Recovery Phase Of Stroke Research Articles

Exploring the relationship between fatigue and circulating levels of the pro-inflammatory biomarkers interleukin-6 and C-reactive protein in the chronic stage of stroke recovery: A cross-sectional study

BackgroundThe precise mechanisms underlying the aetiology of post-stroke fatigue remain poorly understood. Inflammation has been associated with clinically significant fatigue across a number of neurological disorders; however, at present there is a lack of evidence regarding the association of fatigue and inflammation in the chronic phase of stroke recovery. AimsThe aim of this study was to examine fatigue in a cohort of stroke survivors in the chronic phase of stroke, compared with matched controls, and to explore associations between the pro-inflammatory cytokine interleukin-6, high-sensitivity C-reactive Protein and fatigue. MethodsWe performed an exploratory cross-sectional study of 70 people in the chronic phase of stroke recovery, and 70 age matched controls. Fatigue was assessed using the Fatigue Assessment Scale. Interleukin-6 was measured in serum using a commercially available enzyme immunoassay kit. Both outcome measures were assessed contemporaneously. ResultsClinically significant fatigue, defined as a score ≥24 on the Fatigue Assessment Scale, was reported by 60% of stroke survivors, and 15.7% of controls. The odds of experiencing clinically significant fatigue was 8.04 times higher among stroke survivors compared to control participants (odds ratio 8.045; 95% CI: 3.608, 17.939; P ​< ​0.001). The fatigue score was significantly correlated with the level of both interleukin-6 and high-sensitivity c-reactive protein, however once entered into a linear regression model with cardiovascular covariables, this relationship was no longer statistically significant. ConclusionsThis study shows that fatigue may be associated with systemic inflammation in the chronic phase of stroke. The pathological mechanisms underlying post-stroke fatigue and its clinical implications require further study.

Clinical outcomes for moderate and severe stroke survivors receiving early supported discharge: A quasi-experimental cohort study

Introduction The aim of this study was to compare outcomes for functional independence, activities of daily living participation and balance achieved by moderate and severe stroke survivors receiving an early supported discharge model of care with those receiving standard treatment. Method A quasi-experimental cohort method was utilised, with a control group of convenience. Forty-one patients ( n = 28 early supported discharge group, n = 13 control group) who were medically stable post stroke, safe for discharge home, able to be treated in the home environment and requiring intensive rehabilitation from at least two disciplines participated. Results There was no significant difference in outcomes between early supported discharge and control groups for functional independence, activities of daily living participation or balance from baseline to 4 weeks, or 4 weeks to 8 weeks. However, patients receiving early supported discharge made further improvements across the study period, while those receiving standard care made limited improvement between 4 weeks and 8 weeks. All minimal clinically important differences on outcome measures were identified between baseline and 4 weeks. Conclusions Moderate and severe stroke survivors can achieve comparable outcomes when receiving early supported discharge or standard treatment. Early supported discharge models of care may also enhance ongoing improvement during the early phases of stroke recovery.

Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia.

Although VEGF165 (vascular endothelial growth factor-165) is able to enhance both angiogenesis and neurogenesis, it also increases vascular permeability through the blood-brain barrier. Heparan sulfate (HS) sugars play important roles in regulating VEGF bioactivity in the pericellular compartment. Here we asked whether an affinity-purified VEGF165-binding HS (HS7) could augment endogenous VEGF activity during stroke recovery without affecting blood-brain barrier function. Both rat brain endothelial cell line 4 and primary rat neural progenitor cells were used to evaluate the potential angiogenic and neurogenic effects of HS7 in vitro. For in vivo experiments, male Sprague-Dawley rats were subjected to 100 minutes of transient focal cerebral ischemia, then treated after 4 days with either PBS or HS7. One week later, infarct volume, behavioral sequelae, immunohistochemical markers of angiogenesis and neural stem cell proliferation were assessed. HS7 significantly enhanced VEGF165-mediated angiogenesis in rat brain endothelial cell line 4 brain endothelial cells, and increased the proliferation and differentiation of primary neural progenitor cells, both via the VEGFR2 (vascular endothelial growth factor receptor 2) pathway. Intracerebroventricular injection of HS7 improved neurological outcome in ischemic rats without changing infarct volumes. Immunostaining of the compromised cerebrum demonstrated increases in collagen IV/Ki67 and nestin/Ki67 after HS7 exposure, consistent with its ability to promote angiogenesis and neurogenesis, without compromising blood-brain barrier integrity. A VEGF-activating glycosaminoglycan sugar, by itself, is able to enhance endogenous VEGF165 activity during the post-ischemic recovery phase of stroke.

Association between Osteoporosis and Cognitive Impairment during the Acute and Recovery Phases of Ischemic Stroke.

Background and objectives: Little is known about the effect of osteoporosis on cognitive function in the acute and recovery phases of stroke. Early bone mineral density assessments during acute stroke may be a useful marker of cognitive function. We evaluated the effect of osteoporosis on cognitive function at the early and recovery phase of ischemic stroke in patients aged >50 years. Materials and Methods: We retrospectively examined consecutive patients with acute stroke hospitalized between 2016 and 2018. Osteoporosis was defined as a T-score <–2.5 for the femoral neck or lumbar spine bone mineral density. The primary outcome was cognitive impairment measured by the Korean Mini-Mental State Examination in the acute phase and recovery phase of ischemic stroke. Results: Of the 260 included subjects (107 men and 153 women), 70 (26.9%) had osteoporosis. Cognitive impairment was more severe in the osteoporosis group than in the non-osteoporosis group (30.5% versus 47.1%, p = 0.001). After the recovery phase of stroke, the proportion of patients with cognitive impairment remained higher in the osteoporosis group. The multivariate analysis revealed a correlation between a low femoral neck bone mineral density and severe cognitive impairment in the acute and recovery phases of stroke (adjusted odds ratio (OR) 4.09, 95% confidence interval (CI) 1.11–15.14 in the acute phase, and adjusted OR 11.17, 95% CI 1.12–110.98 in the recovery phase). Conclusions: Low bone mineral density is associated with poor cognitive function in the acute and recovery phases of stroke.

Electrical Stimulation of the Motor Cortex or Paretic Muscles Improves Strength Production in Stroke Patients: A Systematic Review and Meta-Analysis.

Transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) are two widely applied methods of electrical stimulation for motor recovery among stroke patients. This systematic review and meta-analysis investigated the efficacy of tDCS and FES for strength production in stroke patients. TYPE: Systematic review. Studies that explored the effects of tDCS or FES on the strength production of paralyzed muscles in stroke patients were retrieved on a comprehensive set of three databases: (1) Google Scholar, (2) PubMed, and (3) the Cochrane Database of Systematic Reviews until July 2019. Systematic study retrieval led to the inclusion of 15 studies that reported on strength production effects after tDCS and FES interventions among stoke patients. A sham control group and randomization were used in each study. The 15 studies included 20 comparisons with sham controls, 7 of which involved tDCS and 13 of which involved FES. Random-effects models showed that strength production was improved after tDCS (effect size [ES] = 0.52, 95% confidence interval [CI] = 0.35-0.69, P < .001, Z = 6.05) and FES (ES = 0.47, 95% CI = 0.16-0.78, P < .003, Z = 2.99). Additionally, tDCS was shown to improve strength production in the acute (ES = 0.52, 95% CI = 0.24-0.80, P < .001, Z = 3.65), subacute (ES = 0.85, 95% CI = 0.37-1.32, P < .001, Z = 3.51), but not chronic (ES = 0.06, 95% CI = -0.47-0.60, P = .82, Z = 0.23) phases of stroke recovery. Out of the 13 studies involving FES, 12 investigated strength production in the chronic phase and one investigated in the acute phase, showing a positive effect in these two stages. The results of the meta-analysis showed that tDCS and FES successfully improved strength production in stroke patients.

Ephrin-Eph Signaling as a Novel Neuroprotection Path in Ischemic Stroke.

The search for novel neuroprotection strategies in ischemic stroke continues, as revascularization using tissue-plasminogen activator is the only pharmacologicalmethod currently available to patients. The purpose of this review article is to summarize research findings regarding the erythropoietin-producing hepatocellular receptor pathway as an emerging novel molecular target for neuroprotection in ischemic stroke. Ephrin-Eph interactions represent a new strategy in neuroprotection. Potential therapeutic targets include the different cellular locations within the neurovascular unit (e.g. astrocytes and neurons) and the different ephrin receptor subtypes. In particular, ephrin-B2/EphB4 receptor stimulation seems to exert neuroprotective effects, while stimulation of other ligands/receptors results in deleterious effects, during the post-ischemic stroke recovery phase. Neuroprotection, assessed by either a decrease in neurovascular unit injury markers or improvement in motor function tests, can be achieved by modulating the activity of different ephrin-Eph receptor subtypes. These novel molecular targets provide multiple potential neuroprotective therapeutic benefits, with meaningful clinical outcomes.

The Stroke-Induced Increase of Somatostatin-Expressing Neurons is Inhibited by Diabetes: A Potential Mechanism at the Basis of Impaired Stroke Recovery

Type 2 diabetes (T2D) hampers recovery after stroke, but the underling mechanisms are mostly unknown. In a recently published study (Pintana et al. in Clin Sci (Lond) 133(13):1367–1386, 2019), we showed that impaired recovery in T2D was associated with persistent atrophy of parvalbumin+ interneurons in the damaged striatum. In the current work, which is an extension of the abovementioned study, we investigated whether somatostatin (SOM)+ interneurons are also affected by T2D during the stroke recovery phase. C57Bl/6j mice were fed with high-fat diet or standard diet (SD) for 12 months and subjected to 30-min transient middle cerebral artery occlusion (tMCAO). SOM+ cell number/density in the striatum was assessed by immunohistochemistry 2 and 6 weeks after tMCAO in peri-infarct and infarct areas. This was possible by establishing a computer-based quantification method that compensates the post-stroke tissue deformation and the irregular cell distribution. SOM+ interneurons largely survived the stroke as seen at 2 weeks. Remarkably, 6 weeks after stroke, the number of SOM+ interneurons increased (vs. contralateral striatum) in SD-fed mice in both peri-infarct and infarct areas. However, this increase did not result from neurogenesis. T2D completely abolished this effect specifically in the in the infarct area. The results suggest that the up-regulation of SOM expression in the post-stroke phase could be related to neurological recovery and T2D could inhibit this process. We also present a new and precise method for cell counting in the stroke-damaged striatum that allows to reveal accurate, area-related effects of stroke on cell number.

Racial Disparities in Stroke Recovery Persistence in the Post-Acute Stroke Recovery Phase: Evidence from the Health and Retirement Study.

Blacks have a higher burden of post-stroke disability. Factors associated with racial differences in long-term post-stroke disability are not well-understood. Our aim was to assess the long-term racial differences in risk factors associated with stroke recovery. We examined Health and Retirement Study (HRS) longitudinal interview data collected from adults living with stroke who were aged >50 years during 2000-2014. Analysis of 1,002 first-time, non-Hispanic, Black (210) or White (792) stroke survivors with data on activities of daily living (ADL), fine motor skills (FMS) and gross motor skills (GMS) was conducted. Ordinal regression analysis was used to assess the impact of sex, race, household residents, household income, comorbidities, and the time since having a stroke on functional outcomes. Black stroke survivors were younger compared with Whites (69 ± 10.4 vs 75 ± 11.9). The majority (~65%) of Black stroke survivors were female compared with about 54% White female stroke survivors (P=.007). Black stroke survivors had more household residents (P<.001) and comorbidities (P<.001). Aging, being female, being Black and a longer time since stroke were associated with a higher odds of having increased difficulty in ADL, FMS and/or GMS. Comorbidities were associated with increased difficulty with GMS. Black race increased the impact of comorbidities on ADL and FMS in comparison with Whites. Our data suggest that the effects of aging, sex and unique factors associated with race should be taken into consideration for future studies of post-stroke recovery and therapy.

The Local and Peripheral Immune Responses to Stroke: Implications for Therapeutic Development.

The immune response to stroke is an exciting target for future stroke therapies. Stroke is a leading cause of morbidity and mortality worldwide, and clot removal (mechanical or pharmacological) to achieve tissue reperfusion is the only therapy currently approved for patient use. Due to a short therapeutic window and incomplete effectiveness, however, many patients are left with infarcted tissue that stimulates inflammation. Although this is critical to promote repair, it can also damage surrounding healthy brain tissue. In addition, acute immunodepression and subsequent infections are common and are associated with worse patient outcomes. Thus, the acute immune response is a major focus of researchers attempting to identify ways to amplify its benefits and suppress its negative effects to improve short-term recovery of patients. Here we review what is known about this powerful process. This includes the role of brain resident cells such as microglia, peripherally activated cells such as macrophages and neutrophils, and activated endothelium. The role of systemic immune activation and subsequent immunodepression in the days after stroke is also discussed, as is the chronic immune responses and its effects on cognitive function. The biphasic role of inflammation, as well as complex timelines of cell production, differentiation, and trafficking, suggests that the relationship between the acute and chronic phases of stroke recovery is complex. Gaining a more complete understanding of this intricate process by which inflammation is initiated, propagated, and terminated may potentially lead to therapeutics that can treat a larger population of stroke patients than what is currently available. The immune response plays a critical role in patient recovery in both the acute and chronic phases after stroke. In patients, the immune response can be beneficial by promoting repair and recovery, and also detrimental by propagating a pro-inflammatory microenvironment. Thus, it is critical to understand the mechanisms of immune activation following stroke in order to successfully design therapeutics.

Effect of intensive rehabilitation on improvement of activity of daily living after intracerebral hemorrhage: a retrospective observational study.

Between 2008 and 2012, the intensity of rehabilitation therapy for the recovery phase of stroke was gradually increased at our hospital in line with the policy of Japan's National Insurance System. Training hours increased from 0.8 to 2.5 hours/day without introducing any new techniques, programs, or equipment. The aim of this study was to investigate the effectiveness of the increased intensity of rehabilitation on the improvement of activity of daily living of patients with intracerebral hemorrhage. We retrospectively compared patient outcomes for the periods 2013-2017 (N = 162) and 2003-2007 (N = 116) using the gain in Barthel Index as an indicator of improvement in activity of daily living. The median (interquartile range) gain was significantly higher in 2013-2017 than in 2003-2007 [30 (20-45) vs. 15 (5-30); P < 0.001]. A stratified analysis showed that this improvement was independent of sex, the patient's Barthel Index on admission, or the side of the brain lesion, but it varied with age or time to admission from onset of the disease. These results, based on a considerable difference in the intensity of rehabilitation between the two periods, support the consensus that increased time spent on rehabilitation results in better functional outcome in post-stroke patients. The results also suggest that age and the timing of starting rehabilitation are important factors to examine the effectiveness of intense rehabilitation in patients with intracerebral hemorrhage.

Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)

BackgroundHuman neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute—chronic...

Abstract 111: Myeloid Specific Deletion of CD36 Increases Microglia-Like CD45 Low Subset and Exacerbates Stroke-Induced Brain Injury

Objective: CD36 regulates biological and pathological processes including inflammation, resolution, phagocytosis, and angiogenesis. Highly expressed in monocytes/macrophages (MM), MM CD36 has been implicated in both detrimental and beneficial effects in acute stroke outcome and recovery. Using myeloid specific deficiency of CD36 (CD36KO MM ) mice, the present study addresses the role of MM CD36 on subset composition of MM in the acute and recovery phases of stroke. Methods: WT (CD36 fl/fl ) and CD36KO MM (M/F, 12w old) mice were subjected to transient focal ischemia. Brain immune cells were collected at 3d, 7d and 2m (n=8-12/timepoint). Infarct volume and hemispheric swelling were measured at 3d (n=13/genotype). In the isolated brain immune cells, CD11b+ cells were further distinguished by CD45 Hi and CD45 Low subsets. The extent of MM trafficking was determined by an intravenous infusion of control GFP+ splenocytes into the stroked WT and CD36KO MM mice 1d prior to sacrifice and MM subset analyses. Results: Compared to WT mice, CD36KO MM mice showed no difference in CD45 Low subset at 3d, 7d and 2m after stroke. However, CD36KO MM mice displayed a significant reduction of CD45 Hi subset, presumably infiltrating cells, at these time points (n=4-8 /group, P&lt;0.01). Adoptive transfer of control GFP+ splenocytes to stroked CD36KO MM mice resulted in an increase of GFP+ cells in CD45 Low but a profound reduction in CD45 Hi subset. Despite the near absence of CD45 Hi and increased CD45 Low population in the post-ischemic brain, CD36KO MM mice displayed exacerbation of brain injury (15.1±13.7 vs 25.8±17.5 mm 3 , p&lt;0.05) and brain swelling (12.1±10.3 vs 18.4±12.7 %, p=0.1). Conclusion: The observed reduction of CD45 Hi subset and exacerbation of brain injury in CD36KO MM mice suggests a beneficial role of infiltrated CD45 Hi MMs in limiting stroke injury. The sustained trafficking at 2m indicates potential involvement of MM CD36 in the recovery process. Further studies to assess long-term outcomes of CD36KO MM mice will provide critical insights on the role of macrophage CD36 in stroke recovery.

Gait and Muscle Activity Changes in Patients in the Recovery Phase of Stroke with Continuous Use of Ankle-Foot Orthosis with Plantarflexion Resistance.

ABSTRACTObjective:Previous studies have suggested that the use of an ankle–foot orthosis may cause disuse atrophy of the tibialis anterior muscle. The objective of this study was to explore gait and muscle activity changes in patients in the recovery phase of stroke with 2-month use of an ankle–foot orthosis that provided plantarflexion resistance.Methods:The participants were 19 patients in the recovery phase of stroke who were prescribed an ankle–foot orthosis that provided plantarflexion resistance. We measured ankle and shank tilt angles as well as electromyography activity of the tibialis anterior and the soleus during 10-m walk tests. Measurements were taken on three occasions. The first was 2 weeks after delivery of the orthosis, 1 and 2 months after the initial measurement, and the third 2 months later. Changes in gait parameters were analyzed between the first and second measurements and between the second and third measurements.Results:Between the second and third measurements, significant increases were observed in plantarflexion and shank forward tilt angles and the activity ratio of the tibialis anterior during loading response compared with other phases.Conclusions:Plantarflexion movement induced by an ankle–foot orthosis with plantarflexion resistance could increase the activity ratio of the tibialis anterior during loading response.

Imbalance in the force: the dark side of the microbiota on stroke risk and progression.

The composition of the gut microbiota depends on many factors, including our lifestyle, diet, metabolism, antibiotic use and hygiene. The contribution of these factors in shaping the gut microbiota and the subsequent effects on the prevention and development of stroke has been under intense investigation. Furthermore, several reports have uncovered the impact of stroke on intestinal dysfunction and gut dysbiosis, highlighting the delicate interplay between the brain, gut and microbiome following this acute brain injury. Despite our growing appreciation of the gut microbiota in shaping brain health, the immune system, host metabolism and disease progression, its therapeutic capability in stroke is yet to be fully exploited. This review will explore the microbiota-gut-brain axis in stroke, and examine the potential role of the gut microbiota in the onset, progression and recovery phase of stroke.

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons.

Type 2 diabetes (T2D) hampers stroke recovery though largely undetermined mechanisms. Few preclinical studies have investigated the effect of genetic/toxin-induced diabetes on long-term stroke recovery. However, the effects of obesity-induced T2D are mostly unknown. We aimed to investigate whether obesity-induced T2D worsens long-term stroke recovery through the impairment of brain's self-repair mechanisms - stroke-induced neurogenesis and parvalbumin (PV)+ interneurons-mediated neuroplasticity. To mimic obesity-induced T2D in the middle-age, C57bl/6j mice were fed 12 months with high-fat diet (HFD) and subjected to transient middle cerebral artery occlusion (tMCAO). We evaluated neurological recovery by upper-limb grip strength at 1 and 6 weeks after tMCAO. Gray and white matter damage, stroke-induced neurogenesis, and survival and potential atrophy of PV-interneurons were quantitated by immunohistochemistry (IHC) at 2 and 6 weeks after tMCAO. Obesity/T2D impaired neurological function without exacerbating brain damage. Moreover, obesity/T2D diminished stroke-induced neural stem cell (NSC) proliferation and neuroblast formation in striatum and hippocampus at 2 weeks after tMCAO and abolished stroke-induced neurogenesis in hippocampus at 6 weeks. Finally, stroke resulted in the atrophy of surviving PV-interneurons 2 weeks after stroke in both non-diabetic and obese/T2D mice. However, after 6 weeks, this effect selectively persisted in obese/T2D mice. We show in a preclinical setting of clinical relevance that obesity/T2D impairs neurological functions in the stroke recovery phase in correlation with reduced neurogenesis and persistent atrophy of PV-interneurons, suggesting impaired neuroplasticity. These findings shed light on the mechanisms behind impaired stroke recovery in T2D and could facilitate the development of new stroke rehabilitative strategies for obese/T2D patients.

Referral patterns of stroke rehabilitation inpatients to a model system of outpatient services in Ontario, Canada: a 7-year retrospective analysis

BackgroundWhile several studies have tracked the care paths of patients in the early phases of stroke recovery, studies examining the transition from inpatient to outpatient rehabilitation are lacking. Examining this transition allows for improved understanding and refinement of the process whereby patients are referred and admitted to programs. The objective of this study was to examine the referral patterns of stroke rehabilitation inpatients to outpatient stroke therapy services, their demographics, and clinical profile.MethodsThis study examined patients who: (1) were admitted to an inpatient stroke rehabilitation unit between January 1, 2009 and March 1, 2016, (2) had a stroke diagnosis, (3) had an inpatient length of stay of > 1 day, and (4) lived within the geographical boundaries of the South West Local Health Integration Network which allowed them access to both hospital-based and home-based stroke rehabilitation outpatient programs. Patient data was collected from the National Rehabilitation Reporting System, as well as three hospital outpatient administrative databases. These databases were cross-referenced to determine each patient’s pathway. Those referred to an outpatient therapy program, and those who attended the outpatient programs, were compared to those who were not, and did not, respectively.Results1497 inpatients were included in the analysis. Upon discharge, 1037 (69.3%) of patients had an outpatient clinic, follow-up appointment scheduled; of those, 902 (87.0%) patients attended at least one outpatient clinic visit. 891 (59.5%) were referred to one of the interdisciplinary outpatient stroke rehabilitation programs; of those, an outpatient therapy program was attended by 80.9% of patients (n = 721). Of those receiving outpatient therapy services, the number of patients attending the in-hospital versus home-based program were equal, 360 and 361 individuals, respectively.ConclusionThis study allows for a better understanding of the transition between inpatient and outpatient stroke care. There is a paucity of this type of information in stroke rehabilitation literature to date. This study acts as a starting point in improving rehabilitation planning across the continuum of care.

Abstract TMP47: Sleep and Endocrine Disturbances Are Associated With Poorer Outcomes During the Post-Acute Phase of Stroke Recovery

Introduction: Sleep disturbances, including decreases in slow wave sleep (SWS) are common following stroke. In this study, we sought to identify the implications of decreased slow wave sleep on endocrine function and cognitive/outcome measures in the post-acute phase of stroke recovery. Methods: Adult stroke patients (n=44) were assessed via overnight polysomnography (PSG). The mean age was 50 ± 1.8 years and mean latency from stroke was 126 ± 16 days. Sleep measures included total sleep time (TST), sleep and REM latency, percent time in sleep stages, apnea/hypopnea index (AHI), wake after sleep onset (WASO), and arousal index. Hormone levels were analyzed within 10 days of PSG. The primary outcome measures were as follows: California Verbal Learning Test (CVLT), Montreal Cognitive Assessment (MoCA), Trails A and B, Mayo Portland Adaptability Inventory (MPAI), and NeuroQOL. Sex differences were also analyzed. Results: Age and BMI were positively correlated with subjective daytime sleepiness using the Epworth Sleepiness Scale (p&lt;.05); however, while BMI was positively correlated with the arousal index (p&lt;.01), it was not correlated with AHI. TST was negatively correlated with subscales of the MPAI (p&lt;.05). Time spent in SWS was associated with decreases in self reported anxiety, fatigue, and sleep disturbances on the NeuroQOL (p&lt;.01). Increases in SWS were also correlated with higher scores on the MoCA (p&lt;.05). Increases in sex hormone binding globulin (SHBG) were associated with decreases in TST (p&lt;.05) and increased percent WASO (p&lt;.01). Additionally, SHBG was negatively associated with the CVLT list B (p&lt;.05). For men, SHBG is positively associated with the number of repetitions on the CVLT (p&lt;.01). As expected, men had a higher arousal index and higher AHI than women. Conclusion: Time spent in SWS is associated with better subjective well-being and improved performance on cognitive measures. Hormone levels, especially SHBG, may serve as early biomarkers for sleep disturbances after stroke and are associated with negative performance on some measures of cognition.

Clinical improvement with intensive robot-assisted arm training in chronic stroke is unchanged by supplementary tDCS.

Intensive robot-assisted arm training in the chronic phase of stroke recovery can lead to clinical improvement. Combinatorial therapeutic approaches are sought to further optimize stroke recovery. Transcranial direct current stimulation (tDCS) is one candidate to combine with robotic training, as transient increases in excitability and improvements in motor behavior have separately been reported. To determine whether tDCS, delivered prior to robotic training, could augment clinical improvement. We conducted a dual-site, randomized controlled trial in 82 chronic ischemic stroke patients (inclusion > 6 m post-injury, dominant hemisphere, first stroke; residual hemiparesis) who were split into two groups to receive tDCS (M1-SO montage, anode ipsilesional, 5×7 cm electrodes, 2 mA, 20 mins) or sham tDCS, prior to robotic upper-limb training (12 weeks; 36 sessions; shoulder-elbow robot or wrist robot on alternating sessions). The primary end-point was taken after 12 weeks of training, and assessed with the Upper Extremity Fugl-Meyer impairment scale (FM). Corticomotor conduction was assessed with transcranial magnetic stimulation (TMS). For the combined group (n = 82; post-training) robotic training increased the FM by 7.36 points compared to baseline (p < 0.0001). There was no difference in the FM increase between the tDCS and sham groups (6.97 and 7.73 respectively, p = 0.46). In both groups, clinically meaningful improvement (≥5 points) from baseline was evident in the majority of patients (56/77), was sustained six months later (54/72), and could be attained in severe, moderate and mild baseline hemiparesis. Clinical improvement was associated with increased excitability in the affected hemisphere as assessed by resting motor threshold (pre-post p = 0.029; pre-post 6 months p = 0.029), but not with threshold-adjusted assessment of MEP amplitude (pre-post p = 0.09; pre-post 6 months p = 0.15). Participants with motor evoked potentials were more likely to improve clinically than those without (17/18, 94%, versus 39/59, 66%, p = 0.018). Our study confirms the benefit of intensive robot-assisted training in stroke recovery, and indicates that conventional tDCS does not confer further advantage to robotic training. We also showed that corticospinal integrity, as assessed by TMS, is a predictor of clinically meaningful response to intensive arm therapy in chronic stroke.

Developing interventions to address sexuality after stroke: Findings from a four-panel modified Delphi study.

Although stroke has a profound impact on sexuality there are limited evidence-based interventions to support rehabilitation professionals in this area. The aim of the current research was to prioritize content areas and approaches to sexual rehabilitation from the perspective of stroke survivors, their partners, stroke rehabilitation clinicians and researchers. A 2-step online Delphi method was used to prioritize the content of, and approaches to, sexual rehabilitation with stroke survivors, their partners, stroke rehabilitation clinicians and researchers. Stroke survivors (n = 30), their partners (n = 18), clinicians and researchers in stroke rehabilitation (n = 45) completed at least 1 of 2 investigator-developed surveys. Participants prioritized 18 core content areas for inclusion in sexual rehabilitation following stroke with a high degree of consensus. Another 27 content areas were considered moderately important. There was strong consensus that sexual rehabilitation should be offered in the subacute and chronic phases of stroke recovery. Participants would prefer health professionals to deliver the intervention face-to-face. This study presents opinions from stroke survivors, partners of stroke survivors, clinicians and researchers. The information about content, timing and mode of delivery will be used to develop and evaluate a comprehensive sexuality rehabilitation programme.

Astrocytic cytochrome P450 4A/20-hydroxyeicosatetraenoic acid contributes to angiogenesis in the experimental ischemic stroke

20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 4A (CYP4A) metabolite of arachidonic acid, is one of the primary eicosanoids in most of microcirculatory beds. Studies have indicated that 20-HETE has important functions in the modulation of vascular tone, ion transport, inflammation reaction, and cellular proliferation. Both we and others have demonstrated that 20-HETE plays an important role in acute phase of ischemic stroke. However, little is known about the effect of 20-HETE on recovery phase of stroke. Crosstalk between the cells within the neurovascular unit is increasingly suspected of playing critical roles in stroke recovery. We found that CYP4A is upregulated in astrocytes exposed to oxygen-glucose deprivation (OGD), which increases the production of 20-HETE that promotes endothelial cell proliferation, tube formation and migration. siRNA suppression of CYP4A or 20-HETE inhibitor prevents this effect. In a mouse model of transient focal cerebral ischemia, inhibition of CYP4A reduces peri-infact angiogenesis and worsens neurological deficits 14 days after stroke. We further showed that ischemia injury increases VEGF and HIF-1α expression in cell cultures and ischemic brains, which is negated by a 20-HETE inhibitor-HET0016. Lastly, we showed that JNK signaling pathway is a component of 20-HETE regulated ischemic angiogenesis after stroke. Taken together, we demonstrated a positive influence of 20-HETE in angiogenesis in later stage of stroke. These molecular and in vivo findings also support a previously undescribed mechanism of crosstalk between reactive astrocytes and endothelial cells wherein 20-HETE promotes neurovascular remodeling and functional recovery after ischemic stroke.