Cortical Excitability Measured with nTMS and MEG during Stroke Recovery

Objective. Stroke alters cortical excitability both in the lesioned and in the nonlesioned hemisphere. Stroke recovery has been studied using transcranial magnetic stimulation (TMS). Spontaneous brain oscillations and somatosensory evoked fields (SEFs) measured by magnetoencephalography (MEG) are modified in stroke patients during recovery. Methods. We recorded SEFs and spontaneous MEG activity and motor threshold (MT) short intracortical inhibition (SICI) and intracortical facilitation (ICF) with navigated TMS (nTMS) at one and three months after first-ever hemispheric ischemic strokes. Changes of MEG and nTMS parameters attributed to gamma-aminobutyrate and glutamate transmission were compared. Results. ICF correlated with the strength and extent of SEF source areas depicted by MEG at three months. The nTMS MT and event-related desynchronization (ERD) of beta-band MEG activity and SICI and the beta-band MEG event-related synchronization (ERS) were correlated, but less strongly. Conclusions. This first report using sequential nTMS and MEG in stroke recovery found intra-and interhemispheric correlations of nTMS and MEG estimates of cortical excitability. ICF and SEF parameters, MT and the ERD of the lesioned hemisphere, and SICI and ERS of the nonlesioned hemisphere were correlated. Covarying excitability in the lesioned and nonlesioned hemispheres emphasizes the importance of the hemispheric balance of the excitability of the sensorimotor system.Peer reviewe

Familial hypercholesterolemia and statins in the COVID-19 era : Mitigating the risk of ischemic stroke

Publisher Copyright: © 2021 The Author(s)There is a continuing need for research about the underlying mechanisms behind ischemic strokes in COVID-19 patients. Pre-existing endothelial dysfunction, especially if it is accompanied by a viral infection of the endothelial cells may present an important mechanism behind the immunothrombotic/thromboembolic complications of the COVID-19 illness. Here we emphasize that pharmacotherapy with statins could partly counteract such pathophysiological scenarios. Accordingly, using familial hypercholesterolemia (FH) as a pertinent example of a lifelong endothelial dysfunction, we aim to make the clinicians and consulting neurologists aware of statins as a possible adjuvant therapy in the context of an increased risk of ischemic stroke in patients with COVID-19. Based on recent clinical evidence, there is a need to encourage clinicians and consulting neurologists to continue or initiate effective statin treatment to prevent an ischemic stroke, particularly when they encounter a hypercholesterolemic COVID-19 patient with FH.Non peer reviewe

Stroke Severity and Comorbidity Index for Prediction of Mortality after Ischemic Stroke from the Virtual International Stroke Trials Archive-Acute Collaboration

M. Kaste on työryhmän VISTA-Acute Collaboration jäsen.Background: There is increasing interest in the use of administrative data (incorporating comorbidity index) and stroke severity score to predict ischemic stroke mortality. The aim of this study was to determine the optimal timing for the collection of stroke severity data and the minimum clinical dataset to be included in models of stroke mortality. To address these issues, we chose the Virtual International Stroke Trials Archive (VISTA), which contains National Institutes of Health Stroke Scale (NIHSS) on admission and at 24 hours, as well as outcome at 90 days. Methods: VISTA was searched for patients who had baseline and 24-hour NIHSS. Improvement in regression models was performed by the net reclassification improvement (NRI) method. Results: The clinical data among 5206 patients were mean age, 69 +/- 13; comorbidity index, 3.3 +/- .9; median NIHSS at baseline, 12 (interquartile range [IQR] 8-17); NIHSS at 24 hours, 9 (IQR 8-15); and death at 90 days in 15%. The baseline model consists of age, gender, and comorbidity index. Adding the baseline NIHSS to model 1 improved the NRI by 0.671 (95% confidence interval [CI] 0.595-0.747) [or 67.1% correct reclassification between model 1 and model 2]. Adding the 24 hour NIHSS term to model 1 (model 3) improved the NRI by 0.929 (95% CI 0.857-1.000) for model 3 versus model 1. Adding the variable thrombolysis to model 3 (model 4) improve NRI by 0.1 (95% CI 0.023-0.178) [model 4 versus model 3]. Conclusion: The optimal model for the prediction of mortality was achieved by adding the 24-hour NIHSS and thrombolysis to the baseline model.Peer reviewe

Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST)

<p><b>Background and Purpose:</b> The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.</p> <p><b>Methods:</b> The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P≤0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.</p> <p><b>Results:</b> The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.</p> <p><b>Conclusions:</b> The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.</p&gt

Familial hypercholesterolaemia and COVID-19 : A two-hit scenario for endothelial dysfunction amenable to treatment

Patients with familial hypercholesterolemia (FH) are likely at increased risk for COVID-19 complications in the acute phase of the infection, and for a long time thereafter. Because in FH patients the level of low density lipoprotein cholesterol (LDL-C) is elevated from birth and it correlates with the degree of systemic endothelial dysfunction, both heterozygous FH (HeFH) patients and, in particular, homozygous FH (HoFH) patients have a dysfunctional endothelium prone to further damage by the direct viral attack and the hyper-inflammatory reaction typical of severe COVID-19. Evidence to date shows the benefit of statin use in patients with COVID-19. In FH patients, the focus should therefore be on the effective lowering of LDL-C levels, the root cause of the expected excess vulnerability to COVID-19 infection in these patients. Moreover, the ongoing use of statins and other lipid-lowering therapies should be encouraged during the COVID pandemic to mitigate the risk of cardiovascular complications from COVID-19. For the reduction of the excess risk in FH patients with COVID-19, we advocate stringent adherence to the guideline determined LDL-C levels for FH patients, or maybe even to lower levels. Unfortunately, epidemiologic data are lacking on the severity of COVID-19 infections, as well as the number of acute cardiac events that have occurred in FH subjects during the COVID-19 pandemic. Such data need to be urgently gathered to learn how much the risk for, and the severity of COVID-19 in FH are increased.Peer reviewe

Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: individual-patient-data meta-analysis of randomized trials

Background: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims: We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods: We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results: Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions: An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality