Samuel S. Wu

Body-weight-supported treadmill rehabilitation after stroke.

BACKGROUND Locomotor training, including the use of body-weight support in treadmill stepping, is a physical therapy intervention used to improve recovery of the ability to walk after stroke. The effectiveness and appropriate timing of this intervention have not been established. METHODS We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment--moderate (able to walk 0.4 to <0.8 m per second) or severe (able to walk <0.4 m per second)--and randomly assigned them to one of three training groups. One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred (early locomotor training), the second group received this training 6 months after the stroke had occurred (late locomotor training), and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke (home-exercise program). Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks. The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke. RESULTS At 1 year, 52.0% of all participants had increased functional walking ability. No significant differences in improvement were found between early locomotor training and home exercise (adjusted odds ratio for the primary outcome, 0.83; 95% confidence interval [CI], 0.50 to 1.39) or between late locomotor training and home exercise (adjusted odds ratio, 1.19; 95% CI, 0.72 to 1.99). All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life. Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year. Ten related serious adverse events were reported (occurring in 2.2% of participants undergoing early locomotor training, 3.5% of those undergoing late locomotor training, and 1.6% of those engaging in home exercise). As compared with the home-exercise group, each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment (P=0.008). Among patients with severe walking impairment, multiple falls were more common in the group receiving early locomotor training than in the other two groups (P=0.02). CONCLUSIONS Locomotor training, including the use of body-weight support in stepping on a treadmill, was not shown to be superior to progressive exercise at home managed by a physical therapist. (Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research; LEAPS ClinicalTrials.gov number, NCT00243919.).

Cognition and Mood in Parkinson's Disease in Subthalamic Nucleus versus Globus Pallidus Interna Deep Brain Stimulation: The COMPARE Trial

Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease.

Improvements in Speed-Based Gait Classifications Are Meaningful

Background and Purpose— Gait velocity is a powerful indicator of function and prognosis after stroke. Gait velocity can be stratified into clinically meaningful functional ambulation classes, such as household ambulation (<0.4 m/s), limited community ambulation (0.4 to 0.8 m/s), and full community ambulation (>0.8 m/s). The purpose of the current study was to determine whether changes in velocity-based community ambulation classification were related to clinically meaningful changes in stroke-related function and quality of life. Methods— In subacute stroke survivors with mild to moderate deficits who participated in a randomized clinical trial of stroke rehabilitation and had a baseline gait velocity of 0.8 m/s or less, we assessed the effect of success versus failure to achieve a transition to the next class on function and quality of life according to domains of the Stroke Impact Scale (SIS). Results— Of 64 eligible participants, 19 were initially household ambulators, and 12 of them (68%) transitioned to limited community ambulation, whereas of 45 initially limited community ambulators, 17 (38%) became full community ambulators. Function and quality-of-life SIS scores after treatment were significantly higher among survivors who achieved a favorable transition compared with those who did not. Among household ambulators, those who transitioned to limited or full community ambulation had significantly better SIS scores in mobility (P=0.0299) and participation (P=0.0277). Among limited community ambulators, those who achieved the transition to full community ambulatory status had significantly better scores in SIS participation (P=0.0085). Conclusions— A gait velocity gain that results in a transition to a higher class of ambulation results in better function and quality of life, especially for household ambulators. Household ambulators possibly had more severe stroke deficits, reducing the risk of “ceiling” effects in SIS-measured activities of daily living and instrumental activities of daily living. Outcome assessment based on transitions within a mobility classification scheme that is rooted in gait velocity yields potentially meaningful indicators of clinical benefit. Outcomes should be selected that are clinically meaningful for all levels of severity.

Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial

BackgroundLocomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention.The objective of the Locomotor Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a difference in the proportion of participants who recover walking ability at one year post-stroke when randomized to a specialized locomotor training program (LTP), conducted at 2- or 6-months post-stroke, or those randomized to a home based non-specific, low intensity exercise intervention (HEP) provided 2 months post-stroke. We will determine if the timing of LTP delivery affects gait speed at 1 year and whether initial impairment severity interacts with the timing of LTP. The effect of number of treatment sessions will be determined by changes in gait speed taken pre-treatment and post-12, -24, and -36 sessions.Methods/DesignWe will recruit 400 adults with moderate or severe walking limitations within 30 days of stroke onset. At two months post stroke, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of three groups: (a) LTP-Early; (b) LTP-Late or (c) Home Exercise Program -Early. The LTP program includes body weight support on a treadmill and overground training. The LTP and HEP interventions are delivered for 36 sessions over 12 weeks.Primary outcome measure include successful walking recovery defined as the achievement of a 0.4 m/s gait speed or greater by persons with initial severe gait impairment or the achievement of a 0.8 m/s gait speed or greater by persons with initial moderate gait impairment.LEAPS is powered to detect a 20% difference in the proportion of participants achieving successful locomotor recovery between the LTP groups and the HEP group, and a 0.1 m/s mean difference in gait speed change between the two LTP groups.DiscussionThe goal of this single-blinded, phase III randomized clinical trial is to provide evidence to guide post-stroke walking recovery programs.Trial registrationNCT00243919.

Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial.

Malcolm MP, Triggs WJ, Light KE, Gonzalez Rothi LJ, Wu S, Reid K, Nadeau SE: Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial. Am J Phys Med Rehabil 2007;86:707–715. Objective:To test the potential adjuvant effect of repetitive transcranial magnetic stimulation (rTMS) on motor learning in a group of stroke survivors undergoing constraint-induced therapy (CIT) for upper-limb hemiparesis. Design:This was a prospective randomized, double-blind, sham-controlled, parallel group study. Nineteen individuals, one or more years poststroke, were randomized to either a rTMS + CIT (n = 9) or a sham rTMS + CIT (n = 10) group and participated in the 2-wk intervention. Results:Regardless of group assignment, participants demonstrated significant gains on the primary outcome measures: the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL)–Amount of Use, and on secondary outcome measures including the Box and Block Test (BBT) and the MAL–How Well. Participants receiving rTMS failed to show differential improvement on either primary outcome measure. Conclusions:Although this study provided further evidence that even relatively brief sessions of CIT can have a substantial effect, it provided no support for adjuvant use of rTMS.

The Relationship Between Quality of Life and Swallowing in Parkinson’s Disease

Few studies exist in the literature investigating the impact of idiopathic Parkinsons Disease (IPD) on swallow‐related quality of life. We therefore aimed in this project to: (1) evaluate swallow‐specific quality of life in IPD; (2) delineate potential relationships between IPD duration and severity with swallow‐specific quality of life; (3) investigate relationships between swallow‐specific quality of life and general health‐related quality of life; and (4) investigate relationships between swallow‐specific quality of life and depression. Thirty‐six patients diagnosed with IPD with and without dysphagia filled out self‐report assessments of the SWAL‐QOL, Parkinsons Disease Questionnaire‐39 (PDQ‐39), and Beck Depression Inventory (BDI). A series of Mann Whitney U tests were performed between non‐dysphagic and dysphagic groups for the total SWAL‐QOL score and the 10 SWAL‐QOL domains. Spearmans Rho correlation analyses were performed between the SWAL‐QOL and (1) PDQ‐39; (2) Hoehn and Yahr stage; (3) PD disease duration; (4) UPDRS “on” score; and (5) the BDI. The dysphagia swallowing group reported significant reductions compared to the non‐dysphagic group for the total SWAL‐QOL score (P = 0.02), mental health domain score (P = 0.002) and social domain score (P = 0.002). No relationships existed between swallow‐specific quality of life and disease duration or severity. Significant relationships existed between swallow‐specific quality of life and general health‐related quality of life (rs =−0.56, P = 0.000) and depression (rs = −0.48, P = 0.003). These exploratory data highlight the psychosocial sequelae that swallowing impairment can have in those with IPD and suggest a possible association between swallowing, social function, and depression.

Fugl-Meyer Assessment of Sensorimotor Function After Stroke Standardized Training Procedure for Clinical Practice and Clinical Trials

Background and Purpose— Outcome measurement fidelity within and between sites of multi-site, randomized, clinical trials is an essential element to meaningful trial outcomes. As important are the methods developed for randomized, clinical trials that can have practical utility for clinical practice. A standardized measurement method and rater training program were developed for the total Fugl-Meyer motor and sensory assessments; inter-rater reliability was used to test program effectiveness. Methods— Fifteen individuals with hemiparetic stroke, 17 trained physical therapists across 5 regional clinical sites, and an expert rater participated in an inter-rater reliability study of the Fugl-Meyer motor (total, upper extremity, and lower extremity subscores) and sensory (total, light touch, and proprioception subscores) assessments. Results— Intra-rater reliability for the expert rater was high for the motor and sensory scores (range, 0.95–1.0). Inter-rater agreement (intraclass correlation coefficient, 2, 1) between expert and therapist raters was high for the motor scores (total, 0.98; upper extremity, 0.99; lower extremity, 0.91) and sensory scores (total, 0.93; light touch, 0.87; proprioception, 0.96). Conclusions— Standardized measurement methods and training of therapist assessors for a multi-site, rehabilitation, randomized, clinical trial resulted in high inter-rater reliability for the Fugl-Meyer motor and sensory assessments. Poststroke sensorimotor impairment severity can be reliably assessed for clinical practice or rehabilitation research with these methods.

The Use of Estrogens and Related Compounds in the Treatment of Damage from Cerebral Ischemia

Abstract: There are 750,000 new cases of stroke each year in the United States, and brain damage from stroke leads to high health care costs and disabilities. Needed, but currently not available, are therapies that can be administered prior to, during, or after cerebral ischemia that reduce or eliminate neuronal damage from stroke. To address this issue, we began to assess the neuroprotective effects of estrogens and related compounds in stroke neuroprotection to determine whether these compounds had potential for clinical application. First, we demonstrated that 17 β‐estradiol (E2) pretreatment exerted potent neuroprotection of the cerebral cortex over a wide dose range and pretreatment interval. Thereafter, we assessed the ability of a variety of non‐feminizing estrogens to protect brain tissue from stroke. We observed that pretreatment with 17 α‐estradiol, the complete enantiomer of E2 (ENT‐E2), 2‐adamantylestrone, and the enantiomer of 17‐desoxyestradiol, were as effective as E2 in pretreatment protection from stroke damage. These data suggest that non‐estrogen receptor mechanisms are involved in brain neuroprotection under our treatment conditions. We then determined whether the observed E2 protection could be extended to times after the onset of the cerebral ischemic event. Using a formulation of E2 that rapidly delivers the steroid, a necessary condition for acute therapy of an ongoing stroke, we demonstrated that 100 mg E2/kg could protect brain tissue for up to 3 h after the onset of the stroke. To determine whether this therapeutic window could be extended with higher doses of the steroid, we conducted a dose‐response assessment of E2 when administered at 6 h after the onset of the ischemic event. While the effectiveness of the 100 μg E2/kg was reduced at this time interval, higher doses of E2 were effective. E2, at doses of 500 and 1000 μg/kg, reduced infarct volume by more than 50%, even with this 6‐h delay in treatment. Collectively, these data indicate that estrogens could prove to be useful therapies in preventing brain damage from strokes.

Foot Drop Stimulation Versus Ankle Foot Orthosis After Stroke 30-Week Outcomes

Background and Purpose— Drop foot after stroke may be addressed using an ankle foot orthosis (AFO) or a foot drop stimulator (FDS). The Functional Ambulation: Standard Treatment versus Electric Stimulation Therapy (FASTEST) trial was a multicenter, randomized, single-blinded trial comparing FDS and AFO for drop foot among people ≥3 months after stroke with gait speed ⩽0.8 m/s. Methods— Participants (n=197; 79 females and 118 males; 61.14±11.61 years of age; time after stroke 4.55±4.72 years) were randomized to 30 weeks of either FDS or a standard AFO. Eight dose-matched physical therapy sessions were provided to both groups during the first 6 weeks of the trial. Results— There was significant improvement within both groups from baseline to 30 weeks in comfortable gait speed (95% confidence interval for mean change, 0.11–0.17 m/s for FDS and 0.12–0.18 m/s for AFO) and fast gait speed. However, no significant differences in gait speed were found in the between-group comparisons. Secondary outcomes (standard measures of body structure and function, activity, and participation) improved significantly in both groups, whereas user satisfaction was significantly higher in the FDS group than in the control group. Conclusions— Using either an FDS or an AFO for 30 weeks yielded clinically and statistically significant improvements in gait speed and other functional outcomes. User satisfaction was higher in the FDS group. Although both groups did receive intervention, this large clinical trial provides evidence that FDS or AFO with initial physical therapy sessions can provide a significant and clinically meaningful benefit even years after stroke. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01138995.

17-β estradiol can reduce secondary ischemic damage and mortality of subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a unique disorder commonly occurring when an aneurysm ruptures, leading to bleeding and clot formation, with a higher incidence in females. To evaluate the influence of 17-β estradiol (E2) in the outcome of subarachnoid hemorrhage, SAH was induced by endovascular puncture of the intracranial segment of internal carotid artery in 15 intact females (INT), 19 ovariectomized females (OVX), and 13 ovariectomized female rats with E2 replacement (OVX + E2). Cerebral blood flow was recorded before and after SAH. All animals were decapitated immediately after death or 24 hours after SAH for clot area analysis. Brains were sliced and stained with 2,3,5-triphenyltetrazolium chloride (TTC) for secondary ischemic lesion analysis. The cortical cerebral blood flow (CBF), which was measured by a laser–Doppler flowmeter, decreased to 29.6% ± 17.7%, 22.8% ± 8.3%, and 43.5% ± 22.9% on the ipsilateral side (P = 0.01), and decreased to 63.4% ± 14.1%, 57.4% ± 11.0%, and 66.6% ± 17.9% on the contralateral side (P = 0.26) in INT, OVX, and OVX + E2, respectively. The subcortical CBF, which were measured by the H2 clearance method, were 7.77 ± 12.03, 7.80 ± 8.65, and 20.58 ± 8.96 mL 100 g−1 min−1 on the ipsilateral side (P < 0.01), and 21.53 ± 2.94, 25.13 ± 3.01, and 25.30 ± 3.23 mL 100 g−1 min−1 on the contralateral side in INT, OVX, and OVX + E2, respectively. The mortality was 53.3%, 68.4%, and 15.4% in INT, OVX, and OVX + E2, respectively (P = 0.01), whereas no significant difference in clot area was noted among the groups. The secondary ischemic lesion volume was 9.3% ± 8.4%, 24.3% ± 16.3%, and 7.0% ± 6.4% in INT, OVX, and OVX + E2, respectively (P < 0.01). This study demonstrated that E2 can reduce the mortality and secondary ischemic damage in a SAH model without affecting the clot volume.