Effect of vitamin C supplementation on stroke recovery: A case-control study

Background and purpose:

Epidemiological studies have associated increased dietary intake of antioxidants (vitamin C, E, and β-carotene) in preventing and decreasing the extent of ischemic brain injury. The effect of vitamin C supplementation on functional recovery after stroke has not been studied.

Method:

In this retrospective, case-control study of 23 patients with ischemic stroke taking vitamin C were identified and matched for age, sex, onset to admission, and admission total functional independence measure (TFIM) with 23 patients with ischemic stroke not taking Vitamin C supplementation. Vitamin C 1000 mg daily was prescribed on admission to our unit mainly to patients who were undernourished (defined as significant weight loss and/or 90% or less ideal body weight for age and sex) and those with pressure sores. The outcome measures were: change in the TFIM, FIM-Cognition (FIM-Cog), and FIM-Motor sub-scores, discharge disposition, and length of stay (LOS).

Results:

The change in TFIM (20 ± 13 standard deviation [SD] vs. 26 ± 6, p = 0.20), FIM-Cog (3 ± 3 SD vs. 4 ± 5, p = 0.41), FIM-Motor (15 ± 11 SD vs. 20 ± 13, p = 0.21) sub-scores were less in the vitamin C treated group, but these differences did not reach statistical significance. Similarly, no significant differences were found in LOS (21 ± 9 SD vs. 23 ± 9, p = 0.59), and discharge disposition (home/institution) (9/10 vs. 13/9, p = 0.60) between the vitamin C and the control groups.

Conclusion:

This study suggests vitamin C supplementation did not enhance functional recovery in undernourished ischemic stroke patients.     

Diabetes hyperglycemia and recovery from stroke

Strokeis a major cause of death and severe disability in older people. Despite the burden of disease, there is still no safe, simple and proven medical therapy for the treatment of acute stroke. Advances in acute stroke treatment have been either consistently disappointing (neuroprotective therapy) or fraught with controversy regarding risk/benefit (thrombolysis), and attention is once again being directed towards physiological variables that may influence outcome. Both insulin-dependent and non-insulin-dependent diabetes mellitus are major risk factors for stroke. Diabetes mellitus has also been shown to be associated with increased mortality and reduced functional outcome after stroke. Hyperglycemia is a frequent finding following stroke and may reflect the metabolic stress of the acute event, so-called stress hyperglycemia, and/or underlying impaired glucose metabolism. Several large clinical studies have now demonstrated a positive association between a raised blood glucose and poor outcome from stroke; greater mortality and reduced functional recovery. What is not clear is to what extent hyperglycemia is a 'normal' physiological response to stroke or whether hyperglycemia per se increases cerebral damage in the acute phase. There are many potential mechanisms by which hyperglycemia can exert a harmful effect upon cerebral tissue and it is probable that an important relationship exists, not only between glucose and stroke outcome, but also between insulin and neuroprotection. It remains to be determined whether lowering and maintaining 'normal' glucose levels in the immediate aftermath of stroke, combined with the administration of insulin as an acute treatment, can modify this outcome.     

舍曲林对脑卒中后抑郁及神经功能康复影响的临床研究

目的观察舍曲林对脑卒中后抑郁及神经功能康复程度的影响。方法将176例脑卒中后抑郁的患者随机分为:舍曲林治疗组89例和对照组87例。于治疗前后,采用汉密尔顿抑郁量表、神经功能缺损评分量表及日常生活能力Barthel指数量表进行分析。结果与对照组比较,治疗组汉密尔顿抑郁量表和神经功能缺损评分明显降低,日常生活能力Barthel指数量表评分明显增高(P0.05)。结论舍曲林治疗脑卒中后抑郁效果明显,并可促进脑卒中后神经功能的康复。     

Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice

Abstract:  Melatonin is a potent antioxidant with neuroprotective activity in animal models of ischemic stroke, which based on its lack of serious toxicity has raised hopes that it might be used for human stroke treatment in the future. This study investigated how subacute delivery of melatonin, starting at 24 hr after stroke onset, and continuing for 29 days (4 mg/kg/day; via drinking water), influences neuronal survival, endogenous neurogenesis, motor recovery and locomotor activity in C57Bl6/j mice submitted to 30-min middle cerebral artery occlusion. Histologic studies showed that melatonin improved neuronal survival and enhanced neurogenesis, even when applied 1 day after stroke. Cell survival was associated with a long-lasting improvement of motor and coordination deficits, evaluated by the grip strength and RotaRod tests, as well as with attenuation of hyperactivity and anxiety of the animals as revealed in open field tests. The robust functional neurologic improvements encourage proof-of-concept studies with melatonin in human stroke patients.     

Depression and functional recovery after a disabling hospitalization in older persons

OBJECTIVES: To determine the association between depression and functional recovery in community‐living older persons who had a decline in function after an acute hospital admission. DESIGN: Prospective cohort study. SETTING: General community in greater New Haven, Connecticut, from March 1998 to December 2008. PARTICIPANTS: Seven hundred fifty‐four persons aged 70 and older. MEASUREMENTS: Hospitalization and disability in essential activities of daily living (ADLs) and mobility were assessed each month for up to 129 months, and depressive symptoms were assessed every 18 months using the Center for Epidemiologic Studies‐Depression Scale (CES‐D). Functional recovery was defined as returning to the community within 6 months at or above the prehospital level of ADL function and mobility. RESULTS: A decline in ADL function and mobility was observed after 42% and 41% of the hospitalizations, respectively. After controlling for several potential confounders, clinically significant depressive symptoms (CES‐D score ≥20) was associated with a lower likelihood of recovering mobility function (hazard ratio (HR)=0.79, 95% confidence interval (CI)=0.63–0.98) but not ADL function (HR=0.91, 95% CI=0.75–1.10) within 6 months of hospitalization. CONCLUSION: After a disabling hospitalization, community‐living older persons with preexisting depression may be less likely to recover their prehospitalization level of mobility function but not ADL function, although the reasons remain to be elucidated.     

卒中后单侧忽略

单侧忽略是卒中的常见高级神经功能缺损之一.文章着重介绍卒中后单侧忽略的定义、发病率、导致忽略的病灶部位、可能的发病机制和临床表现,概述了卒中后单侧忽略的分型和合并症,指出了以上内容对单侧忽略评价和治疗的意义.     

Agonistic analog of growth hormone–releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke

Ischemic stroke can induce neurogenesis. However, most stroke-generated newborn neurons cannot survive. It has been shown that MR-409, a potent synthetic agonistic analog of growth hormone–releasing hormone (GHRH), can protect against some life-threatening pathological conditions by promoting cell proliferation and survival. The present study shows that long-term treatment with MR-409 (5 or 10 μg/mouse/d) by subcutaneous (s.c.) injection significantly reduces the mortality, ischemic insult, and hippocampal atrophy, and improves neurological functional recovery in mice operated on for transient middle cerebral artery occlusion (tMCAO). Besides, MR-409 can stimulate endogenous neurogenesis and improve the tMCAO-induced loss of neuroplasticity. MR-409 also enhances the proliferation and inhibits apoptosis of neural stem cells treated with oxygen and glucose deprivation–reperfusion. The neuroprotective effects of MR-409 are closely related to the activation of AKT/CREB and BDNF/TrkB pathways. In conclusion, the present study demonstrates that GHRH agonist MR-409 has remarkable neuroprotective effects through enhancing endogenous neurogenesis in cerebral ischemic mice.

Stroke is a leading cause of mortality and permanent disability in adults worldwide (1). Although most pharmacological neuroprotectants have beneficial effects in experimental studies, they fail in clinical trials. The current therapies are inadequate to improve the sequelae of neuromotor dysfunction and clinical outcomes of ischemic stroke. The development of novel therapies for ischemic stroke is an urgent need and of top priority.It has been demonstrated that ischemic stroke can markedly induce endogenous neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus. These areas are also most concentrated locations of neuronal precursor cells (NPCs) in the adult brain (2). The recovery of neurological function after cerebral ischemia mainly depends on the migration of newly formed neurons to severe ischemic lesions, such as the striatum and granular layer of the hippocampus, to replace necrotic neurons. However, only a very small portion of newly generated neurons can differentiate into mature neurons (2, 3). In addition to neurogenesis, the recovery of neurological function after a stroke depends on the neuroplasticity of the established networks in the ipsilateral tissue, including axonal sprouting, dendritic remodeling, and synapse strengthening (4, 5). Therefore, pharmacological neuroprotection and neuronal replacement by facilitating endogenous neurogenesis and neuroplasticity to maximize functional outcome are considered as promising strategies for the treatment of ischemic stroke.Growth hormone–releasing hormone (GHRH) is a hypothalamic neuropeptide. Beside being expressed in the pituitary cells, GHRH and its receptors (GHRH-Rs) are also found in various extrapituitary cells or tissues, such as fibroblast, cardiomyocyte, ocular tissue, and mesenchymal stem cells (6–9). In the past few decades, many potent GHRH agonistic analogs of JI and MR class have been synthesized by our group (10, 11). Compared with native GHRH peptides, synthetic agonist of GHRH agonists have a long half-life and high stability and potency without the side effects of stimulating GH axis–induced tumor growth (12, 13). Notably, it has been demonstrated that MR-409 exhibits high potency on the activation of tissue repair and self-renewal and the promotion of cell proliferation and survival in various tissues by binding to GHRH-Rs. A large body of work has shown that MR-409 promotes the repair of cardiac tissue and function and reduces myocardial infarct size in experimental myocardial infarct in animal models (14). MR-409 also improves metabolic function and the survival of pancreatic islets after transplantation into experimental diabetic animals (15) and exerts neurovascular protective effects in diabetic retinopathy (16). These studies indicate that GHRH agonists, particularly MR-409, should have therapeutic applications for tissue repair by promoting cell proliferation, which may apply to cerebral ischemic conditions.In the present study, we investigated the protective effects of long-term MR-409 treatment on neurological function, neurogenesis, and neuroplasticity in the mice operated on for tMCAO. The results demonstrate that MR-409 significantly improves neurological functional outcomes and promotes neurogenesis and neuroplasticity in ischemic damage areas.     

Predicting stroke recovery: three- and six-month rates of patient-centered functional outcomes based on the orpington prognostic scale

OBJECTIVE: To provide recovery rates after stroke for specific functions using the Orpington Prognostic Scale (OPS). DESIGN: Prospective cohort. SETTING: Hospital and community. PARTICIPANTS: 413 stroke survivors entered the study 3 to 14 days after suffering a stroke. MEASUREMENTS: A cohort of hospitalized stroke survivors were recruited 3 to 14 days after stroke and assessed at 1, 3, and 6 months poststroke for neurological, functional, and health status. Baseline OPS score was used to predict five functional outcomes at 3 and 6 months using development and validation datasets and receiver operating characteristic (ROC) curves. RESULTS: In 413 stroke survivors, functional recovery rates at 3 and 6 months were similar. Baseline OPS predicted significant differences in recovery rates for all five outcomes (P < .0001 for all five outcomes at 3 and 6 months). Personal care dependence was present at 3 months in only 3% of persons with baseline OPS scores of 3.2 or less compared with over 50% with OPS of 4.8 or higher. Independent personal care, meal preparation, and self-administration of medication were achieved by 80% who had baseline OPS scores of 2.4 or lower compared with less than 20% when OPS scores were 4.4 or higher. Independent community mobility was achieved in 50% of those who had OPS scores of 2.4 or lower but only 3% of those with OPS scores of 4.4 or higher. The area under ROC curves assessing OPS scores against each of the five outcomes ranged from 0.805 to 0.863 at 3 months and 0.74 to 0.806 at 6 months. CONCLUSION: OPS scores can predict widely differing rates of functional recovery in five important functional abilities. These estimates can be useful to survivors, families, providers, and healthcare systems who need to plan for the future.     

The effects of additional electrical stimulation combined with repetitive transcranial magnetic stimulation and motor imagery on upper extremity motor recovery in the subacute period after stroke: A preliminary study

Background:To evaluate the therapeutic effects of additional electrical stimulation (ES) combined with low frequency (LF)-repetitive transcranial magnetic stimulation (rTMS) and motor imagery (MI) training on upper extremity (UE) motor function following stroke.Methods:The participants with subacute stroke in the experimental group (n = 8) received LF rTMS + MI + active ES interventions, and those in control group (n = 9) received LF rTMS + MI + sham ES interventions. Interventions were performed 5 days a week for 2 weeks, for a total of 10 sessions. All participants were given the same dosage of conventional rehabilitation during the study period. The primary outcome measure was the UE Fugl-Meyer Assessment (FMA). The secondary outcome measures were the shoulder abduction and finger extension scores, modified Barthel Index, Purdue Pegboard Test, and finger tapping test. All scores were measured before and just after the intervention.Results:After the 2-week intervention period, the FMA and modified Barthel Index scores were improved in both groups compared to baseline assessment (P < .001 in the experimental group and P = .008 in the control group). Of note, the change in FMA scores was significantly higher in the experimental group compared with that of the control group (P = .04).Conclusion:These results suggest that the use of LF rTMS + MI combined with additional ES lead to greater improvement of UE motor function after stroke. As such, this intervention may be a promising adjuvant therapy in UE motor training.     

Factors associated with functional recovery and home discharge in stroke patients admitted to a convalescent rehabilitation ward

Aims: This study aimed to determine the predictive factors for functional recovery and home discharge in stroke patients receiving in‐hospital rehabilitation. Methods: This study included a consecutive series of 174 stroke patients (average age 73.0 ± 10.8) admitted to the convalescent rehabilitation ward at Azumino Red Cross Hospital in Japan after acute rehabilitation. The main outcome measures were functional recovery (functional independence measure [FIM] at discharge and Montebello rehabilitation factor score [MRFS]) and home discharge. Results: Total FIM improved from 72.6 ± 27.6 to 87.7 ± 29.9 during the hospital stay (P < 0.001). The average MRFS was 0.30 ± 0.28. Of the 174 patients, 151 were discharged home (87%). Age, stroke type, premorbid independence, motor FIM, and cognitive FIM at admission showed a significant association with FIM at discharge, while age, premorbid independence, motor FIM at admission, and cognitive FIM at admission were statistically significant predictors of MRFS. Female sex, not living with family, premorbid independence, and neglect were negatively associated with home discharge. Conclusions: Premorbid disability and cognitive dysfunction at admission were both negatively associated with functional recovery and home discharge in patients undergoing inpatient stroke rehabilitation. Geriatr Gerontol Int 2012; 12: 215–222.     

神经干细胞的研究现状及其在治疗缺血性卒中的应用

迄今为止,缺血性卒中的临床治疗方法虽然繁多,但效果却不理想,而且卒中急性期后遗留偏瘫、功能障碍等严重残疾的情况非常严重,极大地影响了患者的生存质量,给家庭和社会带来很大负担。因此,如何提高缺血性卒中治疗的效果,这对神经科一直是面临的重大挑战。近年来,临床实践证明,超早期溶栓可使许多患者得到满意疗效。然而,这种溶栓     

Effect of biofeedback cycling training on functional recovery and walking ability of lower extremity in patients with stroke

This study aimed to investigate the effectiveness of biofeedback cycling training on lower limb functional recovery, walking endurance, and walking speed for patients with chronic stroke. Thirty-one patients with stroke (stroke onset >3 months) were randomly assigned into two groups using a crossover design. One group (N = 16; mean: 53.6 ± 10.3 years) underwent conventional rehabilitation and cycling training (30 minutes/time, 5 times per week for 4 weeks), followed by only conventional rehabilitation for another 4 weeks. The other group (N = 15; mean: 54.5 ± 8.0 years) underwent the same training in reverse order. The bike used in this biofeedback cycling training was the MOTOmed viva2 Movement Trainer. Outcome measures included the lower extremity subscale of Fugl-Meyer assessment (LE-FMA), the 6-minute walk test (6MWT), the 10-meter walk test (10MWT), and the modified Ashworth scale (MAS). All participants were assessed at the beginning of the study, at the end of the 4^th week, and at the end of the 8^th week. Thirty participants completed the study, including the cycling training interventions and all assessments. The results showed that improvements in the period with cycling training were significantly better than the noncycling period in the LE-FMA (p < 0.05), 6MWT (p < 0.001), 10MWT (p < 0.001), and MAS (p < 0.001) scores. No significant carryover effects were observed. The improvements on outcome measures were significantly different between the cycling period and the noncycling period after adjusting for potential confounding factors in the multivariate analysis of variance (p < 0.001). The study result indicates that the additional 4-week biofeedback cycling training could lead to improved LE functional recovery, walking endurance, and speed for patients with chronic stroke.     

Poststroke acute dysexecutive syndrome,a disorder resulting from minor stroke due to disruption of network dynamics

Stroke patients with small central nervous system infarcts often demonstrate an acute dysexecutive syndrome characterized by difficulty with attention, concentration, and processing speed, independent of lesion size or location. We use magnetoencephalography (MEG) to show that disruption of network dynamics may be responsible. Nine patients with recent minor strokes and eight age-similar controls underwent cognitive screening using the Montreal cognitive assessment (MoCA) and MEG to evaluate differences in cerebral activation patterns. During MEG, subjects participated in a visual picture–word matching task. Task complexity was increased as testing progressed. Cluster-based permutation tests determined differences in activation patterns within the visual cortex, fusiform gyrus, and lateral temporal lobe. At visit 1, MoCA scores were significantly lower for patients than controls (median [interquartile range] = 26.0 [4] versus 29.5 [3], P = 0.005), and patient reaction times were increased. The amplitude of activation was significantly lower after infarct and demonstrated a pattern of temporal dispersion independent of stroke location. Differences were prominent in the fusiform gyrus and lateral temporal lobe. The pattern suggests that distributed network dysfunction may be responsible. Additionally, controls were able to modulate their cerebral activity based on task difficulty. In contrast, stroke patients exhibited the same low-amplitude response to all stimuli. Group differences remained, to a lesser degree, 6 mo later; while MoCA scores and reaction times improved for patients. This study suggests that function is a globally distributed property beyond area-specific functionality and illustrates the need for longer-term follow-up studies to determine whether abnormal activation patterns ultimately resolve or another mechanism underlies continued recovery.

Advances in acute stroke treatment have significantly reduced motor and language deficits, converting highly morbid large hemispheric lesions into smaller infarcts with better overall long-term outcomes (1, 2). Prior work has shown that the majority of individuals presenting for follow-up 4- to 6-wk postinfarct now exhibit what would be classified as “minor symptoms,” (3) with low stroke severity measured by the NIH Stroke Scale (NIHSS) (4) and modified Rankin Scale (mRS) (5) scores. Although these individuals lack a dense hemiparesis or aphasia, over half endorse some degree of cognitive impairment that significantly impacts their recovery. Interestingly, these symptoms are typically found to be independent of stroke size, location, or coexisting depression (6, 7).Poststroke cognitive decline has a substantial presence in the literature (8–13). However, we find that rather than memory impairment or confusion, patients without prior cognitive disability report immediate difficulty with executive function, focus, concentration, and attention after a minor stroke, hereafter referred to as poststroke acute dysexecutive syndrome (PSADES) (3). Dysexecutive syndrome has been previously described in individuals with anatomic lesions (14) as well as disorders, such as schizophrenia (15) and Alzheimer’s disease (14), affecting the frontal lobes. When mild, the syndrome can be hard for others to appreciate, particularly, in previously high-functioning individuals, but poststroke, these deficits are detectable on screening tests, such as the Montreal cognitive assessment (MoCA) (16) and other scales of activities of daily living compared to age-matched controls (3). Despite the fact that following stroke, symptoms typically improve over the first 3–6 mo of recovery, PSADES impedes many successful well-educated individuals from returning to cognitively driven professions given the uncertainty of their prognosis. These decisions affect lifestyle and quality of life, resulting in lasting long-term consequences.The pathophysiology underlying PSADES is poorly understood, as many times the inciting infarct is small and does not involve an area of the brain classically thought to be important for cognitive processing. Cognitive change due to deep white matter lesions (in multiplicity) has been well described (17), but there is no clear unifying physiological explanation regarding how a single small cortical or subcortical lesion may cause significant generalized cortical dysfunction. Some posit a “network” hypothesis suggesting that an individual requires an extensive system of neuronal connectivity, involving numerous cortical and subcortical regions, in order to complete a task (18). We propose that the cognitive dysfunction of PSADES may be the result of a disruption of general network dynamics due to lesions of the subcortical white matter tracts, which would, in turn, interfere with basic network function.This study was designed as a first step in evaluating the role of network dynamics during tasks requiring attention, concentration, speed, and accuracy; all skills difficult for patients poststroke. We used magnetoencephalography (MEG) to determine the differences in cerebral activation patterns in nine individuals with small strokes versus a group of eight age-similar controls by measuring the amplitude and latency of cerebral responses during a visual comprehension task at two time points: ∼1- and 6-mo postinfarct. Our analysis focused on the early visual, M170, and M400 components of the event-related potential from the occipital lobe, fusiform gyrus, and lateral temporal lobe given their importance in visual recognition and language processing (19–22).     

Subcortical vascular lesions predict functional recovery after rehabilitation in patients with L-dopa refractory parkinsonism

OBJECTIVES: To identify predictors of functional recovery after an intensive rehabilitation training in patients with gait disturbances and refractory parkinsonism. DESIGN: Observational study. SETTING: A hospital geriatric rehabilitation department ("Ancelle della Carità" hospital of Cremona). PARTICIPANTS: Thirty-eight subjects (mean age+/-standard deviation of 78.9+/-6.5; 66% women) with gait disturbances and L-dopa refractory parkinsonism consecutively admitted to a rehabilitation unit within 6 months were recruited. Exclusion criteria were obvious musculoskeletal disorders (severe leg arthritis, hemiparesis, recent stroke), recent surgery, delirium, physical impairment from other identifiable causes, and missing computed tomography (CT) scan. All subjects received an intensive standardized rehabilitative program including conventional physical therapy and specific gait training. MEASUREMENTS: The outcome measure of the rehabilitation training was the gain between admission and discharge on the Unified Parkinson Disease Rating Scale (delta-UPDRS). The following potential predictors were assessed using comprehensive geriatric assessment: physical health (Charlson Comorbidity Index, number of drugs), cognitive performance (Mini-Mental State Examination (MMSE)), functional status (Tinetti scale), depressive symptoms (Geriatric Depression Scale), nutritional status (serum albumin and body mass index), and subcortical cerebrovascular load (four classes of increasing severity based on diffuse leukoariosis, patchy lesions of the white matter, and lacunas on CT scan). Multivariate logistic regression with fixed adjustment for age, cognitive performance, and UPDRS on admission and stepwise selection of variables were used to identify independent predictors. RESULTS: Patients were divided into two groups of equal size based on the delta-UPDRS (high and low functional recovery: delta-UPDRS >8 and 相似文献   

Exploring community-dwelling stroke survivors’ experiences of receiving a nurse-led theory-based stroke self-management programme: A qualitative study

International evidence-based guidelines recommend self-management support for stroke survivors to improve their health outcomes. We developed a 4-week nurse-led stroke self-management programme (SSMP) and conducted a randomised controlled trial to assess its effects. This paper reports the findings of a qualitative study nested within the randomised controlled trial to explore stroke survivors’ experiences of SSMP participation. Semi-structured interviews were conducted with all adult participants who were clinically diagnosed with a first or recurrent ischaemic or haemorrhagic stroke, residing at home, communicable in Cantonese, had a Montreal Cognitive Assessment score below the second percentile, and participated in at least 1 SSMP session. All interviews were conducted in Cantonese, lasted approximately 45 minutes, and were audio-recorded. Interview data were transcribed verbatim and analysed thematically. Sixty-four stroke survivors (mean age 66.33 years, SD 12.34) were recruited, and 59 were interviewed via phone immediately after completion of SSMP. Three themes were derived. Overall, participants were satisfied with the SSMP. Their understanding of self-management was improved, and they recognised its importance in recovery. Their confidence in self-management was also enhanced through the use of multifaceted strategies. Suggestions were made to enhance their participation experiences, including increased home visits and group sessions, making group session attendance optional and arranging them more accessibly, meeting the survivors who shared their survival experiences in the videos, and access to the videos online. This study concurred that the SSMP enhanced stroke survivors’ self-efficacy in self-management. Rearrangement of the programme format and enhancements in accessibility could be further examined to enable more effective stroke self-management.