scholarly journals Transplantation of Human Cortically-Specified Neuroepithelial Progenitor Cells Leads to Improved Functional Outcomes in a Mouse Model of Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Rehnuma Islam ◽  
Stasja Drecun ◽  
Balazs V. Varga ◽  
Ilan Vonderwalde ◽  
Ricky Siu ◽  
...  
Keyword(s):  
Functional Outcomes ◽  
Cell Types ◽  
Survival Times ◽  
Neural Repair ◽  
Neuronal Marker ◽  
Injury Site ◽  
Post Stroke ◽  
Cell Source ◽  
Cortical Stroke

Stroke is a leading cause of death and long-term disability worldwide. Current therapeutic options are limited in terms of their time for implementation and efficacy in promoting recovery. Cell transplantation has been shown to have promise in several animal models however significant challenges remain, including the optimal source of cells to promote neural repair. Here, we report on the use of a population of human ESC derived, cortically specified, neuroepithelial precursor cells (cNEPs) that are neurally restricted in their lineage potential. CNEPs have the potential to give rise to mature neural cell types following transplantation, including neurons, astrocytes and oligodendrocytes. With a view towards translation, we sought to determine whether this human cell source was effective in promoting improved functional outcomes following stroke. Undifferentiated cNEPs were transplanted in a pre-clinical endothelin-1 (ET-1) model of ischemic motor cortical stroke in immunocompromised SCID-beige mice and cellular and functional outcomes were assessed. We demonstrate that cNEP transplantation in the acute phase (4 days post-stroke) improves motor function as early as 20 days post-stroke, compared to stroke-injured, non-transplanted mice. At the time of recovery, a small fraction (<6%) of the transplanted cNEPs are observed within the stroke injury site. The surviving cells expressed the immature neuronal marker, doublecortin, with no differentiation into mature neural phenotypes. At longer survival times (40 days), the majority of recovered, transplanted mice had a complete absence of surviving cNEPS. Hence, human cNEPs grafted at early times post-stroke support the observed functional recovery following ET-1 stroke but their persistence is not required, thereby supporting a by-stander effect rather than cell replacement.

scholarly journals Infarct topography and functional outcomes

2017 ◽  
Vol 38 (9) ◽  
pp. 1517-1532 ◽  
Author(s):  
Mark R Etherton ◽  
Natalia S Rost ◽  
Ona Wu
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcomes ◽  
Brain Regions ◽  
Stroke Recovery ◽  
Acute Ischemia ◽  
Post Stroke ◽  
Neurologic Outcomes ◽  
Recovery Potential

Acute ischemic stroke represents a major cause of long-term adult disability. Accurate prognostication of post-stroke functional outcomes is invaluable in guiding patient care, targeting early rehabilitation efforts, selecting patients for clinical research, and conveying realistic expectations to families. The involvement of specific brain regions by acute ischemia can alter post-stroke recovery potential. Understanding the influences of infarct topography on neurologic outcomes holds significant promise in prognosis of functional recovery. In this review, we discuss the recent evidence of the contribution of infarct location to patient management decisions and functional outcomes after acute ischemic stroke.

scholarly journals Post-stroke Hyperglycemia in Non-diabetic Ischemic Stroke is Related With Worse Functional Outcome: A Cohort Study

2021 ◽  
Vol 45 (5) ◽  
pp. 359-367
Author(s):  
Jin A Yoon ◽  
Yong-Il Shin ◽  
Deog Young Kim ◽  
Min Kyun Sohn ◽  
Jongmin Lee ◽  
...  
Keyword(s):  
Cohort Study ◽  
Ischemic Stroke ◽  
Glucose Level ◽  
Functional Outcomes ◽  
Stroke Patients ◽  
Nihss Score ◽  
Post Stroke ◽  
Significant Difference ◽  
Functional Assessments

Objective To investigate long-term and serial functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia.Methods The Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) is a large, multi-center, prospective cohort study of stroke patients admitted to participating hospitals in nine areas of Korea. From KOSCO, ischemic stroke patients without diabetes were recruited and divided into two groups: patients without diabetes without (n=779) and with post-stroke hyperglycemia (n=223). Post-stroke hyperglycemia was defined as a glucose level >8 mmol/L. Functional assessments were performed 7 days and 3, 6, and 12 months after stroke onset.Results There were no significant differences in baseline characteristics between the groups, except in the age of onset and smoking. Analysis of the linear correlation between the initial National Institutes of Health Stroke Scale (NIHSS) score and glucose level showed no significant difference. Among our functional assessments, NIHSS, Fugl-Meyer Assessment (affected side), Functional Ambulatory Category, modified Rankin Scale, and Korean Mini-Mental State Examination (K-MMSE) showed statistically significant improvements in each group. All functional improvements except K-MMSE were significantly higher in patients without post-stroke hyperglycemia at 7 days and 3, 6, and 12 months.Conclusion The glucose level of ischemic stroke patients without diabetes had no significant correlation with the initial NIHSS score. The long-term effects of stress hyperglycemia showed worse functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia.

scholarly journals Direct reprogramming of astrocytes to neurons leads to functional recovery after stroke

2020 ◽  
Author(s):  
Jessica Livingston ◽  
Tina Lee ◽  
Emerson Daniele ◽  
Clara Phillips ◽  
Alexandra Krassikova ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Functional Outcomes ◽  
Treatment Options ◽  
Brain Repair ◽  
Novel Approach ◽  
Regenerative Approach ◽  
Cortical Stroke ◽  
The Impact

AbstractStroke is the leading cause of adult disability with few treatment options for stroke survivors. Astrocyte reprogramming to neurons enables the targeted in vivo generation of new cells at the site of injury and represents a novel approach for brain repair. A number of studies have demonstrated successful conversion of astrocytes to neurons in various models of brain injury and disease; however, the impact of this strategy on tissue and functional outcome following stroke is not well established. Using AAV delivery of the transcription factor NeuroD1, we reprogrammed astrocytes 7 days after endothelin-1 induced cortical stroke, and studied the long-term cellular and functional outcomes. We found that by 63 days post-stroke, 20% of neurons in the perilesional cortex were reprogrammed. Furthermore, reprogrammed neurons had matured into regionally appropriate neuronal subtypes. Importantly, this treatment was associated with improved functional outcome using the foot fault test and gait analysis. Together, our findings indicate that in vivo reprogramming is a promising regenerative approach for stroke repair.

scholarly journals Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Sungmin Hong ◽  
Anne-Katrin Giese ◽  
Markus D. Schirmer ◽  
Anna K. Bonkhoff ◽  
Martin Bretzner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Outcomes ◽  
Linear Regression Analysis ◽  
Functional Independence ◽  
White Matter Hyperintensity ◽  
Stroke Severity ◽  
Post Stroke

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke.Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to−6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons.Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively].Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.

scholarly journals Long term Post-Stroke Functional Outcomes: a comparison of diabetics and non-diabetics

2021 ◽  
Author(s):  
Deidre Anne de Silva ◽  
Kaavya Narasimhalu ◽  
Ian Wang Huang ◽  
Fung Peng Woon ◽  
John C. Allen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Functional Outcomes ◽  
Age Group ◽  
Stroke Patients ◽  
Poor Functional Outcome ◽  
Post Stroke ◽  
The Impact

Introduction: Diabetes mellitus (DM) is known to influence outcomes in the short-term following stroke. However, the impact of DM on long-term functional outcomes after stroke is unclear. We compared functional outcomes periodically over 7 years between diabetic and non-diabetic ischemic stroke patients and investigated the impact of DM on the long-term trajectory of post-stroke functional outcomes. We also studied the influence of age on the diabetes-functional outcome association. Methods: This is a longitudinal observational cohort study of 802 acute ischemic stroke patients admitted to the Singapore General Hospital from 2005 to 2007. Functional outcomes were assessed using the modified Rankin Scale (mRS) with poor functional outcome defined as mRS≥3. Follow-up data was determined at 6 months and at median follow-up durations of 29 and 86 months. Results: Among the 802 ischemic stroke patients studied (mean age 64 ± 12 years, male 63%), 42% had DM. In regression analyses adjusting for covariates, diabetic patients were more likely to have poor functional outcomes at 6 months (OR=2.12, 95% CI: 1.23–3.67) and at median follow-up durations of 29 months (OR=1.96, 95% CI: 1.37–2.81) and 86 months (OR=2.27, 95% CI: 1.58–3.25). In addition, age modulated the effect of DM, with younger stroke patients (≤65 years) more likely to have long term poor functional outcome at the 29-month (p=0.0179) and 86-month (p=0.0144) time points. Conclusions: DM was associated with poor functional outcomes following ischemic stroke in the long term with the effect remaining consistent throughout the 7-year follow-up period. Age modified the effect of DM in the long term, with an observed increase in risk in the ≤65 age group but not in the >65 age group.

Abstract WP141: Identifying Modifiable Predictors of Long-term Functional Outcome After Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Arunima Kapoor ◽  
Richard Swartz ◽  
Krista Lanctot ◽  
Mark Bayley ◽  
Alex Kiss
Keyword(s):  
Cognitive Impairment ◽  
Sleep Apnea ◽  
Functional Outcomes ◽  
Stroke Severity ◽  
Stroke Patients ◽  
Long Term Outcomes ◽  
Post Stroke ◽  
Baseline Visit ◽  
Modifiable Factors

Introduction: Disability is often an assumed and accepted consequence of stroke. Post-stroke disability is frequently attributed to demographic risk factors such as age and stroke severity. These factors cannot explain all the variability in stroke outcomes. Other factors, such as post-stroke depression, sleep apnea and cognitive impairment can impact function, and yet their relationships to long-term outcomes are rarely assessed. The primary purpose of our research is to understand the role of these potentially modifiable factors in predicting long-term post-stroke functional outcomes. Hypothesis: Stroke patients who screen positive for depression, sleep apnea or cognitive impairment at baseline will have significantly worse long-term functional outcome. Methods: A follow up outcome assessment of stroke patients is being conducted by telephone 2-3 years after an initial baseline visit where their risk of depression, sleep apnea and cognitive impairment was assessed. Baseline predictors such as age and stroke severity are also abstracted from their baseline visit. Assessment measures were selected to evaluate numerous levels of human functioning and include the following: modified Rankin Scale, MoCA, Barthel Index, Frenchay Activites Index and Reintegration to Normal Living Index. The primary outcome is mRS Score, with a score ≥ 2 indicating poor outcome. Results: Seventy six patients have been enrolled in our study and projected enrolled of another 100 patients should be complete by December 2015. Based on preliminary data, our prognostic logistic regression model including only stroke severity and age is statistically significant, χ2(2)= 29.06, p < 0.001. This model explains 42.7% (Nagelkerke R2) of the variance in long-term outcomes and correctly classifies outcome in 78.9% of patients. Future analyses with the full sample size and addition of potentially modifiable factors will verify whether these factors increase the predictive value of our prognostic model. Conclusion: By identifying modifiable factors related to poor functional outcomes, this study may allow the development of novel interventions to alter the trajectory of this vulnerable population to help optimize long-term function after stroke.

Oxygen treatment after perinatal hypoxia-ischemia reduces neuronal damage at short survival times, but worsens injury with long-term survival

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S444-S444 ◽  
Author(s):  
Kristin M Noppens ◽  
J Regino Perez-Polo ◽  
David K Rassin ◽  
Karin N Westlund ◽  
Roderic Fabian ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Perinatal Hypoxia ◽  
Survival Times ◽  
Term Survival ◽  
Long Term Survival ◽  
Short Survival ◽  
Oxygen Treatment ◽  
Hypoxia Ischemia

Long-term outcomes of lumbar microdiscectomy in the pediatric population: a large single-institution case series

2019 ◽  
Vol 24 (5) ◽  
pp. 549-557
Author(s):  
Malia McAvoy ◽  
Heather J. McCrea ◽  
Vamsidhar Chavakula ◽  
Hoon Choi ◽  
Wenya Linda Bi ◽  
...  
Keyword(s):  
Conservative Management ◽  
Functional Outcomes ◽  
Pediatric Patients ◽  
Clinical Presentation ◽  
Case Series ◽  
Csf Leak ◽  
Single Institution ◽  
The Mean

OBJECTIVEFew studies describe long-term functional outcomes of pediatric patients who have undergone lumbar microdiscectomy (LMD) because of the rarity of pediatric disc herniation and the short follow-up periods. The authors analyzed risk factors, clinical presentation, complications, and functional outcomes of a single-institution series of LMD patients over a 19-year period.METHODSA retrospective case series was conducted of pediatric LMD patients at a large pediatric academic hospital from 1998 to 2017. The authors examined premorbid risk factors, clinical presentation, physical examination findings, type and duration of conservative management, indications for surgical intervention, complications, and postoperative outcomes.RESULTSOver the 19-year study period, 199 patients underwent LMD at the authors’ institution. The mean age at presentation was 16.0 years (range 12–18 years), and 55.8% were female. Of these patients, 70.9% participated in competitive sports, and among those who did not play sports, 65.0% had a body mass index greater than 25 kg/m2. Prior to surgery, conservative management had failed in 98.0% of the patients. Only 3 patients (1.5%) presented with cauda equina syndrome requiring emergent microdiscectomy. Complications included 4 cases of postoperative CSF leak (2.0%), 1 case of a noted intraoperative CSF leak, and 3 cases of wound infection (1.5%). At the first postoperative follow-up appointment, minimal or no pain was reported by 93.3% of patients. The mean time to return to sports was 9.8 weeks. During a mean follow-up duration of 8.2 years, 72.9% of patients did not present again after routine postoperative appointments. The total risk of reoperation was a rate of 7.5% (3.5% of patients underwent reoperation for the same level; 4.5% underwent adjacent-level decompression, and one patient [0.5%] ultimately underwent a fusion).CONCLUSIONSMicrodiscectomy is a safe and effective treatment for long-term relief of pain and return to daily activities among pediatric patients with symptomatic lumbar disc disease in whom conservative management has failed.

scholarly journals Post-Stroke Depression and Its Effect on Functional Outcomes during Inpatient Rehabilitation

2021 ◽  
Author(s):  
Gurumayum Sonachand Sharma ◽  
Anupam Gupta ◽  
Meeka Khanna ◽  
Naveen Bangarpet Prakash
Keyword(s):  
Outcome Measures ◽  
Functional Outcomes ◽  
Rating Scale ◽  
Tertiary Care ◽  
Depression Scale ◽  
Inpatient Rehabilitation ◽  
University Hospital ◽  
Post Stroke ◽  
Significant Difference ◽  
Post Stroke Depression

Abstract Objective The aim of the study is to observe the effect of post-stroke depression on functional outcomes during inpatient rehabilitation. Patients and Methods The design involved is prospective observational study. The location involved is Neurological Rehabilitation unit in a tertiary care university hospital. The study period ranges from October 2019 to April 2020. The participants involved are the patients with first ever stroke, male and female with age ≥18 years and duration less than 1 year. All participants were assessed at admission and after 14 sessions of inpatient rehabilitation by depression subscale of Hospital Anxiety and Depression Scale (HADS-D) and Hamilton Depression Rating Scale (HDRS). The stroke outcomes measures used were: Barthel Index (BI), Scandinavian Stroke Scale (SSS), and Modified Rankin Scale (MRS). Results There are a total of 30 participants (18 males) with median stroke duration of 90 days. The median age of the patients was 58 years. Sixteen patients had ischemic and 14 had hemorrhagic stroke. Out of these, 57% (n = 17) had symptoms of depression (HADS-D >7). Participants in both groups (with and without depression) showed improvement in all the functional outcome measures (BI, SSS, MRS) at the time of discharge as compared with admission scores. The changes in the outcome measures were statistically significant within groups (p < 0.05) but not significant between the groups (p > 0.05). Conclusion The post-stroke depression is common among stroke survivors of less than 1 year duration. There was no significant difference in the functional outcomes between stroke patients with depression and those without depression with inpatient rehabilitation program.

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