Objective There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this prospective blinded randomized trial was to compare the cognitive and mood effects of unilateral subthalamic nucleus (STN) vs. unilateral globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with Parkinson disease (PD). Methods Fifty-two subjects with moderate-to-advanced PD were randomized to either unilateral STN or GPi DBS. Right or alternatively left sided stimulation was chosen to address the side of the body with the most bothersome symptoms. The co-primary outcome measures were the change in the 8 subscales of the Visual Analog Mood Scale (VAMS), and the change in the 2 versions of verbal fluency (i.e. semantic and letter), at 7 months post-DBS in the optimal setting compared to the pre-DBS state. In addition, at 7 months post-DBS, after subjects underwent initial evaluation off medications and on optimized DBS therapy, they were tested in four randomized and counterbalanced conditions (optimal DBS, ventral DBS, dorsal DBS, and off DBS) while remaining off medication. Secondary outcome measures then compared the differences in the VAMS items and verbal fluency subscales within the 4 DBS conditions at 7 months, and the change in the VAMS items and verbal fluency subscales from the pre-DBS state to the other 3 DBS conditions (ventral, dorsal and off ) at 7 months. Results Forty-five subjects (23 GPi and 22 STN) completed the protocol. The study revealed no significant difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes from pre- to post-DBS in the optimal setting (Hotelling's T2 test: p=0.16 and 0.08 respectively). When comparing the 4 DBS conditions at 7 months, subjects in both targets were less “happy”, less “energetic” and more “confused” when stimulated ventrally to the optimal stimulation site. When comparing the other 3 DBS conditions (ventral, dorsal and off DBS) to the pre-DBS state, the STN group showed a larger deterioration of letter verbal fluency scores than the GPi group, especially in the off DBS state. A 12-point mean improvement in the UPDRS motor subscale was seen post DBS, but there was no significant difference between targets. Interpretations There were no significant differences in in the co-primary outcome measures of mood and cognition between STN and GPi in the optimal DBS state.. However, adverse mood effects were noted when stimulating ventrally to the optimal site in both targets. Furthermore, a worsening for letter verbal fluency was noted in the 3 non-optimal post-DBS states in the STN target only. The persistence of deterioration in verbal fluency in the off DBS state at 7 months is, suggestive of a surgical rather than a stimulation-induced effect at the STN target. STN and GPi DBS resulted in similar motor improvement.

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.)

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 (Ͻ0.4 m/s), limited community ambulation (0.4 to 0.8 m/s), and full community ambulation (Ͼ0.8 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 (Pϭ0.0299) and participation (Pϭ0.0277). Among limited community ambulators, those who achieved the transition to full community ambulatory status had significantly better scores in SIS participation (Pϭ0.0085). 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.