent with growing evidence that moderate-severe TBI is a progressive and degenerative disorder. Given the responsiveness to treatment of executive control deficits, elucidating the trajectory and underpinnings of inconsistent behavioral responding may reveal novel prognostic and clinical management opportunities.

Feasibility of online self-administered cognitive training in moderate–severe brain injury

Abstract Purpose: Cognitive environmental enrichment (C-EE) offers promise for offsetting neural decline that is observed in chronic moderate–severe traumatic brain injury (TBI). Brain games are a delivery modality for C-EE that can be self-administered over the Internet without therapist oversight. To date, only one study has examined the feasibility of self-administered brain games in TBI, and the study focused predominantly on mild TBI. Therefore, the primary purpose of the current study was to examine the feasibility of self-administered brain games in moderate–severe TBI. A secondary and related purpose was to examine the feasibility of remote monitoring of any C-EE-induced adverse symptoms with a self-administered evaluation tool. Method: Ten patients with moderate–severe TBI were asked to complete 12 weeks (60 min/day, five days/week) of online brain games with bi-weekly self-evaluation, intended to measure any adverse consequences of cognitive training (e.g., fatigue, eye strain). Results: There was modest weekly adherence (42.6% ± 4.4%, averaged across patients and weeks) and 70% patient retention; of the seven retained patients, six completed the self-evaluation questionnaire at least once/week for each week of the study. Conclusions: Even patients with moderate–severe TBI can complete a demanding, online C-EE intervention and a self-administered symptom evaluation tool with limited therapist oversight, though at daily rate closer to 30 than 60 min per day. Further self-administered C-EE research is underway in our lab, with more extensive environmental support. Implications for Rehabilitation Online brain games (which may serve as a rehabilitation paradigm that can help offset the neurodegeneration observed in chronic TBI) can be feasibly self-administered by moderate-to-severe TBI patients. Brain games are a promising therapy modality, as they can be accessed by all moderate-to-severe TBI patients irrespective of geographic location, clinic and/or therapist availability, or impairments that limit mobility and access to rehabilitation services. Future efficacy trials that examine the effect of brain games for offsetting neurodegeneration in moderate-to-severe TBI patients are warranted.