Décider ensemble et autrement de la prise en charge des AVC graves

International audienc

Décider ensemble et autrement de la prise en charge des AVC graves

International audienc

Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial

International audienc

Regenerative stem cell therapy for stroke in Europe (RESSTORE): a multicenter randomized controlled efficacy clinical trial

International audienceIntroduction Encouraging the activation of brain repair mechanisms and fostering spontaneous functional recovery in stroke patients hold great promise for alleviating the global burden of this condition and allowing an extended therapeutic time window. Cell-based regenerative therapy (with mesenchymal stem/stromal cells, such as adipose-derived stem cells [ADSCs]) is particularly attractive considering its excellent safety profile, low immunogenicity after allogeneic application, and well-established functional benefits on stroke recovery in animal models. This study aims to assess the efficacy and safety effects of intravenous (IV) infusion of freshly cultured allogeneic ADSCs on recovery after ischemic stroke. Population and methods RESSTORE is a multicentric, randomized 1:1 controlled double-blind clinical trial. Eighty patients will be enrolled in nine French stroke centers. The main inclusion criteria are ≥18 years of age, acute hemispheric ischemic stroke, and a National Institutes of Health Stroke Scale (NIHSS) score of ≥7, including a motor subscore of ≥3. According to the previous dose-escalation safety trial data, the maximum tolerated dose of 3 million ADSCs/kg was selected. IV infusion was performed within 10 days following stroke onset, with a follow-up over 2 years. Outcomes The primary endpoint is the motor NIHSS subscore, computed as the sum of the upper limb, lower limb, and hand scores, measured 6 months after stroke onset to assess motor recovery. The secondary outcomes are the occurrence of death/serious adverse events, clinical scores (the detailed NIHSS scores, Montreal Cognitive Assessment scores, modified Rankin Scale scores, Aphasia Handicap Scores, Depression Intensity Scale Circles scores, Fatigue Scale scores, etc.), immune monitoring (for the first 30 patients), and multimodal biomarkers derived from diffusion and functional magnetic resonance imaging. Discussion This study may provide some evidence for the effects of freshly cultured allogenic ADSCs IV infusion in subacute stroke that may help design a larger international randomized controlled trial

Penumbral Rescue by Normobaric O=O Administration in Patients with Ischemic Stroke and Target Mismatch ProFile (PROOF): Study Protocol of a Phase IIb Trial.

RATIONALE Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. AIMS PROOF investigates the use of normobaric oxygen therapy (NBO) within six hours of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior circulation occlusion. METHODS AND DESIGN Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. STUDY OUTCOMES Primary outcome is ischemic core growth (mL) from baseline to 24 hours (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 hours, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers are conducted. SAMPLE SIZE Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. DISCUSSION By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 hours on follow-up imaging reduces potential bias due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. TRIAL REGISTRATIONS ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31

Successful Thrombectomy Improves Functional Outcome in Tandem Occlusions with a Large Ischemic Core

International audienceBackground: Emergent stenting in tandem occlusions and mechanical thrombectomy (MT) of acute ischemic stroke related to large vessel occlusion (LVO-AIS) with a large core are tested independently. We aim to assess the impact of reperfusion with MT in patients with LVO-AIS with a large core and a tandem occlusion and to compare the safety of reperfusion between large core with tandem and nontandem occlusions in current practice. Methods: We analyzed data of all consecutive patients included in the prospective Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and March 2023 who presented with a pretreatment ASPECTS (Alberta Stroke Program Early CT Score) of 0–5 and angiographically proven tandem occlusion. The primary end point was a favorable outcome defined by a modified Rankin Scale (mRS) score of 0–3 at 90 days. Results: Among 262 included patients with a tandem occlusion and ASPECTS 0–5, 203 patients (77.5%) had a successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b-3). Reperfused patients had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR], 1.57 [1.22–2.03]; P < 0.001), higher rates of mRS score 0–3 (aOR, 7.03 [2.60–19.01]; P < 0.001) and mRS score 0–2 at 90 days (aOR, 3.85 [1.39–10.68]; P = 0.009) compared with nonreperfused. There was a trend between the occurrence of successful reperfusion and a decreased rate of symptomatic intracranial hemorrhage (aOR, 0.5 [0.22–1.13]; P = 0.096). Similar safety outcomes were observed after large core reperfusion in tandem and nontandem occlusions. Conclusions: Successful reperfusion was associated with a higher rate of favorable outcome in large core LVO-AIS with a tandem occlusion, with a safety profile similar to nontandem occlusion

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons