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Background: This study aimed to examine whether robotic self-training improved upper-extremity function versus conventional self-training in mild-to-moderate hemiplegic chronic stroke patients. Methods: Study design was a multi-center, prospective, randomized, parallel-group study comparing three therapist-guided interventions (1-hour sessions, 3×/wk, 10 weeks). We identified 161 prospective patients with chronic, poststroke, upper-limb hemiplegia treated at participating rehabilitation centers. Patients were enrolled between November 29, 2016, and November 12, 2018 in Japan. A blinded web-based allocation system was used to randomly assign 129 qualifying patients into 3 groups: (1) conventional self-training plus conventional therapy (control, N=42); (2) robotic self-training (ReoGo-J) plus conventional therapy (robotic therapy [RT], N=44); or (3) robotic self-training plus constraint-induced movement therapy (N=43). Primary outcome: Fugl-Meyer Assessment for upper-extremity. Secondary outcomes: Motor Activity Log-14 amount of use and quality of movement; Fugl-Meyer Assessment shoulder/elbow/forearm, wrist, finger, and coordination scores; Action Research Arm Test Score; Motricity Index; Modified Ashworth Scale; shoulder, elbow, forearm, wrist, and finger range of motion; and Stroke Impact Scale (the assessors were blinded). Safety outcomes were adverse events. Results: Safety was assessed in 127 patients. An intention-to-treat full analysis set (N=121), and a per-protocol set (N=115) of patients who attended 80% of sessions were assessed. One severe adverse event was recorded, unrelated to the robotic device. No significant differences in Fugl-Meyer Assessment for upper-extremity scores were observed between groups (RT versus control: −1.04 [95% CI, −2.79 to 0.71], P =0.40; RT versus movement therapy: −0.33 [95% CI, −2.02 to 1.36], P =0.90). The RT in the per-protocol set improved significantly in the Fugl-Meyer Assessment for upper-extremity shoulder/elbow/forearm score (RT versus control: −1.46 [95% CI, −2.63 to −0.29]; P =0.037). Conclusions: Robotic self-training did not improve upper-limb function versus usual self-training, but may be effective combined with conventional therapy in some populations (per-protocol set). Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000022509.

Background and Purpose: This study aimed to assess the efficacy of an ultrasound-guided lateral approach for BoNT-A (botulinum toxin A) injections into the subscapularis in patients with hemiplegic shoulder pain. Methods: This single-center trial used a randomized, double-blind, placebo-controlled design. The key inclusion criteria were a visual analogue scale score of ≥4 cm and a modified Ashworth scale score of ≥1+. The patients were randomized to receive either BoNT-A injections or a placebo. The outcomes included the visual analogue scale score, modified Ashworth scale score, pain-free passive range of motion of the hemiplegic shoulder, Fugl-Meyer assessment score for the upper extremities, and Stroke-Specific Quality-of-Life score. Results: A total of 49 hemiplegic shoulder pain patients were screened, and 36 were included. The participants receiving the BoNT-A injection reported a significant decrease in pain (visual analogue scale, −1.39 [95% CI, −2.41 to −0.36]; P =0.002) and spasticity (modified Ashworth scale score for shoulder internal rotation, −0.72 [95% CI, −1.10 to −0.35]; P =0.001; modified Ashworth scale score for shoulder abduction, −0.44 [95% CI, −0.90 to −0.01]; P =0.026) and improved pain-free passive shoulder internal rotation range of motion (14.56 [95% CI, 6.70–21.41]; P P =0.025) compared with those receiving the placebo at the end point. The shoulder abduction range of motion did not significantly improve after the BoNT-A injection at the end point ( P =0.127). In addition, the patients in the BoNT-A group showed significant improvements in the visual analogue scale score and shoulder external rotation range of motion at the 12-week follow-up. No injection-related adverse events were observed during or after the interventions in either group. Conclusions: The ultrasound-guided lateral approach for BoNT-A injections into the subscapularis is a precise and reliable method for reducing pain and spasticity and improving quality of life in stroke survivors with hemiplegic shoulder pain. Registration: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR1900023513.

Background and Purpose: The ARAT (Action Research Arm Test) has been used to classify upper limb motor outcome after stroke in 1 of 3, 4, or 5 categories. The COVID-19 pandemic has encouraged the development of assessments that can be performed quickly and remotely. The aim of this study was to derive and internally validate decision trees for categorizing upper limb motor outcomes at the late subacute and chronic stages of stroke using a subset of ARAT tasks. Methods: This study retrospectively analyzed ARAT scores obtained in-person at 3 months poststroke from 333 patients. In-person ARAT scores were used to categorize patients’ 3-month upper limb outcome using classification systems with 3, 4, and 5 outcome categories. Individual task scores from in-person assessments were then used in classification and regression tree analyses to determine subsets of tasks that could accurately categorize upper limb outcome for each of the 3 classification systems. The decision trees developed using 3-month ARAT data were also applied to in-person ARAT data obtained from 157 patients at 6 months poststroke. Results: The classification and regression tree analyses produced decision trees requiring 2 to 4 ARAT tasks. The overall accuracy of the cross-validated decision trees ranged from 87.7% (SE, 1.0%) to 96.7% (SE, 2.0%). Accuracy was highest when classifying patients into one of 3 outcome categories and lowest for 5 categories. The decision trees are referred to as FOCUS (Fast Outcome Categorization of the Upper Limb After Stroke) assessments and they remained accurate for 6-month poststroke ARAT scores (overall accuracy range 83.4%–91.7%). Conclusions: A subset of ARAT tasks can accurately categorize upper limb motor outcomes after stroke. Future studies could investigate the feasibility and accuracy of categorizing outcomes using the FOCUS assessments remotely via video call.

We investigated the effect of higher therapeutic exercise doses on walking during inpatient rehabilitation, typically commencing 1 to 4 weeks poststroke.This phase II, blinded-assessor, randomized controlled trial recruited from 6 Canadian inpatient rehabilitation units, between 2014 and 2018. Subjects (n=75; 25/group) were randomized into: control (usual care) physical therapy: typically, 1 hour, 5 days/week; Determining Optimal Post-Stroke Exercise (DOSE1): 1 hour, 5 days/week, more than double the intensity of Control (based on aerobic minutes and walking steps); and DOSE2: 2 hours, 5 days/week, more than quadruple the intensity of Control, each for 4 weeks duration. The primary outcome, walking endurance at completion of the 4-week intervention (post-evaluation), was compared across these groups using linear regression. Secondary outcomes at post-evaluation, and longitudinal outcomes at 6 and 12-month evaluations, were also analyzed.Both DOSE1 (mean change 61 m [95% CI, 9-113],This study provides the first preliminary evidence that patients with stroke can improve their walking recovery and quality of life with higher doses of aerobic and stepping activity within a critical time period for neurological recovery. Furthermore, walking endurance benefits achieved from a 4-week intervention are retained over the first-year poststroke. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01915368.

Background and Purpose— Our aim was to study the efficacy of robotic therapy as an adjuvant to standard therapy during poststroke rehabilitation. Methods— Prospective, open, blinded end point, randomized, multicenter exploratory clinical trial in Japan of 60 individuals with mild to moderate hemiplegia 4 to 8 weeks post stroke randomized to receive standard therapy plus 40 minutes of either robotic or self-guided therapy for 6 weeks (7 days/week). Upper extremity impairment before and after intervention was measured using the Fugl–Meyer assessment, Wolf Motor Function Test, and Motor Activity Log. Results— Robotic therapy significantly improved Fugl–Meyer assessment flexor synergy (2.1±2.7 versus −0.1±2.4; P P P Conclusions— Robotic therapy as an adjuvant to standard rehabilitation may improve upper extremity recovery in moderately impaired poststroke patients. Results of this exploratory study should be interpreted with caution. Clinical Trial Registration— URL: http://www.umin.ac.jp/ . Unique identifier: UMIN000001619.

Author version made available in accordance with the publisher's policy, Background and Purpose: Shoulder pain is a common complication after stroke which can impede participation in rehabilitation and has been associated with poorer outcomes. Evidence based treatments for hemiplegic shoulder pain are limited. Suprascapular nerve block (SSNB) is a safe and effective treatment of shoulder pain associated with arthritic shoulder conditions, but its usefulness in a stroke population is unclear. Methods: We undertook a randomised controlled trial assessing the effectiveness of SSNB in a population of 64 stroke patients (onset < 1 year) with hemiplegic shoulder pain. The primary outcome was pain measured on a visual analogue scale (VAS). Secondary outcomes were disability (Modified Rankin Scale, Croft Disability Index) and quality of life (EuroQol Health Questionnaire). All participants were assessed prior to randomisation, and at 1, 4 and 12 weeks post intervention. Both groups continued with routine therapy. Results: Whilst both intervention and control groups demonstrated reduction in pain score, participants who received SSNB consistently demonstrated superior, statistically significant pain reduction compared to placebo. Mean VAS reduction in the SSNB group was over 18mm greater than participants receiving placebo injection. The number needed to treat with SSNB to reduce one stroke survivor’s pain by 50% at four weeks is 4. No significant differences in function or quality of life were observed. No adverse events were reported. Conclusions: Suprascapular nerve block is a safe and effective treatment for patients with hemiplegic shoulder pain.

Background and Purpose— Although there has been extensive research on the effectiveness of repetitive transcranial magnetic stimulation (rTMS) to improve patients’ motor performance after experiencing chronic stroke, explicit findings on the coupling of different rTMS protocols are meager. We designed this sham-controlled randomized study to investigate the potential for a consecutive suppressive-facilitatory TMS protocol to improve motor outcomes after chronic stroke. Methods— Fifty-four chronic hemiplegic stroke patients were allocated across 4 groups to undergo 20 daily sessions of (1) 1 Hz rTMS over the contralesional primary motor cortex (M1) and then intermittent theta burst stimulation over the ipsilesional M1 (group A); (2) contralesional sham stimulation and then ipsilesional real intermittent theta burst stimulation (group B); (3) contralesional real 1 Hz rTMS and then ipsilesional sham stimulation (group C); or (4) bilateral sham-control procedures (group D). We tested cortical excitability and motor activity assessments at the baseline, postpriming rTMS, and postconsequent rTMS periods. Results— At post, group A showed greater muscle strength, Fugl-Meyer Assessment (FMA), Wolf Motor Function test, and reaction time improvement in comparison with group B ( P P =0.001≈0.003). Correlation analyses in group A revealed a close relation between contralesional map area decrement and Wolf Motor Function test gain ( P =0.005; r =−0.75), and also revealed ipsilesional map area increment and reaction time decrement ( P =0.02; r =−0.87). We detected no such relations in the other 3 groups. Conclusions— Our clinical trials established an extended timeframe during which conditioning could be safely continued and produced more favorable outcomes in facilitating motor performance and ameliorating interhemispheric imbalance than those obtained from single-course rTMS modulation alone.

Background and Purpose— Animal studies provide strong evidence that aerobic exercise training positively influences cerebral blood flow, but no human studies support the use of exercise for improving cerebral hemodynamics. This randomized study in stroke survivors assessed the effects of treadmill aerobic exercise training (TM) on cerebral blood flow parameters compared to a control intervention of nonaerobic stretching. Methods— Thirty-eight participants (19 in TM group and 19 in control group) with remote stroke (>6 months) and mild to moderate gait deficits completed middle cerebral artery blood flow velocity measurements by transcranial Doppler ultrasonography before and after a 6-month intervention period. Middle cerebral artery blood flow velocity was assessed bilaterally during normocapnia and hypercapnia (6% CO 2 ). Cerebral vasomotor reactivity (cVMR) was calculated as percent change in middle cerebral artery blood flow velocity from normocapnia to hypercapnia (cVMR percent) and as an index correcting percent change for absolute increase in end tidal CO 2 (cVMR index). Results— The TM group had significantly larger improvements than did controls for both ipsilesional and contralesional cVMR index ( P ≤0.05) and contralesional cVMR percent ( P ≤0.01). Statin users in the TM group (n=10) had higher baseline cVMR and lower training-induced cVMR change, indicating that cVMR change among those not using statins (n=9) primarily accounted for the between-group effects. There was a 19% increase in V o 2 peak for the TM group compared to a 4% decrease in the control group ( P r =0.55; P Conclusions— Our data provide the first evidence to our knowledge of exercise-induced cVMR improvements in stroke survivors, implying a protective mechanism against recurrent stroke and other brain-related disorders. Statin use appears to regulate cVMR and the cVMR training response.

Background and Purpose— The aim of the present study was to determine if outcome in terms of upper limb function at 6 months after stroke can be predicted in hospital stroke units using clinical parameters measured within 72 hours after stroke. In addition, the effect of the timing of assessment after stroke on the accuracy of prediction was investigated by measurements on days 5 and 9. Methods— Candidate determinants were measured in 188 stroke patients within 72 hours and at 5 and 9 days after stroke. Logistic regression analysis was used for model development to predict upper limb function at 6 months measured with the action research arm test (ARAT). Results— Patients with an upper limb motor deficit who exhibit some voluntary extension of the fingers and some abduction of the hemiplegic shoulder on day 2 have a probability of 0.98 to regain some dexterity at 6 months, whereas the probability was 0.25 for those without this voluntary motor activity. Sixty percent of patients with some early finger extension achieved full recovery at 6 months in terms of action research arm test score. Retesting the model on days 5 and 9 resulted in a gradual decline in probability from 0.25 to 0.14 for those without voluntary motor activity of shoulder abduction and finger extension, whereas the probability remained 0.98 for those with this motor activity. Conclusions— Based on 2 simple bedside tests, finger extension and shoulder abduction, functional recovery of the hemiplegic arm at 6 months can be predicted early in a hospital stroke unit within 72 hours after stroke onset.

Background and Purpose— To assess cognitive outcome at early school age in term-born children with middle cerebral arterial (MCA) territory infarction of perinatal onset and examine the correlation between cognitive abilities and the extent of lesions as seen on neonatal MRI, epilepsy, and hemiplegia. Methods— Thirty-one children were seen as newborns with an acutely evolving MCA territory infarction documented on neonatal MRI scan. IQ was assessed (WIPPSI/WISC where appropriate) and they had a standardized neurological examination at early school age. Lesion(s) site was recorded from the neonatal images. Results— Twenty-eight of 31 children were assessed (median age 5.75 range 5.33 to 10.33 years); 1 child died and 2 were abroad. IQ was within the normal range (mean 104, range 82 to 144) in 21 (78%); 1 child did not complete all tests but had a normal PIQ; 3 had a low and 3 an exceptionally low IQ. Verbal IQs were more varied and lower than performance IQs especially in children from multilingual backgrounds. There was no consistent association between cognitive impairment, side, or extent of the MCA lesion. Cognitive impairments were more frequent in children with seizures or hemiplegia. All 6 children with low IQ also had behavioral problems or unusual associated clinical or scan features. Conclusions— In our cohort a low IQ at early school age did not occur in children with the common presentation of neonatal unilateral MCA territory infarction. Cognitive impairment appeared more frequently when an MCA arterial territory infarction, even if relatively small, was associated with other risk factors.

Background and Purpose— The success of gait rehabilitation after stroke depends on active walking exercises. However, the disabling after-effects of stroke often make such exercises impossible at the onset of therapy. To facilitate treadmill training of paraparetic patients, a robot-driven gait orthosis (Lokomat) was developed. We investigated the effects of the Lokomat when used with hemiparetic patients. Methods— The authors conducted a randomized, controlled pilot study of 30 acute stroke survivors. The treatment group received 30 minutes of robotic training daily and the control group 30 minutes of conventional physiotherapy daily in addition to 30 minutes of conventional physiotherapy for each group. Outcome measures were independence of gait, gait speed, gait parameters, and body tissue composition. Results— After 4 weeks of therapy, the walking ability of the Lokomat group and the control group expressed as the functional ambulation classification was significantly improved. The functional ambulation category (median± interquartile range) was at baseline 0±0 in control and 0±1 in the therapy group and increased after therapy to 1±3 in both groups significantly ( P =0.01). There was no significant difference in gain of these parameters between the groups. The Lokomat group had a significantly longer single stance phase (sec; mean±SEM) on the paretic leg when walking on the floor. At baseline, it was 0.19±0.17 and after therapy 0.49±0.07 ( P =0.014). The control group had increased their body weight approximately 1.33±1.40 kg (mean±SEM; P =0.046), mostly as fat mass, whereas the Lokomat group had lost fat mass approximately −2.9±1.0 kg (mean±SEM; P =0.016) and increased their muscle mass approximately 3.36±1.4 kg (mean± SEM; P =0.031). Conclusions— This pilot study indicates that Lokomat therapy is a promising intervention for gait rehabilitation. Although there was no difference between groups in gain of functional scores, the Lokomat group showed an advantage of robotic training over conventional physiotherapy in improvement of gait abnormality and body tissue composition.

Background and Purpose— Splints are commonly applied to the wrist and hand to prevent and treat contracture after stroke. However, there have been few randomized trials of this intervention. We sought to determine whether wearing a hand splint, which positions the wrist in either a neutral or an extended position, reduces wrist contracture in adults with hemiplegia after stroke. Methods— Sixty-three adults who had experienced a stroke within the preceding 8 weeks participated. They were randomized to either a control group (routine therapy) or 1 of 2 intervention groups (routine therapy plus splint in either a neutral or an extended wrist position). Splints were worn overnight for, on average, between 9 and 12 hours, for 4 weeks. The primary outcome, measured by a blinded assessor, was extensibility of the wrist and long finger flexor muscles (angle of wrist extension at a standardized torque). Results— Neither splint appreciably increased extensibility of the wrist and long finger flexor muscles. After 4 weeks, the effect of neutral wrist splinting was to increase wrist extensibility by a mean of 1.4° (95% CI, −5.4° to 8.2°), and splinting the wrist in extension reduced wrist extensibility by a mean of 1.3° (95% CI, −4.9° to 2.4°) compared with the control condition. Conclusions— Splinting the wrist in either the neutral or extended wrist position for 4 weeks did not reduce wrist contracture after stroke. These findings suggest that the practice of routine wrist splinting soon after stroke should be discontinued.

Background and Purpose— Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. Methods— Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3×/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (V o 2 peak), o 2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. Results— Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, δ% T-AEX versus R-CONTROL, P P P o 2 peak ( r =0.43, P r =0.41, P Conclusions— T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.

Background and Purpose— To evaluate the effectiveness of a device that automates Constraint-Induced Movement therapy (CI therapy), termed AutoCITE, when only partially supervised by therapists. Methods— Twenty-seven participants with chronic stroke trained with AutoCITE for 3 hours per day for 10 consecutive weekdays. Participants were assigned to 1 of 3 groups in a fixed irregular order (ie, in alternating blocks): supervision from a therapist for 100%, 50%, or 25% of training time. Results— The effect sizes of the treatment gains for the 3 groups on the Motor Activity Log (MAL) were very large and for the Wolf Motor Function Test they were large (all P P Conclusion— These results demonstrate that AutoCITE training with greatly reduced supervision from a therapist is as effective as standard one-on-one CI therapy.

Enhancing recovery from stroke with effective rehabilitation interventions remains an elusive goal.1 Although intensive rehabilitation therapies such as constraint-induced movement therapy (CIMT) show promise,2 the intervention has not been deployed in routine clinical practice. Slow uptake of CIMT in routine clinical practice has been attributed to its large demand on professional resources and patient compliance, as well as the costs associated with delivering high doses of therapy in a relatively short time. To remediate these limitations, there have been calls for modified versions of CIMT that are less intensive, lower cost, and easier to deliver.3 Recent work by Barzel et al4 attempted to advance the understanding of modified forms of CIMT by applying this therapy in the home setting. Home CIMT includes the basic elements of CIMT including repetitive training, transfer of activities, and constraint of the nonparetic hand. However, Home CIMT attempts to accomplish each of these goals within the individual’s home setting under the supervision of a nonprofessional coach.4 Although study participants were involved in overall goal setting for their therapeutic program, they only interacted with professional rehabilitation practitioners (Occupational or Physical Therapists) in 5 visits: 2 initial home visits to set up the program in the first week of a 4-week program and 3 additional sessions to adjust the program during the next 3 weeks. The overall goal was 40 hours of task practice with the paretic arm for a 20-day period.

A previously healthy, right-handed 43-year-old man was found lying on the floor in his apartment. His relatives had been unable to contact him for more than a day. On admission, he was somnolent but attempted to obey commands and had a right-sided hemiplegia, dense sensory loss, severe word-finding difficulty, and anisocoria with miosis and ptosis in left eye (National Institutes of Health Stroke Scale, 21). Emergent computerized tomographic scan revealed an extensive left-hemispheric infarction (Figure [A]). Computerized tomographic angiography showed a left carotid dissection. The neurosurgeon recommended medical management; hypertonic saline was initiated. Fifteen hours after admission, his level of consciousness had deteriorated (Glasgow coma score, 10), his left pupil was enlarged and fixed, and increased midline shift was visible on computerized tomography (Figure [B]). The patient was referred to decompressive hemicraniectomy (DHC), which was performed 20 hours after admission. By 72 hours, the patient was more alert and his left pupil was reactive (still enlarged). Because of ventilatory problems, he required intermediate care for subsequent 2 weeks. After tracheostomy removal 18 days after admission, the patient was alert but hemiplegic and hemianopic, obeying commands, and able to communicate with single words and short phrases. He was discharged to a rehabilitation hospital 10 days later and thereafter to a supported residential home. Six years later, he was able to walk with a cane, go shopping unaided, communicate reasonably, and read short sentences with difficulty. His right …

Background and Purpose —Risk of hip fracture after stroke is 2 to 4 times that in a reference population. Osteomalacia is present in some patients with hip fractures in the absence of stroke, while disabled elderly stroke patients occasionally have severe deficiency in serum concentrations of 25-hydroxyvitamin D (25-OHD) (≤5 ng/mL). To determine the effects of vitamin D status on hip fracture risk, we prospectively studied a cohort of patients with hemiplegia after stroke who were aged at least 65 years. Methods —We compared baseline serum indices of bone metabolism, bone mineral density, and hip fracture occurrence in stroke patients with serum 25-OHD ≤25 nmol/L (≤10 ng/mL; deficient group, n=88) with findings in patients from the same cohort who had 25-OHD levels 26 to 50 nmol/L (10 to 20 ng/mL; insufficient group, n=76) or ≥51 nmol/L (≥21 ng/mL; sufficient group, n=72). Results —Over a 2-year follow-up interval, hip fractures on the paretic side occurred in 7 patients in the deficient group and 1 patient in the insufficient group ( P Conclusions —Elderly disabled stroke patients with serum 25-OHD concentrations ≤12 nmol/L (≤5 ng/mL) have an increased risk of hip fracture. Immobilization and advanced age cause severe 25-OHD deficiency and consequent reduction of BMD.

Background and Purpose —Early poststroke depression (PSD) is a frequent and specific entity that impairs the rehabilitation and functional recovery of hemiplegic patients. This trial was designed to study the efficacy and tolerance of fluoxetine (FLX) in the treatment of early PSD. Methods —This was a multicenter, double-blind, placebo-controlled study. Recent hemiplegic patients (19) were randomized to receive either 20 mg/d fluoxetine (FLX) or placebo for 6 weeks. Patients were evaluated by use of the Motricity Index, Mini-Mental State Examination, Functional Independence Measure, and MADRS. Statistical analysis was performed by using an intent-to-treat approach comparing the 2 groups at day 0 (baseline) and days 15, 30, and 45 (end point). Results —Of 121 patients screened, 31 were included in the study, 16 in the FLX group and 15 in the placebo group. There were no significant differences in baseline characteristics among the 2 groups. The FLX-treated patients compared with placebo-treated patients demonstrated significant improvement in mean MADRS scores at end point (11.8±6.7 [mean±SD] versus 18.7±10.0, respectively; P =0.05). FLX-treated patients compared with placebo-treated patients also demonstrated greater response rate (62.5% versus 33.3%, respectively) and greater mean decrease of MADRS (16.6 versus 8.4, respectively; P =0.02). There were no differences in motor, cognitive, or functional improvement and no significant side effects after FLX treatment, except for a patient with a moderate and transient increase of transaminases. Conclusions —FLX is an efficacious and well-tolerated treatment for early PSD. Further research is needed to evaluate the efficacy and safety of long-term treatment in this population.

Background and Purpose —Recovery from hemiparesis due to corticospinal tract infarction is well documented, but the mechanism of recovery is unknown. Functional MRI (fMRI) provides a means of identifying focal brain activity related to movement of a paretic hand. Although prior studies have suggested that supplementary motor regions in the ipsilesional and contralesional hemisphere play a role in recovery, little is known about the time course of cortical activation in these regions as recovery proceeds. Methods —Eight patients with first-ever corticospinal tract lacunes causing hemiparesis had serial fMRIs within the first few days after stroke and at 3 to 6 months. Six healthy subjects were used as controls. Statistically significant voxels during a finger-thumb opposition task were identified with an automated image processing program. An index of ipsilateral versus contralateral activity was used to compare relative contributions of the 2 hemispheres to motor function in the acute and chronic phases after stroke. Results —Controls showed expected activation in the contralateral sensorimotor cortex (SMC), premotor, and supplementary motor areas. Stroke patients differed from control patients in showing greater activation in the ipsilateral SMC, ipsilateral posterior parietal, and bilateral prefrontal regions. Compared with the nonparetic hand, the ratio of contralateral to ipsilateral SMC activity during movement of the paretic hand increased significantly over time as the paretic hand regained function. Conclusions —The evolution of activation in the SMC from early contralesional activity to late ipsilesional activity suggests that a dynamic bihemispheric reorganization of motor networks occurs during recovery from hemiparesis.

Background and Purpose —Recovery from hemiparesis after stroke has been shown to involve reorganization in motor and premotor cortical areas. However, whether poststroke recovery also depends on changes in remote brain structures, ie, diaschisis, is as yet unresolved. To address this question, we studied regional cerebral blood flow in 7 patients (mean±SD age, 54±8 years) after their first hemiparetic stroke. Methods —We analyzed imaging data voxel by voxel using a principal component analysis by which coherent changes in functional networks could be disclosed. Performance was assessed by a motor score and by the finger movement rate during the regional cerebral blood flow measurements. Results —The patients had recovered ( P P P Conclusions —Motor recovery after hemiparetic brain infarction is subserved by brain structures in locations remote from the stroke lesion. The topographic overlap of the lesion-affected and recovery-related networks suggests that diaschisis may play a critical role in stroke recovery.

Background and Purpose —Cortical reorganization of motor systems has been found in recovered stroke patients. Reorganization in nonrecovered hemiplegic stroke patients early after stroke, however, is less well described. We used positron emission tomography to study the functional reorganization of motor and sensory systems in hemiplegic stroke patients before motor recovery. Methods —Regional cerebral blood flow (rCBF) was measured in 6 hemiplegic stroke patients with a single, subcortical infarct and 3 normal subjects with the [ 15 O]H 2 O injection technique. Brain activation was achieved by passive elbow movements driven by a torque motor. Increases of rCBF comparing passive movements and rest were assessed with statistical parametric mapping. Significant differences were defined at P Results —In normal subjects, significant increases of rCBF were found in the contralateral sensorimotor cortex, supplementary motor area, cingulate cortex, and bilaterally in the inferior parietal cortex. In stroke patients, significant activation was observed bilaterally in the inferior parietal cortex and in the contralateral sensorimotor cortex, ipsilateral prefrontal cortex, supplementary motor area, and cingulate cortex. Significantly larger increases of rCBF in patients compared with normal subjects were found bilaterally in the sensorimotor cortex, stronger in the ipsilateral, unaffected hemisphere, and in both parietal lobes, including the ipsilateral precuneus. Conclusions —Passive movements in hemiplegic stroke patients before clinical recovery elicit some of the brain activation patterns that have been described during active movements after substantial motor recovery. Changes of cerebral activation in sensory and motor systems occur early after stroke and may be a first step toward restoration of motor function after stroke.

Background and Purpose —Subluxation is a significant problem in poststroke hemiplegia, resulting in pain and loss of function. Current treatments are not proved and not considered effective. It has been demonstrated that cyclical electrical stimulation of the shoulder muscles can reduce existing subluxation. The purpose of this study was to determine whether electrical stimulation could prevent subluxation in both the short and long terms. Methods —A prospective, randomized controlled study was used to determine the efficacy of electrical stimulation in preventing shoulder subluxation in patients after cerebrovascular accidents. Forty patients were selected and randomly assigned to a control or treatment group. They had their first assessment within 48 hours of their stroke, and those in the treatment group were immediately put on a regimen of electrical stimulation for 4 weeks. All patients were assessed at 4 weeks after stroke and then again at 12 weeks after stroke. Assessments were made of shoulder subluxation, pain, and motor control. Results —The treatment group had significantly less subluxation and pain after the treatment period, but at the end of the follow-up period there were no significant differences between the 2 groups. Conclusions —Electrical stimulation can prevent shoulder subluxation, but this effect was not maintained after the withdrawal of treatment.

Background and Purpose —The hyperdense middle cerebral artery sign (HMCAS) is a marker of thrombus in the middle cerebral artery. The aim of our study was to find out the frequency of the HMCAS, its association with initial neurological severity and early parenchymal ischemic changes on CT, its relevance to clinical outcome, and the efficacy of intravenous recombinant tissue plasminogen activator (rtPA) in patients with the HMCAS. Methods —Secondary analysis of the data from 620 patients who received either rtPA or placebo in the European Cooperative Acute Stroke Study I (ECASS I), a double-blind, randomized, multicenter trial. The baseline CT scans were obtained within 6 hours from the onset of symptoms. Functional and neurological outcomes were assessed using the modified Rankin Scale and the Scandinavian Stroke Scale at day 90. Results —We found an HMCAS in 107 patients(17.7%). The initial neurological deficit was more severe in patients with the HMCAS than in those lacking this sign ( P P P P =0.0297). Conclusions —The HMCAS is associated with severe brain ischemia and poor functional outcome. However, it has no significant independent prognostic value when accounting for the effect of initial severity of neurological deficit and of early parenchymal ischemic changes on CT. Patients with the HMCAS may benefit from intravenous rtPA.

Background and Purpose— Hemiparetic stroke patients with disturbed awareness for their motor weakness (anosognosia for hemiparesis/-plegia [AHP]) may exhibit further abnormal attitudes toward or perceptions of the affected limb(s). The present study investigated the clinical relationship and the anatomy of such abnormal attitudes and AHP. Methods— In a new series of 79 consecutively admitted acute stroke patients with right brain damage and hemiparesis/ -plegia, different types of abnormal attitudes toward the hemiparetic/plegic limb (asomatognosia, somatoparaphrenia, anosodiaphoria, misoplegia, personification, kinaesthetic hallucinations, supernumerary phantom limb) were investigated. Results— Ninty-two percent of the patients with AHP showed additional “disturbed sensation of limb ownership” (DSO) for the paretic/plegic limb. The patients had the feeling that their contralesional limb(s) do not belong to their body or even belong to another person. Analysis of lesion location revealed that the right posterior insula is a crucial structure involved in these phenomena. Conclusions— DSO for hemiparetic/-plegic limbs and AHP are tightly linked both clinically and anatomically. The right posterior insula seems to be a crucial structure involved in the genesis of our sense of limb ownership and self-awareness of actions.

Background and Purpose —A new gait training strategy for patients with stroke proposes to support a percentage of the patient’s body weight while retraining gait on a treadmill. This research project intended to compare the effects of gait training with body weight support (BWS) and with no body weight support (no-BWS) on clinical outcome measures for patients with stroke. Methods —One hundred subjects with stroke were randomized to receive one of two treatments while walking on a treadmill: 50 subjects were trained to walk with up to 40% of their body weight supported by a BWS system with overhead harness (BWS group), and the other 50 subjects were trained to walk bearing full weight on their lower extremities (no-BWS group). Treatment outcomes were assessed on the basis of functional balance, motor recovery, overground walking speed, and overground walking endurance. Results —After a 6-week training period, the BWS group scored significantly higher than the no-BWS group for functional balance ( P =0.001), motor recovery ( P =0.001), overground walking speed ( P =0.029), and overground walking endurance ( P =0.018). The follow-up evaluation, 3 months after training, revealed that the BWS group continued to have significantly higher scores for overground walking speed ( P =0.006) and motor recovery ( P =0.039). Conclusions —Retraining gait in patients with stroke while a percentage of their body weight was supported resulted in better walking abilities than gait training while the patients were bearing their full weight. This novel gait training strategy provides a dynamic and integrative approach for the treatment of gait dysfunction after stroke.

Background and Purpose —Autonomic dysfunction is frequently present in patients with cerebrovascular accidents (CVA). However, the pathophysiological mechanisms of these disorders are not clear. The purpose of the study was to assess the effects of CVA on the autonomic nervous system. Methods —In eight male patients with a history of CVA with damage of the cortical or subcortical structures, we measured the cold pressor response during recording of muscle sympathetic nerve activity (MSNA) from the peroneal nerve on the hemiplegic side. We also studied 10 age-matched male control subjects. Tests were performed before, during, and after immersion of the nonhemiplegic hand in ice water for a period of 3 minutes in each phase. We also recorded changes in heart rate (HR), arterial blood pressure, skin temperature of the middle finger, and perception of pain using the Borg’s score. Results —During the control period, the mean burst count of MSNA in CVA (57.2±3.9 beats/100 HR) was higher than in control subjects (36.3±3.2 beats/100 HR) ( P Conclusions —The present results suggest that increased MSNA in CVA may be due to damage of cortical or subcortical structures or stroke-related changes in other areas or nonspecific changes that cause continuous increase in basal MSNA.

Background and Purpose It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients, which might increase their risk of hip fracture. We evaluated the efficacy of 1α-hydroxyvitamin D 3 [1α(OH)D 3 ] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke. Methods In a randomized study, 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 μg 1α(OH)D 3 daily (treatment group, n=30) or an inactive placebo (placebo group, n=34) for 6 months and were observed for this duration. Both groups received 300 mg of elemental calcium daily. The bone mineral density (BMD) and metacarpal index (MCI) in the second metacarpals were determined by computed x-ray densitometry. The incidence of hip fractures in these patients was recorded. Results BMD on the hemiplegic side decreased by 2.4% in the treatment group and 8.9% in the placebo group ( P =.0021), while BMD on the intact side increased by 3.5% and decreased by 6.3% in the treated and placebo groups, respectively ( P =.0177). In the treatment group, the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before randomization. This difference increased in the placebo group. We observed a similar improvement in MCI in the treatment group but not in the placebo group. Four patients in the placebo group suffered a hip fracture compared with none in the treatment group ( P =.0362). Conclusions Treatment with 1α(OH)D 3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-standing stroke. Treatment also may improve these indices on the intact side.

Background Williams syndrome is a genetic disorder characterized by a high incidence of heart disease, arterial stenosis, and hypertension. Despite these features, cerebrovascular accidents have been described only recently and only in association with stenoses of the cerebral vasculature. Case Description A 19-year-old girl with Williams syndrome developed an acute-onset hemiparesis. MRI demonstrated an infarct involving the internal capsule and putamen. No stenotic areas were seen on angiography. Conclusions Stroke should be considered as a possible consequence of Williams syndrome, even in the absence of stenoses of the cerebral vasculature. Comparison of this case with those previously reported in the literature emphasizes the multiplicity of features in Williams syndrome that can contribute to the risk of stroke.

Background and Purpose The clinical features of thalamic hemorrhage in terms of localization are of great interest in many studies. To better understand the relationship between the localization of thalamic hemorrhage and clinical features, we evaluated the characteristics of patients with four different topographic types of thalamic hemorrhage. Methods We prospectively studied 100 patients with thalamic hemorrhage who were admitted consecutively to our primary care unit. We divided them into two groups according to large (>2 cm in diameter and/or >4 mL in volume) and small thalamic hemorrhage. Four topographic subgroups (large and small) were compared to identify clinical syndromes associated with distinct lesion locations. Results All patients with posterolateral thalamic hemorrhage had severe sensorimotor deficit. Neuropsychological disturbances in patients with posterolateral thalamic hemorrhage were prominent, with primarily transcortical aphasia in those with left-sided lesions and hemineglect and anosognosia in those with right-sided lesions. Several variants of vertical gaze dysfunction, skew ocular deviation, gaze preference toward the site of the lesion, and miotic pupils were frequent in posterolateral thalamic hemorrhage, particularly in the large type. Patients with small and large anterolateral thalamic hemorrhage were characterized by severe motor and sensory deficits; language and oculomotor disturbances were also observed, although less frequently than in posterolateral hemorrhage. Sensorimotor deficits were observed in patients with medial thalamic hemorrhage (moderate in small hemorrhages and severe in large hemorrhages because of involvement of the adjacent internal capsule). Language disturbances in patients with left-sided lesions and neglect in patients with right-sided lesions were seen only in large medial thalamic hemorrhage. Dorsal thalamic hemorrhage was rare and characterized by mild and transient sensorimotor disturbances. Among patients with dorsal thalamic hemorrhages, only those with large lesions had oculomotor and neuropsychological disturbances. Conclusions We concluded that despite clinical similarity among the four types of thalamic hemorrhage, there was some discrepancy in the clinical features of small and large thalamic hemorrhages. The most important predictors of death were initial consciousness, nuchal rigidity, maximum size, volume and ventricular extension of hemorrhage, and occurrence of hydrocephalus.

Background and Purpose Pain-related somatosensory evoked potentials (SEPs) were applied to study abnormality of pain sensation in stroke, together with electrically stimulated SEPs for deep sensation. Methods We recorded pain-related SEPs after CO 2 laser stimulation to the dorsum of the hand and electrically stimulated SEPs after median nerve stimulation at the wrist in 12 patients with stroke. We analyzed P340 in pain-related and parietal N20 in electrically stimulated SEPs. Results In 5 patients with a putaminal lesion, P340 was absent or its latency was delayed, and N20 was absent or reduced in amplitude. In 3 patients with a thalamic lesion, P340 and N20 showed various patterns according to the involved sites. In 4 patients with a lesion in the corona radiata, P340 and N20 were normal. Conclusions Abnormalities of P340 and N20 in the stroke location were related to impairment of the pain and vibration senses, respectively. Thus, pain-related and electrically stimulated SEPs were useful to investigate the sensory function of each structure in the central nervous system in patients with stroke.

Background and Purpose— Distinguishing between symptoms of posterior circulation infarction (PCI) and anterior circulation infarction (ACI) can be challenging. This study evaluated the frequency of symptoms/signs in the 2 vascular territories to determine the diagnostic value of particular symptoms/signs for PCI. Methods— Neurological deficits were reviewed and compared from 1174 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. The diagnostic value of specific symptoms/signs for PCI was determined by measuring their sensitivity, specificity, positive predictive value (PPV), and the OR. Results— Homolateral hemiplegia (PCI, 53.6% versus ACI, 74.9%; P P P =0.479) were the 3 most common symptoms/signs in PCI and ACI. The signs with the highest predictive values favoring a diagnosis of PCI were Horner's syndrome (4.0% versus 0%; P P P P P Conclusions— This study indicates that the symptoms/signs considered typical of PCI occur far less often than was expected. Inaccurate localization would occur commonly if clinicians relied on the clinical neurological deficits alone to differentiate PCI from ACI. Neuroimaging is vital to ensure accurate localization of cerebral infarction.

Pure dysarthria, isolated supranuclear facial paresis, and their combination without somatic motor dysfunction are rarely encountered clinical syndromes and have not yet been clearly characterized. Thirteen patients (9 men, 4 women; aged 33 to 72 [mean, 56] years) with unilateral strokes who developed dysarthria with or without facial paresis but without somatic motor dysfunction were reviewed in addition to case reports from previous literature. Computed tomographic scan and/or magnetic resonance imaging showed infarcts on the corona radiata in 4 patients, basal ganglia abutting the internal capsule in 3, basal ganglia-corona radiata in 1, pontine base in 3, and cortical-subcortical bulbar motor area in 2. The dysarthria and facial paresis were usually mild and transient, and either one was likely to be unnoticed. It is suggested that pure dysarthria or isolated facial paresis syndrome be considered as an extreme continuum of dysarthria-facial paresis syndrome, which is likely to be a variant of dysarthria-clumsy hand syndrome.

Although gait training is prominent in the rehabilitation of hemiparetic stroke patients, little is known about its outcome and prognostic factors in mildly affected patients. We therefore intended to assess gait in ambulatory stroke patients before and after a 4-week inpatient rehabilitation program based on the neurodevelopmental technique. We measured vertical ground reaction forces by force plates in 148 stroke patients. Variables were stance durations, peak vertical ground reaction forces at heel strike (Fz1) and toe-off (Fz2), loading and deloading rates, time to Fz1, and time to Fz2. The absolute changes for both legs and symmetry outcome were calculated. In addition, we assessed maximal walking speed, walking endurance, stair climbing ability, and the Motricity Index. Stance duration, weight acceptance, push-off of both legs, and the stance duration symmetry improved independent of changes of gait velocity. The symmetry of the ground reaction forces did not improve. Results were even worse for Fz1 and the loading rate at the end of treatment. Sex, age, side of hemiparesis, motor strength, stroke interval, and sensory impairment had no influence on the outcome of symmetry. Functional performance did not improve considerably. The absolute changes of the ground reaction forces indicated better weight acceptance and push-off of both legs and thus confirmed the efficacy of the neurodevelopmental technique. The symmetry outcome and the functional performance at the end of treatment, however, challenge the efficacy of intensive rehabilitation therapy for 4 weeks in its attempts to restore physiological gait in these mildly affected patients.

Many patients suffering from stroke exhibit denial of illness. As part of this symptom complex we observed denial of eye closure. We therefore aimed to document the frequency and phenomenology of denial of eye closure in acute stroke. Denial of eye closure was sought in 43 cases of denial of illness from a series of 400 acute strokes. Subjects underwent a neurological examination, and audiotaped interviews were performed during which they were asked to finger count through their closed eyes and their denial was challenged. Five of 43 patients with denial of hemiplegia after acute stroke were also found to have denial of eye closure (12%). Denial of eye closure was associated with drowsiness and in all but one patient with disorientation. In the three cases with imaging or autopsy data available, lesions were moderate to large, in the right hemisphere, and involved the frontal lobe. Three subjects confabulated as to what they saw through their closed eyes. One subject mislocalized the hospital closer to her home. Denial of eye closure occurs in a minority of patients with denial of illness after acute stroke. This phenomenon sheds light on denial as a whole and cannot easily be accounted for by unilateral explanations, such as inattention to one half of the body or loss of sensory input. There are aspects of denial, such as denial of eye closure, mislocalization, and the delusional intensity of beliefs, that can only be understood in cognitive terms.

In a randomized study of hemiparetic stroke patients with a median age of 75 years, functional recovery was significantly better in those who received additional sensory stimulation (n = 38), including electrostimulation, than in control patients (n = 40) given the same physiotherapy and occupational therapy; group differences for balance, mobility, and activities of daily living were significant. The present study was designed to investigate postural control in patients who survived more than 2 years after stroke onset. The 48 survivors (mean, 2.7 years; range, 2.0 to 3.8 years), 22 from the treatment group and 26 from the control group, were compared with 23 age-matched healthy subjects. Subjects were perturbed by vibrators applied to calf muscles or with galvanic vestibular stimulation. We evaluated postural control in terms of sway variances or sway velocities and the dynamics of postural control as a feedback system using system identification with a model previously validated for human postural control. Significantly more patients of the treatment group than of the control group maintained stance during perturbations (P < .01). Among patients capable of maintaining stance during perturbation, the control patients were characterized by significant divergence from normal values in two of the three characteristic parameters of dynamic postural control (ie, swiftness and stiffness; P < .05) compared with the treatment subgroup or age-matched subjects. The course of sensory stimulation enhanced recovery of postural function, an enhancement still significant 2 years after the lesion and treatment. The differences and near normalization of characteristic parameters of dynamic postural control among treated patients suggest that improved recovery after sensory stimulation may be achieved by patients regaining normal or near normal dynamics of human postural control.

Motor recovery is remarkable when the brain is damaged early in life. We describe a case of early damage to the right hemisphere with remarkable reorganization and plastic functional changes, studied by computed neuroimaging. A 31-year-old man had a left-sided hemiplegia at the age of 12, followed by good motor recovery despite a large right cortical-subcortical lesion. Single-photon emission computed tomography with motor activation study showed cerebral blood flow increase in the left premotor and sensorimotor cortices irrespective of the hand he was moving, without flow changes in the right hemisphere. A remarkable reorganization and plastic brain functional changes occurred in a patient after early diffuse damage of the right hemisphere. The study points to a potential role of ipsilateral cortical efferent pathways in subserving hand movements after early cerebral damage.

Clinical differentiation of lacunar from nonlacunar strokes in the very early phase could help to exclude patients with lacunar stroke from pharmacologic trials designed for nonlacunar strokes, namely, those with thrombolytic agents. In a continuous series of acute ischemic stroke patients, we evaluated how accurately a clinical diagnosis of pure motor hemiparesis or sensorimotor stroke formulated in the first hours from onset predicts a lacunar stroke documented by cerebral computed tomography or by autopsy. We examined 517 patients (299 men, 218 women; mean +/- SD age, 67 +/- 10 years) within 12 hours (mean +/- SD, 6.1 +/- 3.2 hours) of the event. At hospital admission, we observed 151 (29%) patients with pure motor hemiparesis and 68 (13%) patients with sensorimotor stroke. Computed tomography or autopsy was compatible with a lacunar stroke (ie, detection of a lacune or permanently negative computed tomography) in 170 (33%) patients, of whom 123 (72%) had pure motor hemiparesis and 47 (28%) had sensorimotor stroke. This led to a sensitivity of 72%, a specificity of 72%, a positive predictive value of 56%, and a negative predictive value of 84%. Overall positive predictive value of pure motor hemiparesis was 58% (60% for two areas and 58% for three areas involved), and that of sensorimotor stroke was 51% (87% for two areas and 40% for three areas involved). By separately evaluating the sides of lesions, we found a positive predictive value of 46% for right-side infarcts and of 72% for left-side infarcts. Right-side lesions constituted 51% of lesions in lacunar syndrome patients with lacunar stroke, 76% in those with nonlacunar stroke, 19% in nonlacunar syndrome patients with lacunar stroke, and 31% in those with nonlacunar stroke (P < .0001). During the first days of hospital stay we observed a deterioration of 21% of lacunar syndrome patients with nonlacunar stroke and an improvement of 49% of nonlacunar syndrome patients with lacunar stroke, with appearance and disappearance of symptoms of cortical involvement, respectively. The examination of these patients after the occurrence of these clinical changes would have led to a daily increase of the positive predictive value up to a maximum of 66% at day 7. Pure motor hemiparesis and sensorimotor stroke diagnosed within 12 hours of the event are poorly predictive of lacunar strokes. Hence, the very early identification of these syndromes cannot be used for patient selection in therapeutic trials.

Background — Excitotoxic insults such as stroke may induce release of fatty acid ethanolamides (FAEs), contributing to the downstream events in the ischemic cascade. We therefore studied release of FAEs such as anandamide, palmitylethanolamide (PEA), and oleylethanolamide (OEA) in the brain of a patient suffering from malignant hemispheric infarction treated with hypothermia. Case Description — A patient with life-threatening hemispheric stroke was treated with moderate hypothermia (33°C) that was maintained for 3 days, followed by a 3-day rewarming period. Microdialysis was applied to measure glutamate, lactate, and glycerol by using a microdialysis analyzer. FAEs were measured by microdialysis coupled with high-performance liquid chromatography/mass spectrometry. Release of neuroprotective fatty amides occurred within the first day after ischemia and reached high concentrations for all 3 substances in tissue surrounding the primary ischemic lesion: anandamide up to 42 pmol/mL, PEA up to 120 pmol/mL, and OEA up to 242 pmol/mL. There was a significant correlation with elevation of lactate as early marker for the hypoxic insult. Conclusions — This is the first report demonstrating release of FAEs in vivo during human stroke and may suggest contribution of the FAE signaling system to the pathophysiological events after ischemia.

This study was designed to assess the quality of life after an active poststroke period of rehabilitation and to investigate the possibility of a return to a working environment for those still of working age. The study was conducted on 180 consecutive patients affected by stroke who were hospitalized for the first time and discharged at least 1 year before the study. The group consisted of 65% men and 35% women with a mean age 65.29 years (SD, 11.22). The period between the stroke and the interview ranged from 12 to 196 months, with a mean of 37.5 months. The average Rankin score on discharge from the rehabilitation center was 2.718 (moderate handicap). The interview took place at home after consent obtained by telephone. The questionnaire included general and personal information regarding the individuals, their socioeconomic position, and scales for daily activity, depression, social activity, and stress produced in the family. The control group consisted of 167 age-matched subjects. A close correlation was observed in all patients between depression, social activity, and stress caused to relatives. The scores on the individual scales were clearly worse than those for control subjects. The patients received approximately 5 months of rehabilitation after the stroke. Differences emerged between men and women for depression and social activities, with the women scoring worse. In reference to daily life, 70% of prestroke ability was required on average after rehabilitation. The daily activity score at the time of the interview was also strongly influenced by the discharge score. The majority of patients were retired. Of the total, 20.64% returned to work, but not always to the same job and often after readapting to new conditions. Of this population, only 31.5% were women. With regard to the population aged younger than 65 years, 21.42% returned to work. Lesions in the dominant hemisphere do not necessarily seem to rule out return to work, even if associated with aphasia. The main discriminating element was the ability to understand language. The patients were often criticized by their cohabitants; the criticisms most often raised concerned apathy, irritability, and self-centeredness. Sexual activity was depressed in almost all cases. Despite the progress made in studying cerebral vasculopathies, patients in the aftermath of a stroke still seem to live unsatisfactorily, as they did many years ago. Useful measures include valid treatment against spasticity, psychological assistance, and greater social support.

Although persistent amnesia due to bilateral limbic system infarction is well described, reports of amnesic syndromes due to unilateral stroke have appeared infrequently and unsystematically. We report six new cases and review previously published reports to expand and consolidate knowledge regarding amnesic stroke. Six patients developed acute amnesia associated with unilateral stroke. Brain computed tomography or magnetic resonance imaging revealed lesions in limbic structures, which accounted for the memory deficit. Based on these as well as similar cases in the literature, we delineate three distinct syndromes of unilateral amnesic stroke involving the territories of the posterior cerebral, anterior choroidal, and thalamic penetrating arteries. Eighty-five percent of reported cases have involved the left hemisphere. Persistent as well as transient amnesia may be the sole or primary manifestation of unilateral hemispheric stroke. The vascular mechanisms of amnesic stroke are diverse. Patients presenting with acute amnesia possibly related to cerebral ischemia should be classified by documented or presumed lesion site as well as the involved vascular territory. Left amygdalohippocampal or diencephalic dysfunction may produce a particular vulnerability to global amnesia.

Epidemiological study of middle cerebral artery occlusion is important because the indication for extracranial-intracranial arterial bypass remains in dispute. To help clarify this issue, we investigated the prognosis of thrombotic middle cerebral artery occlusion in Japanese patients. We studied 40 patients with thrombotic middle cerebral artery occlusion who were selected on the basis of clinical features, computed tomographic findings, and angiographic findings. Patients with causes of embolism (i.e., cardiomyopathy, valvular heart disease, cardiac arrhythmia, and carotid ulceration) were excluded. The 40 patients were classified into three groups according to the site of middle cerebral artery occlusion: there were 13 patients with occlusion of the proximal portion of the M1 segment, 13 with distal M1 segment occlusion, and 14 with occlusion of the M2 segment. Good collateral circulation was associated with improved outcomes both clinically and by computed tomography in patients with occlusion of the proximal and distal portions of the M1 segment but not in those with M2 occlusion. It is reasonable to assume that not only collateral circulation but also the site of occlusion plays an important role in the outcome of middle cerebral artery occlusion. Our finding that good collateral circulation improves the outcome for thrombotic occlusion of the proximal and distal M1 segments supports the possible benefits of such surgery.

The purpose of this study was to examine the relations between host characteristics (age and side of body affected) and program variables (lengths of stay in acute care and rehabilitation, levels of functional ability at admission and discharge, and rates of community discharge). A sample of 7,905 patients was drawn from medical rehabilitation facilities enrolled in the Uniform Data System for Medical Rehabilitation who were admitted and discharged for the first time between January 1988 and June 1989. Data were analyzed using either chi 2 tests or z normal tests of proportions, and analyses of variance (ANOVA) and/or t tests. Significance was set at p less than 0.05, and statistically significant F ratios were examined using Student-Newman-Keuls tests. The average age of patients was 70.7 years (24% less than 65 years, 53% 65-79 years, and 23% greater than 79 years). Lengths of stay in acute care and rehabilitation, admission and discharge functional independence ratings, and rates of community discharge were generally inversely related to patient age. Patients with bilateral paresis had lower rates of community discharge than those with unilateral paresis, although this distinction was not evident in the older group. Results showed that older age and bilateral paresis are negatively associated with levels of independence at admission and discharge and with rates of community discharge.

Recently, it has been proposed that shoulder subluxation in hemiplegia is accompanied by 1) the appearance of a V-shaped articular configuration occurring between the humeral head and glenoid fossa and 2) the presence of chronic pain. The main purpose of this study was to investigate the validity of these statements. We evaluated 40 hemiplegic subjects over 3 months. Radiographs of the affected and nonaffected shoulders were taken at both a frontal plane (0 degree) and a 45 degree incidence. From these patients, subluxed (n = 19) and nonsubluxed (n = 21) groups were formed. Pain was evaluated using the Present Pain Intensity index of the McGill Pain Questionnaire. On these x-ray films, measurements were taken of the V-shaped space, abduction of the arm, and rotation of the scapula. The statistical analysis (analysis of variance for repeated measures) contrasted the results obtained from the nonaffected side with those from the affected side over the 3 months studied. At the 45 degree angle, which better exposes the articular configuration of the shoulder, the difference in the V angle between the affected and nonaffected shoulders was significant for the subluxed group (p less than 0.01), indicating that such a V-shaped space can be identified. The measures taken also indicate that a downward subluxation of the humeral head occurs relative to the scapula without any systematic abduction of the humerus or downward rotation of the scapula. None of the results obtained from the frontal plane x-ray films was significant. Finally, no significant relation was found between subluxation and shoulder pain.

We reviewed the medical records and cranial computed tomograms of 74 patients with acute capsular infarcts to investigate the correlation between infarct size and clinical symptoms. Average infarct size varied significantly by clinical syndrome; patients with sensorimotor stroke had the largest infarcts, patients with pure motor hemiparesis had middle-sized infarcts, and patients with ataxic hemiparesis or the dysarthria-clumsy hand syndrome had the smallest infarcts. Although it has been proposed that the type of lacunar syndrome is determined entirely by the infarct location, our results suggest that infarct size is another important factor influencing the clinical presentation of lacunar syndromes.

We interviewed 120 elderly hemiplegic patients 1 year after their acute stroke to assess cognitive impairment using the Mini-Mental State Examination, functional autonomy using the Barthel Index, mood disorders using the Hamilton Rating Depression Scale, and social integration using the Social Functioning Exam. Of the 76 patients admitted to this study, eight (12.1% of those testable) had significant cognitive impairment, 41 (53.9%) were functionally self-sufficient, 27 (35.5%) showed depressive symptoms, and 44 (57.9%) had problems in social and family integration. We suggest that a complete rehabilitation program aimed at producing a good quality of life for elderly hemiplegic patients should take into account all these aspects of human existence.

Background and Purpose— Shoulder pain is frequent after stroke and interferes with the rehabilitative process and outcome. However, treatments used for hemiplegic shoulder pain are limited and largely ineffective. This prospective, randomized, double-blind controlled study was conducted to compare the efficacies of botulinum toxin type A (BoNT-A) and triamcinolone acetonide (TA) on hemiplegic shoulder pain and their effects on arm function in patients with stroke. Methods— Twenty-nine hemiplegic stroke patients with shoulder pain (duration ≤24 months, pain on numeric rating scale ≥6/10) were randomized into 2 groups. One group received intramuscular injections of BoNT-A (BOTOX 100 U total) during one session to the infraspinatus, pectoralis and subscapularis muscles in conjunction with an intraarticular injection of normal saline to painful shoulder joint, whereas the other group received an intraarticular injection of TA (40 mg) and an intramuscular injection of normal saline to the same muscles. Outcome measures were pain (measured using a numeric rating scale), physician’s global rating scale, shoulder range of motion (ROM) in 4 directions, arm function measured using Fugl-Meyer score, and spasticity measured using the modified Ashworth scale. Measurements were made at baseline and 2, 6, and 12 weeks after injection. Results— At 12 weeks after treatment mean decrease in pain was 4.2 in the BoNT-A–treated group versus 2.5 in the TA-treated group ( P =0.051), and improvements in overall ROM were 82.9 o versus 51.8 o in these groups ( P =0.059), showing a strong trend toward there being less pain and better ROM among those treated with BoNT-A than with TA. However, no significant differences were observed between the 2 groups in terms of improvement in physician global rating, Fugl-Meyer score or modified Ashworth scales. No adverse effect was observed in either group. Conclusions— Results from this study suggest that injection of BoNT-A into selected muscles of the shoulder girdle might provide more pain relief and ROM improvement than intraarticular steroid in patients with hemiplegic shoulder pain. A larger clinical trial needs to be undertaken to confirm the benefits of this approach.