Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke.
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ABSTRACT:
SUBMITTER: Chang WH
PROVIDER: S-EPMC4776414 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
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Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke.
Chang Won Hyuk WH Park Chang-hyun CH Kim Deog Young DY Shin Yong-Il YI Ko Myoung-Hwan MH Lee Ahee A Jang Shin Yi SY Kim Yun-Hee YH
BMC neurology 20160302
<h4>Background</h4>Cerebrolysin is a neuropeptide preparation with neuroprotective and neurorestorative effects. Combining Cerebrolysin treatment with a standardized rehabilitation program may have a potential synergistic effect in the subacute stage of stroke. This study aims to evaluate whether Cerebrolysin provides additional motor recovery on top of rehabilitation therapy in the subacute stroke patients with moderate to severe motor impairment.<h4>Methods</h4>This phase IV trial was designed ...[more]
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Project description:The objective of this study was to evaluate whether Cerebrolysin combined with rehabilitation therapy supports additional motor recovery in stroke patients with severe motor impairment. This study analyzed the combined data from the two phase IV prospective, multicenter, randomized, double-blind, placebo-controlled trials. Stroke patients were included within seven days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo with standardized rehabilitation therapy. Assessments were performed at baseline, immediately after the treatment course, and 90 days after stroke onset. The plasticity of the motor system was assessed by diffusion tensor imaging and resting state fMRI. In total, 110 stroke patients were included for the full analysis set (Cerebrolysin n = 59, placebo n = 51). Both groups showed significant motor recovery over time. Repeated-measures analysis of varianceshowed a significant interaction between time and type of intervention as measured by the Fugl-Meyer Assessment (p < 0.05). The Cerebrolysin group demonstrated less degenerative changes in the major motor-related white matter tracts over time than the placebo group. In conclusion, Cerebrolysin treatment as an add-on to a rehabilitation program is a promising pharmacologic approach that is worth considering in order to enhance motor recovery in ischemic stroke patients with severe motor impairment.
| S-EPMC8231166 | biostudies-literature
Project description:BackgroundAt the moment, the possible options for the management of cognitive dysfunctions in patients with MS (pMS) are pharmacological interventions, cognitive rehabilitation (CR), and physical exercise. However, worldwide, multimodal programs are infrequently applied in pMS and CR is not easily accessible through the National Health System as MR.ObjectiveThe aim of the study is to explore if the combination of motor and cognitive rehabilitation may favor better outcomes on cognitive efficiency compared to separate trainings.MethodsForty-eight pMS were submitted to detailed neuropsychological and motor assessments, before (T0) and after (T1) having performed one of three rehabilitation conditions (two cognitive trainings/week-Reha1; one cognitive and one motor training/week-Reha2; two motor trainings/week-Reha3, for 12 weeks); they were randomly assigned to one condition or another. The CR was focused on memory functioning and performed with the Rehacom program.ResultsNo significant differences in age, sex, education, and disease course were found between the three groups (sig. > .05). Reha1 patients increased only their cognitive performance, and Reha3 only increased their motor performance, while Reha2 increased both cognitive and motor performances. This benefit was also confirmed by the cognitive efficiency expressed by the Cognitive Impairment Index.ConclusionsThese data confirm that to include cognitive training within rehabilitation programs may induce important benefits in pMS. Furthermore, pMS seem to benefit from a combined approach (cognitive and motor) more than from CR and motor rehabilitation separately (ClinicalTrial.gov ID: NCT05462678; 14 July 2022, retrospectively registered).
| S-EPMC9769485 | biostudies-literature
Project description:OBJECTIVES:To evaluate effects of somatosensory stimulation in the form of repetitive peripheral nerve sensory stimulation (RPSS) in combination with transcranial direct current stimulation (tDCS), tDCS alone, RPSS alone, or sham RPSS?+?tDCS as add-on interventions to training of wrist extension with functional electrical stimulation (FES), in chronic stroke patients with moderate to severe upper limb impairments in a crossover design. We hypothesized that the combination of RPSS and tDCS would enhance the effects of FES on active range of movement (ROM) of the paretic wrist to a greater extent than RPSS alone, tDCS alone or sham RPSS?+?tDCS. MATERIALS AND METHODS:The primary outcome was the active ROM of extension of the paretic wrist. Secondary outcomes were ROM of wrist flexion, grasp, and pinch strength of the paretic and nonparetic upper limbs, and ROM of wrist extension of the nonparetic wrist. Outcomes were blindly evaluated before and after each intervention. Analysis of variance with repeated measures with factors "session" and "time" was performed. RESULTS:After screening 2499 subjects, 22 were included. Data from 20 subjects were analyzed. There were significant effects of "time" for grasp force of the paretic limb and for ROM of wrist extension of the nonparetic limb, but no effects of "session" or interaction "session x time." There were no significant effects of "session," "time," or interaction "session x time" regarding other outcomes. CONCLUSIONS:Single sessions of PSS?+?tDCS, tDCS alone, or RPSS alone did not improve training effects in chronic stroke patients with moderate to severe impairment.
| S-EPMC5801160 | biostudies-literature
Project description:Fasudil, a Rho-associated protein kinase (ROCK) inhibitor, has a protective effect on the central nervous system. In addition, environmental enrichment is a promising technique for inducing the recovery of motor impairments in ischemic stroke models. The present study aimed to explore whether environmental enrichment combined with fasudil can facilitate motor function recovery and induce cortical axonal regeneration after stroke. First, a mouse model of ischemic cerebral stroke was established by photochemical embolization of the left sensorimotor cortex. Fasudil solution (10 mg/kg per day) was injected intraperitoneally for 21 days after the photothrombotic stroke. An environmental enrichment intervention was performed on days 7-21 after the photothrombotic stroke. The results revealed that environmental enrichment combined with fasudil improved motor function, increased growth-associated protein 43 expression in the infarcted cerebral cortex, promoted axonal regeneration on the contralateral side, and downregulated ROCK, p-LIM domain kinase (LIMK)1, and p-cofilin expression. The combined intervention was superior to monotherapy. These findings suggest that environmental enrichment combined with fasudil treatment promotes motor recovery after stroke, at least partly by stimulating axonal regeneration. The underlying mechanism might involve ROCK/LIMK1/cofilin pathway regulation. This study was approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 20160858A232) on February 24, 2016.
| S-EPMC8374579 | biostudies-literature
Project description:Thorough assessment of cerebral dysfunction after acute lesions is paramount to optimize predicting clinical outcomes. We here built random forest classifier-based prediction models of acute motor impairment and recovery post-stroke. Predictions relied on structural and resting-state fMRI data from 54 stroke patients scanned within the first days of symptom onset. Functional connectivity was estimated via static and dynamic approaches. Motor performance was phenotyped in the acute phase and 6 months later. A model based on the time spent in specific dynamic connectivity configurations achieved the best discrimination between patients with and without motor impairments (out-of-sample area under the curve, 95% confidence interval: 0.67 ± 0.01). In contrast, patients with moderate-to-severe impairments could be differentiated from patients with mild deficits using a model based on the variability of dynamic connectivity (0.83 ± 0.01). Here, the variability of the connectivity between ipsilesional sensorimotor cortex and putamen discriminated the most between patients. Finally, motor recovery was best predicted by the time spent in specific connectivity configurations (0.89 ± 0.01) in combination with the initial impairment. Here, better recovery was linked to a shorter time spent in a functionally integrated configuration. Dynamic connectivity-derived parameters constitute potent predictors of acute impairment and recovery, which, in the future, might inform personalized therapy regimens to promote stroke recovery.
| S-EPMC8578497 | biostudies-literature
Project description:Objective: Aphasia and apraxia of speech (AOS) after stroke frequently co-occur with a hand motor impairment but few studies have investigated stroke recovery across motor and speech-language domains. In this study, we set out to test the shared recovery hypothesis. We aimed to (1) describe the prevalence of AOS and aphasia in subacute stroke patients with a hand motor impairment and (2) to compare recovery across speech-language and hand motor domains. In addition, we also explored factors predicting recovery from AOS. Methods: Seventy participants with mild to severe paresis in the upper extremity were assessed; 50% of these (n = 35) had left hemisphere (LH) lesions. Aphasia, AOS and hand motor assessments and magnetic resonance imaging were conducted at 4 weeks (A1) and at 6 months (A2) after stroke onset. Recovery was characterized in 15 participants showing initial aphasia that also had complete follow-up data at 6 months. Results: All participants with AOS and/or aphasia had LH lesions. In LH lesioned, the prevalence of aphasia was 71% and of AOS 57%. All participants with AOS had aphasia; 80% of the participants with aphasia also had AOS. Recovery in aphasia (n = 15) and AOS (n = 12) followed a parallel pattern to that observed in hand motor impairment and recovery correlated positively across speech-language and motor domains. The majority of participants with severe initial aphasia and AOS showed a limited but similar amount of recovery across domains. Lesion volume did not correlate with results from behavioral assessments, nor with recovery. The initial aphasia score was the strongest predictor of AOS recovery. Conclusion: Our findings confirm the common occurrence of AOS and aphasia in left hemisphere stroke patients with a hand motor impairment. Recovery was similar across speech-language and motor domains, even in patients with severe impairment, supporting the shared recovery hypothesis and that similar brain recovery mechanisms are involved in speech-language and motor recovery post stroke. These observations contribute to the knowledge of AOS and its relation to motor and language functions and add information that may serve as a basis for future studies of post stroke recovery. Studies including neuroimaging and/or biological assays are required to gain further knowledge on shared brain recovery mechanisms.
| S-EPMC8044583 | biostudies-literature
Project description:Background. Spontaneous recovery early after stroke is most evident during a time-sensitive window of heightened neuroplasticity, known as spontaneous neurobiological recovery. It is unknown whether poststroke upper-limb motor and somatosensory impairment both reflect spontaneous neurobiological recovery or if somatosensory impairment and/or recovery influences motor recovery. Methods. Motor (Fugl-Meyer upper-extremity [FM-UE]) and somatosensory impairments (Erasmus modification of the Nottingham Sensory Assessment [EmNSA-UE]) were measured in 215 patients within 3 weeks and at 5, 12, and 26 weeks after a first-ever ischemic stroke. The longitudinal association between FM-UE and EmNSA-UE was examined in patients with motor and somatosensory impairments (FM-UE ? 60 and EmNSA-UE ? 37) at baseline. Results. A total of 94 patients were included in the longitudinal analysis. EmNSA-UE increased significantly up to 12 weeks poststroke. The longitudinal association between motor and somatosensory impairment disappeared when correcting for progress of time and was not significantly different for patients with severe baseline somatosensory impairment. Patients with a FM-UE score ?18 at 26 weeks (n = 55) showed a significant positive association between motor and somatosensory impairments, irrespective of progress of time. Conclusions. Progress of time, as a reflection of spontaneous neurobiological recovery, is an important factor that drives recovery of upper-limb motor as well as somatosensory impairments in the first 12 weeks poststroke. Severe somatosensory impairment at baseline does not directly compromise motor recovery. The study rather suggests that spontaneous recovery of somatosensory impairment is a prerequisite for full motor recovery of the upper paretic limb.
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Project description:Brain-machine interfaces (BMI) based on scalp EEG have the potential to promote cortical plasticity following stroke, which has been shown to improve motor recovery outcomes. However, the efficacy of BMI enabled robotic training for upper-limb recovery is seldom quantified using clinical, EEG-based, and kinematics-based metrics. Further, a movement related neural correlate that can predict the extent of motor recovery still remains elusive, which impedes the clinical translation of BMI-based stroke rehabilitation. To address above knowledge gaps, 10 chronic stroke individuals with stable baseline clinical scores were recruited to participate in 12 therapy sessions involving a BMI enabled powered exoskeleton for elbow training. On average, 132 ± 22 repetitions were performed per participant, per session. BMI accuracy across all sessions and subjects was 79 ± 18% with a false positives rate of 23 ± 20%. Post-training clinical assessments found that FMA for upper extremity and ARAT scores significantly improved over baseline by 3.92 ± 3.73 and 5.35 ± 4.62 points, respectively. Also, 80% participants (7 with moderate-mild impairment, 1 with severe impairment) achieved minimal clinically important difference (MCID: FMA-UE >5.2 or ARAT >5.7) during the course of the study. Kinematic measures indicate that, on average, participants' movements became faster and smoother. Moreover, modulations in movement related cortical potentials, an EEG-based neural correlate measured contralateral to the impaired arm, were significantly correlated with ARAT scores (ρ = 0.72, p < 0.05) and marginally correlated with FMA-UE (ρ = 0.63, p = 0.051). This suggests higher activation of ipsi-lesional hemisphere post-intervention or inhibition of competing contra-lesional hemisphere, which may be evidence of neuroplasticity and cortical reorganization following BMI mediated rehabilitation therapy.
| S-EPMC7749405 | biostudies-literature
Project description:Upper limb motor deficits in severe stroke survivors often remain unresolved over extended time periods. Novel neurotechnologies have the potential to significantly support upper limb motor restoration in severely impaired stroke individuals. Here, we review recent controlled clinical studies and reviews focusing on the mechanisms of action and effectiveness of single and combined technology-aided interventions for upper limb motor rehabilitation after stroke, including robotics, muscular electrical stimulation, brain stimulation and brain computer/machine interfaces. We aim at identifying possible guidance for the optimal use of these new technologies to enhance upper limb motor recovery especially in severe chronic stroke patients. We found that the current literature does not provide enough evidence to support strict guidelines, because of the variability of the procedures for each intervention and of the heterogeneity of the stroke population. The present results confirm that neurotechnology-aided upper limb rehabilitation is promising for severe chronic stroke patients, but the combination of interventions often lacks understanding of single intervention mechanisms of action, which may not reflect the summation of single intervention's effectiveness. Stroke rehabilitation is a long and complex process, and one single intervention administrated in a short time interval cannot have a large impact for motor recovery, especially in severely impaired patients. To design personalized interventions combining or proposing different interventions in sequence, it is necessary to have an excellent understanding of the mechanisms determining the effectiveness of a single treatment in this heterogeneous population of stroke patients. We encourage the identification of objective biomarkers for stroke recovery for patients' stratification and to tailor treatments. Furthermore, the advantage of longitudinal personalized trial designs compared to classical double-blind placebo-controlled clinical trials as the basis for precise personalized stroke rehabilitation medicine is discussed. Finally, we also promote the necessary conceptual change from 'one-suits-all' treatments within in-patient clinical rehabilitation set-ups towards personalized home-based treatment strategies, by adopting novel technologies merging rehabilitation and motor assistance, including implantable ones.
| S-EPMC6658861 | biostudies-literature
Project description:While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later. Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction. Sensorimotor network ROIs were derived from a meta-analysis of arm voluntary movement tasks. Bootstrapping with 1000 replications was used for internal model validation. During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Compared to controls, patients showed: 1) lower task-related activity in ipsilesional MI, SMA and contralesional cerebellum (lobules V-VI) and 2) higher activity in contralesional MI, superior temporal gyrus and OP1-OP4. Using multiple regression, we found that the combination of baseline motor-FMS, activity in ipsilesional MI (BA4a), putamen and ipsilesional OP1 predicted motor outcome measured 6 months later (adjusted-R2 = 0.85; bootstrap p < 0.001). Baseline motor-FMS alone predicted only 54% of the variance. When baseline motor-FMS was removed, the combination of increased activity in ipsilesional MI-BA4a, ipsilesional thalamus, contralesional mid-cingulum, contralesional OP4 and decreased activity in ipsilesional OP1, predicted better motor outcome (djusted-R2 = 0.96; bootstrap p < 0.001). In subacute stroke, fMRI brain activity related to passive movement measured in a sensorimotor network defined by activity during voluntary movement predicted motor recovery better than baseline motor-FMS alone. Furthermore, fMRI sensorimotor network activity measures considered alone allowed excellent clinical recovery prediction and may provide reliable biomarkers for assessing new therapies in clinical trial contexts. Our findings suggest that neural reorganization related to motor recovery from moderate to severe stroke results from balanced changes in ipsilesional MI (BA4a) and a set of phylogenetically more archaic sensorimotor regions in the ventral sensorimotor trend, in which OP1 and OP4 processes may complement the ipsilesional dorsal motor cortex in achieving compensatory sensorimotor recovery.
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