Microglia Involvement into Acute and Chronic Brain Damage in Diabetic Rats: Impact of GLP-1RA and SGLT-2i.

BACKGROUND: Acute and chronic brain damage in type 2 diabetes mellitus (DM) determines the need to investigate the neuroprotective potential of glucose-lowering drugs. The purpose was to directly compare the neuroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with different duration of action and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in type 2 diabetic rats with and without stroke. METHODS: DM was modelled using high-fat diet and nicotinamide+streptozotocin protocol. The following groups (n = 15 each) were formed: DM without treatment, treatment with liraglutide, dulaglutide, canagliflozin as well as control group without DM and treatment. After 8 weeks, 10 rats from each group underwent middle cerebral artery occlusion. In the reperfusion period neurological deficit, neuroglial damage markers and brain necrosis were evaluated. Brain slices from the remaining 5 animals in each group were histologically examined for microglial activation and neuronal damage. RESULTS: Brain damage was similar in "DM" and "Control" (17.53 [14.23; 26.58] and 15.87 [13.40; 22.68] % of total brain volume, respectively). All study drugs diminished damage volume comparing with "DM" and "Control" whereas the necrosis volume in "DM+Liraglutide" was smaller than in "DM+Canagliflozin" and did not significantly differ from "DM+Dulaglutide" (2.9 [1.83; 4.71], 6.17 [3.88; 8.88] and 4.57 [3.27; 7.90] %). The neurological deficit was more prominent in "DM" than in "Control", while all the drugs demonstrated similar positive effect. Neurofilament light chains (NLC) did not differ between "DM" and "Control". Dulaglutide and canagliflozin caused a marked decrease in NLC. Protein S100BB level was similar in "DM" and "Control". Liraglutide caused the largest S100BB decrease, while canagliflozin did not influence it. In chronic brain ischaemia, all drugs increased the number of normal neurons, but GLP-1RAs had a more pronounced effect. DM was accompanied by increased number of activated microglial cells in Cornu Ammonis (CA)1 hippocampal region. Both GLP-1RAs reduced the number of Iba-1-positive cells, with dulaglutide being more effective than liraglutide, whereas canagliflozin did not affect this parameter. CONCLUSIONS: GLP-1RAs and SGLT-2i have neuroprotective properties against acute and chronic brain damage in diabetic rats, although the infarct-limiting effect of GLP-1RAs may be more pronounced. GLP-1RAs and SGLT-2i exert their protective effects by directly influencing neuronal survival, whereas GLP-1RAs also affect microglia.

Long-term outcomes after new onset seizure in children living with HIV: A cohort study.

OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. SIGNIFICANCE: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. PLAIN LANGUAGE SUMMARY: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.

Functional connectivity interacts with visual perceptual learning for visual field recovery in chronic stroke.

A reciprocal relationship between perceptual learning and functional brain changes towards perceptual learning effectiveness has been demonstrated previously; however, the underlying neural correlates remain unclear. Further, visual perceptual learning (VPL) is implicated in visual field defect (VFD) recovery following chronic stroke. We investigated resting-state functional connectivity (RSFC) in the visual cortices associated with mean total deviation (MTD) scores for VPL-induced VFD recovery in chronic stroke. Patients with VFD due to chronic ischemic stroke in the visual cortex received 24 VPL training sessions over 2 months, which is a dual discrimination task of orientation and letters. At baseline and two months later, the RSFC in the ipsilesional, interhemispheric, and contralesional visual cortices and MTD scores in the affected hemi-field were assessed. Interhemispheric visual RSFC at baseline showed the strongest correlation with MTD scores post-2-month VPL training. Notably, only the subgroup with high baseline interhemispheric visual RSFC showed significant VFD improvement following the VPL training. The interactions between the interhemispheric visual RSFC at baseline and VPL led to improvement in MTD scores and largely influenced the degree of VFD recovery. The interhemispheric visual RSFC at baseline could be a promising brain biomarker for the effectiveness of VPL-induced VFD recovery.

Recurrent Acute Disseminated Encephalomyelitis Presenting as Conus Medullaris Syndrome: A Case Report.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that typically follows an infection or recent vaccination. Symptoms such as encephalopathy and focal neurological deficits appear weeks after the initial illness, leading to swift and progressive neurological decline. While ADEM in the brain has been well documented, reports of ADEM, specifically in the spinal cord, are relatively limited. A 58-year-old male presented with rapidly progressive bilateral lower extremity tingling, numbness, and mild gait disturbance approximately two days prior to visiting the emergency room. Spinal magnetic resonance imaging revealed a diffuse, longitudinal, high-signal lesion with mild enlargement of the conus and proximal cauda equina. The lesions were predominantly localized in the distal conus and cauda equina, and serial electrodiagnostic studies showed that the lesions progressed toward the proximal conus in tandem with symptom evolution and lacked clear lateralization. The patient was subsequently treated with high-dose steroids for seven days (intravenous methylprednisolone, 1 mg/kg). The patient's lower extremity weakness gradually improved and he was able to walk independently under supervision three weeks after symptom onset. In this case of spinal ADEM in a middle-aged adult, high-dose steroid treatment led to outstanding neurological recovery from both the initial occurrence and subsequent attacks.

The effect of processing speed on verbal and visual memory of adults with a chronic acquired brain injury.

OBJECTIVE: Memory problems are among the most frequently reported cognitive complaints by individuals with an acquired brain injury (ABI). Processing speed and working memory deficits are often the result of ABI. These cognitive deficits significantly impact the acquisition and retention of information necessary for memory formation. This study investigated the influence of processing speed and working memory on immediate and delayed recall for verbal and visual memory, as well as overall memory recall in adults living with a chronic ABI. METHODS: Sixty-three participants living with a chronic ABI, who were at least one-year post-injury, were cognitively assessed with the CNS-Vital Signs (CNS-VS) computerized cognitive battery and Wechsler Test of Adult Reading. RESULTS: The CNS-VS Processing Speed significantly predicted delayed recall for verbal memory and overall memory performance. The CNS-VS Working Memory was not a significant predictor of memory recall. CONCLUSIONS: Processing speed deficits negatively impact memory in individuals with a chronic ABI. These findings suggest the memory recall of adults with a chronic ABI is associated with poor processing speed and poor acquisition of information. Therefore, cognitive rehabilitation that improves processing speed should be the focus for individuals with ABI to improve memory performance as well as impaired processing speed.

Pearls & Oy-sters: Mesial Temporal Seizures in the Absence of the Mesial Temporal Lobe. Seizure Onset vs Seizure Network

Seizure semiology represents the clinical expression of the activation of the several brain regions comprising an epileptic network. In mesial temporal lobe epilepsy (MTLE), this network includes the insular-opercular-neocortical temporal-hippocampal (IONTH) regions. In this study, we present the case of a patient with pharmacoresistant seizures characterized by nausea, lip-smacking, semipurposeful hand movements, and speechlessness, suggesting dominant hemisphere MTLE, with scalp video-EEG findings and left hippocampal sclerosis on brain MRI confirming the diagnosis. She underwent anterior temporal lobectomy with amygdalohippocampectomy and was seizure-free for 14 years before relapsing. Recurrent seizure semiology was similar to preoperative seizures, that is, consistent with left MTLE, despite the medial temporal lobe missing. Seizures were therefore assumed to arise from remnant portions of the IONTH network-the insula, operculum, and posterolateral temporal neocortex. Reinvestigation including MEG localization of spikes and acute MRI changes following a seizure cluster suggested a left opercular region epilepsy. Our patient thus demonstrated the principle that seizures with mesial temporal characteristics may arise from outside the mesial temporal lobe (MTL). MTLE semiology arises from the activation of a set of structures (the seizure network) associated with the MTL, which can be triggered by foci both within and outside the MTL itself, and indeed even in its absence. However, it is not necessary to resect the entire extended network to bring about extended periods of seizure freedom in patients with refractory MTLE.

The Brazilian version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0) is reliable and valid for chronic stroke survivors.

BACKGROUND: Stroke is the leading cause of disability worldwide. Assessing stroke's impact on patients' daily activities and social participation can provide important complementary information to their rehabilitation process. However, no previous study had been conducted on the psychometric properties of the Brazilian version of the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) in the stroke population. OBJECTIVES: This study aimed to examine the internal consistency, test-retest and inter-rater reliability, convergent validity and floor/ceiling effect of the Brazilian version of the WHODAS 2.0 in individuals after chronic stroke. METHODS: Two examiners interviewed 53 chronic stroke individuals who responded to the Brazilian 36-item version of the WHODAS 2.0 three times to analyze test-retest and inter-rater reliabilities. Floor/ceiling effects were calculated as relative frequencies of the lowest or the highest possible WHODAS 2.0 scores. Participants also responded to the Stroke Impact Scale 3.0 (SIS 3.0) and the Functional Independence Measure (FIM) to analyze convergent validity. RESULTS: The internal consistency analyses for domains of WHODAS showed a strong correlation among the items of each domain (0.76-0.91) except for the "getting along" domain, which presented a moderate correlation (ρ = 0,62). Total scores of WHODAS 2.0 showed satisfactory internal consistency (α = 0.93), good inter-rater reliability (ICC = 0.85), excellent test-retest reliability (ICC = 0.92) and no significant floor/ceiling effect. Convergent validity indicated moderate to strong correlations (ρ=-0.51 to ρ=-0.88; p < 0.001), with the highest values associated with the correlation with the SIS scale. CONCLUSIONS: The Brazilian version of the WHODAS 2.0 instrument presented evidence of reliability and validity for chronic post-stroke individuals.

Estimating the minimal clinically important difference of upper extremity outcome measures in chronic stroke patients with moderate to severe impairment: a cross-sectional study.

BACKGROUND: Approximately 70% of chronic stroke patients experience upper extremity (UE) functional impairments, and UE outcome measures are often used as quality-of-life indicators. OBJECTIVE: The purpose of this study was to estimate minimal clinically important difference (MCID) values for UE outcome measures in chronic stroke patients with moderate to severe UE hemiplegia. METHODS: This study was a cross-sectional study, conducted as a secondary analysis of data from the ReoGo-J study, a multicenter, prospective, randomized, parallel-group trial of robot-assisted self-training for UE hemiplegia in chronic stroke. The patients were randomized to 1 of 3 treatment groups. Treatment was provided 3 times a week for 10 weeks, and UE outcome measures were evaluated before and after treatment. The anchor-based method was used to estimate MCID values for UE outcome measures, with Stroke Impact Scale (SIS) subscales as anchors. MCID values were estimated by identifying cutoff values in a receiver operating characteristic (ROC) curve. RESULTS: Between-group comparisons of UE outcome measures, based on the clinically important difference (CID) values of SIS subscales, revealed significant differences in both the Amount of Use (AOU) and Quality of Movement (QOM) components of the Motor Activity Log (MAL)-14. The estimated MCID values were 0.89 for the AOU component and 0.77 for the QOM component. CONCLUSIONS: The estimated MCID values for the MAL-14 not only add information regarding the clinical characteristics of the MAL-14 but also facilitate interpretations of changing scores in chronic stroke patients with moderate to severe UE hemiplegia undergoing rehabilitation therapy. STUDY REGISTRATION: https://www.umin.ac.jp/ctr/index.htm (UMIN000022509; 1 July 2016).

Effect of using an 8-figure shoulder brace on arm swing angle and gait parameters in chronic stroke patients: a pilot randomized controlled study.

BACKGROUND: The 8-figure shoulder brace during treadmill training (8-FSBTT) intervention can stabilize the shoulder joint, improve the upright of the thoracic spine, induces a change in the angle of the arm during walking, and consequently improve walking ability in stroke patients. OBJECTIVES: Our objective is to compare the effects of a 4-week program of 8-FSBTT with those of only treadmill training (OT) on arm swing angle, and gait parameters (gait speed, cadence, and both side stride lengths) in chronic stroke patients. METHODS: Participants were randomized to either the 8-FSBTT (n = 11) or OT (n = 11) group. Patients in both groups underwent standard physiotherapy for 30 min per session. In addition, 8-FSBTT and OT interventions were performed 10 min, 5 times per week for 4 weeks. Arm swing angle, gait speed, cadence, and both side stride lengths were measured after 4 weeks of training. RESULTS: After 4 weeks of training, the 8-FSBTT group showed significant improvement in all outcome measures compared with baseline (p < 0.05). Furthermore, Arm swing angle, gait speed, cadence, and both side stride lengths showed greater improvement in the 8-FSBTT group compared to the OT group (p < 0.05). CONCLUSIONS: This study demonstrated that 8-FSBTT training, combined with standard physiotherapy, improved Arm swing angle, gait speed, cadence, and both side stride lengths in the chronic stroke patients.

Validity of the two-minute walk test to assess exercise capacity and estimate cardiorespiratory fitness in individuals after stroke: a cross-sectional study.

OBJECTIVES: The purpose of this study was to investigate the construct validity of the 2-minute walk test (2MWT) to assess the exercise capacity and the criterion-concurrent validity of the 2MWT and the 6-minute walk test (6MWT) to estimate the cardiorespiratory fitness of ambulatory individuals with chronic stroke. In addition, to provide an equation to predict the distance covered in the 6MWT and another to predict the peak oxygen consumption (VO2peak) for these individuals. METHODS: This is a cross-sectional and prospective study. A convenience sample with 57 individuals with chronic stroke was recruited. The 2MWT, the 6MWT and the cardiopulmonary exercise test (CPET) were performed in a laboratory. The Spearman's correlation coefficient was used to investigate the validity. To develop the equations, stepwise multiple linear regression analysis was used. RESULTS: A significant correlation of very high magnitude between the distance covered in the 2MWT and the 6MWT was found (rs = 0.93; p < 0.001). A significant correlation of moderate magnitude between the distance covered in the 2MWT and the VO2peak (rs = 0.53; p < 0.001) similar to the correlation between the 6MWT and the VO2peak (rs = 0.55; p < 0,001) were found. Furthermore, an equation was developed to predict the VO2peak (R2 = 0.690; p < 0.001; VO2peak = 13.532 + 0.078*distance walked in the 2MWT +4.509*sex-0.172*age), and another to predict the distance covered in the 6MWT (R2 = 0.827; p < 0.001; MWT = -1.867 + 3.008*distance walked in the 2MWT). CONCLUSION: 2MWT showed adequate construct and concurrent validity. Furthermore, it is possible to use the prediction equations developed to estimate the VO2peak or the distance covered in the 6MWT.

Characterizing the impact of multiple chronic conditions on return to participation in chronic stroke survivors.

BACKGROUND: Each year, 795,000 Americans experience a stroke. As stroke mortality declines, more individuals are in the chronic phase of recovery (>6 months post-stroke). Over 80% of stroke survivors have multiple, chronic health conditions (MCC). While the relationship between MCC and mortality and function during acute recovery has been explored, less is known about how MCC burden affects participation in chronic stroke survivors. OBJECTIVE: This study investigated whether MCC burden is related to participation in those with chronic stroke. METHODS: Two hundred and sixty-six participants with chronic (≥6 months) stroke were included in this cross-sectional and retrospective analysis. Participants had a mean age of 62.2 ± 12.8 years, and time since stroke (TSS) of 36.0 ± 44.6 months (114F/152 M). Participants completed the 6-minute Walk Test (6MWT), Activities-Specific Balance Confidence Scale (ABC), Modified Cumulative Illness Rating Scale (MCIR) to quantify the presence and severity of chronic illness across 14 body systems, and the Stroke Impact Scale - Participation subscale (SIS-P). Participation (SIS-P) was the dependent variable. Independent variables were entered into a sequential regression model in three blocks: demographic variables, physical capacity (6MWT distance) and balance self-efficacy (ABC), and MCC burden (MCIR). RESULTS: After adjusting for age, sex, and time since stroke, physical capacity and balance self-efficacy explained 31.4% (p < 0.001), and the MCC burden explained 2.0% (p = 0.004). Higher participation was related to lower MCC burden. CONCLUSIONS: MCC burden is a significant contributor to variance in participation in chronic stroke survivors, above and beyond demographics, physical capacity, and self-efficacy, and therefore should be considered when creating rehabilitation programs to improve participation.

Intracerebral electrographic activity following a single dose of diazepam nasal spray: A pilot study.

OBJECTIVE: Rescue benzodiazepine medication can be used to treat seizure clusters, which are intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. The NeuroPace RNS® System is a device that detects abnormal electrographic activity through intracranial electrodes and administers electrical stimulation to control seizures. Reductions in electrographic activity over days to weeks have been associated with the longer-term efficacy of daily antiseizure medications (ASMs). In this pilot study, electrographic activity over hours to days was examined to assess the impact of a single dose of a proven rescue therapy (diazepam nasal spray) with a rapid onset of action. METHODS: Adult volunteers (>18 years old) with clinically indicated RNS (stable settings and ASM usage) received a weight-based dose of diazepam nasal spray in the absence of a clinical seizure. Descriptive statistics for a number of detections and a sum of durations of detections at 10-min, hourly, and 24-h intervals during the 7-day (predose) baseline period were calculated. Post-dose detections at each time interval were compared with the respective baseline-detection intervals using a 1 SD threshold. The number of long episodes that occurred after dosing also were compared with the baseline. RESULTS: Five participants were enrolled, and four completed the study; the excluded participant had recurrent seizures during the study. There were no consistent changes (difference >1 SD) in detections between post-dose and mean baseline values. Although variability was high (1 SD was often near or exceeded the mean), three participants showed possible trends for reductions in one or more electrographic variables following treatment. SIGNIFICANCE: RNS-assessed electrographic detections and durations were not shown to be sensitive measures of short-term effects associated with a single dose of rescue medication in this small group of participants. The variability of detections may have masked a measurable drug effect. PLAIN LANGUAGE SUMMARY: Rescue drugs are used to treat seizure clusters. Responsive neurostimulation (RNS) devices detect and record epilepsy brain waves and then send a pulse to help stop seizures. This pilot study looked at whether one dose of a rescue treatment changes brain activity detected by RNS. There was a very wide range of detections, which made it difficult to see if or how the drug changed brain activity. New studies should look at other types of brain activity, multiple doses, and larger patient groups.

Robotic gait training and botulinum toxin injection improve gait in the chronic post-stroke phase: A randomized controlled trial.

BACKGROUND: Improving walking ability is one of the main goals of rehabilitation after stroke. When lower limb spasticity increases walking difficulty, botulinum toxin type A (BTx-A) injections can be combined with non-pharmacologic interventions such as intensive rehabilitation using a robotic approach. To the best of our knowledge, no comparisons have been made between the efficacy of robotic gait training and conventional physical therapy in combination with BTx-A injections. OBJECTIVE: To conduct a randomized controlled trial to compare the efficacy on gait of robotic gait training versus conventional physiotherapy after BTx-A injection into the spastic triceps surae in people after stroke. METHOD: Thirty-three participants in the chronic stroke phase with triceps surae spasticity inducing gait impairment were included. After BTx-A injection, participants were randomized into 2 groups. Group A underwent robotic gait training (Lokomat®) for 2 weeks, followed by conventional physiotherapy for 2 weeks (n = 15) and Group B underwent the same treatment in reverse order (n = 18). The efficacy of these methods was tested using the 6-minute walk test (6MWT), comparing post-test 1 and post-test 2 with the pre-test. RESULTS: After the first period, the 6MWT increased significantly more in Group A than in Group B: the mean difference between the interventions was 33 m (95%CI 9; 58 p = 0.007; g = 0.95), in favor of Group A; after the second period, the 6MWT increased in both groups, but the 30 m difference between the groups still remained (95%CI 5; 55 p = 0.019; g = 0.73). CONCLUSION: Two weeks of robotic gait training performed 2 weeks after BTx-A injections improved walking performance more than conventional physiotherapy. Large-scale studies are now required on the timing of robotic rehabilitation after BTx-A injection.

Cortical effects of wrist tendon vibration during an arm tracking task in chronic stroke survivors: An EEG study.

The purpose of this study was to characterize changes in cortical activity and connectivity in stroke survivors when vibration is applied to the wrist flexor tendons during a visuomotor tracking task. Data were collected from 10 chronic stroke participants and 10 neurologically-intact controls while tracking a target through a figure-8 pattern in the horizontal plane. Electroencephalography (EEG) was used to measure cortical activity (beta band desynchronization) and connectivity (beta band task-based coherence) with movement kinematics and performance error also being recorded during the task. All participants came into our lab on two separate days and performed three blocks (16 trials each, 48 total trials) of tracking, with the middle block including vibration or sham applied at the wrist flexor tendons. The order of the sessions (Vibe vs. Sham) was counterbalanced across participants to prevent ordering effects. During the Sham session, cortical activity increased as the tracking task progressed (over blocks). This effect was reduced when vibration was applied to controls. In contrast, vibration increased cortical activity during the vibration period in participants with stroke. Cortical connectivity increased during vibration, with larger effect sizes in participants with stroke. Changes in tracking performance, standard deviation of hand speed, were observed in both control and stroke groups. Overall, EEG measures of brain activity and connectivity provided insight into effects of vibration on brain control of a visuomotor task. The increases in cortical activity and connectivity with vibration improved patterns of activity in people with stroke. These findings suggest that reactivation of normal cortical networks via tendon vibration may be useful during physical rehabilitation of stroke patients.

Positive and negative cell therapy in randomized control trials for central nervous system diseases.

Neurorestorative cell therapies have been tested to treat patients with nervous system diseases for over 20 years. Now it is still hard to answer which kinds of cells can really play a role on improving these patients' quality of life. Non-randomized clinical trials or studies could not provide strong evidences in answering this critical question. In this review, we summarized randomized clinical trials of cell therapies for central nervous diseases, such as stroke, spinal cord injury, cerebral palsy (CP), Parkinson's disease (PD), multiple sclerosis (MS), brain trauma, amyotrophic lateral sclerosis (ALS), etc. Most kinds of cell therapies demonstrated negative results for stoke, brain trauma and amyotrophic lateral sclerosis. A few kinds of cell therapies showed neurorestorative effects in this level of evidence-based medicine, such as olfactory ensheating cells for chronic ischemic stroke. Some kinds of cells showed positive or negative effects from different teams in the same or different diseases. We analyzed the possible failed reasons of negative results and the cellular bio-propriety basis of positive results. Based on therapeutic results of randomized control trials and reasonable analysis, we recommend: (1) to further conduct trials for successful cell therapies with positive results to increase neurorestorative effects; (2) to avoid in repeating failed cell therapies with negative results in same diseases because it is nonsense for them to be done with similar treatment methods, such as cell dosage, transplanting way, time of window, etc. Furthermore, we strongly suggest not to do non-randomized clinical trials for cells that had shown negative results in randomized clinical trials.

Effect of lower limb resistance training on ICF components in chronic stroke: A systematic review and meta-analysis of RCTs.

BACKGROUND: Resistance training (RT) effectively promotes functional independence after stroke. OBJECTIVES: To investigate the effect of lower limb RT on body structure and function (muscle strength, postural balance), activity (mobility, gait) and participation (quality of life, impact of stroke on self-perceived health) outcomes in individuals with chronic stroke. METHODS: Six databases were searched from inception until September 2022 for randomized controlled trials comparing lower limb RT to a control intervention. The random-effects model was used in the meta-analyses. Effect sizes were reported as standardized mean differences (SMD). Quality of evidence was assessed using the GRADE approach. RESULTS: Fourteen studies were included. Significant improvements were found in body structure and function after lower limb RT: knee extensors (paretic side - SMD: 1.27; very low evidence), knee flexors (paretic side - SMD: 0.51; very low evidence; non-paretic side - SMD: 0.52; low evidence), leg press (paretic side - SMD: 0.83; very low evidence) and global lower limb muscle strength (SMD: -1.47; low evidence). No improvement was found for knee extensors (p = 0.05) or leg press (p = 0.58) on the non-paretic side. No improvements were found in the activity domain after lower limb RT: mobility (p = 0.16) and gait (walking speed-usual: p = 0.17; walking speed-fast: p = 0.74). No improvements were found in the participation domain after lower limb RT: quality of life (p > 0.05), except the bodily pain dimension (SMD: 1.02; low evidence) or the impact of stroke on self-perceived health (p = 0.38). CONCLUSION: Lower limb RT led to significant improvements in the body structure and function domain (knee extensors and flexors, leg press, global lower limb muscle strength) in individuals with chronic stroke. No improvements were found in the activity (mobility, gait [walking speed]) or participation (quality of life, impact of stroke on self-perceived health) domains. PROSPERO REGISTRATION NUMBER: CRD42021272645.

Persian version of the Chalder Fatigue Questionnaire and Multidimensional Fatigue Symptom Inventory-Short Form: psychometric properties in Iranian chronic stroke survivors.

BACKGROUND: Post-stroke fatigue is a disturbing condition with various physical and psychological facets, which needs to be assessed by meaningful and psychometrically valid and reliable tools. The Chalder Fatigue Questionnaire (CFQ) and Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) have been designed to assess diverse dimensions of fatigue. OBJECTIVES: The present study aimed to investigate the psychometric properties of the CFQ and MFSI-SF in people with chronic stroke. METHODS: Both measures were translated according to forward-backward standard protocol. This cross-sectional study was conducted with 130 first-time stroke survivors. The multidimensional fatigue inventory, checklist individual strength, fatigue assessment scale, fatigue subscale of profiles of mood state, fatigue severity scale, visual analogue scale-fatigue, beck anxiety inventory, center for epidemiologic studies of depression scale, and 36-item short-form health survey were administered in addition to the CFQ and MFSI-SF. Reliability, precision, known-groups validity, and convergent validity were examined for the CFQ and MFSI-SF. RESULTS: The results showed an acceptable (Cronbach's alpha = 0.81-0.97) internal consistency and test-retest reliability (intra-class correlation = 0.75-0.97). The CFQ and MFSI-SF revealed good ability (P < 0.001) to differentiate chronic stroke survivors with different disability levels. Significant high correlation (P = -0.61-0.87) was found between CFQ and MFSI-SF and other fatigue scales. CONCLUSIONS: The results of this study showed that the CFQ and MFSI-SF have high reliability and validity for chronic stroke survivors.

Ankle stiffness asymmetry is associated with balance function in individuals with chronic stroke.

Ankle joint is one of important contributors on balance in stroke survivors. This study aimed to investigate the relationships of ankle stiffness symmetry ratios along the talocrural and subtalar axes with clinical balance measures and weight distribution during quiet standing in ambulatory chronic post-stroke survivors. The clinical trials involved 15 ambulatory elderly with chronic post-stroke hemiparesis and 15 healthy controls. Ankle stiffness was evaluated during non-weight-bearing isokinetic passive biaxial ankle movements, and ankle stiffness symmetry ratios between paretic and non-paretic ankle stiffness (SR: Inversion/Eversion SRIE & Dorsi-/Plantarflexion SRDP) were measured. A certified physiotherapist evaluated the Berg Balance Scale (BBS) and weight-distribution ratio (WDR) on bilateral force plates during quiet standing. Correlation coefficients, the factor analysis, and Pearson linear multiple regression were assessed with measured parameters. Correlation coefficients showed significances in-betweens; BBS and SRDP (r = -0.543, p = 0.022), WDR and SRIE (r = -0.667, p = 0.004), SRIE and SRDP (r = -0.604, p = 0.011). The exploratory factor analysis suggested four extracted factors; (1) Balance & Gait, (2) Stroke, (3) Symmetry and (4) Dimension. The first and second factors include general and pathological characteristics in stoke participants respectively. The third factor is associated with symmetrical characteristics explaining up to 99.9% of the variance. Multiple regression analysis showed ankle stiffness ratios predict BBS up to 60% of variance. The biaxial ankle stiffness ratio is a useful clinical variable that assesses balance function, in ambulatory chronic stroke survivors.

Improved processing speed and decreased functional connectivity in individuals with chronic stroke after paired exercise and motor training.

After stroke, impaired motor performance is linked to an increased demand for cognitive resources. Aerobic exercise improves cognitive function in neurologically intact populations and may be effective in altering cognitive function post-stroke. We sought to determine if high-intensity aerobic exercise paired with motor training in individuals with chronic stroke alters cognitive-motor function and functional connectivity between the dorsolateral prefrontal cortex (DLPFC), a key region for cognitive-motor processes, and the sensorimotor network. Twenty-five participants with chronic stroke were randomly assigned to exercise (n = 14; 66 ± 11 years; 4 females), or control (n = 11; 68 ± 8 years; 2 females) groups. Both groups performed 5-days of paretic upper limb motor training after either high-intensity aerobic exercise (3 intervals of 3 min each, total exercise duration of 23-min) or watching a documentary (control). Resting-state fMRI, and trail making test part A (TMT-A) and B were recorded pre- and post-intervention. Both groups showed implicit motor sequence learning (p < 0.001); there was no added benefit of exercise for implicit motor sequence learning (p = 0.738). The exercise group experienced greater overall cognitive-motor improvements measured with the TMT-A. Regardless of group, the changes in task score, and dwell time during TMT-A were correlated with a decrease in DLPFC-sensorimotor network functional connectivity (task score: p = 0.025; dwell time: p = 0.043), which is thought to reflect a reduction in the cognitive demand and increased automaticity. Aerobic exercise may improve cognitive-motor processing speed post-stroke.

Disability and persistent motor deficits are linked to structural crossed cerebellar diaschisis in chronic stroke.

Brain imaging has significantly contributed to our understanding of the cerebellum being involved in recovery after non-cerebellar stroke. Due to its connections with supratentorial brain networks, acute stroke can alter the function and structure of the contralesional cerebellum, known as crossed cerebellar diaschisis (CCD). Data on the spatially precise distribution of structural CCD and their implications for persistent deficits after stroke are notably limited. In this cross-sectional study, structural MRI and clinical data were analyzed from 32 chronic stroke patients, at least 6 months after the event. We quantified lobule-specific contralesional atrophy, as a surrogate of structural CCD, in patients and healthy controls. Volumetric data were integrated with clinical scores of disability and motor deficits. Diaschisis-outcome models were adjusted for the covariables age, lesion volume, and damage to the corticospinal tract. We found that structural CCD was evident for the whole cerebellum, and particularly for lobules V and VI. Lobule VI diaschisis was significantly correlated with clinical scores, that is, volume reductions in contralesional lobule VI were associated with higher levels of disability and motor deficits. Lobule V and the whole cerebellum did not show similar diaschisis-outcome relationships across the spectrum of the clinical scores. These results provide novel insights into stroke-related cerebellar plasticity and might thereby promote lobule VI as a key area prone to structural CCD and potentially involved in recovery and residual motor functioning.