Phase II Randomized Controlled Trial of Constraint-Induced Movement Therapy in Multiple Sclerosis. Part 1: Effects on Real-World Function.

BACKGROUND: Constraint-Induced Movement therapy (CIMT) has controlled evidence of efficacy for improving real-world paretic limb use in non-progressive physically disabling disorders (stroke, cerebral palsy). OBJECTIVE: This study sought to determine whether this therapy can produce comparable results with a progressive disorder such as multiple sclerosis (MS). We conducted a preliminary phase II randomized controlled trial of CIMT versus a program of complementary and alternative medicine (CAM) treatments for persons with MS, to evaluate their effect on real-world disability. METHODS: Twenty adults with hemiparetic MS underwent 35 hours of either CIMT or CAM over 10 consecutive weekdays. The primary clinical outcome was change from pretreatment on the Motor Activity Log (MAL). RESULTS: The CIMT group improved more on the MAL (2.7 points, 95% confidence interval 2.2-3.2) than did the CAM group (0.5 points, 95% confidence interval -0.1 to 1.1; P < .001). These results did not change at 1-year follow-up, indicating long-term retention of functional benefit for CIMT. The treatments were well tolerated and without adverse events. CONCLUSION: These results suggest that CIMT can increase real-world use of the more-affected arm in patients with MS for at least 1 year. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01081275.

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).

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.

A telerehabilitation approach to delivery of constraint-induced movement therapy.

We have developed a device called AutoCITE (Automated Constraint-Induced Therapy Extension) that automates the intensive training component of constraint-induced (CI) movement therapy, also known as CI therapy. This study evaluated the effectiveness of AutoCITE training in a telerehabilitation setting when supervised remotely and with only intermittent interaction with a therapist. Seven participants with chronic stroke trained with AutoCITE for 3 h/d for 10 consecutive weekdays. The therapist supervised the training from a different room in the clinic using remote control of the AutoCITE computer and teleconferencing equipment when needed. Treatment gains on the Motor Activity Log were quite large (p < 0.001, d' = 3), while gains on the Wolf Motor Function Test and the Jebsen-Taylor Hand Function Test were large (p < 0.05, d' > 0.9). Gains were comparable in size with those previously reported for participants who received equal intensities of directly supervised AutoCITE training or standard one-on-one CI therapy without the device.

AutoCITE: automated delivery of CI therapy with reduced effort by therapists.

BACKGROUND AND PURPOSE: To evaluate the effectiveness of a device that automates Constraint-Induced Movement therapy (CI therapy), termed AutoCITE, when only partially supervised by therapists. METHODS: Twenty-seven participants with chronic stroke trained with AutoCITE for 3 hours per day for 10 consecutive weekdays. Participants were assigned to 1 of 3 groups in a fixed irregular order (ie, in alternating blocks): supervision from a therapist for 100%, 50%, or 25% of training time. RESULTS: The effect sizes of the treatment gains for the 3 groups on the Motor Activity Log (MAL) were very large and for the Wolf Motor Function Test they were large (all P<0.001) but were not significantly different from one another. Gains were comparable to those previously reported for participants who received an equal amount of standard one-on-one CI therapy without the device. At 1-month and long-term follow-up, gains from pretreatment on the MAL were also significant (P<0.001). CONCLUSIONS: These results demonstrate that AutoCITE training with greatly reduced supervision from a therapist is as effective as standard one-on-one CI therapy.