A proactive clinical approach to stroke care improved functional outcomes with implementation of specialized in-hospital stroke units, urgently delivered systemic thrombolysis, mechanical ...thrombectomy and most recently with mobile stroke units deployed in the field. An 18% absolute difference in outcomes as a shift across all modified Rankin Scale strata at 3 months in the recent Berlin study may not be explained by just 8.8% more patients treated within the golden hour for thrombolytic treatment from symptom onset. These findings parallel the findings in the largest controlled multi-center BEST-MSU trial (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit) to date. A shortcoming in blinding of the investigators to the mode of transportation is similar to blinding to the endovascular treatment in PROBE (Prospective Randomized Open, Blinded End-Point) design used in thrombectomy trials. A faster access to stroke experts and brain imaging in the field for all patients suspect of stroke regardless symptom nature, severity, duration or resolution delivered by mobile stroke units is likely the reason for improved outcomes akin the impact observed in the initial multidisciplinary approach to in-hospital stroke units and reperfusion therapies delivery.
Although current guidelines advocate pretreatment with intravenous thrombolysis (IVT) in all eligible patients with acute ischemic stroke with large-vessel occlusion before mechanical thrombectomy, ...there are observational data questioning the efficacy of this approach. One of the main arguments in favor of IVT pretreatment is the potential for tissue-type plasminogen activator-induced successful reperfusion (SR) before the onset of endovascular procedure.
We performed a systematic review and meta-analysis of randomized controlled clinical trials and observational cohorts providing rates of SR with IVT in patients with large-vessel occlusion before the initiation of mechanical thrombectomy. We also performed subgroup analyses according to study type (randomized controlled clinical trials versus observational) and according to the inclusion per protocol of patients with tandem (intracranial/extracranial) occlusions.
We identified 13 eligible studies (7 randomized controlled clinical trials and 6 observational cohorts), including 1561 patients with acute ischemic stroke (median National Institutes of Health Stroke Scale score, 17) with large-vessel occlusion. SR following IVT and before mechanical thrombectomy was documented in 11% (95% confidence interval, 7%-16%), with no difference among cohorts derived from randomized controlled clinical trials and observational studies. There was significant heterogeneity across included studies both in the overall analysis and among subgroups (I
>84%;
for Cochran Q, <0.001). Higher tissue-type plasminogen activator-induced SR rates were documented in studies reporting the exclusion of tandem occlusions (17%; 95% confidence interval, 11%-23%) compared with the rest (7%; 95% confidence interval, 4%-11%;
for subgroup differences, 0.003).
Pretreatment with systemic thrombolysis in patients with large-vessel occlusion eligible for mechanical thrombectomy results in SR in 1 of 10 cases, negating the need for additional endovascular reperfusion. Tandem occlusions seem to be the least responsive to IVT pretreatment.
The timely diagnosis of stroke at the initial examination is extremely important given the disease morbidity and narrow time window for intervention. The goal of this study was to develop a ...supervised learning method to recognize acute cerebral ischemia (ACI) and differentiate that from stroke mimics in an emergency setting.
Consecutive patients presenting to the emergency department with stroke-like symptoms, within 4.5 hours of symptoms onset, in 2 tertiary care stroke centers were randomized for inclusion in the model. We developed an artificial neural network (ANN) model. The learning algorithm was based on backpropagation. To validate the model, we used a 10-fold cross-validation method.
A total of 260 patients (equal number of stroke mimics and ACIs) were enrolled for the development and validation of our ANN model. Our analysis indicated that the average sensitivity and specificity of ANN for the diagnosis of ACI based on the 10-fold cross-validation analysis was 80.0% (95% confidence interval, 71.8-86.3) and 86.2% (95% confidence interval, 78.7-91.4), respectively. The median precision of ANN for the diagnosis of ACI was 92% (95% confidence interval, 88.7-95.3).
Our results show that ANN can be an effective tool for the recognition of ACI and differentiation of ACI from stroke mimics at the initial examination.
Background
There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N‐acetylcysteine (NAC), widely known as an ...antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways.
Aim and discussion
Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht–Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease.
Conclusion
Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage.
Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans with non‐psychiatric disorders. We discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht‐Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. We review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage. Correction added on 6 February 2014, after first online publication: graphical text has been changed.
Objective
Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and highlight the potential impact of coronavirus ...disease (COVID‐19) on the management and outcomes of acute stroke. We conducted a systematic review and meta‐analysis to evaluate the aforementioned considerations.
Methods
We performed a meta‐analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS‐CoV‐2 infection status. We used a random‐effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs).
Results
We identified 18 cohort studies including 67,845 patients. Among patients with SARS‐CoV‐2, 1.3% (95% CI = 0.9–1.6%, I2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8–1.3%, I2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1–0.3%, I2 = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS‐CoV‐2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43–8.92, I2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62–9.77, I2 = 0%). Diabetes mellitus was found to be more prevalent among SARS‐CoV‐2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00–1.94, I2 = 0%). SARS‐CoV‐2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65–3.10, I2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35–1.74, I2 = 0%) among hospitalized ischemic stroke patients during the COVID‐19 pandemic. Odds of in‐hospital mortality were higher among SARS‐CoV‐2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19–9.80, I2 = 45%).
Interpretation
SARS‐CoV‐2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380–388
There are limited data evaluating the effect of post mechanical thrombectomy (MT) blood pressure (BP) levels on early outcomes of patients with large vessel occlusions (LVO). We sought to investigate ...the association of BP course following MT with early outcomes in LVO.
Consecutive patients with LVO treated with MT during a 3-year period were evaluated. Hourly systolic BP (SBP) and diastolic BP (DBP) values were recorded for 24 hours following MT and maximum SBP and DBP levels were identified. LVO patients with complete reperfusion following MT were stratified in 3 groups based on post-MT achieved BP goals: <140/90 mm Hg (intensive), <160/90 mm Hg (moderate), and <220/110 mm Hg or <180/105 mm Hg when pretreated with IV thrombolysis (permissive hypertension). Three-month functional independence was defined as modified Rankin Scale score of 0-2.
A total of 217 acute ischemic stroke patients with LVO were prospectively evaluated. A 10 mm Hg increment in maximum SBP documented during the first 24 hours post MT was independently (
= 0.001) associated with a lower likelihood of 3-month functional independence (odds ratio OR 0.70; 95% confidence interval CI 0.56-0.87) and a higher odds of 3-month mortality (OR 1.49; 95% CI 1.18-1.88) after adjusting for potential confounders. In addition, achieving a BP goal of <160/90 mm Hg during the first 24 hours following MT was independently associated with a lower likelihood of 3-month mortality (OR 0.08; 95% CI 0.01-0.54;
= 0.010) in comparison to permissive hypertension.
High maximum SBP levels following MT are independently associated with increased likelihood of 3-month mortality and functional dependence in LVO patients. Moderate BP control is also related to lower odds of 3-month mortality in comparison to permissive hypertension.
Our aim was to evaluate the diagnostic yield of transesophageal echocardiography (TEE) in consecutive patients with ischemic stroke (IS) fulfilling the diagnostic criteria of embolic strokes of ...undetermined source (ESUS).
We prospectively evaluated consecutive patients with acute IS satisfying ESUS criteria who underwent in-hospital TEE examination in 3 tertiary care stroke centers during a 12-month period. We also performed a systematic review and meta-analysis estimating the cumulative effect of TEE findings on therapeutic management for secondary stroke prevention among different IS subgroups.
We identified 61 patients with ESUS who underwent investigation with TEE (mean age 44 ± 12 years, 49% men, median NIH Stroke Scale score = 5 points interquartile range: 3-8). TEE revealed additional findings in 52% (95% confidence interval CI: 40%-65%) of the study population. TEE findings changed management (initiation of anticoagulation therapy, administration of IV antibiotic therapy, and patent foramen ovale closure) in 10 (16% 95% CI: 9%-28%) patients. The pooled rate of reported anticoagulation therapy attributed to abnormal TEE findings among 3,562 acute IS patients included in the meta-analysis (12 studies) was 8.7% (95% CI: 7.3%-10.4%). In subgroup analysis, the rates of initiation of anticoagulation therapy on the basis of TEE investigation did not differ (p = 0.315) among patients with cryptogenic stroke (6.9% 95% CI: 4.9%-9.6%), ESUS (8.1% 95% CI: 3.4%-18.1%), and IS (9.4% 95% CI: 7.5%-11.8%).
Abnormal TEE findings may decisively affect the selection of appropriate therapeutic strategy in approximately 1 of 7 patients with ESUS.
Background
Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) ...patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke.
Methods
Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models.
Results
We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0–2) (RR = 1.31; 95% CI 0.98–1.74,
p
= 0.06) and 3-month BI (MD = 6.92; 95% CI − 0.92, 14.75;
p
= 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0–2 (RR = 1.59; 95% CI 1.19–2.12,
p
= 0.002;
I
2
= 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14,
p
= 0.0003;
I
2
= 47%), whereas reduced the 3-month NIHSS (MD − 2.84; 95% CI − 5.55, − 0.13;
p
= 0.04; I
2
= 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion.
Conclusions
Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.
Acute basilar artery occlusion (BAO) is a catastrophe with high mortality and disability. Randomized controlled trial (RCT) data supporting/refuting reperfusion treatment are sparse in acute BAO. The ...study objective was to pool risk estimates for death or dependency (DoD), mortality, and intracerebral hemorrhage (ICH) from published studies on BAO.
Medline, Embase, The Cochrane Library, and clinicaltrials.gov were searched through August 2013 for studies of reperfusion therapies in acute BAO. Two independent authors selected studies and abstracted the data. Pooled risk ratios (RR) and mean weighted probabilities (MWP) were calculated using random effects model.
45 studies (n=2056) met the inclusion criteria. Recanalization was associated with a lower risk of DoD (RR 0.67; number needed to treat (NNT) 3) and mortality (RR 0.49; NNT 2.5). ICH rate (MWP) with acute therapies was 13%. With recanalization, RR for DoD in those treated ≤12 h was 0.63, and for those treated >12 h, it was 0.67. With recanalization, RR for DoD in the intravenous thrombolysis (IVT) subgroup was 0.68; in the intra-arterial/endovascular therapy (IA/EVT) subgroup, DoD RR was 0.67. Recanalization resulted in mortality RR of 0.46 in those treated ≤12 h; for >12 h group, RR was 0.50. Recanalization resulted in mortality RR of 0.53 in the IVT subgroup, and RR of 0.48 in the IA/EVT subgroup. ICH rate for ≤12 h was 10%; ICH rate for >12 h was 14%. With IVT, the ICH rate was 9%, and with IA/EVT the ICH rate was 14%.
Recanalization of acute BAO leads to reduction in mortality by two-fold and reduction in the risk of DoD by 1.5-fold. This study underscores the equipoise in acute BAO for comparing systemic and endovascular therapies, and testing different time windows through RCTs.
Shortening door-to-needle time may lead to inadvertent intravenous thrombolysis (IVT) administration in stroke mimics (SMs). We sought to determine the safety of IVT in SMs using prospective, ...single-center data and by conducting a comprehensive meta-analysis of reported case-series.
We prospectively analyzed consecutive IVT-treated patients during a 5-year period at a tertiary care stroke center. A systematic review and meta-analysis of case-series reporting safety of IVT in SMs and confirmed acute ischemic stroke were conducted. Symptomatic intracerebral hemorrhage was defined as imaging evidence of ICH with an National Institutes of Health Stroke scale increase of ≥4 points. Favorable functional outcome at hospital discharge was defined as a modified Rankin Scale score of 0 to 1.
Of 516 consecutive IVT patients at our tertiary care center (50% men; mean age, 60±14 years; median National Institutes of Health Stroke scale, 11; range, 3-22), SMs comprised 75 cases. Symptomatic intracerebral hemorrhage occurred in 1 patient, whereas we documented no cases of orolingual edema or major extracranial hemorrhagic complications. In meta-analysis of 9 studies (8942 IVT-treated patients), the pooled rates of symptomatic intracerebral hemorrhage and orolingual edema among 392 patients with SM treated with IVT were 0.5% (95% confidence interval, 0%-2%) and 0.3% (95% confidence interval, 0%-2%), respectively. Patients with SM were found to have a significantly lower risk for symptomatic intracerebral hemorrhage compared with patients with acute ischemic stroke (risk ratio=0.33; 95% confidence interval, 0.14-0.77; P=0.010), with no evidence of heterogeneity or publication bias. Favorable functional outcome was almost 3-fold higher in patients with SM in comparison with patients with acute ischemic stroke (risk ratio=2.78; 95% confidence interval, 2.07-3.73; P<0.00001).
Our prospective, single-center experience coupled with the findings of the comprehensive meta-analysis underscores the safety of IVT in SM.
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