a focus on stroke in women

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Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study.

ObjectiveFunctional magnetic resonance imaging and transcranial magnetic stimulation studies suggest that human cortex shows evidence of neuroplasticity. Preclinical studies in rats and monkeys suggest that motor cortical stimulation can enhance plasticity and improve recovery after stroke. This study assesses the safety and preliminary efficacy of targeted subthreshold epidural cortical stimulation delivered concurrently with intensive rehabilitation therapy while using an investigational device in patients with chronic hemiparetic stroke.MethodsThis is a prospective, multicenter, and nonblinded trial randomizing patients to rehabilitation with or without cortical stimulation. Patients aged 20 to 75 years who had had an ischemic stroke at least 4 months previously causing persistent moderate weakness of the arm were included. Functional magnetic resonance imaging localized hand motor function before surgery to place an epidural cortical electrode. Both groups then underwent rehabilitation for 3 weeks after which the electrode was removed. Outcome measures were obtained at baseline, during therapy, and at 1, 4, 8, and 12 weeks postprocedure.ResultsTen patients were randomized; six patients to surgery, four to the control group. No patient deaths, neurological deterioration, or seizures occurred. There were two infections from nonprotocol-related causes. Of the eight patients completing the treatment, the stimulation plus rehabilitation group improved significantly better than controls in the Upper Extremity Fugl-Meyer (P = 0.003 overall) and the hand function score of the Stroke Impact Scale (P =0.001 overall).ConclusionThe technique of cortical stimulation to enhance stroke recovery is well tolerated and safe

Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study.

ObjectiveFunctional magnetic resonance imaging and transcranial magnetic stimulation studies suggest that human cortex shows evidence of neuroplasticity. Preclinical studies in rats and monkeys suggest that motor cortical stimulation can enhance plasticity and improve recovery after stroke. This study assesses the safety and preliminary efficacy of targeted subthreshold epidural cortical stimulation delivered concurrently with intensive rehabilitation therapy while using an investigational device in patients with chronic hemiparetic stroke.MethodsThis is a prospective, multicenter, and nonblinded trial randomizing patients to rehabilitation with or without cortical stimulation. Patients aged 20 to 75 years who had had an ischemic stroke at least 4 months previously causing persistent moderate weakness of the arm were included. Functional magnetic resonance imaging localized hand motor function before surgery to place an epidural cortical electrode. Both groups then underwent rehabilitation for 3 weeks after which the electrode was removed. Outcome measures were obtained at baseline, during therapy, and at 1, 4, 8, and 12 weeks postprocedure.ResultsTen patients were randomized; six patients to surgery, four to the control group. No patient deaths, neurological deterioration, or seizures occurred. There were two infections from nonprotocol-related causes. Of the eight patients completing the treatment, the stimulation plus rehabilitation group improved significantly better than controls in the Upper Extremity Fugl-Meyer (P = 0.003 overall) and the hand function score of the Stroke Impact Scale (P = 0.001 overall).ConclusionThe technique of cortical stimulation to enhance stroke recovery is well tolerated and safe

Rationale and design of the AXIOMATIC-SSP phase II trial: Antithrombotic treatment with factor XIa inhibition to Optimize Management of Acute Thromboembolic events for Secondary Stroke Prevention

MRI; Milvexian; Stroke preventionResonancia magnética; Milvexian; Prevención de ictusRessonància magnètica; Milvexian; Prevenció d'ictusBackground Individuals with ischemic stroke or transient ischemic attack (TIA) have a high early risk of ischemic stroke despite dual antiplatelet therapy. The risk of ischemic stroke, and associated disability, represents a significant unmet clinical need. Genetic variants resulting in reduced factor XI levels are associated with reduced risk for ischemic stroke but are not associated with increased intracranial bleeding. Milvexian is an oral small-molecule inhibitor of FXIa that binds activated factor XI with high affinity and selectivity and may reduce the risk of stroke when added to antiplatelet drugs without significant bleeding. We aimed to evaluate the dose-response relationship of milvexian in participants treated with dual antiplatelets. Methods We began a phase II, double-blinded, randomized, placebo-controlled trial at 367 sites in 2019. Participants (N = 2366) with ischemic stroke (National Institutes of Health Stroke Scale score ≤7) or high-risk TIA (ABCD2 score ≥6) were randomized to 1 of 5 doses of milvexian or placebo for 90 days. Participants also received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg for 90 days. The efficacy endpoint was the composite of ischemic stroke or incident infarct on magnetic resonance imaging. Major bleeding, defined as type 3 or 5 bleeding according to the Bleeding Academic Research Consortium, was the safety endpoint. Participant follow-up will end in 2022. Conclusion The AXIOMATIC-SSP trial will evaluate the dose-response of milvexian for ischemic stroke occurrence in participants with ischemic stroke or TIA.This study is sponsored by Bristol Myers Squibb and Janssen Research & Development, LLC

Epidural Electrical Stimulation for Stroke Rehabilitation: Results of the Prospective, Multicenter, Randomized, Single-Blinded Everest Trial.

BackgroundThis prospective, single-blinded, multicenter study assessed the safety and efficacy of electrical epidural motor cortex stimulation (EECS) in improving upper limb motor function of ischemic stroke patients with moderate to moderately severe hemiparesis.MethodsPatients ≥ 4 months poststroke were randomized 2:1 to an investigational (n = 104) or control (n = 60) group, respectively. Investigational patients were implanted (n = 94) with an epidural 6-contact lead perpendicular to the primary motor cortex and a pulse generator. Both groups underwent 6 weeks of rehabilitation, but EECS was delivered to investigational patients during rehabilitation. The primary efficacy endpoint (PE) was defined as attaining a minimum improvement of 4.5 points in the upper extremity Fugl-Meyer (UEFM) scale as well as 0.21 points in the Arm Motor Ability Test (AMAT) 4 weeks postrehabilitation. Follow-up assessments were performed 1, 4, 12, and 24 weeks postrehabilitation. Safety was evaluated by monitoring adverse events (AEs) that occurred between enrollment and the end of rehabilitation.ResultsPrimary intent-to-treat analysis showed no group differences at 4 weeks, with PE being met by 32% and 29% of investigational and control patients, respectively (P = .36). Repeated-measures secondary analyses revealed no significant treatment group differences in mean UEFM or AMAT scores. However, post hoc comparisons showed that a greater proportion of investigational (39%) than control (15%) patients maintained or achieved PE (P = .003) at 24 weeks postrehabilitation. Investigational group mean AMAT scores also improved significantly (P < .05) when compared to the control group at 24 weeks postrehabilitation. Post hoc analyses also showed that 69% (n = 9/13) of the investigational patients who elicited movement thresholds during stimulation testing met PE at 4 weeks, and mean UEFM and AMAT scores was also significantly higher (P < .05) in this subgroup at the 4-, 12-, and 24-week assessments when compared to the control group. Headache (19%), pain (13%), swelling (7%), and infection (7%) were the most commonly observed implant procedure-related AEs. Overall, there were 11 serious AEs in 9 investigational group patients (7 procedure related, 4 anesthesia related).ConclusionsThe primary analysis pertaining to efficacy of EECS during upper limb motor rehabilitation in chronic stroke patients was negative at 4 weeks postrehabilitation. A better treatment response was observed in a subset of patients eliciting stimulation induced upper limb movements during motor threshold assessments performed prior to each rehabilitation session. Post hoc comparisons indicated treatment effect differences at 24 weeks, with the control group showing significant decline in the combined primary outcome measure relative to the investigational group. These results have the potential to inform future chronic stroke rehabilitation trial design

Use of functional MRI to guide decisions in a clinical stroke trial.

Background and purposeAn investigational trial examined safety and efficacy of targeted subthreshold cortical stimulation in patients with chronic stroke. The anatomical location for the target, hand motor area, varies across subjects, and so was localized with functional MRI (fMRI). This report describes the experience of incorporating standardized fMRI into a multisite stroke trial.MethodsAt 3 enrollment centers, patients moved (0.25 Hz) the affected hand during fMRI. Hand motor function was localized at a fourth center guiding intervention for those randomized to stimulation.ResultsThe fMRI results were available within 24 hours. Across 12 patients, activation site variability was substantial (12, 23, and 11 mm in x, y, and z directions), exceeding stimulating electrode dimensions.ConclusionsUse of fMRI to guide decision-making in a clinical stroke trial is feasible

Mapping individual brains to guide restorative therapy after stroke: rationale and pilot studies.

Some treatments under development to improve motor outcome after stroke require information about organization of individual subject's brain. The current study aimed to characterize normal inter-subject differences in localization of motor functions, and to consider these findings in relation to a potential treatment of motor deficits after stroke. Functional MRI (fMRI) scanning in 14 subjects examined right index finger tapping, shoulder rotation, or facial movement. The largest activation cluster in left sensorimotor cortex was identified for each task, and its center expressed in Talairach stereotaxic coordinates. Across subjects, each task showed considerable variability in activation site coordinates. For example, during finger tapping, the range for center of activation was 7 mm in the x-axis, 19 mm in the y-axis, and 11 mm in the z-axis. The mean value for center of activation was significantly different for all three coordinates for all pairwise task comparisons. However, the distribution of activation site centers for the finger task overlapped with the other two tasks in the x- and y-axes, and with the shoulder task in the z-axis. On average, the center of activation for the three motor tasks were spatially separated and somatotopically distributed. However, across the population, there was considerable overlap in the center of activation site, especially for finger and shoulder movements. Restorative therapies that aim to target specific body segments, such as the hand, in the post-stroke motor system may need to map the individual brain rather than rely on population averages. Initial details are presented of a study using this approach to evaluate such a therapy

Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial

BackgroundPresent mechanical devices are unable to achieve recanalisation in up to 20-40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever.MethodsIn this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18-85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8-29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69-85 years) and NIHSS scores (≤18 vs 19-29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01270867.FindingsBetween Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92-9·69; p(superiority)<0·0001). Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0·1826).InterpretationPatients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever.FundingStryker Neurovascular