Protocol for a Randomized Controlled Trial of CI Therapy for Rehabilitation of Upper Extremity Motor Deficit: The Bringing Rehabilitation to American Veterans Everywhere Project.

Constraint-induced movement therapy (CI therapy) has been shown to reduce disability for individuals with upper extremity (UE) hemiparesis following different neurologic injuries. This article describes the study design and methodological considerations of the Bringing Rehabilitation to American Veterans Everywhere (BRAVE) Project, a randomized controlled trial of CI therapy to improve the motor deficit of participants with chronic and subacute traumatic brain injury. Our CI therapy protocol comprises 4 major components: (1) intensive training of the more-affected UE for target of 3 hour/day for 10 consecutive weekdays, (2) a behavioral technique termed shaping during training, (3) a "transfer package," 0.5 hour/day, of behavioral techniques to transfer therapeutic gains from the treatment setting to the life situation, and (4) prolonged restraint of use of the UE not being trained. The primary endpoint is posttreatment change on the Motor Activity Log, which assesses the use of the more-affected arm outside the laboratory in everyday life situations. Data from a number of secondary outcome measures are also being collected and can be categorized as physical, genomic, biologic, fitness, cognitive/behavioral, quality of life, and neuroimaging measures.

Comparison of reproducibility of single voxel spectroscopy and whole-brain magnetic resonance spectroscopy imaging at 3T.

To date, single voxel spectroscopy (SVS) is the most commonly used MRS technique. SVS is relatively easy to use and provides automated and immediate access to the resulting spectra. However, it is also limited in spatial coverage. A new and very promising MRS technique allows for whole-brain MR spectroscopic imaging (WB-MRSI) with much improved spatial resolution. Establishing the reproducibility of data obtained using SVS and WB-MRSI is an important first step for using these techniques to evaluate longitudinal changes in metabolite concentration. The purpose of this study was to assess and directly compare the reproducibility of metabolite quantification at 3T using SVS and WB-MRSI in 'hand-knob' areas of motor cortices and hippocampi in healthy volunteers. Ten healthy adults were scanned using both SVS and WB-MRSI on three occasions one week apart. N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) were quantified using SVS and WB-MRSI with reference to both Cr and H2 O. The reproducibility of each technique was evaluated using the coefficient of variation (CV), and the correspondence between the two techniques was assessed using Pearson correlation analysis. The measured mean (range) intra-subject CVs for SVS were 5.90 (2.65-10.66)% for metabolites (i.e. NAA, Cho, mI) relative to Cr, and 8.46 (4.21-21.07)% for metabolites (NAA, Cr, Cho, mI) relative to H2 O. The mean (range) CVs for WB-MRSI were 7.56 (2.78-11.41)% for metabolites relative to Cr, and 7.79 (4.57-14.11)% for metabolites relative to H2 O. Significant positive correlations were observed between metabolites quantified using SVS and WB-MRSI techniques when the Cr but not H2 O reference was used. The results demonstrate that reproducibilities of SVS and WB-MRSI are similar for quantifying the four major metabolites (NAA, Cr, Cho, mI); both SVS and WB-MRSI exhibited good reproducibility. Our findings add reference information for choosing the appropriate 1 H-MRS technique in future studies.

Improving sleep apnea treatment adherence after traumatic brain injury: A nonrandomized feasibility study.

PURPOSE/OBJECTIVE: To evaluate the feasibility of a psychological intervention designed to increase Positive Airway Pressure (PAP) adherence, adapted with cognitive accommodations for comorbid obstructive sleep apnea (OSA) and traumatic brain injury (TBI). RESEARCH METHOD/DESIGN: This was an open-label single arm (nonrandomized) study. Eligibility criteria were moderate-to-severe TBI, OSA diagnosis, prescribed PAP, nonadherent, and able to consent. Participants were recruited from inpatient and outpatient settings at a tertiary care hospital. The four-module manualized intervention was delivered primarily via telehealth. Feasibility aspects measured included eligibility, recruitment, and retention rates; session duration and attendance; and characteristics of outcome and process measures (e.g., completion rates, data distribution). Symptom measures included the Epworth Sleepiness Scale, Fatigue Severity Scale, Functional Outcomes of Sleep Questionnaire, Self-Efficacy Measure for Sleep Apnea, OSA Treatment Barriers Questionnaire (OTBQ), and Kim Alliance Scale-Revised. RESULTS: Of 230 persons screened, 14.3% were eligible. Recruitment rate (n = 17) was 51.5%. Retention rate (n = 13) was 76.5%. Treatment completers had no missing data. The OTBQ deviated from normality, but other measures had adequate skew (< 2.0) and kurtosis (< 7.0) and were free from significant floor and ceiling effects (<15%). Change score effect sizes were minimal to moderate (d = .10-.77). There were no adverse events. CONCLUSIONS/IMPLICATIONS: These results inform ways in which procedures should be modified to enhance the success of a future clinical trial testing the efficacy of this adherence intervention. Inclusion criteria should be reconsidered, and recruitment sites expanded, to capture eligible persons and adequately power an efficacy study. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Relation of white matter hyperintensities and motor deficits in chronic stroke.

BACKGROUND: Infarct size and location account for only a relatively small portion of post-stroke motor impairment, suggesting that other less obvious factors may be involved. OBJECTIVE: Examine the relationship between white matter hyperintensity (WMH) load among other factors and upper extremity motor deficit in patients with mild to moderate chronic stroke. METHODS: The magnetic resonance images of 28 patients were studied. WMH load was assessed as total WMH volume and WMH overlap with the corticospinal tract in the centrum semiovale. Hemiparetic arm function was measured using the Motor Activity Log (MAL) and Wolf Motor Function Test (WMFT). RESULTS: Hierarchical multiple regression models found WMH volume predicted motor deficits in both real-world arm use (MAL;ΔR2 = 0.12, F(1, 22) = 4.73, p = 0.04) and in arm motor capacity as measured by a laboratory motor function test (WMFT;ΔR2 = 0.18, F(1, 22) = 6.32, p = 0.02) over and above age and lesion characteristics. However, these models accounted for less than half of the variance in post-stroke motor deficits. CONCLUSION: The results suggest that WMH may be an important factor to consider in stroke-related upper extremity motor impairment. Nonetheless, the basis of the largest part of the post-stroke motor deficit remains unaccounted for by structural CNS factors. This component may be behavioral or learned, involving learned nonuse.

Phase II Randomized Controlled Trial of Constraint-Induced Movement Therapy in Multiple Sclerosis. Part 2: Effect on White Matter Integrity.

BACKGROUND: Constraint-induced movement therapy (CIMT) is a method of physical rehabilitation that has demonstrated clinical efficacy in patients with chronic stroke, cerebral palsy, and multiple sclerosis (MS). OBJECTIVE: This pilot randomized controlled trial tested whether CIMT can also induce increases in white matter integrity in patients with MS. METHODS: Twenty adults with chronic hemiparetic MS were randomized to receive either CIMT or complementary and alternative medicine (CAM) treatment (reported in the first article of this pair). Structural white matter change was assessed by tract-based spatial statistics (TBSS); measures included fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: CIMT and CAM groups did not differ in pretreatment disability or expectancy to benefit. As noted in the companion paper, the motor activity log (MAL) improved more after CIMT than CAM ( P < .001); the within-group effect size for CIMT was 3.7 (large d' = 0.57), while for CAM it was just 0.7. Improvements in white matter integrity followed CIMT and were observed in the contralateral corpus callosum (FA, P < .05), ipsilateral superior occipital gyrus (AD, P < .05), ipsilateral superior temporal gyrus (FA, P < .05), and contralateral corticospinal tract (MD and RD, P < .05). CONCLUSION: CIMT produced a very large improvement in real-world limb use and induced white matter changes in patients with hemiparetic MS when compared with CAM. The findings suggest in preliminary fashion that the adverse changes in white matter integrity induced by MS might be reversed by CIMT. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT01081275).

Upper extremity motor training of a subject with initially motor complete chronic high tetraplegia using constraint-induced biofeedback therapy.

INTRODUCTION: The purpose of this case study was to determine if a subject with chronic high tetraplegia (C3 AIS A) could learn to use an initially paralyzed upper extremity on the basis of training procedures alone. CASE PRESENTATION: Initially, an AIS examination revealed no purposive movement below the neck other than minimal shoulder movement. Training was carried out weekly over 39 months. Training began based on electromyographic biofeedback; the electrical activity of a muscle (biceps or triceps) was displayed visually on a computer monitor and the subject was encouraged to progressively increase the magnitude of the response in small increments on a trial-by-trial basis (i.e., shaping). When small, overt movements began to appear; these were, in turn, shaped so that their excursion progressively increased. Training then progressed to enable lifting the arm with the aid of the counterweight of a Swedish Help Arm. Mean movement excursions in the best session were: internal rotation 52.5 cm; external rotation 26.9 cm; shoulder extension 22.1 cm; shoulder flexion 15.2 cm; pronation/supination 120°; extension of index finger (D2) 2.5 cm. Movements were initially saltatory, becoming smoother over time. With the Swedish Help Arm, the subject was able to lift her hand an average of 24.3 cm in the best session with 0.7 kg counterweight acting at the wrist (1.9 J of work). DISCUSSION: Results suggest in preliminary fashion the effectiveness of this approach for improving upper extremity function after motor complete high tetraplegia. Thus, future studies are warranted. Possible mechanisms are discussed.

Peripheral administration of D-cycloserine rescues memory consolidation following bacterial endotoxin exposure.

In the current study, the partial NMDA receptor agonist D-cycloserine (DCS) rescued memory consolidation following systemic bacterial endotoxin exposure. DCS failed, however, to restore hippocampal BDNF mRNA levels that were diminished following a systemic administration of LPS, and did not alter NR1 or NR2C NMDA receptor subunit expression. These results extend prior research into the role of DCS in neural-immune interactions, and indicate that the detrimental effects of peripheral LPS administration on consolidation of contextual fear memory may be ameliorated with DCS treatment, though the mechanisms underlying these effects are currently unclear.