Restorative neurology and neuroscience最新文献

Background: Upper-limb robot-mediated therapy is usually carried out in active-assisted mode because it enables performance of many movements. However, assistance may reduce the patient's own efforts which could limit motor recovery.

Objective: The aim of this study was to compare the effects of active-assisted and active-unassisted robotic interactions on motor recovery in subacute stroke patients with moderate hemiparesis.

Methods: Fourteen patients underwent a 6-week combined upper limb program of usual therapy and robotic therapy using either the active-unassisted (n = 8) or active-assisted (n = 6) modes. In the active-assisted group, assistance was only provided for the first 3 weeks (1st period) and was then switched off for the remaining 3 weeks (2nd period). The Fugl-Meyer Assessment (FMA) was carried out pre- and post-treatment. The mean number of movements performed and the mean working distance during the 1st and 2nd periods were compared between groups.

Results: FMA score improved post-treatment in both groups with no between-group differences: active-assisted group: +8±6 pts vs active-unassisted group: +10±6 pts (ns). Between the 1st and 2nd periods, there was a statistical trend towards an improvement in the number of movements performed (p = 0.06) in the active-unassisted group (526±253 to 783±434, p = 0.06) but not in the active-assisted group (882±211 to 880±297, ns). Another trend of improvement was found for the working distance in the active-unassisted group (8.7±4.5 to 9.9±4.7, p = 0.09) but not in the active-assisted group (14.0±0 to 13.5±1.1, ns).

Conclusions: The superiority of the non-assistive over assistive robotic modes has not been demonstrated. However, the non-assistive mode did not appear to reduce motor recovery in this population, despite the performance of fewer movements on shorter working distance compared with the group who had assistance. It seems that the requirement of effort could be a determinant factor for recovery in neurorehabilitation however further well-design studies are needed to fully understand this phenomenon.

Background: Physical exercise can improve cognitive dysfunction. Its specific mechanism remains unknown. Recent studies have indicated that elevating or peripherally overexpressing brain-derived neurotrophic factors (BDNF) improve cognitive impairment.

Objective: This meta-analysis aimed to investigate whether physical exercise improves cognitive performance in patients with cognitive dysfunction, such as mild cognitive impairment (MCI) or Alzheimer's disease (AD), by increasing peripheral BDNF.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched up to June 2020 for studies that assayed the changes in peripheral BDNF levels in MCI and AD patients after exercise training.

Results: Peripheral BDNF levels were significantly elevated after a single exercise session (SMD = 0.469, 95% CI: 0.150-0.787, P = 0.004) or regular exercise interventions (SMD = 0.418, 95% CI: 0.105-0.731, P = 0.009). Subgroup analysis showed that only regular aerobic exercise interventions (SMD = 0.543, 95% CI: 0.038-1.049, P = 0.035) and intervention duration of 16 weeks or greater (SMD = 0.443, 95% CI: 0.154 -0.733, P = 0.003) significantly increased peripheral BDNF levels. Only plasma BDNF levels (SMD = 0.365, 95% CI:0.066-0.664, P = 0.017) were significantly increased after exercise interventions.

Conclusions: Acute and chronic physical exercises may improve cognitive impairment by increasing peripheral BDNF levels. Aerobic exercises and a longer duration of exercising increased BDNF levels. These findings also suggest that BDNF may be a suitable biomarker for evaluating the effect of exercise in patients with cognitive impairment, such as AD or MCI.

Background: There is a growing concern among the scientific community that the effects of transcranial direct current stimulation (tDCS) are highly variable across studies. The use of different tDCS devices and electrode sizes may contribute to this variability; however, this issue has not been verified experimentally.

Objective: To evaluate the effects of tDCS device and electrode size on quadriceps motor cortical excitability.

Methods: The effect of tDCS device and electrode size on quadriceps motor cortical excitability was quantified across a range of TMS intensities using a novel evoked torque approach that has been previously shown to be highly reliable. In experiment 1, anodal tDCS-induced excitability changes were measured in twenty individuals using two devices (Empi and Soterix) on two separate days. In experiment 2, anodal tDCS-induced excitability changes were measured in thirty individuals divided into three groups based on the electrode size. A novel Bayesian approach was used in addition to the classical hypothesis testing during data analyses.

Results: There were no significant main or interaction effects, indicating that cortical excitability did not differ between different tDCS devices or electrode sizes. The lack of pre-post time effect in both experiments indicated that cortical excitability was minimally affected by anodal tDCS. Bayesian analyses indicated that the null model was more favored than the main or the interaction effects model.

Conclusions: Motor cortical excitability was not altered by anodal tDCS and did not differ by devices or electrode sizes used in the study. Future studies should examine if behavioral outcomes are different based on tDCS device or electrode size.

Background: Although Constraint-Induced Movement therapy (CIMT) has been deemed efficacious for adults with persistent, mild-to-moderate, post-stroke upper-extremity hemiparesis, CIMT is not available on a widespread clinical basis. Impediments include its cost and travel to multiple therapy appointments. To overcome these barriers, we developed an automated, tele-health form of CIMT.

Objective: Determine whether in-home, tele-health CIMT has outcomes as good as in-clinic, face-to-face CIMT in adults ≥1-year post-stroke with mild-to-moderate upper-extremity hemiparesis.

Methods: Twenty-four stroke patients with chronic upper-arm extremity hemiparesis were randomly assigned to tele-health CIMT (Tele-AutoCITE) or in-lab CIMT. All received 35 hours of treatment. In the tele-health group, an automated, upper-extremity workstation with built-in sensors and video cameras was set-up in participants' homes. Internet-based audio-visual and data links permitted supervision of treatment by a trainer in the lab.

Results: Ten patients in each group completed treatment. All twenty, on average, showed very large improvements immediately afterwards in everyday use of the more-affected arm (mean change on Motor Activity Log Arm Use scale = 2.5 points, p < 0.001, d' = 3.1). After one-year, a large improvement from baseline was still present (mean change = 1.8, p < 0.001, d' = 2). Post-treatment outcomes in the tele-health group were not inferior to those in the in-lab group. Neither were participants' perceptions of satisfaction with and difficulty of the interventions. Although everyday arm use was similar in the two groups after one-year (mean difference = -0.1, 95% CI = -1.3-1.0), reductions in the precision of the estimates of this parameter due to drop-out over follow-up did not permit ruling out that the tele-health group had an inferior long-term outcome.

Conclusions: This proof-of-concept study suggests that Tele-AutoCITE produces immediate benefits that are equivalent to those after in-lab CIMT in stroke survivors with chronic upper-arm extremity hemiparesis. Cost savings possible with this tele-health approach remain to be evaluated.

Background: In this trial we combined the effect of purposeful activity and electrical stimulation therapy (PA-EST) to promote transition of severely hemiparetic upper limb to auxiliary upper limb in chronic stroke survivors in a single-case study.

Objective: The purpose of this study was to examine the effect of PA-EST on the upper limb motor function in a crossover randomized controlled trial.

Methods: The study included eight stroke survivors (age: 63.1±10.9 years) who were receiving home-based visiting occupational therapy. The average time since stroke onset was 8.8±5.6 years. All participants had severely hemiparetic upper limb, with the Fugl-Meyer Assessment upper extremity (FMA-U) score of 21.3±8.5. Participants were randomly assigned to group A or B. Group A received PA-EST for 3 months (phase 1), followed by standard stretching and exercise for 3 months (phase 2), whereas group B had the inverse order of treatments. To avoid carry-over effect, 1-month washout period was provided between the phase 1 and 2. Two-way analysis of variance (ANOVA) with repeated measures was used for the analysis. The primary outcome was FMA-U, and the secondary outcomes were, Motor Activity Log (MAL; amount of use [AOU] and quality of movement [QOM]), and Goal attainment scale-light (GAS-light).

Results: Repeated measures-ANOVA revealed a significant interaction between type of intervention and time for FMA-U (F = 16.303, P = 0.005), MAL AOU (F = 7.966, P = 0.026) and QOM (F = 6.408, P = 0.039), and GAS-light (F = 6.905, P = 0.034), where PA-EST was associated with significantly improved motor function and goal achievement compared with standard stretching.

Conclusions: The PA-EST may have greater effects than stretch/exercise in the recovery of hand function as reflected in FMA-U, MAL, and GAS-light. Our results suggest that PA-EST is an important and useful home-based rehabilitation program for promoting the use of the severely hemiparetic upper limb in chronic stroke survivors.

Background: The diterpenoid cryptotanshinone (CTS) has wide biological functions, including inhibition of tumor growth, inflammation and apoptosis. The present study aimed to explore the possible effect of CTS on cerebral ischemia/reperfusion (I/R) injury and the underlying mechanisms.

Methods: Male C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO) and murine microglia BV2 cells were challenged by Oxygen/glucose deprivation, to mimic I/R and ischemic/hypoxic and reperfusion (H/R) injury, respectively. CTS was administered 0.5 h (10 mg/kg) after the onset of MCAO or 2 h (20μM) post OGD. Infarct volume and neurological deficit were measured. Immunofluorescence, qPCR, and western blot, were performed to detect the expression of cytokines, apoptotic marker, and M1/M2 phenotype-specific genes. Flow cytometry was applied for M1/M2 subpopulation or Annexin V/PI apoptosis assessment.

Results: CTS significantly reduced cerebral infarct volume, neurologic deficit scores, pro-inflammatory cytokine production (IL-6, TNF-α, and IL-1β), apoptotic protein expression (cleaved caspase-3) of mice after tMCAO challenge. Furthermore, CTS attenuated CD16+ M1-type and elevated CD206+ M2-type microglia in vivo or in vitro.

Conclusions: We propose that the neuroprotective effect of CTS in the I/R or H/R context are explained modulation of microglial polarization, suggesting therapeutic potential for cerebral ischemic stroke.

Background: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases.

Objectives: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke.

Methods: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months.

Results: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%).

Conclusions: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions.

Background: The evaluation of motor imagery in persons with prolonged Disorders of Consciousness (pDOC) is a practical approach to differentiate between patients with Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) and to identify residual awareness even in individuals with UWS. Investigating the influence of motor observation on motor imagery could be helpful in this regard.

Objective: In order to corroborate the clinical diagnosis and identify misdiagnosed individuals, we used EEG recordings, to assess the influence of the low-level perceptual and motoric mechanisms on motor observation on motor imagery, taking into account the role of the high-level cognitive mechanisms in patients with pDOC.

Methods: We assessed the influence of motor observation of walking in first-person or third-person view (by a video provision) on motor imagery of walking in the first-person view on the visual N190 (expression of motor observation processing), the readiness potential (RP) (expressing motor preparation), and the P3 component (high-level cognitive processes) in a sample of 10 persons with MCS, 10 with UWS, and 10 healthy controls (CG). Specifically, the video showed a first-view or third-view walk down the street while the participants were asked to imagine a first-view walking down the street.

Results: CG showed greater N190 response (low-level sensorimotor processing) in the non-matching than in the matching condition. Conversely, the P3 and RP responses (high-level sensorimotor processing) were greater in the matching than in the non-matching condition. Remarkably, 6 out of 10 patients with MCS showed the preservation of both high- and low-level sensorimotor processing. One UWS patient showed responses similar to those six patients, suggesting a preservation of cognitively-mediated sensorimotor processing despite a detrimental motor preparation process. The remaining patients with MCS did not show diversified EEG responses, suggesting limited cognitive functioning.

Conclusions: Our study suggests that identifying the low-level visual and high-level motor preparation processes in response to a simple influence of motor observation of motor imagery tasks potentially supports the clinical differential diagnosis of with MCS and UWS. This might help identify UWS patients which were misdiagnosed and who deserve more sophisticated diagnoses.

Background: Open heart surgery is performed with the aid of cardiopulmonary bypass (CPB) techniques that may cause neuronal injuries.

Objective: This study investigated the potential protective effect of oleocanthal pre-treatment against CPB-induced cerebral injury.

Methods: Oleocanthal 30 mg/kg i.p. was administered 3 h before CPB induction in the treated group. Behavioral neurological scores and cerebral injury were assessed to determine the effects of oleocanthal, based on oxidative stress and serum mediators of inflammation by enzyme-linked immunosorbent assay (ELISA). Quantitative Polymerase Chain Reaction (qRT-PCR) was used to estimate the mRNA expression of Toll-like receptor 4 (TLR4) and Interleukin 1 Receptor Associated Kinase 4 (IRAK4) proteins in the cerebral tissue of rats CPB-induced injury. Western blot assay and histopathology were also performed.

Results: The findings suggest that pre-treatment with oleocanthal reduced neurological dysfunction and cerebral injury. Parameters of oxidative stress and cytokine levels were reduced in the serum of the oleocanthal treated group compared with the CPB-only group. Pre-treatment with oleocanthal ameliorated the expression of TLR-4, IRAK4, and Zonula occludens-1 (ZO-1) proteins in the cerebral tissue of the CPB-injured rats.

Conclusions: The results revealed that treatment with oleocanthal protected against cerebral damage by controlling microglia inflammation through the TLR-4 pathway.

Background: Physical therapy with whole body vibration (WBV) following compressive spinal cord injury (SCI) in rats restores density of perisomatic synapses, improves body weight support and leads to a better bladder function. The purpose of the study was to determine whether the combined treatment with WBV plus erythropoietin (EPO) would further improve motor, sensory and vegetative functions after SCI in rats.

Methods: Severe compressive SCI at low thoracic level was followed by a single i.p. injection of 2,5μg (250 IU) human recombinant EPO. Physical therapy with WBV started on 14th day after injury and continued over a 12-week post injury period. Locomotor recovery, sensitivity tests and urinary bladder scores were analysed at 1, 3, 6, 9, and 12 weeks after SCI. The closing morphological measurements included lesion volume and numbers of axons in the preserved perilesional neural tissue bridges (PNTB).

Results: Assessment of motor performance sensitivity and bladder function revealed no significant effects of EPO when compared to the control treatments. EPO treatment neither reduced the lesion volume, nor increased the number of axons in PNTB.

Conclusions: The combination of WBV + EPO exerts no positive effects on hind limbs motor performance and bladder function after compressive SCI in rats.