Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke

Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation. To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study. A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring. The median (IQR) number of weekly hours of therapy was different: IRT 15 (15-16) vs. NO-IRT 7.5 (5-9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05). Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers

BRIVA-LIFE–A multicenter retrospective study of the long-term use of brivaracetam in clinical practice

Objectives: Evaluate long-term effectiveness and tolerability of brivaracetam in clinical practice in patients with focal epilepsy. Materials and Methods: This was a multicenter retrospective study. Patients aged =16 years were started on brivaracetam from November 2016 to June 2017 and followed over 1 year. Data were obtained from medical records at 3, 6 and 12 months after treatment initiation for evaluation of safety- and seizure-related outcomes. Results: A total of 575 patients were included in analyses; most had been treated with =4 lifetime antiepileptic drugs. Target dosage was achieved by 30.6% of patients on the first day. Analysis of primary variables at 12 months revealed that mean reduction in seizure frequency was 36.0%, 39.7% of patients were =50% responders and 17.5% were seizure-free. Seizure-freedom was achieved by 37.5% of patients aged =65 years. Incidence of adverse events (AEs) and psychiatric AEs (PAEs) was 39.8% and 14.3%, respectively, and discontinuation due to these was 8.9% and 3.7%, respectively. Somnolence, irritability, and dizziness were the most frequently reported AEs. At baseline, 228 (39.7%) patients were being treated with levetiracetam; most switched to brivaracetam (dose ratio 1:10-15). Among those who switched because of PAEs (n = 53), 9 (17%) reported PAEs on brivaracetam, and 3 (5.7%) discontinued because of PAEs. Tolerability was not highly affected among patients with learning disability or psychiatric comorbidity. Conclusions: In a large population of patients with predominantly drug-resistant epilepsy, brivaracetam was effective and well-tolerated; no unexpected AEs occurred over 1 year, and the incidence of PAEs was lower compared with levetiracetam

Endovascular Stroke Treatment and Risk of Intracranial Hemorrhage in Anticoagulated Patients.

Background and Purpose- We aimed to determine the safety and mortality after mechanical thrombectomy in patients taking vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Methods- In a multicenter observational cohort study, we used multiple logistic regression analysis to evaluate associations of symptomatic intracranial hemorrhage (sICH) with VKA or DOAC prescription before thrombectomy as compared with no anticoagulation. The primary outcomes were the rate of sICH and all-cause mortality at 90 days, incorporating sensitivity analysis regarding confirmed therapeutic anticoagulation. Additionally, we performed a systematic review and meta-analysis of literature on this topic. Results- Altogether, 1932 patients were included (VKA, n=222; DOAC, n=98; no anticoagulation, n=1612); median age, 74 years (interquartile range, 62-82); 49.6% women. VKA prescription was associated with increased odds for sICH and mortality (adjusted odds ratio [aOR], 2.55 [95% CI, 1.35-4.84] and 1.64 [95% CI, 1.09-2.47]) as compared with the control group, whereas no association with DOAC intake was observed (aOR, 0.98 [95% CI, 0.29-3.35] and 1.35 [95% CI, 0.72-2.53]). Sensitivity analyses considering only patients within the confirmed therapeutic anticoagulation range did not alter the findings. A study-level meta-analysis incorporating data from 7462 patients (855 VKAs, 318 DOACs, and 6289 controls) from 15 observational cohorts corroborated these observations, yielding an increased rate of sICH in VKA patients (aOR, 1.62 [95% CI, 1.22-2.17]) but not in DOAC patients (aOR, 1.03 [95% CI, 0.60-1.80]). Conclusions- Patients taking VKA have an increased risk of sICH and mortality after mechanical thrombectomy. The lower risk of sICH associated with DOAC may also be noticeable in the acute setting. Improved selection might be advisable in VKA-treated patients. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064. Systematic Review and Meta-Analysis: CRD42019127464

Workflow times and outcomes in patients triaged for a suspected severe stroke

Introduction: Current recommendations for regional stroke destination suggest that patients with severe acute stroke in non-urban areas should be triaged based on the estimated transport time to a referral thrombectomy-capable center. Methods: We performed a post hoc analysis to evaluate the association of pre-hospital workflow times with neurological outcomes in patients included in the RACECAT trial. Workflow times evaluated were known or could be estimated before transport allocation. Primary outcome was the shift analysis on the modified Rankin score at 90 days. Results: Among the 1,369 patients included, the median time from onset to emergency medical service (EMS) evaluation, the estimated transport time to a thrombectomy-capable center and local stroke center, and the estimated transfer time between centers were 65 minutes (interquartile ratio [IQR] = 43–138), 61 minutes (IQR = 36–80), 17 minutes (IQR = 9–27), and 62 minutes (IQR = 36–73), respectively. Longer time intervals from stroke onset to EMS evaluation were associated with higher odds of disability at 90 days in the local stroke center group (adjusted common odds ratio (acOR) for each 30-minute increment = 1.03, 95% confidence interval [CI] = 1.01–1.06), with no association in the thrombectomy-capable center group (acOR for each 30-minute increment = 1.01, 95% CI = 0.98–1.01, pinteraction = 0.021). No significant interaction was found for other pre-hospital workflow times. In patients evaluated by EMS later than 120 minutes after stroke onset, direct transport to a thrombectomy-capable center was associated with better disability outcomes (acOR = 1.49, 95% CI = 1.03–2.17). Conclusion: We found a significant heterogeneity in the association between initial transport destination and neurological outcomes according to the elapse of time between the stroke onset and the EMS evaluation (ClinicalTrials.gov: NCT02795962). ANN NEUROL 2022;92:931–942

Clínica alucinatoria secundaria a enfermedad médica: características clínicas y manejo

Las alucinaciones son percepciones en ausencia del estímulo sensorial causal correspondiente. Son un síntoma característico de los trastornos psicóticos, aunque también aparecen en otras patologías como en trastornos afectivos o clínica disociativa, así como en múltiples entidades de base orgánica, principalmente en forma de alteraciones sensoperceptivas de tipo visual. En esta revisión se describirán las características de las alucinaciones que aparecen en el contexto de enfermedades neurológicas o en patologías que afectan a los órganos de los sentidos, así como el manejo de los cuadros más frecuentes

Abstract 268: Validation of an automated method to assess 24‐hour infarct volume in stroke patients

Introduction In stroke patients, accurate infarct volume assessment at 24 hours typically requires manual segmentation of lesions that often are not well defined. We aimed to validate an automated machine learning algorithm (MethinksFIV) specifically trained to automatically segment and measure subacute infarcts on non‐contrast CT (NCCT) scans. Methods We retrospectively studied stroke patients with a large vessel occlusion prospectively admitted to a comprehensive stroke center. The final infarct volume was segmented on the 24h NCCT manually (man‐FIV) and with the automated method (auto‐FIV). Both measurements were correlated with clinical outcomes. Results We included 346 patients. On 24h‐NCCT median auto‐FIV was lower than man‐FIV (8.6 ml [2.3‐40.7] vs. 16.9 ml [1.1‐70.8], p2 at three months (OR: 1.02 95%CI 1.01‐1.13, p=0.002) than manual segmentation (OR=1.01, 95%CI 1.00‐1.01, p=0.01). In a multivariable analysis, only auto‐FIV remained a significant predictor of mRS>2 at three months (aOR: 1.03 95% CI 1.01‐1.05, p=0.004). Conclusion An automated method to measure subacute infarct volumes in stroke patients is accurate and correlates well with further clinical outcomes. The method appears to outperform manual segmentation and may be used to facilitate infarct characterization in large clinical trials

Noncontrast Computed Tomography vs Computed Tomography Perfusion or Magnetic Resonance Imaging Selection in Late Presentation of Stroke With Large-Vessel Occlusion

In patients with proximal anterior circulation occlusion stroke presenting in the extended window, are rates of favorable outcomes at 90 days comparable in the patients selected for thrombectomy with noncontrast computed tomography vs patients selected with computed tomography perfusion or magnetic resonance imaging? In a multicenter cohort of 1604 patients in the extended window with large-vessel occlusion, patients selected by noncontrast computed tomography had comparable clinical and safety outcomes with patients selected by computed tomography perfusion or magnetic resonance imaging. These findings suggest noncontrast computed tomography alone may be used as an alternative to advanced imaging in selecting patients with late-presenting large-vessel occlusion for mechanical thrombectomy. This cohort study compares the clinical outcomes of patients with stroke who presented 6 to 24 hours after symptom onset and were selected for mechanical thrombectomy by noncontrast computed tomography vs those selected by computed tomography perfusion or magnetic resonance imaging. Advanced imaging for patient selection in mechanical thrombectomy is not widely available. To compare the clinical outcomes of patients selected for mechanical thrombectomy by noncontrast computed tomography (CT) vs those selected by computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) in the extended time window. This multinational cohort study included consecutive patients with proximal anterior circulation occlusion stroke presenting within 6 to 24 hours of time last seen well from January 2014 to December 2020. This study was conducted at 15 sites across 5 countries in Europe and North America. The duration of follow-up was 90 days from stroke onset. Computed tomography with Alberta Stroke Program Early CT Score, CTP, or MRI. The primary end point was the distribution of modified Rankin Scale (mRS) scores at 90 days (ordinal shift). Secondary outcomes included the rates of 90-day functional independence (mRS scores of 0-2), symptomatic intracranial hemorrhage, and 90-day mortality. Of 2304 patients screened for eligibility, 1604 patients were included, with a median (IQR) age of 70 (59-80) years; 848 (52.9%) were women. A total of 534 patients were selected to undergo mechanical thrombectomy by CT, 752 by CTP, and 318 by MRI. After adjustment of confounders, there was no difference in 90-day ordinal mRS shift between patients selected by CT vs CTP (adjusted odds ratio [aOR], 0.95 [95% CI, 0.77-1.17]; P = .64) or CT vs MRI (aOR, 0.95 [95% CI, 0.8-1.13]; P = .55). The rates of 90-day functional independence (mRS scores 0-2 vs 3-6) were similar between patients selected by CT vs CTP (aOR, 0.90 [95% CI, 0.7-1.16]; P = .42) but lower in patients selected by MRI than CT (aOR, 0.79 [95% CI, 0.64-0.98]; P = .03). Successful reperfusion was more common in the CT and CTP groups compared with the MRI group (474 [88.9%] and 670 [89.5%] vs 250 [78.9%]; P < .001). No significant differences in symptomatic intracranial hemorrhage (CT, 42 [8.1%]; CTP, 43 [5.8%]; MRI, 15 [4.7%]; P = .11) or 90-day mortality (CT, 125 [23.4%]; CTP, 159 [21.1%]; MRI, 62 [19.5%]; P = .38) were observed. In patients undergoing proximal anterior circulation mechanical thrombectomy in the extended time window, there were no significant differences in the clinical outcomes of patients selected with noncontrast CT compared with those selected with CTP or MRI. These findings have the potential to widen the indication for treating patients in the extended window using a simpler and more widespread noncontrast CT-only paradigm

Endovascular versus medical therapy in posterior cerebral artery stroke: role of baseline NIHSS and occlusion site.

Background: Acute ischemic stroke (AIS) with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO-AIS is modified by initial stroke severity (baseline NIHSS) and arterial occlusion site. Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO-AIS patients (PLATO study), we assessed the heterogeneity of EVT outcomes compared to medical management (MM) for iPCAO, according to baseline NIHSS (≤6 vs. >6) and occlusion site (P1 vs. P2), using multivariable regression modelling with interaction terms. The primary outcome was the favorable shift of 3-month mRS. Secondary outcomes included excellent outcome (mRS 0-1), functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH) and mortality. Results: From 1344 patients assessed for eligibility, 1,059 were included (median age 74 years, 43.7% women, 41.3% had intravenous thrombolysis), 364 receiving EVT and 695 MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (pint=0.312), but did with functional independence (pint=0.010), with a similar trend on excellent outcome (pint=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS>6 (mRS 0-1: 30.6% vs. 17.7%, aOR=2.01, 95%CI=1.22-3.31; mRS 0-2: 46.1% vs. 31.9%, aOR=1.64, 95%CI=1.08-2.51), but not in those with NIHSS≤6 (mRS 0-1: 43.8% vs. 46.3%, aOR=0.90, 95%CI=0.49-1.64; mRS 0-2: 65.3% vs. 74.3%, aOR=0.55, 95%CI=0.30-1.0). EVT was associated with more sICH regardless of baseline NIHSS (pint=0.467), while the mortality increase was more pronounced in patients with NIHSS≤6 (pint=0.044, NIHSS≤6: aOR=7.95,95%CI=3.11-20.28, NIHSS>6: aOR=1.98,95%CI=1.08-3.65). Arterial occlusion site did not modify the association of EVT with outcomes compared to MM. Conclusion: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS>6) had more favorable disability outcomes with EVT than MM, despite increased mortality and sICH

Clinical and Safety Outcomes of Endovascular Therapy 6 to 24 Hours After Large Vessel Occlusion Ischemic Stroke With Tandem Lesions

Background and PurposeEffect of endovascular therapy (EVT) in acute large vessel occlusion (LVO) patients with tandem lesions (TLs) within 6-24 hours after last known well (LKW) remains unclear. We evaluated the clinical and safety outcomes among TL-LVO patients treated within 6-24 hours. MethodsThis multicenter cohort was divided into two groups, based on LKW to puncture time: early window (<6 hours), and late window (6-24 hours). Primary clinical and safety outcomes were 90-day functional independence measured by the modified Rankin Scale (mRS: 0-2) and symptomatic intracranial hemorrhage (sICH). Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), first-pass effect, early neurological improvement, ordinal mRS, and in-hospital and 90-day mortality. ResultsOf 579 patients (median age 68, 32.1% females), 268 (46.3%) were treated in the late window and 311 (53.7%) in the early window. Late window group had lower median National Institutes of Health Stroke Scale score at admission, Alberta Stroke Program Early Computed Tomography Score, rates of intravenous thrombolysis, and higher rates for perfusion imaging. After adjusting for confounders, the odds of 90-day mRS 0-2 (47.7% vs. 45.0%, adjusted odds ratio [aOR] 0.71, 95% confidence interval [CI] 0.49-1.02), favorable shift in mRS (aOR 0.88, 95% CI 0.44-1.76), and sICH (3.7% vs. 5.2%, aOR 0.56, 95% CI 0.20-1.56) were similar in both groups. There was no difference in secondary outcomes. Increased time from LKW to puncture did not predicted the probability of 90-day mRS 0-2 (aOR 0.99, 95% CI 0.96-1.01, for each hour delay) among patients presenting <24 hours. Conclusion EVT for acute TL-LVO treated within 6-24 hours after LKW was associated with similar rates of clinical and safety outcomes, compared to patients treated within 6 hours

Functional and Safety Outcomes of Carotid Artery Stenting and Mechanical Thrombectomy for Large Vessel Occlusion Ischemic Stroke With Tandem Lesions

Approximately 10% to 20% of large vessel occlusion (LVO) strokes involve tandem lesions (TLs), defined as concomitant intracranial LVO and stenosis or occlusion of the cervical internal carotid artery. Mechanical thrombectomy (MT) may benefit patients with TLs; however, optimal management and procedural strategy of the cervical lesion remain unclear. To evaluate the association of carotid artery stenting (CAS) vs no stenting and medical management with functional and safety outcomes among patients with TL-LVOs. This cross-sectional study included consecutive patients with acute anterior circulation TLs admitted across 17 stroke centers in the US and Spain between January 1, 2015, and December 31, 2020. Data analysis was performed from August 2021 to February 2022. Inclusion criteria were age of 18 years or older, endovascular therapy for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) demonstrated on pre-MT computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography. Patients with TLs were divided into CAS vs nonstenting groups. Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale (mRS) score of 0 to 2 and symptomatic intracranial hemorrhage (sICH), respectively. Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), discharge mRS score, ordinal mRS score, and mortality at 90 days. Of 685 patients, 623 (mean [SD] age, 67 [12.2] years; 406 [65.2%] male) were included in the analysis, of whom 363 (58.4%) were in the CAS group and 260 (41.6%) were in the nonstenting group. The CAS group had a lower proportion of patients with atrial fibrillation (38 [10.6%] vs 49 [19.2%], P = .002), a higher proportion of preprocedural degree of cervical stenosis on digital subtraction angiography (90%-99%: 107 [32.2%] vs 42 [20.5%], P < .001) and atherosclerotic disease (296 [82.0%] vs 194 [74.6%], P = .003), a lower median (IQR) National Institutes of Health Stroke Scale score (15 [10-19] vs 17 [13-21], P < .001), and similar rates of intravenous thrombolysis and stroke time metrics when compared with the nonstenting group. After adjustment for confounders, the odds of favorable functional outcome (adjusted odds ratio [aOR], 1.67; 95% CI, 1.20-2.40; P = .007), favorable shift in mRS scores (aOR, 1.46; 95% CI, 1.02-2.10; P = .04), and successful reperfusion (aOR, 1.70; 95% CI, 1.02-3.60; P = .002) were significantly higher for the CAS group compared with the nonstenting group. Both groups had similar odds of sICH (aOR, 0.90; 95% CI, 0.46-2.40; P = .87) and 90-day mortality (aOR, 0.78; 95% CI, 0.50-1.20; P = .27). No heterogeneity was noted for 90-day functional outcome and sICH in prespecified subgroups. In this multicenter, international cross-sectional study, CAS of the cervical lesion during MT was associated with improvement in functional outcomes and reperfusion rates without an increased risk of sICH and mortality in patients with TLs