Neurorehabilitation and Neural Repair

Objective. The aim of the study was to present a systematic review of studies that investigate the effects of robot-assisted therapy on motor and functional recovery in patients with stroke. Methods. A database of articles published up to October 2006 was compiled using the following Medline key words: cerebral vascular accident, cerebral vascular disorders, stroke, paresis, hemiplegia, upper extremity, arm, and robot. References listed in relevant publications were also screened. Studies that satisfied the following selection criteria were included: (1) patients were diagnosed with cerebral vascular accident; (2) effects of robot-assisted therapy for the upper limb were investigated; (3) the outcome was measured in terms of motor and/or functional recovery of the upper paretic limb; and (4) the study was a randomized clinical trial (RCT). For each outcome measure, the estimated effect size (ES) and the summary effect size (SES) expressed in standard deviation units (SDU) were calculated for motor recovery and functional ability (activities of daily living [ADLs]) using fixed and random effect models. Ten studies, involving 218 patients, were included in the synthesis. Their methodological quality ranged from 4 to 8 on a (maximum) 10-point scale. Results. Meta-analysis showed a nonsignificant heterogeneous SES in terms of upper limb motor recovery. Sensitivity analysis of studies involving only shoulder-elbow robotics subsequently demonstrated a significant homogeneous SES for motor recovery of the upper paretic limb. No significant SES was observed for functional ability (ADL). Conclusion. As a result of marked heterogeneity in studies between distal and proximal arm robotics, no overall significant effect in favor of robot-assisted therapy was found in the present meta-analysis. However, subsequent sensitivity analysis showed a significant improvement in upper limb motor function after stroke for upper arm robotics. No significant improvement was found in ADL function. However, the administered ADL scales in the reviewed studies fail to adequately reflect recovery of the paretic upper limb, whereas valid instruments that measure outcome of dexterity of the paretic arm and hand are mostly absent in selected studies. Future research into the effects of robot-assisted therapy should therefore distinguish between upper and lower robotics arm training and concentrate on kinematical analysis to differentiate between genuine upper limb motor recovery and functional recovery due to compensation strategies by proximal control of the trunk and upper limb.

Mục tiêu. Nghiên cứu hiệu quả của việc huấn luyện bằng thực tế ảo (VR) trên máy tính cho bàn tay bị liệt nửa người sau đột quỵ, sử dụng hệ thống cung cấp đào tạo tái giáo dục vận động lặp đi lặp lại và tái thu nhận kỹ năng. Phương pháp. Tám đối tượng trong giai đoạn mãn tính sau đột quỵ đã tham gia vào một chương trình kéo dài 3 tuần, sử dụng bàn tay bị liệt nửa người trong một loạt trò chơi máy tính tương tác trong 13 ngày huấn luyện, nghỉ cuối tuần và các kiểm tra trước và sau. Mỗi đối tượng tham gia huấn luyện khoảng 2 đến 2,5 giờ mỗi ngày. Các biện pháp đánh giá bao gồm các thay đổi trong các chỉ số đo trên máy tính về phạm vi chuyển động ngón cái và ngón tay, tốc độ ngón cái và ngón tay, phân khúc (khả năng di chuyển các ngón tay một cách độc lập), sức mạnh ngón cái và ngón tay, Bài kiểm tra Chức năng Tay của Jebsen, và kiểm tra Kinematic nhằm nắm bắt. Kết quả. Nhóm đối tượng đã cải thiện khả năng phân khúc ngón tay, phạm vi chuyển động và tốc độ của ngón cái và ngón tay, duy trì những tiến bộ này trong kiểm tra giữ lại sau một tuần. Chuyển giao các cải thiện này được chứng minh qua sự thay đổi trong Bài kiểm tra Chức năng Tay của Jebsen và sự giảm thiểu thời gian tổng thể từ đỉnh tốc độ tay đến lúc nâng vật từ bàn sau liệu trình trị liệu. Kết luận. Hiện tại, rất khó để cung cấp cường độ thực hành cần thiết cho sự tái tổ chức thần kinh và những thay đổi chức năng sau đột quỵ trong các mô hình cung cấp dịch vụ hiện nay. Các hệ thống bài tập máy tính có thể là một cách để tối ưu hóa thời gian của cả bệnh nhân và bác sĩ lâm sàng. Dữ liệu trong nghiên cứu này bổ sung bằng chứng để đề xuất khám phá các công nghệ mới để tích hợp vào thực hành hiện tại.

Objectives. This study aimed to establish the minimal detectable change (MDC) and clinically important differences (CID) of the Wolf Motor Function Test (WMFT) in patients with stroke, and to assess the proportions of patients' change scores exceeding the MDC and CID after stroke rehabilitation. Methods. A total of 57 patients received 1 of the 3 treatments for 3 weeks and underwent clinical assessments before and after treatment. The MDC, at 90% confidence (MDC ₉₀), was calculated from the standard error of measurement to indicate a real change for individual patients. Anchor-based and distribution-based approaches were used to triangulate the values of minimal CID. The percentages of patients exceeding the MDC and minimal CID were also examined. Results. The MDC₉₀ of the WMFT was 4.36 for the performance time (WMFT time) and 0.37 for the functional ability scale (WMFT FAS). The minimal CID ranged from 1.5 to 2 seconds on the WMFT time and from 0.2 to 0.4 points on the WMFT FAS. The MDC and CID proportions ranged from 14% to 30% on the WMFT time and from 39% to 65% on the WMFT FAS, respectively. Conclusions. The change score of an individual patient has to reach 4.36 and 0.37 on the WMFT time and WMFT FAS to indicate a real change. The mean change scores of a stroke group on the WMFT time and WMFT FAS should achieve 1.5 to 2 seconds and 0.2 to 0.4 points to be regarded as clinically important changes. Furthermore, the WMFT FAS may be more responsive than the WMFT time based on the results of proportions exceeding the threshold criteria.

This study examines the potential of using mental practice (MP) to promote the learning of 2 mobility tasks in persons with stroke. Twelve patients were trained with MP to increase the loading of the affected limb while standing up from a chair and sitting down. Vertical forces were recorded using force plates under each foot and the chair. Changes in the loading of the affected limb and in task duration, immediately after 1 training session and 24 h later, served as outcomes. After training, the loading of the affected limb had increased {P < 0.001) during standing up (16.2%) and sitting down (17.9%), and the improvement remained significant 24 h later, indicating a learning effect. In contrast, the duration of the performance did not change with training. The results indicate that, in the early stage of learning with MP, changes in limb-loading strategies are a more sensitive measure of performance than is speed.

Background and Objective . Loss of hand function in people with hemiparesis is a major contributor to disability poststroke. To use the hand for functional activities, a person may need control of the more proximal upper extremity segments to position and orient the hand with respect to the environment and may need control of the fingers to manipulate objects within the environment. The purpose of this project was to investigate how movement control at proximal, middle, and distal upper extremity segments contributed to loss of hand function in people with chronic hemiparesis. Methods. 32 patients with hemiparesis (avg 21.4 months postlesion) were studied making isolated movements of shoulder flexion, elbow flexion, forearm pronation/supination, wrist flexion/extension, and individual finger flexion using 3D kinematic techniques. For each segment, 3 variables were obtained: how far a segment could move (active range of motion [AROM]), how well a segment could move by itself (individuation index), and how well a segment could remain still when it was not supposed to move (stationary index). Hand function was measured with a battery of clinical tests, and principal components analysis was used to create a single hand function score for each patient from the test battery. Correlation and regression analyses were used to examine relationships between segmental movement control and hand function. Results. Movement control at all 9 segments of the upper extremity was related to hand function. Of the 9 segments, the thumb tended to have the weakest relationship with hand function. Of the 3 measures of movement control, AROM had strong relationships with and predicted the most variance in hand function (73%). Most of this variance was shared across segments, such that, for AROM, there were no unique contributions provided by proximal, middle, or distal segments. Conclusions. These data support the idea that loss of movement control covaries across segments and that loss of hand function is due to loss of movement control at all segments, not just at distal ones.

Changes in sensory function including chronic pain and allodynia are common sequelae of spinal cord injury (SCI) in humans. The present study documents the extent and time course of mechanical allodynia and cold hyperalgesia after contusion SCI in the rat using stimulation with graded von Frey filaments (4.97–50.45 g force) and ice probes. Fore- and hind-paw withdrawal thresholds to plantar skin stimulation were determined in rats with a range of SCI severities (10-g weight dropped from 6.25, 12.5, or 25 mm using the MASCIS injury device); animals with 25-mm injuries most consistently showed decreased hind-paw withdrawal thresholds to touch and cold, which developed over several weeks after surgery. Stimulation of the torso with graded von Frey hairs was performed at specified locations on the back and sides from the neck to the haunch. Suprasegmental responses (orientation, vocalization, or escape) to mechanical stimulation of these sites were elicited infrequently in the laminectomy control rats and only during the first 3 weeks after surgery, whereas in 25-mm SCI rats, such responses were obtained for the entire 10 weeks of the study. These data suggest that rats with contusion SCI may exhibit sensory alterations relevant to human spinal cord injuries.

Background and Objective. Tinnitus is the perception of a phantom sound. The aim of this study was to compare current intensity (center anode 1 mA and 2 mA), duration (10 minutes and 20 minutes), and location (left temporoparietal area [LTA] and dorsolateral prefrontal cortex [DLPFC]) using 4 × 1 high-definition transcranial direct current stimulation (HD-tDCS) for tinnitus reduction. Methods. Twenty-seven participants with chronic tinnitus (>2 years) and mean age of 53.5 years underwent 2 sessions of HD-tDCS of the LTA and DLPFC in a randomized order with a 1 week gap between site of stimulation. During each session, a combination of 4 different settings were used in increasing dose (1 mA, 10 minutes; 1 mA, 20 minutes; 2 mA, 10 minutes; and 2 mA, 20 minutes). The impact of different settings on tinnitus loudness and annoyance was documented. Results. Twenty-one participants (77.78%) reported a minimum of 1 point reduction on tinnitus loudness or annoyance scales. There were significant changes in loudness and annoyance for duration of stimulation, F(1, 26) = 10.08, P < .005, and current intensity, F(1, 26) = 14.24, P = .001. There was no interaction between the location, intensity, and duration of stimulation. Higher intensity (2 mA) and longer duration (20 minutes) of stimulation were more effective. Conclusions. A current intensity of 2 mA for 20-minute duration was the most effective setting used for tinnitus relief. The stimulation of the LTA and DLPFC were equally effective for suppressing tinnitus loudness and annoyance.

Background. The authors have shown that rats can be retrained to swim after a moderately severe thoracic spinal cord contusion. They also found that improvements in body position and hindlimb activity occurred rapidly over the first 2 weeks of training, reaching a plateau by week 4. Overground walking was not influenced by swim training, suggesting that swimming may be a task-specific model of locomotor retraining. Objective. To provide a quantitative description of hindlimb movements of uninjured adult rats during swimming, and then after injury and retraining. Methods. The authors used a novel and streamlined kinematic assessment of swimming in which each limb is described in 2 dimensions, as 3 segments and 2 angles. Results. The kinematics of uninjured rats do not change over 4 weeks of daily swimming, suggesting that acclimatization does not involve refinements in hindlimb movement. After spinal cord injury, retraining involved increases in hindlimb excursion and improved limb position, but the velocity of the movements remained slow. Conclusion. These data suggest that the activity pattern of swimming is hardwired in the rat spinal cord. After spinal cord injury, repetition is sufficient to bring about significant improvements in the pattern of hindlimb movement but does not improve the forces generated, leaving the animals with persistent deficits. These data support the concept that force (load) and pattern generation (recruitment) are independent and may have to be managed together with respect to postinjury rehabilitation.

Background. Mesenchymal stem cell (MSC)-derived exosomes play a critical role in regenerative medicine. Objective. To determine the dose- and time-dependent efficacy of exosomes for treatment of traumatic brain injury (TBI). Methods. Male rats were subjected to a unilateral moderate cortical contusion. In the dose-response study, animals received a single intravenous injection of exosomes (50, 100, 200 µg per rat) or vehicle, with treatment initiated at 1 day after injury. In the therapeutic window study, animals received a single intravenous injection of 100 µg exosomes or vehicle starting at 1, 4, or 7 days after injury. Neurological functional tests were performed weekly after TBI for 5 weeks. Spatial learning was measured on days 31 to 35 after TBI using the Morris water maze test. Results. Compared with the vehicle, regardless of the dose and delay in treatment, exosome treatment significantly improved sensorimotor and cognitive function, reduced hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis, and reduced neuroinflammation. Exosome treatment at 100 µg per rat exhibited a significant therapeutic effect compared with the 50- or 200-µg exosome groups. The time-dependent exosome treatment data demonstrated that exosome treatment starting at 1 day post-TBI provided a significantly greater improvement in functional and histological outcomes than exosome treatments at the other 2 delayed treatments. Conclusions. These results indicate that exosomes have a wide range of effective doses for treatment of TBI with a therapeutic window of at least 7 days postinjury. Exosomes may provide a novel therapeutic intervention in TBI.

Background. Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. Objective. To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Methods. Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Results. Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb–hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Conclusion. Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries.