David C. Good

Constraint-induced movement therapy results in increased motor map area in subjects 3 to 9 months after stroke.

Background. Constraint-induced movement therapy (CIMT) has received considerable attention as an intervention to enhance motor recovery and cortical reorganization after stroke. Objective. The present study represents the first multi-center effort to measure cortical reorganization induced by CIMT in subjects who are in the subacute stage of recovery. Methods. A total of 30 stroke subjects in the subacute phase (>3 and <9 months poststroke) were recruited and randomized into experimental (receiving CIMT immediately after baseline evaluation) and control (receiving CIMT after 4 months) groups. Each subject was evaluated using transcranial magnetic stimulation (TMS) at baseline, 2 weeks after baseline, and at 4-month follow-up (ie, after CIMT in the experimental groups and before CIMT in the control groups). The primary clinical outcome measure was the Wolf Motor Function Test. Results. Both experimental and control groups demonstrated improved hand motor function 2 weeks after baseline. The experimental group showed significantly greater improvement in grip force after the intervention and at follow-up (P = .049). After adjusting for the baseline measures, the experimental group had an increase in the TMS motor map area compared with the control group over a 4-month period; this increase was of borderline significance (P = .053). Conclusions. Among subjects who had a stroke within the previous 3 to 9 months, CIMT produced statistically significant and clinically relevant improvements in arm motor function that persisted for at least 4 months. The corresponding enlargement of TMS motor maps, similar to that found in earlier studies of chronic stroke subjects, appears to play an important role in CIMT-dependent plasticity.

Pathologic changes associated with intracranial hypotension and meningeal enhancement On MRI

We report a patient with a 6-week history of postural headache due to intracranial hypotension whose MRI revealed findings typical of this syndrome, including diffuse meningeal enhancement following gadolinium infusion. Biopsy revealed extensive fibrocollagenous proliferation in the leptomeninges without evidence of inflammation. The pathologic changes in this patient, which occurred soon after the onset of symptoms, are probably related to the striking meningeal enhancement seen in this syndrome.

Contralesional motor deficits after unilateral stroke reflect hemisphere-specific control mechanisms

We have proposed a model of motor lateralization, in which the left and right hemispheres are specialized for different aspects of motor control: the left hemisphere for predicting and accounting for limb dynamics and the right hemisphere for stabilizing limb position through impedance control mechanisms. Our previous studies, demonstrating different motor deficits in the ipsilesional arm of stroke patients with left or right hemisphere damage, provided a critical test of our model. However, motor deficits after stroke are most prominent on the contralesional side. Post-stroke rehabilitation has also, naturally, focused on improving contralesional arm impairment and function. Understanding whether contralesional motor deficits differ depending on the hemisphere of damage is, therefore, of vital importance for assessing the impact of brain damage on function and also for designing rehabilitation interventions specific to laterality of damage. We, therefore, asked whether motor deficits in the contralesional arm of unilateral stroke patients reflect hemisphere-dependent control mechanisms. Because our model of lateralization predicts that contralesional deficits will differ depending on the hemisphere of damage, this study also served as an essential assessment of our model. Stroke patients with mild to moderate hemiparesis in either the left or right arm because of contralateral stroke and healthy control subjects performed targeted multi-joint reaching movements in different directions. As predicted, our results indicated a double dissociation; although left hemisphere damage was associated with greater errors in trajectory curvature and movement direction, errors in movement extent were greatest after right hemisphere damage. Thus, our results provide the first demonstration of hemisphere specific motor control deficits in the contralesional arm of stroke patients. Our results also suggest that it is critical to consider the differential deficits induced by right or left hemisphere lesions to enhance post-stroke rehabilitation interventions.

Dynamic dominance varies with handedness: reduced interlimb asymmetries in left-handers

Our previous studies of interlimb asymmetries during reaching movements have given rise to the dynamic-dominance hypothesis of motor lateralization. This hypothesis proposes that dominant arm control has become optimized for efficient intersegmental coordination, which is often associated with straight and smooth hand-paths, while non-dominant arm control has become optimized for controlling steady-state posture, which has been associated with greater final position accuracy when movements are mechanically perturbed, and often during movements made in the absence of visual feedback. The basis for this model of motor lateralization was derived from studies conducted in right-handed subjects. We now ask whether left-handers show similar proficiencies in coordinating reaching movements. We recruited right- and left-handers (20 per group) to perform reaching movements to three targets, in which intersegmental coordination requirements varied systematically. Our results showed that the dominant arm of both left- and right-handers were well coordinated, as reflected by fairly straight hand-paths and low errors in initial direction. Consistent with our previous studies, the non-dominant arm of right-handers showed substantially greater curvature and large errors in initial direction, most notably to targets that elicited higher intersegmental interactions. While the right, non-dominant, hand-paths of left-handers were slightly more curved than those of the dominant arm, they were also substantially more accurate and better coordinated than the non-dominant arm of right-handers. Our results indicate a similar pattern, but reduced lateralization for intersegmental coordination in left-handers. These findings suggest that left-handers develop more coordinated control of their non-dominant arms than right-handers, possibly due to environmental pressure for right-handed manipulations.

Open-Label Dose-Titration Safety and Efficacy Study of Tizanidine Hydrochloride in the Treatment of Spasticity Associated With Chronic Stroke

Background and Purpose— Spasticity is a frequently observed motor impairment that develops after stroke; it can cause pain and disability in those affected. The objective of the present study was to evaluate the safety and efficacy of tizanidine, a centrally acting &agr;2-adrenergic agonist, in the treatment of stroke-related spasticity. Methods— Forty-seven patients, who were a minimum of 6 months poststroke and had significant spasticity, were studied at 4 centers. Tizanidine was administered in an open-label manner for 16 weeks, beginning at 2 mg/d and slowly titrated to a maximum of 36 mg/d. The Modified Ashworth Scale, muscle strength testing, functional assessments, and Pain and Functional Spasticity Questionnaires were administered at baseline and at 4, 8, 16, and 18 weeks (after 1 week off tizanidine). Results— Spasticity was significantly improved between baseline and week 16, with a decrease in total upper extremity Modified Ashworth Scale score of 2.80±0.47 (P <0.0001). No decline in strength was noted. Treatment with tizanidine resulted in a significant improvement in pain intensity (P =0.0375), quality of life (P =0.0001), and physician assessment of disability (P =0.0001). The most frequent side effects were somnolence (62%) and dizziness (32%). No serious adverse events were considered to be drug related. Ten of 47 patients (21%) were able to reach the maximum daily dosage of 36 mg. Conclusions— Overall, the data suggest that tizanidine is safe and efficacious in the treatment of stroke-related spasticity, preserving muscle strength while reducing muscle tone and painful spasms in affected patients.

Poststroke chronic disease management: towards improved identification and interventions for poststroke spasticity‐related complications

This paper represents the opinion of a group of researchers and clinicians with an established interest in poststroke care and is based on the recognised need for long-term care following stroke, especially in view of the global increase of disability due to stroke. Among the more frequent long-term complications following stroke are spasticity-related disabilities. Although spasticity alone occurs in up to 60% of stroke survivors, disabling spasticity affects only 4–10%. Spasticity further interferes with important functions of daily life when it occurs in association with pain, motor impairment, and overall declines of cognitive and neurological function. It is proposed that the aftermath of stroke be considered a chronic disease requiring a multifactorial and multilevel approach. There are, however, knowledge gaps related to the prediction and recognition of poststroke disability. Interventions to prevent or minimise such disabilities require further development and evaluation. Poststroke spasticity research should focus on reducing disability and be considered as part of a continuum of chronic care requirements and should be recognised as a part of a comprehensive poststroke disease management programme.

Comparison of Two Therapy Approaches in the Rehabilitation of the Pure Motor Hemiparetic Stroke Patient

Although there are a variety of therapeutic philosophies applied in stroke rehabilitation, it has not been determined whether one approach is superior to another. We prospectively evaluated twenty-seven patients with pure motor hemiparetic strokes admitted to an acute neurorehabilitation unit and randomized them to treatment with either a traditional functional retraining approach (TFR) or neurodevelopmental techniques (NDT). NDT and TFR treated patients did not differ with regard to age, gender, side of stroke, or days from stroke to study entry. Other than an increased gait velocity in NDT treated patients at hospital discharge (p = 0.04), there was no significant difference in gait measures, upper extremity motor skills, or Functional Independence Measure (FIM) scores at hospital discharge, six month, or twelve month follow-up. Rehab length of stay did not differ significantly between the two treatment groups. This data suggests that TFR and NDT approaches are equally efficacious in treating pure motor hemiparetic strokes in terms of functional outcomes, gait measures, and upper extremity motor skills. Key Words: Stroke—Rehabilitation—Physical therapy— Neurodevelopmental technique.

Dynamic Course of Intracortical TMS Paired-Pulse Responses During Recovery of Motor Function After Stroke:

Background. Recovery of motor function after stroke may be associated with changes in inhibitory and facilitatory circuits within the motor cortex. Objective. We explored such changes longitudinally after stroke, using transcranial magnetic stimulation (TMS). Methods. Subjects (N = 27) with a single cerebral infarction affecting movement of either hand were studied at <10 days poststroke, 1 month, and 6 months. Age-matched control subjects (N = 9) were studied at 2 times. Results. In contrast to previous studies, paired-pulse inhibition was increased in patients with a subcortical stroke compared to control subjects. After a cortical stroke, paired-pulse facilitation was also increased. Stroke location affected the time course of inhibition. Subcortical stroke resulted in increased inhibition initially that decreased over time, whereas cortical stroke had no significant effect on inhibition and a more immediate and lasting effect on facilitation. Conclusions. The time course of a decline in inhibition based on TMS after subcortical stroke followed the gain in motor recovery. Increased facilitation in cortical stroke patients is more likely to represent the effect of early cortical circuit disruption and may not play a role in subacute changes in motor function.

Co-registration of cortical magnetic stimulation and functional magnetic resonance imaging

FUNCTIONAL magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are noninvasive techniques recently used to investigate cortical motor physiology. However, these modalities measure different phenomena, and in studies of human motor control they have given inconsistent results. We have developed a reproducible technique which co-registers TMS and fMRI, using a frameless method. In four normal subjects, the TMS map and fMRI activation were present on the primary motor cortex contralateral to the target hand, with some extension into primary sensory cortex. fMRI activation alone was also present in the medial motor cortex bilaterally and in the sensori-motor cortex ipsilateral to the target hand. This technique allows a more comprehensive evaluation of the physiologic events involved in motor control.

Hand Motor Recovery after Stroke: A Transcranial Magnetic Stimulation Mapping Study of Motor Output Areas and Their Relation to Functional Status

The respective contributions of the stroke and undamaged hemispheres to motor recovery after stroke remains controversial. The aim of this article is to evaluate the relationship between location and size of cortical motor areas and outcome after stroke. Twelve controls and 12 stroke patients were studied. Hand cortical motor output areas were determined using transcranial magnetic stimulation. Motor-evoked potentials were recorded simultaneously from both hands. Functional motor abilities were evaluated using well-validated measures. Surface area, weighted surface area, and center of gravity of motor output areas were calculated. Different patterns of motor output areas to the paretic hand were observed; there was no motor output from the stroke hemisphere in patients with poor outcome, contrasting to large motor output area in the stroke hemisphere in patients with good outcome, regardless of infarct size or location. A significant correlation was found between measures of motor outcome in the stroke-affected upper extremity and both the surface area and weight of the central motor output area in the stroke hemisphere. No ipsilateral motor response was obtained after stimulation of either hemisphere. These data support an association between preservation of cortical motor output area to the paretic hand in the stroke hemisphere and good motor outcome.