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Tong Chao Geng,1 Victor W Mark2 1Department of Neurology, Yuquan Hospital of Tsinghua University, Beijing, People's Republic of China; 2Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: With the chronic progress of the disease, the majority of patients with multiple sclerosis will eventually become severely disabled and unable to live independently. Neurorestorative strategies, including cell therapy and neuromodulation, combined with neurorehabilitation, have shown encouraging signs that may benefit multiple sclerosis patients. This review indicates current progress in this area. Keywords: demyelinating disease, immunosuppression, cell therapy, neuromodulation, neurorehabilitation

Objective: To evaluate in a preliminary fashion whether several standard cognitive assessments predict treatment outcomes on real-world functional activities following Constraint-Induced Movement therapy (CI therapy) for either the upper extremity (UE) or the lower extremity (LE) for chronic stroke hemiparesis in the outpatient therapy clinic. Methods: 15 UE and 14 LE patients in the clinic underwent a short battery of cognitive assessments that evaluated sustained attention, episodic memory, executive control abilities, and general cognitive function. Spearman correlation analysis was used to evaluate whether each cognitive test predicted treatment outcome on the limb-specific Motor Activity Log (MAL). Results: Two assessments (delayed verbal memory and Trail Making Test form B) significantly correlated with LE MAL change that followed therapy. Conclusions: We tentatively conclude from this exploratory and preliminary study that cognitive performance may predict treatment changes in response to CI therapy for the LE. Moderate to large correlations that we observed between other cognitive assessments and CI therapy outcomes recommend replicating this study with a larger and more cognitively diverse sample of stroke patients to learn if these findings are generalizable. [ABSTRACT FROM AUTHOR]

Constraint-Induced Movement therapy (CI therapy) is a recognized rehabilitation approach for persons having stroke with mild to moderately severe motor upper extremity deficits. To date, no rehabilitation treatment protocol has been proven effective that addresses both motor performance and spontaneous upper extremity use in the life situation for chronic stroke participants having severe upper extremity impairment with no active finger extension or thumb abduction. This case report describes treatment of a chronic stroke participant with a plegic hand using a CI therapy protocol that combines CI therapy with selected occupational and physical therapy techniques. Treatment consisted of six sessions of adaptive equipment and upper extremity orthotics training followed by a three-week, six-hour daily intervention of CI therapy plus neurodevelopmental treatment. Outcome measures included the Motor Activity Log for very low functioning patients (Grade 5 MAL), upper extremity portion of the Fugl-Meyer Motor Assessment, Graded Wolf Motor Function Test - for very low functioning patients (gWMFT- Grade 5), and Modified Ashworth Scale. The participant showed improvement on each outcome measure with the largest improvement on the Grade 5 MAL. In follow-up, the participant had good retention of his gains in motor performance and use of his more affected arm for real world activities after 3 months; after a one-week brush-up at 3 months, and at one year post-treatment. [ABSTRACT FROM AUTHOR]

The great prevalence of traumatic brain injury (TBI) and its high economic costs make reducing TBI-related disability a national health care priority. In our research laboratory, CI therapy has been found to significantly improve upper extremity function for persons with chronic TBI. The results have suggested that persons with TBI are less likely to adhere to critical components of the CI therapy protocol than participants with stroke in other studies. Treatment outcomes have also been more variable. Our findings suggest that some cognitive skills appear related to treatment outcome. In addition, cognitive and behavioral deficits, commonly seen with participants with TBI, challenge the delivery of the standard CI therapy protocol with some persons. We discuss the implications of these neuropsychological factors for CI therapy used for chronic TBI and propose further research to more thoroughly investigate these issues. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Functional neurological disorder, or FND, is widely misunderstood, particularly when considering recent research indicating that the illness has numerous biological markers in addition to its psychiatric disorder associations. Nonetheless, the long-held view that FND is a mental illness without a biological basis, or even a contrived (malingered) illness, remains pervasive both in current medical care and general society. This is because FND involves intermittent disability that rapidly and involuntarily alternates with improved neurological control. This has in turn caused shaming, perceived low self-efficacy, and social isolation for the patients. Until now, biomarker reviews for FND tended not to examine the features that are shared with canonical neurological disorders. This review, in contrast, examines current research on FND biomarkers, and in particular their overlap with canonical neurological disorders, along with the encouraging outcomes for numerous physical rehabilitation trials for FND. These findings support the perspective endorsed here that FND is unquestionably a neurological disorder that is also associated with many biological markers that lie outside of the central nervous system. These results suggest that FND entails multiple biological abnormalities that are widely distributed in the body. General healthcare providers would benefit their care for their patients through their improved understanding of the illness and recourses for support and treatment that are provided in this review.

Purpose: Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study's objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae., Design: Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a) ≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed., Results: Fourteen completed Immediate-CICT ( n =7) or TAU ( n =7); two withdrew from TAU before their second testing session. Completers were [ M (S D )]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance ( M =3.7 points, p<.001, d =2.6) and brain fog ( M =-4 points, p<.001, d =-2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did, p =.048., Conclusions: CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group.

Background: Neuropathic pain following spinal cord injury (SCI) affects approximately 60% of individuals with SCI. Effective pharmacological and non-pharmacological treatments remain elusive. We recently demonstrated that our immersive virtual reality walking intervention (VRWalk) may be effective for SCI NP. Additionally, we found that SCI NP may result from a decrease in thalamic γ-aminobutyric-acid (GABA), which disturbs central sensorimotor processing., Objective: While we identified GABAergic changes associated with SCI NP, a critical outstanding question is whether a decrease in SCI NP generated by our VRWalk intervention causes GABA content to rise., Method: A subset of participants ( n = 7) of our VRWalk trial underwent magnetic resonance spectroscopy pre- and post-VRWalk intervention to determine if the decrease in SCI NP is associated with an increase in thalamic GABA., Results: The findings revealed a significant increase in thalamic GABA content from pre- to post-VRWalk treatment., Conclusion: While the current findings are preliminary and should be interpreted with caution, pre- to post-VRWalk reductions in SCI NP may be mediated by pre- to post-treatment increases in thalamic GABA by targeting and normalizing maladaptive sensorimotor cortex reorganization. Understanding the underlying mechanisms of pain recovery can serve to validate the efficacy of home-based VR walking treatment as a means of managing pain following SCI. Neuromodulatory interventions aimed at increasing thalamic inhibitory function may provide more effective pain relief than currently available treatments.

Background: The term "functional neurological disorder," or "FND," applies to disorders whose occurrence of neurological symptoms fluctuate with the patient's attention to them. However, many other disorders that are not called "FND" nonetheless can also follow this pattern. Consequently, guidelines are unclear for diagnosing "FND.", Objective: To review the neurological conditions that follow this pattern, but which have not so far been termed "FND," to understand their overlap with conditions that have been termed "FND," and to discuss the rationale for why FND has not been diagnosed for them., Method: A systematic review of the PubMed literature registry using the terms "fluctuation," "inconsistency," or "attention" did not yield much in the way of these candidate disorders. Consequently, this review instead relied on the author's personal library of peer-reviewed studies of disorders that have resembled FND but which were not termed this way, due to his longstanding interest in this problem. Consequently, this approach was not systematic and was subjective regarding disease inclusion., Results: This review identified numerous, diverse conditions that generally involve fluctuating neurological symptoms that can vary with the person's attention to them, but which have not been called "FND." The literature was unclear for reasons for not referring to "FND" in these instances., Conclusion: Most likely because of historical biases, the use of the term "FND" has been unnecessarily restricted. Because at its core FND is an attentionally-influenced disorder that can respond well to behavioral treatments, the field of neurological rehabilitation could benefit by extending the range of conditions that could be considered as "FND" and referred for similar behavioral treatments. Because the term "FND" has been viewed unfavorably by some patients and clinical practitioners and whose treatment is not implied, the alternative term attentionally-modifiable disorder is proposed.

Background: Functional movement disorders (FMDs) are a common cause of disability. With an increasing research interest in FMD, including the emergence of intervention trials, it is crucial that research methodology be examined, and standardized protocols be developed., Objective: To characterize the current inclusion criteria used to select patients for FMD research studies and review the consistency and appropriateness of these criteria., Methods: We identified studies of potential biomarkers for FMD that were published over the last two decades and performed a qualitative analysis on the finally included studies., Results: We identified 79 articles and found inconsistent inclusion criteria. The Fahn-Williams and DSM-IV criteria were the most commonly applied, but neither accounted for the majority (Fahn-Williams 46%, DSM-IV 32% of the total). The selection of the inclusion criteria depended in part on the phenotype of FMD under investigation. We also identified inclusion methodologies that were not appropriate, such as the inclusion of low-certainty diagnoses and diagnosing by excluding specific biomarkers rather than including patients based on clinical characteristics that commonly are thought to suggest FMD., Conclusions: Significant variability exists with the inclusion criteria for FMD research studies. This variability could limit reproducibility and the appropriate aggregation of data for meta-analysis. Advancing FMD rehabilitation research will need standardized inclusion criteria. We make some suggestions.

Three studies that used experimental manipulations of stimulus context and correlational analyses were conducted to examine how contextual effects influence magnitude estimation and the crossover effect on line bisection. Previous work had shown that although orienting attention to one end of a line prior to bisection determines the direction in which crossover occurs, bias in magnitude estimation actually produces the crossover effect. The influence of contextual effects on magnitude estimation, however, was not examined in these previous models of crossover. Consequently, the purpose of the present investigation was to examine these effects. Subjects in the current studies were healthy controls and people who had right and left hemisphere injury due to stroke, both with and without spatial neglect. Study 1 examined the crossover effect for lines bisected with and without a stimulus context. Study 2 examined both stimulus order as well as response order context effects on magnitude estimation. Study 3 examined how much variance in magnitude estimation was accounted for by stimulus contextual effects and how stimulus context influenced the crossover effect. The results showed that contextual bias was ubiquitous but relatively small in the magnitude estimates of normal subjects. Contextual bias was exaggerated to a similar degree in subjects with right or left hemisphere injury due to stroke, but the amount of variance accounted by contextual bias was still quite small. A novel finding of study 2 was that contextual effects can be induced by previous responses to stimuli as well as by the magnitude of preceding stimuli in subjects with unilateral brain injury. This may be a contextual effect related to response perseveration. Finally, studies 1 and 3 indicated that contextual effects strengthened the crossover effect on line bisection, primarily on relatively short lines. Contextual effects, however, cannot fully account for the crossover effect, because crossover bisections were observed also in the absence of a stimulus context. It is concluded that the crossover effect is explained by biases in attentional orientation and magnitude estimation. Contextual effects represent one source of bias in magnitude estimation that influences the crossover effect by promoting contralateral errors on short line lengths (<2 cm)., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare.

Objective: To assess the personal perspectives of persons with multiple sclerosis (MS) on the acceptability of a novel physical therapy program that is designed to transfer gains from the clinic to their real-world lower extremity (LE) use, termed LE constraint-induced therapy (CIT). The program includes several behavior change techniques (prescribed home exercises, daily structured therapist interviews and problem solving for LE activities, keeping an activity diary) and a concentrated physical treatment schedule., Design: Anonymous internet survey., Setting: Participants accessed the survey from computers in the community., Participants: Five hundred adults (N=500) were recruited from an MS support organization's registry for having indicated from mild to total limb spasticity because they were anticipated to have markedly impaired LE use in the community., Interventions: Not applicable., Main Outcome Measures: Participants were offered the options on a nonnumerical Likert scale of "Very likely," "Likely," "Neutral," "Unlikely," or "Very unlikely" to indicate their personal acceptability for each of 5 different key treatment procedures after these were explained. Totals for each option within each key procedure were analyzed for their acceptability., Results: Of the 281 persons who responded, 90% expressed interest in participating in LE CIT. A large majority of persons who completed the survey selected either "Very likely" or "Likely" for each key procedure (median=88%, range=65%-90%, P <.01). This indicated strong acceptance for the procedures of LE CIT. In addition, more respondents who already had had previous physical therapy accepted LE CIT than did respondents who had not had physical therapy ( P <.01)., Conclusions: The results suggest there is strong acceptance of CIT for mobility with preliminary evidence of benefiting community LE use for persons with MS. The results support further clinical trials of LE CIT for persons with MS., (© 2021 The Authors.)

BACKGROUND Research indicates intermittent theta burst stimulation (iTBS) is a potential treatment of post-stroke aphasia. MATERIAL AND METHODS In this double-blind, sham-controlled trial (NCT01512264) participants were randomized to receive 3 weeks of sham (G₀), 1 week of iTBS/2 weeks of sham (G₁), 2 weeks of iTBS/1 week of sham (G₂), or 3 weeks of iTBS (G₃). FMRI localized residual language function in the left hemisphere; iTBS was applied to the maximum fMRI activation in the residual language cortex in the left frontal lobe. FMRI and aphasia testing were conducted pre-treatment, at ≤1 week after completing treatment, and at 3 months follow-up. RESULTS 27/36 participants completed the trial. We compared G0 to each of the individual treatment group and to all iTBS treatment groups combined (G₁₋₃). In individual groups, participants gained (of moderate or large effect sizes; some significant at P<0.05) on the Boston Naming Test (BNT), the Semantic Fluency Test (SFT), and the Aphasia Quotient of the Western Aphasia Battery-Revised (WAB-R AQ). In G₁₋₃, BNT, and SFT improved immediately after treatment, while the WAB-R AQ improved at 3 months. Compared to G₀, the other groups showed greater fMRI activation in both hemispheres and non-significant increases in language lateralization to the left hemisphere. Changes in IFG connectivity were noted with iTBS, showing differences between time-points, with some of them correlating with the behavioral measures. CONCLUSIONS The results of this pilot trial support the hypothesis that iTBS applied to the ipsilesional hemisphere can improve aphasia and result in cortical plasticity.

Objectives: To determine the test-retest reliability and validity of the Lower Extremity Motor Activity Log (LE-MAL) for assessing LE use in the community in adults with multiple sclerosis (MS)., Design: Prospective analysis of measures conducted by trained examiners., Setting: Participants were evaluated by telephone on several measures of LE use., Participants: Adults with MS (N=43)., Interventions: Not applicable., Main Outcome Measures: The LE-MAL has 3 subscales (Assistance, Functional Performance, and Confidence). It was administered twice, at least 2 weeks apart. The Multiple Sclerosis Walking Scale (MSWS-12), Patient Determined Disease Steps (PDDS), and Mobility Scale were only administered during the first call., Results: The test-retest reliability of the composite and the 3 subscale LE-MAL scores were high (intraclass correlation, >0.94). The composite and subscale LE-MAL scores were strongly correlated with the MSWS-12, PDDS, and Mobility Scale scores (r=-0.56 to -0.77; P<.001)., Conclusion: This initial study suggests that the LE-MAL reliably and validly measures LE use in the community in adults with MS., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Multiple sclerosis (MS) is a progressive neurological illness whose typically young adult onset results in a nearly entire lifetime of worsening disability. But despite being an unrelenting neurodegenerative disease, numerous clinical trials over the past 40 years for MS have vigorously attempted to improve or at least stabilize declining physical function. Although the vast majority of the studies assessed training effects only within controlled laboratory or clinic settings, in recent years a growing interest has emerged to test whether newer therapies can instead benefit real-life activities in the community. Nonetheless, comparatively little attention has been paid to whether the training gains can be retained for meaningful periods. This review discusses the comparative success of various physical training methods to benefit within-community activities in MS, and whether the gains can be retained long afterward. This review will suggest future research directions toward establishing efficacious treatments that can allow persons with MS to reclaim their physical abilities and maximize functionality for meaningful periods., Competing Interests: None., (Thieme. All rights reserved.)

Background: Although Constraint-Induced Movement therapy (CIMT) has been deemed efficacious for adults with persistent, mild-to-moderate, post-stroke upper-extremity hemiparesis, CIMT is not available on a widespread clinical basis. Impediments include its cost and travel to multiple therapy appointments. To overcome these barriers, we developed an automated, tele-health form of CIMT., Objective: Determine whether in-home, tele-health CIMT has outcomes as good as in-clinic, face-to-face CIMT in adults ≥1-year post-stroke with mild-to-moderate upper-extremity hemiparesis., Methods: Twenty-four stroke patients with chronic upper-arm extremity hemiparesis were randomly assigned to tele-health CIMT (Tele-AutoCITE) or in-lab CIMT. All received 35 hours of treatment. In the tele-health group, an automated, upper-extremity workstation with built-in sensors and video cameras was set-up in participants' homes. Internet-based audio-visual and data links permitted supervision of treatment by a trainer in the lab., Results: Ten patients in each group completed treatment. All twenty, on average, showed very large improvements immediately afterwards in everyday use of the more-affected arm (mean change on Motor Activity Log Arm Use scale = 2.5 points, p < 0.001, d' = 3.1). After one-year, a large improvement from baseline was still present (mean change = 1.8, p < 0.001, d' = 2). Post-treatment outcomes in the tele-health group were not inferior to those in the in-lab group. Neither were participants' perceptions of satisfaction with and difficulty of the interventions. Although everyday arm use was similar in the two groups after one-year (mean difference = -0.1, 95% CI = -1.3-1.0), reductions in the precision of the estimates of this parameter due to drop-out over follow-up did not permit ruling out that the tele-health group had an inferior long-term outcome., Conclusions: This proof-of-concept study suggests that Tele-AutoCITE produces immediate benefits that are equivalent to those after in-lab CIMT in stroke survivors with chronic upper-arm extremity hemiparesis. Cost savings possible with this tele-health approach remain to be evaluated.

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.

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 H 2 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 H 2 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 H 2 O. Significant positive correlations were observed between metabolites quantified using SVS and WB-MRSI techniques when the Cr but not H 2 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., (Copyright © 2018 John Wiley & Sons, Ltd.)

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).

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.

Purpose: The purpose of this feasibility study was to assess whether combined intermittent theta burst suppression (iTBS) applied to the ipsilesional hemisphere and modified constraint-induced aphasia therapy (mCIAT) are safe and logistically feasible within the time interval associated with iTBS induced long-term potentiation in patients with post-stroke aphasia. We also wanted to determine whether combining priming with iTBS and CIAT improves language functions after treatment., Methods: Twelve participants received fMRI (semantic decision/tone decision task) and neuropsychological testing of language skills at three time points - before starting the iTBS/mCIAT intervention (T1), immediately after completing 2-week long course of intervention (T2), and at 3-months follow-up (T3). ITBS was applied to the individually determined fMRI language "hot spot" located in the left fronto-temporal regions., Results: There were no serious adverse events, and all mCIAT group therapy sessions (3-4 subjects each) were initiated within 30 minutes of the first group subject receiving iTBS. Neuropsychological assessments of language showed a significant effect of session on Western Aphasia Battery aphasia quotient (WAB-AQ; p = 0.04) and spontaneously correct responses on Boston Naming Test (BNT; p = 0.002), with improvement noted at T2 (p = 0.002) and T3 (p = 0.05) versus T1. FMRI showed significant changes between all timepoints. Post-hoc correlations showed associations between improvements in WAB-AQ from T2 to T3 and decreased BOLD signal in left inferior parietal lobe, and improvements in BNT from T1 to T3 with decreased signal in right inferior frontal gyrus., Conclusion: This study shows feasibility and safety for combining behavioral and neurostimulation interventions for chronic post-stroke aphasia. Observed changes in linguistic measures were relatively small. However, they were statistically significant and associated with parallel changes observed in the neuroimaging. Our findings support further development and testing of the combined mCIAT and iTBS protocol and comparisons to either CIAT/mCIAT or iTBS applied alone for the treatment of post-stroke aphasia.

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.

Purpose: To evaluate the efficacy of an expanded form of Constraint-Induced Movement Therapy (eCIMT) that renders CIMT, originally designed for treating mild-to-moderate upper-extremity hemiparesis, suitable for treating severe hemiparesis., Methods: Twenty-one adults ≥1 year after stroke with severe upper-extremity hemiparesis (with little or no capacity to make movements with the more-affected hand) were randomly assigned to eCIMT (n = 10), a placebo-control procedure (n = 4), or usual care (n = 7). The participants who received usual care were crossed over to eCIMT four months after enrollment. The CIMT protocol was altered to include fitting of orthotics and adaptive equipment, selected neurodevelopmental techniques, and electromyography-triggered functional electrical stimulation. Treatment was given for 15 consecutive weekdays with 6 hours of therapy scheduled daily for the immediate eCIMT group and 3.5 hours daily for the cross-over eCIMT group., Results: At post-treatment, the immediate eCIMT group showed significant gains relative to the combination of the control groups on the Grade-4/5 Motor Activity Log (MAL; mean = 1.5 points, P < 0.001, f = 4.2) and a convergent measure, the Canadian Occupational Performance Measure (COPM; mean = 2.3, P = 0.014, f = 1.1; f values ≥0.4 are considered large, on the COPM changes ≥2 are considered clinically meaningful). At 1-year follow-up, the MAL gains in the immediate eCIMT group were only 13% less than at post-treatment. The short and long-term outcomes of the crossover eCIMT group were similar to those of the immediate eCIMT group., Conclusions: This small, randomized controlled trial (RCT) suggests that eCIMT produces a large, meaningful, and persistent improvement in everyday use of the more-affected arm in adults with severe upper-extremity hemiparesis long after stroke. These promising findings warrant confirmation by a large RCT.

Objective: Depressive symptoms after stroke have been associated with negative outcomes, including poorer functional ability, less efficient use of rehabilitation services, decreased quality of life, and increased mortality. It has been anecdotally noted that depressive symptoms do not limit motor recovery in patients who undergo Constraint-Induced Movement Therapy (CIMT), an efficacious intervention for chronic poststroke hemiparesis. Here we analyze depressive symptom and motor scores from 40 participants who received CIMT in 2 previously published studies., Method: Adults more than 1-year after stroke with mild to moderate upper-extremity hemiparesis completed the Zung Self-Rating Depression Scale and Motor Activity Log (MAL) before and after CIMT. We used regression analysis to test whether Zung scores predicted response to CIMT and paired t tests to test whether depressive symptoms changed from pre- to posttreatment., Results: Pretreatment Zung score did not predict outcome on the MAL Arm Use scale, ΔR2 (1, 30) = 0.004, p = .19, after controlling for pretreatment MAL scores. Additionally, participants had a small but statistically significant decrease in Zung score, t(39) = 3.0, p = .005, mean change = -3.6., Conclusion: These results suggest that depressive symptoms do not significantly limit motor recovery in patients treated with CIMT for chronic poststroke hemiparesis. Additionally, treatment with CIMT may improve depressive symptoms. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Purpose: The purpose of this article is to present the results of a study evaluating the psychometric properties of 2 new measures that exclusively assess the amount of real-world spoken language in patients with aphasia., Method: Forty individuals with aphasia were evaluated on several measures of spoken language in real-world settings. The Verbal Activity Log (VAL; Johnson et al., 2014) has participants, aided by caregivers, indicate current amount and quality of real-world spoken language compared with before stroke. In addition, digital voice recorders objectively measured the amount of real-world spoken language. The Communicative Effectiveness Index (Lomas et al., 1989), a previously validated measure of functional communication, was used as a comparison measure. Nineteen participants received follow-up assessment ≥ 3 weeks later., Results: Validity was supported by Pearson correlations between spoken language recordings and the VAL, r(38) = .70, p < .001. Likewise, correlation with the Communicative Effectiveness Index was strong, r(38) = .73, p < .001. Test-retest reliability for both VAL and audio recording was high, with intraclass correlations ≥ .96 and .90, respectively., Conclusions: These results present preliminary evidence for the reliability and validity of the VAL and spoken language recording for assessment of the amount of real-world spoken language in aphasia. As a simple patient-reported outcome, the VAL may assist diverse therapies for aphasia.

Most patients who have endured a stroke sustain behavioral changes, although in many instances these effects can be subtle. Although behavioral changes after a stroke tend to improve, they may persist and have serious effects on daily living activities. This article reviews the more familiar behavioral changes that follow stroke, as well as exotic, less often encountered manifestations. This article acquaints the clinician with the diversity of the behavioral effects of stroke, along with methods for their assessment and management., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We address here the question of whether the techniques of Constraint Induced (CI) therapy, a family of treatments that has been employed in the rehabilitation of movement and language after brain damage might apply to the rehabilitation of such visual deficits as unilateral spatial neglect and visual field deficits. CI therapy has been used successfully for the upper and lower extremities after chronic stroke, cerebral palsy (CP), multiple sclerosis (MS), other central nervous system (CNS) degenerative conditions, resection of motor areas of the brain, focal hand dystonia, and aphasia. Treatments making use of similar methods have proven efficacious for amblyopia. The CI therapy approach consists of four major components: intensive training, training by shaping, a "transfer package" to facilitate the transfer of gains from the treatment setting to everyday activities, and strong discouragement of compensatory strategies. CI therapy is said to be effective because it overcomes learned nonuse, a learned inhibition of movement that follows injury to the CNS. In addition, CI therapy produces substantial increases in the gray matter of motor areas on both sides of the brain. We propose here that these mechanisms are examples of more general processes: learned nonuse being considered parallel to sensory nonuse following damage to sensory areas of the brain, with both having in common diminished neural connections (DNCs) in the nervous system as an underlying mechanism. CI therapy would achieve its therapeutic effect by strengthening the DNCs. Use-dependent cortical reorganization is considered to be an example of the more general neuroplastic mechanism of brain structure repurposing. If the mechanisms involved in these broader categories are involved in each of the deficits being considered, then it may be the principles underlying efficacious treatment in each case may be similar. The lessons learned during CI therapy research might then prove useful for the treatment of visual deficits.

For the nineteenth and the better part of the twentieth centuries two correlative beliefs were strongly held by almost all neuroscientists and practitioners in the field of neurorehabilitation. The first was that after maturity the adult CNS was hardwired and fixed, and second that in the chronic phase after CNS injury no substantial recovery of function could take place no matter what intervention was employed. However, in the last part of the twentieth century evidence began to accumulate that neither belief was correct. First, in the 1960s and 1970s, in research with primates given a surgical abolition of somatic sensation from a single forelimb, which rendered the extremity useless, it was found that behavioral techniques could convert the limb into an extremity that could be used extensively. Beginning in the late 1980s, the techniques employed with deafferented monkeys were translated into a rehabilitation treatment, termed Constraint Induced Movement therapy or CI therapy, for substantially improving the motor deficit in humans of the upper and lower extremities in the chronic phase after stroke. CI therapy has been applied successfully to other types of damage to the CNS such as traumatic brain injury, cerebral palsy, multiple sclerosis, and spinal cord injury, and it has also been used to improve function in focal hand dystonia and for aphasia after stroke. As this work was proceeding, it was being shown during the 1980s and 1990s that sustained modulation of afferent input could alter the structure of the CNS and that this topographic reorganization could have relevance to the function of the individual. The alteration in these once fundamental beliefs has given rise to important recent developments in neuroscience and neurorehabilitation and holds promise for further increasing our understanding of CNS function and extending the boundaries of what is possible in neurorehabilitation.

Objective: To investigate the relationship of white matter integrity and path of the corticospinal tract (CST) on arm function before and after constraint-induced (CI) movement therapy in children with hemiparetic cerebral palsy (CP) and adults with chronic stroke., Design: Study 1 used a multiple-baseline pre-post design. Study 2 was a randomized controlled trial., Setting: Outpatient rehabilitation laboratory., Participants: Study 1 included children with hemiparetic CP (n=10; mean age ± SD, 3.2±1.7y). Study 2 included adults with chronic stroke (n=26; mean age ± SD, 65.4±13.6y) who received either CI therapy or a comparison therapy., Interventions: Children in study 1 received CI therapy for 3.5h/d for 15 consecutive weekdays. Adults in study 2 received either CI therapy or a comparison therapy for 3.5h/d for 10 consecutive weekdays., Main Outcome Measures: Diffusion tensor imaging was performed to quantify white matter integrity. Motor ability was assessed in children using the Pediatric Motor Activity Log-Revised and Pediatric Arm Function Test, and in adults with the Motor Activity Log and Wolf Motor Function Test., Results: Participants in both studies improved in real-world arm function and motor capacity. Children and adults with disrupted/displaced CSTs and children with reduced fractional anisotropy values were worse on pretreatment tests of motor function than participants with unaltered CSTs. However, neither integrity (fractional anisotropy) nor distorted or disrupted path of the CST affected motor improvement after treatment., Conclusions: Participants who had reduced integrity, displacement, or interruption of their CST performed worse on pretreatment motor testing. However, this had no effect on their ability to benefit from CI therapy. The results for children and adults are consistent with one another., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The initial version of Constraint-Induced Aphasia Therapy (CIAT I) consisted of a single exercise. This study sought to evaluate the feasibility for future trials of an expanded and restructured protocol designed to increase the efficacy of CIAT I., Method: The subjects were 4 native English speakers with chronic stroke who exhibited characteristics of moderate Broca's aphasia. Treatment was carried out for 3.5 hr/day for 15 consecutive weekdays. It consisted of 3 components: (a) intensive training by a behavioral method termed shaping using a number of expressive language exercises in addition to the single original language card game, (b) strong discouragement of attempts to use gesture or other nonverbal means of communication, and (c) a transfer package of behavioral techniques to promote transfer of treatment gains from the laboratory to real-life situations., Results: Participation in speech in the life situation improved significantly after treatment. The effect sizes (i.e., d') in this domain were ≥ 2.2; d' values ≥ 0.8 are considered large. Improvement in language ability on a laboratory test, the Western Aphasia Battery-Revised (Kertesz, 2006), did not achieve statistical significance, although the effect size was large--that is, 1.3 (13.1 points)., Conclusion: These pilot results suggest in preliminary fashion that CIAT II may produce significant improvements in everyday speech.

Purpose: The purpose of this study was to delineate the relationship between several types of T1-weighted MRI pathology and motor rehabilitation potential following Constraint Induced Movement therapy (CI therapy) in chronic stroke., Methods: Stepwise regression was employed (n = 80) to identify predictors of motor recovery (prior to therapy) and of response to Constraint-Induced Movement therapy [measured via the Wolf Motor Function Test (WMFT) and Motor Activity Log (MAL)] from among the following: age, side of motor deficit, chronicity, gender, lesion volume, peri-infarct damage volume, white matter hypointensity volume, ventricular asymmetry, and lesion location., Results: Although extent of total stroke damage weakly correlated with poorer performance on the WMFT prior to therapy, this relationship was mediated by the location of the damage. No metric of tissue damage examined here was associated with real-world arm use at baseline (MAL at pre-treatment) or with CI therapy-induced improvement in either best motor performance upon request (WMFT) or spontaneous arm use for daily activities (MAL)., Conclusions: In sum, the extent of brain tissue damage of any type examined here poorly predicted motor function and response to rehabilitation in chronic stroke.

Background and Purpose: Constraint-induced movement therapy is a set of treatments for rehabilitating motor function after central nervous system damage. We assessed the roles of its 2 main components., Methods: A 2 × 2 factorial components analysis with random assignment was conducted. The 2 factors were type of training and presence/absence of a set of techniques to facilitate transfer of therapeutic gains from the laboratory to the life situation (Transfer Package; TP). Participants (N=40) were outpatients ≥ 1-year after stroke with hemiparesis. The different treatments, which in each case targeted the more affected arm, lasted 3.5 hours/d for 10 weekdays. Spontaneous use of the more affected arm in daily life and maximum motor capacity of that arm in the laboratory were assessed with the Motor Activity Log and the Wolf Motor Function Test, respectively., Results: Use of the TP, regardless of the type of training received, resulted in Motor Activity Log gains that were 2.4 times as large as the gains in its absence (P<0.01). These clinical results parallel previously reported effects of the TP on neuroplastic change. Both the TP and training by shaping enhanced gains on the Wolf Motor Function Test (P<0.05). The Motor Activity Log gains were retained without loss 1 year after treatment. An additional substudy (N=10) showed that a single component of the TP, weekly telephone contact with participants for 1 month after treatment, doubled Motor Activity Log scores at 6-month follow-up., Conclusions: The TP is a method for enhancing both spontaneous use of a more affected arm after chronic stroke and its maximum motor capacity. Shaping enhances the latter.

Objective: To evaluate in a preliminary manner the feasibility, safety, and efficacy of Constraint-Induced Movement therapy (CIMT) of persons with impaired lower extremity use from multiple sclerosis (MS)., Design: Clinical trial with periodic follow-up for up to 4 years., Setting: University-based rehabilitation research laboratory., Participants: A referred sample of ambulatory adults with chronic MS (N=4) with at least moderate loss of lower extremity use (average item score ≤6.5/10 on the functional performance measure of the Lower Extremity Motor Activity Log [LE-MAL])., Interventions: CIMT was administered for 52.5 hours over 3 consecutive weeks (15 consecutive weekdays) to each patient., Main Outcome Measures: The primary outcome was the LE-MAL score at posttreatment. Secondary outcomes were posttreatment scores on laboratory assessments of maximal lower extremity movement ability., Results: All the patients improved substantially at posttreatment on the LE-MAL, with smaller improvements on the laboratory motor measures. Scores on the LE-MAL continued to improve for 6 months afterward. By 1 year, patients remained on average at posttreatment levels. At 4 years, half of the patients remained above pretreatment levels. There were no adverse events, and fatigue ratings were not significantly changed by the end of treatment., Conclusions: This initial trial of lower extremity CIMT for MS indicates that the treatment can be safely administered, is well tolerated, and produces substantially improved real-world lower extremity use for as long as 4 years afterward. Further trials are needed to determine the consistency of these findings., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the combination of Constraint-Induced Movement Therapy (CIMT) and conventional rehabilitation techniques can produce meaningful motor improvement in chronic stroke patients with initially fisted hands., Design: Case series., Setting: University hospital outpatient laboratory., Participants: Consecutive sample (N=6) >1 year poststroke with plegic hands., Interventions: Treatment consisted of an initial period of 3 weeks (phase A) when adaptive equipment in the home, orthotics, and splints were employed to improve ability to engage in activities of daily living. This was continued in phase B, when CIMT and selected neurodevelopmental treatment techniques were added., Main Outcome Measures: Motor Activity Log (MAL), accelerometry, Fugl-Meyer Motor Assessment (F-M)., Results: Patients exhibited a large improvement in spontaneous real-world use of the more-affected arm (mean lower-functioning MAL change=1.3±0.4 points; P<.001; d'=3.0) and a similar pattern of increase in an objective measure of real-world more-affected arm movement (mean change in ratio of more- to less-affected arm accelerometer recordings=0.12±0.1 points; P=.016; d'=1.2). A large improvement in motor status was also recorded (mean F-M change=5.3±3.3 points; P=.005; d'=1.6)., Conclusions: The findings of this pilot study suggest that stroke patients with plegic hands can benefit from CIMT combined with some conventional rehabilitation techniques, even long after brain injury. More research is warranted., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage., Methods: Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery., Results: Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy., Conclusions: Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Background and Purpose: Infarct volume and location have a weak relationship with motor deficit in patients with chronic stroke. Recent research has focused on the relationship between spared or seemingly "healthy" neural tissue and motor function. In this study we examined MRI scans of patients with chronic stroke to determine if characteristics of seemingly normal parenchyma could predict either response to different forms of upper extremity physical rehabilitation or to pre-treatment motor status., Methods: Individuals with chronic stroke (ages 60.6 ± 11.9 years) and mild/moderate upper extremity hemiparesis were administered either CI therapy (n = 14) or a comparison therapy (n = 29). The patients were assessed prior to and following therapy with MRI scans and the Wolf Motor Function Test (WMFT) Performance Time measure. Total voxels in combined grey matter (GM) and white matter (WM) segments (parenchymal volume) were divided by total voxels in GM, WM, and cerebrospinal fluid segments (intracranial volume) to obtain the brain parenchymal fraction (BPF)., Results: BPF correlated with treatment gains on the WMFT (r(43) = -0.31, p = 0.04). Significant correlations between pre-treatment motor function and BPF were not observed., Conclusions: Individuals with greater BPFs after stroke show larger arm function gains after CI therapy, suggesting that reductions in volume of normal-appearing tissue may relate to ability to benefit from rehabilitation therapy in chronic stroke.

This third chapter discusses the evidence for the rehabilitation of the most common movement disorders of the upper extremity. The authors also present a framework, building on the computation, anatomy, and physiology (CAP) model, for incorporating some of the principles discussed in the 2 previous chapters by Frey et al and Sathian et al in the practice of rehabilitation and for discussing potentially helpful interventions based on emergent neuroscience principles.

Objective: To establish feasibility for the hypothesis that patients in acute rehabilitation who are hospitalized for disorders not known to involve cerebral injury can have significant cognitive impairment., Design: A comparison of performances on neuropsychological tests between 2 samples of subjects: inpatients in an acute rehabilitation hospital without known cerebral disease and normal community-dwelling persons., Setting: Acute inpatient rehabilitation hospital., Patients and Participants: Nineteen hospitalized patients without delirium who were screened for pre-existing cerebral and psychiatric illness, dementia, and dependency in basic self-care skills before hospitalization. Eighteen community-dwelling persons who were not different in terms of age and education served as the control group., Methods: Participants completed 10 commonly used neuropsychological tests of executive, language, and memory functions. Data were analyzed by using multivariate analysis of variance., Main Outcome Measurements: Raw scores on the 10 neuropsychological tests., Results: Hospitalized patients performed significantly worse on 9 of 10 tests than community-dwelling participants. Older hospitalized participants had significantly greater cognitive impairment than younger hospitalized participants, which suggested increased susceptibility to effects of hospitalization on cognition., Conclusions: Patients hospitalized without brain injury, and especially elderly patients, should be carefully monitored for cognitive deficits that may affect posthospitalization quality of living. Further research is needed to determine whether the cognitive deficits in such patients persist after discharge and affect functional independence, and to identify mechanisms for the deficits. Furthermore, the use of hospitalized participants without brain injury as control subjects in neuropsychological studies of brain injury should be balanced with an additional comparison group of matched, neurologically healthy, normal subjects who live in the community to control for cognitive impairments that are associated with acute hospitalization., (Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate whether Constraint-Induced Movement therapy (CI therapy) may benefit chronic upper extremity hemiparesis in progressive multiple sclerosis (MS)., Methods: Five patients with progressive MS, who had chronic upper extremity hemiparesis and evidence for learned non-use of the paretic limb in the life situation, underwent 30 hours of repetitive task training and shaping for the paretic limb over 2-10 consecutive weeks, along with physical restraint of the less-affected arm and a "transfer package" of behavioral techniques to reinforce treatment adherence., Results: The patients showed significantly improved spontaneous, real-world limb use at post-treatment and 4 weeks post-treatment, along with improved fatigue ratings and maximal movement ability displayed in a laboratory motor test. Conclusions The findings suggest for the first time that slowly progressive MS may benefit from CI therapy. Further studies are needed to determine the retention of treatment responses.

Background and Purpose: Methods have not been well developed and tested to predict the extent of remote degeneration in the central nervous system that follows cerebral infarction. We hypothesized that the extent of infarction overlap with the cerebral hemispheric course of the corticospinal tract (CST) on structural MR imaging predicts the extent of ipsilateral cerebral peduncular atrophy in patients with chronic stroke., Materials and Methods: Hemiparetic patients (n = 34) with supratentorial unilateral infarctions who were at least 1 year poststroke onset and enrolled in research protocols of Constraint-Induced Movement therapy underwent volumetric T1 MR imaging of the brain. The following measures were calculated for each patient: 1) the maximal proportion of the CST in the cerebral hemisphere on axial section that was overlapped by infarction, 2) total infarction volume, and 3) the ratio of the cross-sectional area of the ipsilateral cerebral peduncle to the area of the contralateral cerebral peduncle (peduncular asymmetry ratio). Correlation analyses evaluated the predictive value of CST injury or infarction volume for the peduncular asymmetry ratio., Results: CST injury correlated significantly with the peduncular asymmetry ratio (r = -0.65; P < .001), whereas infarction volume did not (r = -0.31; P = .09)., Conclusions: The extent of postinfarction CST injury in the cerebral hemisphere predicts the extent of ipsilateral cerebral peduncular atrophy. More generally, the findings suggest that the extent of remote wallerian degeneration of a fiber tract is strongly related to its extent of injury directly at the site of infarction.

Purpose: To evaluate the effect of total cerebral infarction volume on motor status and treatment responses to Constraint-Induced Movement therapy (CI therapy) in patients with chronic post-stroke hemiparesis and limb nonuse. In most studies of clinical-radiological correspondences, infarct volume has been found to predict clinical status., Methods: 60 adult patients who met inclusion criteria for CI therapy underwent standard structural brain MRI around the time of treatment. We tested whether the total volume of infarcted tissue predicted pre-treatment values and pre- to post-treatment changes on standard assessments of laboratory- and real-world-based upper extremity movement., Results: The patients significantly improved from baseline clinical motor measures after CI therapy. The range of infarction volumes was comparable to those of other stroke studies. In contrast, total infarction volume was not correlated with any of the motor measures. The absence of correlation was maintained even when evaluating only patients with either unilateral or solitary cerebral infarctions, or with respect to severity of baseline motor impairment or variations in the forms of therapy., Conclusion: The findings suggest that certain standard motor measures in chronic hemiparetic stroke (limb movement in the laboratory, limb use in the life situation, changes in these measures following efficacious CI therapy) are insensitive to infarction load. Our findings are consistent with the hypothesis that plastic brain reorganization after stroke attenuates the effect of infarct volume on purposive limb movement. However, we cannot exclude the possibilities that the specific methods we used to assess upper limb status may be generally insensitive to infarction load, or that the stringent inclusion criteria for this research precluded detecting an effect of infarction load. Further study to evaluate these relationships in the acute-subacute stroke phases and among patients with more severe motor deficits would help to clarify the basis for the lack of an infarction load effect.