To test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.
In this prospective, open-label, randomized controlled trial with blinded ...outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.
A total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range 28-83) years, and mean interval between stroke onset to randomization was 20.2 (range 5-89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (
= 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index,
= 0.023), which was notable among patients with low predicted recovery potential. There were no serious treatment-related adverse events.
IV application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.
This study provides Class III evidence that autologous MSCs do not improve 90-day outcomes in patients with chronic stroke.
NCT01716481.
Research into rehabilitation robotics has grown rapidly and the number of therapeutic rehabilitation robots has expanded dramatically during the last two decades. Robotic rehabilitation therapy can ...deliver high-dosage and high-intensity training, making it useful for patients with motor disorders caused by stroke or spinal cord disease. Robotic devices used for motor rehabilitation include end-effector and exoskeleton types; herein, we review the clinical use of both types. One application of robot-assisted therapy is improvement of gait function in patients with stroke. Both end-effector and the exoskeleton devices have proven to be effective complements to conventional physiotherapy in patients with subacute stroke, but there is no clear evidence that robotic gait training is superior to conventional physiotherapy in patients with chronic stroke or when delivered alone. In another application, upper limb motor function training in patients recovering from stroke, robot-assisted therapy was comparable or superior to conventional therapy in patients with subacute stroke. With end-effector devices, the intensity of therapy was the most important determinant of upper limb motor recovery. However, there is insufficient evidence for the use of exoskeleton devices for upper limb motor function in patients with stroke. For rehabilitation of hand motor function, either end-effector and exoskeleton devices showed similar or additive effects relative to conventional therapy in patients with chronic stroke. The present evidence supports the use of robot-assisted therapy for improving motor function in stroke patients as an additional therapeutic intervention in combination with the conventional rehabilitation therapies. Nevertheless, there will be substantial opportunities for technical development in near future.
Objective
We sought to identify potentially modifiable determinants associated with variability in leptomeningeal collateral status in patients with acute ischemic stroke.
Methods
Data are from the ...Keimyung Stroke Registry. Consecutive patients with M1 segment middle cerebral artery ± intracranial internal carotid artery occlusions on baseline computed tomographic angiography (CTA) from May 2004 to July 2009 were included. Baseline and follow‐up imaging was analyzed blinded to all clinical information. Two raters assessed leptomeningeal collaterals on baseline CTA by consensus, using a previously validated regional leptomeningeal score (rLMC).
Results
Baseline characteristics (N = 206) were: mean age = 66.9 ± 11.6 years, median baseline National Institutes of Health Stroke Scale = 14 (interquartile range IQR = 11–20), and median time from stroke symptom onset to CTA = 166 minutes (IQR = 96–262). Poor collateral status at baseline (rLMC score = 0–10) was seen in 73 of 206 patients (35.4%). On univariate analyses, patients with poor collateral status at baseline were older; were hypertensive; had higher white blood cell count, blood glucose, D‐dimer, and serum uric acid levels; and were more likely to have metabolic syndrome. Multivariate modeling identified metabolic syndrome (odds ratio OR = 3.22, 95% confidence interval CI = 1.69–6.15, p < 0.001), hyperuricemia (per 1mg/dl serum uric acid; OR = 1.35, 95% CI = 1.12–1.62, p < 0.01), and older age (per 10 years; OR = 1.34, 95% CI = 1.02–1.77, p = 0.03) as independent predictors of poor leptomeningeal collateral status at baseline.
Interpretation
Metabolic syndrome, hyperuricemia, and age are associated with poor leptomeningeal collateral status in patients with acute ischemic stroke. Ann Neurol 2013;74:241–248
Functional MRI (fMRI) studies could provide crucial information on the neural mechanisms of motor recovery in patients with stroke. Resting-state fMRI is applicable to patients with stroke who are ...not capable of proper performance of the motor task. In this study, we explored neural correlates of motor recovery in patients with stroke by investigating longitudinal changes in resting-state functional connectivity of the ipsilesional primary motor cortex (M1).
A longitudinal observational study using repeated fMRI experiments was conducted in 12 patients with stroke. Resting-state fMRI data were acquired 4 times over a period of 6 months. Patients participated in the first session of fMRI shortly after onset and thereafter in subsequent sessions at 1, 3, and 6 months after onset. Resting-state functional connectivity of the ipsilesional M1 was assessed and compared with that of healthy subjects.
Compared with healthy subjects, patients demonstrated higher functional connectivity with the ipsilesional frontal and parietal cortices, bilateral thalamus, and cerebellum. Instead, functional connectivity with the contralesional M1 and occipital cortex were decreased in patients with stroke. Functional connectivity between the ipsilesional and contralesional M1 showed the most asymmetry at 1 month after onset to the ipsilesional side. Functional connectivity of the ipsilesional M1 with the contralesional thalamus, supplementary motor area, and middle frontal gyrus at onset was positively correlated with motor recovery at 6 months after stroke.
Resting-state fMRI elicited distinctive but comparable results with previous task-based fMRI, presenting complementary and practical values for use in the study of patients with stroke.
Recent advances in diagnoses, management, and rehabilitation have had a significant impact to reduce mortality and functional recovery in stroke patients. In spite of these medical advances, many ...stroke survivors still suffer from significant disabilities. Stroke is a complex disease caused by a combination of multiple risk factors. Therefore, personalized medicine is more important than any other field to overcome the limitations of current stroke management and rehabilitation. It is necessary to apply accurate evaluation for functions and a personalized approach in consideration of various characteristics of each stroke patient to improve function. The objective of this Special Issue is to inform the recent scientific knowledge, current limitations, and challenges for an individually tailored strategy in the areas of diagnosis, treatment, and rehabilitation of stroke. A multidisciplinary approach and research will be strongly encouraged for personalized medicine in the field of stroke treatment and rehabilitation.
•The relationship between conduction current and the behavioral outcomes after tDCS was studied.•The current density at DLPFC was related with working memory performance after tDCS.•Inconsistent ...outcomes of tDCS may originate from anatomical differences among individuals.
Transcranial direct current stimulation (tDCS) is a neuromodulation protocol that can facilitate or inhibit cortical excitability in particular areas of the brain. Although recent studies have reported that tDCS can successfully modulate the excitability of various brain sites, outcomes of tDCS were not consistent between subjects even when identical stimulation protocols were applied. Thus far, however, no studies have clearly verified the main cause of this individual variability. In this study, the main hypothesis was that individual variability in tDCS effects might be partly explained by anatomical differences among subjects. To verify our hypothesis, we investigated the relationship between the behavioral outcomes of a verbal working memory (WM) task and current density values at the dorsolateral prefrontal cortex (DLPFC) simulated using the finite element method (FEM). A 3-back verbal working memory task experiment was conducted in 17 healthy subjects before and after tDCS with cathode and anode electrodes located at the right supraorbital and F3 locations, respectively. The results showed that participants who showed evidence of enhanced WM task performance after tDCS had a significantly larger current density at the DLPFC than other participants, suggesting that inconsistent behavioral outcomes of tDCS might be partly due to individual anatomical differences.
White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive ...impairment in older adults. The purpose of this study was to evaluate the association between WMLs and cerebral amyloid-β (Aβ) burden in patients with cognitive impairment.
A total of 83 patients with cognitive impairment, who underwent brain MRI and F-18 florbetaben PET, were included prospectively: 19 patients were cognitively unimpaired, 30 exhibited mild cognitive impairment (MCI), and 34 exhibited dementia. The Fazekas scale was used to quantify WMLs on T2-weighted brain MR images. Cerebral Aβ burden was quantitatively estimated using volume-of-interest analysis. Differences in cerebral Aβ burden were evaluated between low-WML (Fazekas scale ≤1) and high-WML (Fazekas scale ≥2) groups. The relationship between the Fazekas rating and cerebral Aβ burden was evaluated using linear regression analysis after adjusting for age and sex.
In the overall cohort, the high-WML group exhibited significantly higher Aβ burden compared with the low-WML group (P = 0.011) and cerebral Aβ burden was positively correlated with Fazekas rating (β = 0.299, P = 0.006). In patients with MCI, the high-WML group exhibited significantly higher Aβ burden compared with the low-WML group (P = 0.019) and cerebral Aβ burden was positively correlated with Fazekas rating (β = 0.517, P = 0.003).
The presence of WMLs was associated with cerebral Aβ burden in patients with MCI. Our findings suggest that small vessel disease in the brain is related to Alzheimer's disease pathology.
Freezing of gait (FOG) affects mobility and balance seriously. Few reports have investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on FOG in Parkinson's disease (PD). We ...investigated the efficacy of high-frequency rTMS for the treatment of FOG in PD.
Seventeen patients diagnosed with PD were recruited in a randomized, double-blinded, cross-over study. We applied high frequency rTMS (90% of resting motor threshold, 10 Hz, 1,000 pulses) over the lower leg primary motor cortex of the dominant hemisphere (M1-LL) for five sessions in a week. We also administered alternative sham stimulation with a two-week wash out period. The primary outcomes were measured before, immediately after, and one week after the intervention using the Standing Start 180° Turn Test (SS-180) with video analysis and the Freezing of Gait Questionnaire (FOG-Q). The secondary outcome measurements consisted of Timed Up and Go (TUG) tasks and the Unified Parkinson's Disease Rating Scale part III (UPDRS-III). Motor cortical excitability was also evaluated.
There were significant improvements in the step required to complete the SS-180 and FOG-Q in the rTMS condition compared to the sham condition, and the effects continued for a week. The TUG and UPDRS-III also showed significant ameliorations over time in the rTMS condition. The MEP amplitude at 120% resting motor threshold and intracortical facilitation also increased after real rTMS condition.
High frequency rTMS over the M1-LL may serve as an add-on therapy for improving FOG in PD.
Highlights • The minimum number of pulses for reliable amplitude and latency of motor evoked potentials was 21 and 23 in response to neuronavigated single-pulse TMS, respectively. • The minimum ...number of pulses for reliable short-interval intracortical inhibition and intracortical facilitation was 20 and 25, respectively. • Navigated transcranial magnetic stimulation might reduce the number of pulses necessary for reliable measurements.
•Effect of dual-mode tDCS on the unilateral spatial neglect (USN) was assessed in stroke patients.•There were significant improvements in both dual and single mode tDCS for the line bisection test.•A ...significant interaction was found between the time and the tDCS modes.•The dual tDCS over the bilateral PPC was an effective method for treatment of USN in stroke patients.
Based on the interhemispheric inhibition model of unilateral visuospatial neglect (USN) after stroke, the effects of dual-mode transcranial direct current stimulation (tDCS) over the parietal cortices were assessed in a double-blind random-order cross-over experiment. Ten chronic right hemispheric stroke patients (4 men; mean age: 62.6 years) with USN were recruited. All participants underwent three randomly arranged tDCS sessions: (1) dual-mode, anodal tDCS over the right posterior parietal cortex (PPC) and cathodal tDCS over the left PPC; (2) single-mode, anodal tDCS over the right PPC; and (3) sham mode. Each session lasted 20min. Before and immediately after the stimulation, a line bisection test and star cancelation test were carried out. In the line bisection test, significant improvements were observed after both the dual- and the single-mode tDCS (p<0.05), but not after sham stimulation. Statistical analysis showed a significant interaction between time and tDCS mode, where the dual tDCS had a stronger effect than the single or sham stimulation modes (p<0.05). The star cancelation test did not show any significant change. These results suggest that dual tDCS over the bilateral PPC is an effective method for the treatment of USN in stroke patients.
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