Study adherence in a tDCS longitudinal clinical trial with people with spinal cord injury

Study design Secondary analysis of a clinical trial.Objectives To analyze adherence to 1-year transcranial Direct Current Stimulation (tDCS) clinical trial in people with chronic pain due to spinal cord injury (SCI). We also explore the association between dropout and several baseline variables such as age, depression levels, pain severity, number of days with pain in the last 7 days, walking ability, sleep, work, relationship with others, and enjoyment with life.Setting Boston, USA.Methods Forty-six participants were enrolled in this trial, and 33 participants were randomized to receive either active or sham tDCS.Results Using the full intention-to-treat (ITT) criteria, only 8 participants (24%) finished the study. The median time to dropout was seven (IQR:6,19) sessions (i.e., immediately after the first follow-up), regardless of the type of stimulation that participants received (active vs. sham tDCS) (chi(2) = 0.025, p = 0.875). An exploratory analysis suggested that only the number of days with pain in the last 7 days was moderately associated with dropout, with people experiencing less pain being more prone to dropout from the study.Conclusions Despite all the measures to improve study adherence (such as providing parking, flexibility to schedule sessions, follow-up with participants by phone), it seems that long follow-up periods may increase the likelihood of dropout. Given the need to understand long-term effects of interventions, longitudinal trials need to consider alternative designs or methods of treatment (for instance home treatment or home assessment) to decrease attrition rate.This project was supported by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant numbers H133N110010 and 90SI5021-01-00). SC and JL are supported by the Portuguese Foundation for Science and Technology PTDC/MHC-PCN/3950/2014; SC is also funded by the following FCT grant IF/00091/2015

Increased Gray Matter Diffusion Anisotropy in Patients with Persistent Post-Concussive Symptoms following Mild Traumatic Brain Injury

A significant percentage of individuals diagnosed with mild traumatic brain injury (mTBI) experience persistent post-concussive symptoms (PPCS). Little is known about the pathology of these symptoms and there is often no radiological evidence based on conventional clinical imaging. We aimed to utilize methods to evaluate microstructural tissue changes and to determine whether or not a link with PPCS was present. A novel analysis method was developed to identify abnormalities in high-resolution diffusion tensor imaging (DTI) when the location of brain injury is heterogeneous across subjects. A normative atlas with 145 brain regions of interest (ROI) was built from 47 normal controls. Comparing each subject’s diffusion measures to the atlas generated subject-specific profiles of injury. Abnormal ROIs were defined by absolute z-score values above a given threshold. The method was applied to 11 PPCS patients following mTBI and 11 matched controls. Z-score information for each individual was summarized with two location-independent measures: “load” (number of abnormal regions) and “severity” (largest absolute z-score). Group differences were then computed using Wilcoxon rank sum tests. Results showed statistically significantly higher load (p = 0.018) and severity (p = 0.006) for fractional anisotropy (FA) in patients compared with controls. Subject-specific profiles of injury evinced abnormally high FA regions in gray matter (30 occurrences over 11 patients), and abnormally low FA in white matter (3 occurrences over 11 subjects). Subject-specific profiles provide important information regarding the pathology associated with PPCS. Increased gray matter (GM) anisotropy is a novel in-vivo finding, which is consistent with an animal model of brain trauma that associates increased FA in GM with pathologies such as gliosis. In addition, the individualized analysis shows promise for enhancing the clinical care of PPCS patients as it could play a role in the diagnosis of brain injury not revealed using conventional imaging

Multiple prior concussions are associated with symptoms in high school athletes

Objectives: The purpose of this study was to evaluate the association of prior concussion on baseline computerized neurocognitive testing in a large cohort of high school athletes. Methods: This is a retrospective cohort study of student athletes from 49 Maine High Schools in 2010 who underwent baseline computerized neurocognitive evaluation with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®). As part of the ImPACT®, subjects reported a prior history of concussion as well as demographic information and a symptom questionnaire. We used linear regression to evaluate the association of prior concussion with baseline: (1) ImPACT® composite scores; and (2) symptom scores. Results: Six thousand seventy-five subjects were included in the study, of whom 57% were boys. The majority of student athletes (85.3%) reported no prior history of concussion while 4.6% reported having sustained two or more prior concussions. On simple linear regression, increasing number of concussions was related to worse performance in verbal memory (P = 0.039) and greater symptoms scores (P < 0.001). On multivariate modeling, only the association with baseline symptoms remained (P < 0.001). Other factors associated with baseline symptom reporting in the multivariate model included mental health history, headache/migraine history, gender, developmental and/or learning problems, and number of prior concussions. Interpretation In this large-scale, retrospective survey study, history of multiple prior concussions was associated with higher symptom burden but not baseline computerized neurocognitive testing. The association between baseline symptom reporting and clinical and demographic factors was greater than the association with a history of multiple concussions

Feasibility of remotely-supervised tDCS in a person with neuropathic pain due to spinal cord injury

[Excerpt] Nearly 40% of people with spinal cord injury (SCI) report neuropathic pain that is often refractory to medications.1,2 Substantial research has shown that anodal transcranial direct current stimulation (tDCS) over the motor cortex can induce clinically significant pain relief in chronic pain.3–6 However, these clinical trials often require multiple study visits per trial and are associated to poor adherence to the study protocol. For instance, in our recent tDCS study in SCI, only 7 participants from the initial 46 that were enrolled completed the study.7 In fact, despite all attempts to improve adherence, such as flexibility to schedule sessions, free parking and follow-ups by the phone, most participants ended up dropping out from the study. Since many people with SCI have limited mobility, alternatives for home-based care are needed. Here we report the feasibility of supervised home-based tDCS application in a 57-year old woman with tetraplegia and sublesional neuropathic pain secondary to SCI since 2012. At time of enrollment, she self-reported pain as being 9 out of 10 in a visual analogue scale. [...]This project was supported by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant numbers 90DP0035 and H133N110010)

Duration of Posttraumatic Amnesia Predicts Neuropsychological and Global Outcome in Complicated Mild Traumatic Brain Injury.

OBJECTIVES: Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI). PARTICIPANTS: A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 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, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury. RESULTS: Despite all having a Glasgow Coma Scale Score of 13 to 15, a quarter of the sample had a PTA duration of greater than 7 days; half had PTA duration of 1 of 7 days. Both cognitive performance and Extended Glasgow Outcome Scale outcomes were strongly associated with time since injury and PTA duration, with those with PTA duration of greater than 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 computed tomographic criteria and use of severity indices beyond Glasgow Coma Scale to characterize cmTBI

Examining Criteria for Defining Persistent Post-Concussion Symptoms in Children and Adolescents

Researchers operationalize persistent post-concussion symptoms in children and adolescents using varied definitions. Many pre-existing conditions, personal characteristics, and current health issues can affect symptom endorsement rates in the absence of, or in combination with, a recent concussion, and the use of varied definitions can lead to differences in conclusions about persistent symptoms and recovery across studies. This study examined how endorsement rates varied by 14 different operational definitions of persistent post-concussion symptoms for uninjured boys and girls with and without pre-existing or current health problems. This cross-sectional study included a large sample (age range: 11–18) of girls (n = 21,923) and boys (n = 26,556) without a recent concussion who completed the Post-Concussion Symptom Scale at preseason baseline. Endorsements rates varied substantially by definition, health history, and current health issues. The most lenient definition (i.e., a single mild symptom) was endorsed by most participants (54.5% of boys/65.3% of girls). A large portion of participants with pre-existing mental health problems (42.7% of boys/51.5% of girls), current moderate psychological distress (70.9% of boys/72.4% of girls), and insufficient sleep prior to testing (33.4% of boys/47.6% of girls) endorsed symptoms consistent with mild ICD-10 postconcussional syndrome; whereas participants with no current or prior health problems rarely met this definition (1.6% of boys/1.6% of girls). The results illustrate the tremendous variability in the case definitions of persistent symptoms and the importance of harmonizing definitions across future studies

Disorders of Consciousness due to Traumatic Brain Injury: Functional Status Ten Years Post-Injury

Few studies have assessed the long-term functional outcomes of patients with a disorder of consciousness due to traumatic brain injury (TBI). This study examined functional status during the first 10 years after TBI among a cohort with disorders of consciousness (i.e., coma, vegetative state, minimally conscious state). The study sample included 110 individuals with TBI who were unable to follow commands prior to inpatient rehabilitation and for whom follow-up data were available at 1, 2, 5, and 10 years post-injury. The sample was subdivided into those who demonstrated command-following early (before 28 days post-injury) versus late (≥ 28 days post-injury or never). Functional Independence Measure (FIM) at 1, 2, 5, and 10 years following TBI was used to measure functional outcomes. Measureable functional recovery occurred throughout the 10-year period, with more than two thirds of the sample achieving independence in mobility and self-care, and about one quarter achieving independent cognitive function by 10 years. Following commands prior to 28 days was associated with greater functional independence at all outcome time-points. Multi-trajectory modeling of recovery of three FIM subscales (self-care, mobility, cognition) revealed four distinct prognostic groups with different temporal patterns of change on these subscales. More than half the sample achieved near-maximal recovery by 1 year post-injury, while the later command-following subgroups recovered over longer periods of time. Significant late functional decline was not observed in this cohort. Among a cohort of patients unable to follow commands at the time of inpatient rehabilitation, a substantial proportion achieved functional independence in self-care, mobility, and cognition. The proportion of participants achieving functional independence increased between 5 and 10 years post-injury. These findings suggest that individuals with disorders of consciousness may benefit from ongoing functional monitoring and updated care plans for at least the first decade after TBI

Amantadine Did Not Positively Impact Cognition in Chronic Traumatic Brain Injury: A Multi-Site, Randomized, Controlled Trial

Despite limited evidence to support the use of amantadine to enhance cognitive function after traumatic brain injury (TBI), the clinical use for this purpose is highly prevalent and is often based on inferred belief systems. The aim of this study was to assess effect of amantadine on cognition among individuals with a history of TBI and behavioral disturbance using a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine 100 mg twice-daily versus placebo for 60 days. Included in the study were 119 individuals with two or more neuropsychological measures greater than 1 standard deviation below normative means from a larger study of 168 individuals with chronic TBI (>6 months post-injury) and irritability. Cognitive function was measured at treatment days 0, 28, and 60 with a battery of neuropsychological tests. Composite indices were generated: General Cognitive Index (included all measures), a Learning Memory Index (learning/memory measures), and Attention/Processing Speed Index (attention and executive function measures). Repeated-measures analysis of variance revealed statistically significant between-group differences favoring the placebo group at day 28 for General Cognitive Index (p = 0.002) and Learning Memory Index (p = 0.001), but not Attention/Processing Speed Index (p = 0.25), whereas no statistically significant between-group differences were found at day 60. There were no statistically significant between-group differences on adverse events. Cognitive function in individuals with chronic TBI is not improved by amantadine 100 mg twice-daily. In the first 28 days of use, amantadine may impede cognitive processing. However, the effect size was small and mean scores for both groups were generally within expectations for persons with history of complicated mild-to-severe TBI, suggesting that changes observed across assessments may not have functional significance. The use of amantadine to enhance cognitive function is not supported by these findings

Multisystem afflictions in former National Football League players

Background: The long-term health consequences of participation in American style football (ASF) are not well understood. Methods: We conducted a retrospective cohort study of men who had played in the NFL after 1960. Participants were studied using a standardized self-administered questionnaire designed to determine both the exposure history to ASF and the prevalence of chronic pain, sleep apnea, cardiometabolic disease, and neurocognitive impairment. Logistic regression and negative binomial regression models were used to assess associations between age, ethnicity, body-mass index during professional football career, field position, and football career duration with individual and multiple afflictions. Results: In this cohort of former NFL players (n = 3745), approximately one quarter of the eligible former players (27%) reported two or more medical afflictions (chronic pain, cardiometabolic disease, sleep apnea, or neurocognitive impairment). Career duration was significantly associated with an increase in the number of comorbidities. Age, race, and body-mass index were associated with all affliction categories, other than neurocognitive impairment, which was similarly prevalent in middle-aged players and older players. Earlier age when first playing the sport was protective against cardiometabolic affliction. Conclusions: Former NFL players report significant combinations of cross-system afflictions. Future work will be required to determine mechanistic underpinnings. However, attention to the whole player, rather than specific organ systems seems critical to improve long-term health outcomes in former ASF professional athletes