Constraint-Induced Movement therapy can improve hemiparetic progressive multiple sclerosis. Preliminary findings.

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.

Poststroke cerebral peduncular atrophy correlates with a measure of corticospinal tract injury in the cerebral hemisphere.

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.

The learned nonuse phenomenon: implications for rehabilitation.

Research on monkeys with a single forelimb from which sensation is surgically abolished demonstrates that such animals do not use their deafferented limb even though they possess sufficient motor innervation to do so, a phenomenon labeled learned nonuse. This dissociation also occurs after neurological injury in humans. Instruments that measure these two aspects of motor function are discussed. The effects of a neurological injury may differ widely in regard to motor ability assessed on a laboratory performance test in which movements are requested and actual spontaneous use of an extremity in real-world settings, indicating that these parameters need to be evaluated separately. The methods used in Constraint-Induced Movement therapy (CI therapy) research to independently assess these two domains are reliable and valid. We suggest that these tests have applicability beyond studies involving CI therapy for stroke and may be of value for determining motor status in other types of motor disorders and with other types of treatment. The learned nonuse formulation also predicts that a rehabilitation treatment may have differential effects on motor performance made on request and actual spontaneous amount of use of a more affected upper extremity in the life situation. CI therapy produces improvements in the former, but focuses attention on the latter and, in fact, spontaneous use of the limb is where this intervention has by far its greatest effect. The evidence suggests that this result is driven by use of a ''transfer package'' of techniques, which can be used with other therapies to increase the transfer of improvements made in the clinic to the life situation. The use of CI therapy in humans began with the upper extremity after stroke and was then extended for the upper extremity to cerebral palsy in young children (8 months to 8 years old) and traumatic brain injury. A form of CI therapy was developed for the lower extremities and was used effectively after stroke, spinal cord injury, and fractured hip. Adaptations of CI therapy have also been developed for aphasia (CI aphasia therapy), focal hand dystonia in musicians and phantom limb pain. The range of these applications suggests that CI therapy is not only a treatment for stroke, for which it is most commonly used, but for learned nonuse in general, which manifests as excess motor disability in a number of conditions which until now have been refractory to treatment.

Constraint-induced movement therapy: characterizing the intervention protocol.

Constraint-induced movement therapy (CI therapy) is a rehabilitation treatment approach that improves more-affected extremity use following a stroke, especially in the life situation. The originators of the approach describe CI therapy as consisting of a family of therapies including a number of treatment components and subcomponents. When thinking of CI therapy, rehabilitation researchers and clinicians frequently cite a restraining mitt on the less affected arm as the main active ingredient behind improvements in motor function. However, substantial data suggest that restraint makes actually a relatively small contribution to treatment outcome. This paper provides a detailed description of the multiple treatment elements included in the CI therapy protocol as used in our research laboratory. Our aim is to improve understanding of CI therapy and the research supporting its use.

Neuroplasticity and constraint-induced movement therapy.

Recent years have seen a proliferation of animal and human studies that have associated significant changes in regional brain physiology with sustained altered environmental or somatic stimuli. The behavioral consequences in such instances can be adaptive or maladaptive. As would be expected, constraint-induced movement therapy (CI therapy), which has been found to be beneficial for chronic stroke hemiparesis, has been repeatedly associated with significant plastic brain changes in a variety of studies that have included transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), or other approaches. In some instances, the initial degree of brain reorganization occurred in parallel with the improvement in spontaneous, real-world use by the more-affected hand, which suggests that plastic brain changes in some manner support therapeutic effects. However, the studies are also inconsistent with respect to whether the reorganization changes occur more in the lesioned vs unlesioned hemisphere. Interpreting the physiological outcomes post-treatment is compromised by inconsistencies in study design in the nature of treatment administered, participant recruitment, imaging modality, and extent of follow-up. Improved understanding of the biological basis for neuroplasticity in CI therapy may be obtained through rigorous control of study approaches and through evaluating treatment changes with more than one modality in the same patients concurrently. New quantitative structural brain imaging techniques may allow measuring morphological changes following CI therapy to test hypotheses of regional brain recruitment in use-dependent therapy while avoiding the variability of functional imaging and mapping techniques and the difficulties and assumptions imposed by requiring active limb movement during scanning.

Disorganized search on cancellation is not a consequence of neglect.

BACKGROUND: Some studies have suggested that in stroke patients, spatial inattention on the cancellation test is closely related to disorganized visual search. However, methods to assess spatial aspects of search organization on cancellation tests have not been well developed. In this study the authors design and evaluate new methods to quantify strategies of spatial exploration on the cancellation test in stroke patients who showed a broad range of spatial attentional abilities, and test whether disorganization and inattention are related. METHODS: Twenty stroke patients were videotaped while they performed a cancellation test. Several variables that reflect spatial aspects of search organization were measured through subsequent video playback. Two patients with severe neglect were excluded from further analysis to avoid constraining the spatial expression of search organization. Spearman correlations were used to assess whether severity of spatial inattention correlated with the individual search organization measures. RESULTS: Of the 18 remaining patients, 10 had mild-moderate spatial neglect (pathologic inattention), while the other 8 omitted at most one target (normal performance). There were no significant correlations between the number of targets omitted and any of the search organization measures. CONCLUSIONS: Spatial inattention on cancellation due to neglect following stroke is not closely related to the organization of visual search. Instead, search disorganization during cancellation may reflect disturbance of an unspecified executive control mechanism.

Diagonal spatial neglect.

OBJECTIVE: To determine whether stroke patients with diagonal neglect on cancellation may show diagonal neglect on line bisection, and hence to indicate whether diagonal neglect may be related solely to the type of test used or whether instead it may reflect a fundamental spatial disorder. METHODS: Nine patients with subacute right hemispheric stroke who neglected targets primarily in the near left direction on line cancellation bisected diagonal lines of two opposing orientations: near left to far right and far left to near right. The errors were assessed to determine whether line orientation significantly affected bisection error. RESULTS: Eight patients had significant bisection errors. One of these showed no effect of line orientation on error, consistent with lateral neglect. The remaining seven patients had a line orientation effect, indicating a net diagonal spatial bias. For the group, cancellation errors were significantly correlated with the line orientation effect on bisection errors. CONCLUSIONS: A significant diagonal bias on two tests of spatial attention may appear in stroke patients, although the directions of the biases may differ within individual patients. None the less, diagonal neglect may be a fundamental spatial attentional disturbance of right hemispheric stroke. Greater severity of stroke deficit as indicated by cancellation error score may be associated with a greater degree of diagonal neglect on line bisection.

Diagonal neglect on cancellation.

Patients with right hemisphere injury frequently neglect to cancel targets primarily in the left part of the page nearest the body. Since this region is diagonally opposite the area from where such patients usually begin cancelling, near left ('diagonal') neglect may be consequent to stimulus order effects ('fatigue'). We evaluated the persistence of near left neglect in nine stroke patients when they had to cancel either the near or the far half of the page before proceeding to the other half. Our results showed that near left neglect on the page was largely unaffected by cancellation order. Furthermore, a near left gradient of omissions was established within both radial (near and far) halves of the page, as well as for the entire page. Our findings suggest that diagonal cancellation neglect is unrelated to fatigue and reflects a consistent, two-dimensional disorder of spatial attention. Such neglect may be related to the extent of the visible stimulus array, as well as to the array's location in egocentric space.

Two-dimensional cancellation neglect a review and suggested method of analysis.

Directional bias on cancellation has thus far not been standardized. While cancellation tasks are primarily used to assess lateral performance asymmetries, they may also reveal two-dimensional (i.e., combined lateral and radial) neglect patterns. We propose a method to evaluate and report cancellation neglect regardless of whether the neglect pattern is strictly unilateral or two-dimensional. Our method establishes the location of the geographic center of all neglected stimuli relative to the page center by averaging their Cartesian coordinates. This "neglect center" is reported in polar coordinates to indicate its distance and direction from the page center. We apply our method to published examples of two-dimensional neglect. We find that neglect centers from different cancellation performances may not be statistically distinct even though they may occupy different quadrants. In addition, the net direction of neglect found by the coordinate method may differ from that inferred from measuring differences in quadrant omission totals. The suitability of the coordinate vs. the quadrant method will depend on the mechanism hypothesized for visuospatial exploration under particular test conditions. Using both approaches may detect different attentional biases operating during the same task. The coordinate method is appropriate for conventional cancellation testing. By incorporating the precise locations of all neglected stimuli and determining the net neglect direction in two dimensions, the technique may stimulate more comprehensive explanations for directional bias.

The effects of gender, menstrual phase and practice on the perceived location of the midsagittal plane.

Women show menstrual phase-related cognitive changes that suggest altered hemispheric activation for a particular task, such that they demonstrate the greatest lateral performance differences on prototypical left hemisphere tasks during the luteal phase and on prototypical right hemisphere tasks during menstruation. Additionally, menstrual phase may alter total cerebral responsiveness, such that response times and performance accuracy for many tasks are best during the luteal phase and most impaired during the menstrual phase. We evaluated the effect of menstrual phase on spatial bisection (a perceptuospatial task) to help further understand hormonally-mediated changes in interhemispheric dynamics. Healthy young adult women and men blindly pointed to their midsagittal plane with either hand. Women were repeatedly tested according to menstrual phase, and men were tested at similar intervals. The mean pointing error in the luteal phase differed significantly from that of all other phases and did not differ significantly from those of men, who pointed significantly to the left across test sessions. These findings suggest that, in space bisection tasks, women are more likely to have asymmetric hemispheric activation during the luteal phase than during the menstrual phase. Thus, space bisection did not resemble other prototypical right hemisphere behaviors. The luteal phase may have nonspecifically activated both hemispheres on this task instead of suppressing right hemisphere function, and a slight functional asymmetry favoring the right hemisphere may have been promoted. In addition, intermanual pointing discrepancies in both subject groups decreased over repeated sessions. This suggests that, while practice alters an internal kinesthetic reference, it does not influence an imaginal extrapersonal spatial reference.

Bodily neglect and orientational biases in unilateral neglect syndrome and normal subjects.

Patients with neglect erred toward the right when attempting to locate the intercepts of their midsagittal planes with a horizontal line placed in front of them. When control subjects could not see their bodies, they also pointed to the right. While control subjects improved when they were able to see their bodies, neglect subjects did not. When the horizontal line was moved toward the right, both neglect and control subjects increased their rightward pointing errors. However, patients with neglect made greater errors than did controls. When the line was in far left hemispace, controls pointed accurately to their midsagittal planes. The neglect subjects, in contrast, erred toward the left. Our results suggest that patients with neglect from right hemisphere lesions are not only inattentive to their bodies, but are also distracted by extracorporeal stimuli, especially on the right. Our results also suggest that normal subjects have a propensity to orient to or be distracted by stimuli in right hemispace.

An experimental analysis of factors underlying neglect in line bisection.

The finding that patients with neglect make larger errors when bisecting longer lines could be due to failure to disengage attention from a segment of the line on the ipsilesional side, or to a reduced ability to direct attention and/or action contralaterally. The findings are reported from a patient with left-sided neglect who set the midpoint further away from the right end of lines as their length increased, a finding consistent with the latter interpretation. His errors were significantly related to length and lateral extent of lines presented in left hemispace, but only to length of lines presented in right hemispace.