Evaluating effects of normobaric oxygen therapy in acute stroke with MRI-based predictive models

<p>Abstract</p> <p>Background</p> <p>Voxel-based algorithms using acute multiparametric-MRI data have been shown to accurately predict tissue outcome after stroke. We explored the potential of MRI-based predictive algorithms to objectively assess the effects of normobaric oxygen therapy (NBO), an investigational stroke treatment, using data from a pilot study of NBO in acute stroke.</p> <p>Methods</p> <p>The pilot study of NBO enrolled 11 patients randomized to NBO administered for 8 hours, and 8 Control patients who received room-air. Serial MRIs were obtained at admission, during gas therapy, post-therapy, and pre-discharge. Diffusion/perfusion MRI data acquired at admission (pre-therapy) was used in generalized linear models to predict the risk of lesion growth at subsequent time points for both treatment scenarios: NBO or Control.</p> <p>Results</p> <p>Lesion volume sizes 'during NBO therapy' predicted by Control-models were significantly larger (P = 0.007) than those predicted by NBO models, suggesting that ischemic lesion growth is attenuated during NBO treatment. No significant difference was found between the predicted lesion volumes at later time-points. NBO-treated patients, despite showing larger lesion volumes on Control-models than NBO-models, tended to have reduced lesion growth.</p> <p>Conclusions</p> <p>This study shows that NBO has therapeutic potential in acute ischemic stroke, and demonstrates the feasibility of using MRI-based algorithms to evaluate novel treatments in early-phase clinical trials.</p

Diffusion tensor and volumetric magnetic resonance imaging using an MR-compatible hand-induced robotic device suggests training-induced neuroplasticity in patients with chronic stroke

Stroke is the third leading cause of mortality and a frequent cause of long-term adult impairment. Improved strategies to enhance motor function in individuals with chronic disability from stroke are thus required. Post-stroke therapy may improve rehabilitation and reduce long-term disability; however, objective methods for evaluating the specific impact of rehabilitation are rare. Brain imaging studies on patients with chronic stroke have shown evidence for reorganization of areas showing functional plasticity after a stroke. In this study, we hypothesized that brain mapping using a novel magnetic resonance (MR)-compatible hand device in conjunction with state-of-the-art magnetic resonance imaging (MRI) can serve as a novel biomarker for brain plasticity induced by rehabilitative motor training in patients with chronic stroke. This hypothesis is based on the premises that robotic devices, by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain and that these changes can then be monitored by advanced MRI. We serially examined 15 healthy controls and 4 patients with chronic stroke. We employed a combination of diffusion tensor imaging (DTI) and volumetric MRI using a 3-tesla (3T) MRI system using a 12-channel Siemens Tim coil and a novel MR-compatible hand-induced robotic device. DTI data revealed that the number of fibers and the average tract length significantly increased after 8 weeks of hand training by 110% and 64%, respectively (p<0.001). New corticospinal tract (CST) fibers projecting progressively closer to the motor cortex appeared during training. Volumetric data analysis showed a statistically significant increase in the cortical thickness of the ventral postcentral gyrus areas of patients after training relative to pre-training cortical thickness (p<0.001). We suggest that rehabilitation is possible for a longer period of time after stroke than previously thought, showing that structural plasticity is possible even after 6 months due to retained neuroplasticity. Our study is an example of personalized medicine using advanced neuroimaging methods in conjunction with robotics in the molecular medicine era

Combination therapy with normobaric oxygen (NBO) plus thrombolysis in experimental ischemic stroke

<p>Abstract</p> <p>Background</p> <p>The widespread use of tissue plasminogen activator (tPA), the only FDA-approved acute stroke treatment, remains limited by its narrow therapeutic time window and related risks of brain hemorrhage. Normobaric oxygen therapy (NBO) may be a useful physiological strategy that slows down the process of cerebral infarction, thus potentially allowing for delayed or more effective thrombolysis. In this study we investigated the effects of NBO started simultaneously with intravenous tPA, in spontaneously hypertensive rats subjected to embolic middle cerebral artery (MCA) stroke. After homologous clot injection, animals were randomized into different treatment groups: saline injected at 1 hour; tPA at 1 hour; saline at 1 hour plus NBO; tPA at 1 hour plus NBO. NBO was maintained for 3 hours. Infarct volume, brain swelling and hemorrhagic transformation were quantified at 24 hours. Outcome assessments were blinded to therapy.</p> <p>Results</p> <p>Upon clot injection, cerebral perfusion in the MCA territory dropped below 20% of pre-ischemic baselines. Both tPA-treated groups showed effective thrombolysis (perfusion restored to nearly 100%) and smaller infarct volumes (379 ± 57 mm³saline controls; 309 ± 58 mm³NBO; 201 ± 78 mm³tPA; 138 ± 30 mm³tPA plus NBO), showing that tPA-induced reperfusion salvages ischemic tissue and that NBO does not significantly alter this neuroprotective effect. NBO had no significant effect on hemorrhagic conversion, brain swelling, or mortality.</p> <p>Conclusion</p> <p>NBO can be safely co-administered with tPA. The efficacy of tPA thrombolysis is not affected and there is no induction of brain hemorrhage or edema. These experimental results require clinical confirmation.</p

Functional MRI of Rehabilitation in Chronic Stroke Patients Using Novel MR-Compatible Hand Robots

We monitored brain activation after chronic stroke by combining functional magnetic resonance imaging (fMRI) with a novel MR-compatible, hand-induced, robotic device (MR_CHIROD). We evaluated 60 fMRI datasets on a 3 T MR system from five right-handed patients with left-sided stroke ≥6 months prior and mild to moderate hemiparesis. Patients trained the paretic right hand at approximately 75% of maximum strength with an exercise ball for 1 hour/day, 3 days/week for 4 weeks. Multi-level fMRI data were acquired before, during training, upon completion of training, and after a non-training period using parallel imaging employing GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) while the participant used the MR_CHIROD. Training increased the number of activated sensorimotor cortical voxels, indicating functional cortical plasticity in chronic stroke patients. The effect persisted four weeks after training completion, indicating the potential of rehabilitation in inducing cortical plasticity in chronic stroke patients

Recognition and management of stroke in young adults and adolescents.

Approximately 15% of all ischemic strokes (IS) occur in young adults and adolescents. To date, only limited prior public health and research efforts have specifically addressed stroke in the young. Early diagnosis remains challenging because of the lack of awareness and the relative infrequency of stroke compared with stroke mimics. Moreover, the causes of IS in the young are heterogeneous and can be relatively uncommon, resulting in uncertainties about diagnostic evaluation and cause-specific management. Emerging data have raised public health concerns about the increasing prevalence of traditional vascular risk factors in young individuals, and their potential role in increasing the risk of IS, stroke recurrence, and poststroke mortality. These issues make it important to formulate and enact strategies to increase both awareness and access to resources for young stroke patients, their caregivers and families, and health care professionals. The American Academy of Neurology recently convened an expert panel to develop a consensus document concerning the recognition, evaluation, and management of IS in young adults and adolescents. The report of the consensus panel is presented herein

Lower Hemoglobin Correlates with Larger Stroke Volumes in Acute Ischemic Stroke

www.karger.com/cee This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License (www.karger.com/OA-license), applicable to the online version of the article only. Distribution for non-commercial purposes only

Functional MRI of Rehabilitation in Chronic Stroke Patients Using Novel MR-Compatible Hand Robots

We monitored brain activation after chronic stroke by combining functional magnetic resonance imaging (fMRI) with a novel MR-compatible, hand-induced, robotic device (MR_CHIROD). We evaluated 60 fMRI datasets on a 3 T MR system from five right-handed patients with left-sided stroke ≥6 months prior and mild to moderate hemiparesis. Patients trained the paretic right hand at approximately 75% of maximum strength with an exercise ball for 1 hour/day, 3 days/week for 4 weeks. Multi-level fMRI data were acquired before, during training, upon completion of training, and after a non-training period using parallel imaging employing GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) while the participant used the MR_CHIROD. Training increased the number of activated sensorimotor cortical voxels, indicating functional cortical plasticity in chronic stroke patients. The effect persisted four weeks after training completion, indicating the potential of rehabilitation in inducing cortical plasticity in chronic stroke patients

The TeleStroke Mimic (TM)‐Score: A Prediction Rule for Identifying Stroke Mimics Evaluated in a Telestroke Network

Background: Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). As telestroke consultation expands across the world, increasing numbers of SM patients are likely being evaluated via Telestroke. We developed a model to prospectively identify ischemic SMs during Telestroke evaluation. Methods and Results: We analyzed 829 consecutive patients from January 2004 to April 2013 in our internal New England–based Partners TeleStroke Network for a derivation cohort, and 332 cases for internal validation. External validation was performed on 226 cases from January 2008 to August 2012 in the Partners National TeleStroke Network. A predictive score was developed using stepwise logistic regression, and its performance was assessed using receiver‐operating characteristic (ROC) curve analysis. There were 23% SM in the derivation, 24% in the internal, and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (iCVD), SM had lower mean age, fewer vascular risk factors, more frequent prior seizure, and a different profile of presenting symptoms. The TeleStroke Mimic Score (TM‐Score) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness, and National Institutes of Health Stroke Scale >14. The TM‐Score performed well on ROC curve analysis (derivation cohort AUC=0.75, internal validation AUC=0.71, external validation AUC=0.77). Conclusions: SMs differ substantially from their iCVD counterparts in their vascular risk profiles and other characteristics. Decision‐support tools based on predictive models, such as our TM Score, may help clinicians consider alternate diagnosis and potentially detect SMs during complex, time‐critical telestroke evaluations

Risk score to predict gastrointestinal bleeding after acute ischemic stroke

© 2014 Ji et al.; licensee BioMed Central Ltd. Background: Gastrointestinal bleeding (GIB) is a common and often serious complication after stroke. Although several risk factors for post-stroke GIB have been identified, no reliable or validated scoring system is currently available to predict GIB after acute stroke in routine clinical practice or clinical trials. In the present study, we aimed to develop and validate a risk model (acute ischemic stroke associated gastrointestinal bleeding score, the AIS-GIB score) to predict in-hospital GIB after acute ischemic stroke.Methods: The AIS-GIB score was developed from data in the China National Stroke Registry (CNSR). Eligible patients in the CNSR were randomly divided into derivation (60%) and internal validation (40%) cohorts. External validation was performed using data from the prospective Chinese Intracranial Atherosclerosis Study (CICAS). Independent predictors of in-hospital GIB were obtained using multivariable logistic regression in the derivation cohort, and β-coefficients were used to generate point scoring system for the AIS-GIB. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively.Results: A total of 8,820, 5,882, and 2,938 patients were enrolled in the derivation, internal validation and external validation cohorts. The overall in-hospital GIB after AIS was 2.6%, 2.3%, and 1.5% in the derivation, internal, and external validation cohort, respectively. An 18-point AIS-GIB score was developed from the set of independent predictors of GIB including age, gender, history of hypertension, hepatic cirrhosis, peptic ulcer or previous GIB, pre-stroke dependence, admission National Institutes of Health stroke scale score, Glasgow Coma Scale score and stroke subtype (Oxfordshire). The AIS-GIB score showed good discrimination in the derivation (0.79; 95% CI, 0.764-0.825), internal (0.78; 95% CI, 0.74-0.82) and external (0.76; 95% CI, 0.71-0.82) validation cohorts. The AIS-GIB score was well calibrated in the derivation (P = 0.42), internal (P = 0.45) and external (P = 0.86) validation cohorts.Conclusion: The AIS-GIB score is a valid clinical grading scale to predict in-hospital GIB after AIS. Further studies on the effect of the AIS-GIB score on reducing GIB and improving outcome after AIS are warranted.Link_to_subscribed_fulltex

Risk score to predict gastrointestinal bleeding after acute ischemic stroke

BackgroundGastrointestinal bleeding (GIB) is a common and often serious complication after stroke. Although several risk factors for post-stroke GIB have been identified, no reliable or validated scoring system is currently available to predict GIB after acute stroke in routine clinical practice or clinical trials. In the present study, we aimed to develop and validate a risk model (acute ischemic stroke associated gastrointestinal bleeding score, the AIS-GIB score) to predict in-hospital GIB after acute ischemic stroke.MethodsThe AIS-GIB score was developed from data in the China National Stroke Registry (CNSR). Eligible patients in the CNSR were randomly divided into derivation (60%) and internal validation (40%) cohorts. External validation was performed using data from the prospective Chinese Intracranial Atherosclerosis Study (CICAS). Independent predictors of in-hospital GIB were obtained using multivariable logistic regression in the derivation cohort, and β-coefficients were used to generate point scoring system for the AIS-GIB. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively.ResultsA total of 8,820, 5,882, and 2,938 patients were enrolled in the derivation, internal validation and external validation cohorts. The overall in-hospital GIB after AIS was 2.6%, 2.3%, and 1.5% in the derivation, internal, and external validation cohort, respectively. An 18-point AIS-GIB score was developed from the set of independent predictors of GIB including age, gender, history of hypertension, hepatic cirrhosis, peptic ulcer or previous GIB, pre-stroke dependence, admission National Institutes of Health stroke scale score, Glasgow Coma Scale score and stroke subtype (Oxfordshire). The AIS-GIB score showed good discrimination in the derivation (0.79; 95% CI, 0.764-0.825), internal (0.78; 95% CI, 0.74-0.82) and external (0.76; 95% CI, 0.71-0.82) validation cohorts. The AIS-GIB score was well calibrated in the derivation (P = 0.42), internal (P = 0.45) and external (P = 0.86) validation cohorts.ConclusionThe AIS-GIB score is a valid clinical grading scale to predict in-hospital GIB after AIS. Further studies on the effect of the AIS-GIB score on reducing GIB and improving outcome after AIS are warranted