Intravenous thrombolysis (IVT) represents the only systemic reperfusion therapy able to reverse neurological deficit in patients with acute ischemic stroke (AIS). Despite its effectiveness in ...patients with or without large vessel occlusion, it can be offered only to a minority of them, because of the short therapeutic window and additional contraindications derived from stringent but arbitrary inclusion and exclusion criteria used in landmark randomized controlled clinical trials. Many absolute or relative contraindications lead to disparities between the official drug label and guidelines or expert recommendations. Based on recent advances in neuroimaging and evidence from cohort studies, off-label use of IVT is increasingly incorporated into the daily practice of many stroke centers. They relate to extension of therapeutic time windows, and expansion of indications in co-existing conditions originally listed in exclusion criteria, such as use of alternative thrombolytic agents, pre-treatment with antiplatelets, anticoagulants or low molecular weight heparins. In this narrative review, we summarize recent randomized and real-world data on the safety and efficacy of off-label use of IVT for AIS. We also make some practical recommendations to stroke physicians regarding the off-label use of thrombolytic agents in complex and uncommon presentations of AIS or other conditions mimicking acute cerebral ischemia. Finally, we provide guidance on the risks and benefits of IVT in numerous AIS subgroups, where equipoise exists and guidelines and treatment practices vary.
To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for ...nonvalvular atrial fibrillation (NVAF).
We evaluated consecutive patients with NVAF with nontraumatic, anticoagulant-related ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA- or DOAC-related ICH.
We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.6 ± 9.8 years, 57.8% men, median admission NIH Stroke Scale NIHSS
score 13 points, interquartile range 6-21). DOAC-related (n = 47) and VKA-related (n = 114) ICH did not differ in demographics, vascular risk factors, HAS-BLED and CHA
DS
-VASc scores, and antiplatelet pretreatment except for a higher prevalence of chronic kidney disease in VKA-related ICH. Patients with DOAC-related ICH had lower median NIHSS
scores (8 3-14 vs 15 7-25 points,
= 0.003), median baseline hematoma volume (12.8 4-40 vs 24.3 11-58.8 cm
,
= 0.007), and median ICH score (1 0-2 vs 2 1-3 points,
= 0.049). Severe ICH (>2 points) was less prevalent in DOAC-related ICH (17.0% vs 36.8%,
= 0.013). In multivariable analyses, DOAC-related ICH was independently associated with lower baseline hematoma volume (
= 0.006), lower NIHSS
scores (
= 0.022), and lower likelihood of severe ICH (odds ratio OR 0.34, 95% confidence interval CI 0.13-0.87,
= 0.025). In meta-analysis of eligible studies, DOAC-related ICH was associated with lower baseline hematoma volumes on admission CT (standardized mean difference = -0.57, 95% CI -1.02 to -0.12,
= 0.010) and lower in-hospital mortality rates (OR = 0.44, 95% CI 0.21-0.91,
= 0.030).
DOAC-related ICH is associated with smaller baseline hematoma volume and lesser neurologic deficit at hospital admission compared to VKA-related ICH.
Background:
Endovascular treatment (EVT) for acute ischemic stroke (AIS) patients presenting with Alberta Stroke Program Early CT Score (ASPECTS) 0–5 has not yet proven safe and effective by clinical ...trials.
Objectives:
The aim of the study was to assess whether EVT in AIS patients presenting with low ASPECTS is beneficial.
Design:
Systematic review and meta-analysis of available studies in accordance with the PRISMA statement.
Data sources and Methods:
We have searched MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 28 May 2022 with the aim to calculate (1) modified Rankin scale (mRS) score 0–3 at 3 months, (2) mRS score 0–2 at 3 months, (3) symptomatic intracranial hemorrhage (sICH), and (3) mortality at 3 months.
Results:
Overall, 24 eligible studies were included in the meta-analysis, comprising a total of 2539 AIS patients with ASPECTS 0–5 treated with EVT. The pooled proportion of EVT-treated patients achieving mRS 0–3 at 3 months was calculated at 38.4%. The pooled proportion of EVT-treated patients achieving mRS 0–2 at 3 months was 25.7%. Regarding safety outcomes, sICH occurred in 12.8% of patients. The 3-month pooled mortality was 30%. In pairwise meta-analysis, patients treated with EVT had a higher likelihood of achieving mRS 0–3 at 3 months compared with patients treated with best medical therapy (BMT, OR: 2.41). sICH occurred more frequently in EVT-treated patients compared with the BMT-treated patients (OR: 2.30). Mortality at 3 months was not different between the two treatment groups (OR: 0.71).
Conclusion:
EVT may be beneficial for AIS patients with low baseline ASPECTS despite an increased risk for sICH. Further data from randomized-controlled clinical trials are needed to elucidate the role of EVT in this subgroup of AIS patients.
Registration:
The protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO; Registration Number: CRD42022334417.
The clinical manifestations of proximal (extracranial) internal carotid artery occlusions (pICAOs) may range from asymptomatic to acute, large, and devastating ischemic strokes. The etiology and ...pathophysiology of the occlusion, intracranial collateral status and patient’s premorbid status are among the factors determining the clinical presentation and outcome of pICAOs. Rapid and accurate diagnosis is crucial and may be assisted by the combination of carotid and transcranial duplex sonography, or a computed tomography/magnetic resonance angiography (CTA/MRA). It should be noted that with either imaging modalities, the discrimination of a pseudo-occlusion of the extracranial internal carotid artery (ICA) from a true pICAO may not be straightforward. In the absence of randomized data, the management of acute, symptomatic pICAOs remains individualized and relies largely on expert opinion. Administration of intravenous thrombolysis is reasonable and probably beneficial in the settings of acute ischemic stroke with early presentation. Unfortunately, rates of recanalization are rather low and acute interventional reperfusion therapies emerge as a potentially powerful therapeutic option for patients with persistent and severe symptoms. However, none of the pivotal clinical trials on mechanical thrombectomy for acute ischemic stroke randomized patients with isolated extracranial large vessel occlusions. On the contrary, several lines of evidence from non-randomized studies have shown that acute carotid endarterectomy, or endovascular thrombectomy/stenting of the ICA are feasible and safe, and pοtentially beneficial. The heterogeneity in the pathophysiology and clinical presentation of acute pICAOs renders patient selection for an acute interventional treatment a complicated decision-making process. The present narrative review will outline the pathophysiology, clinical presentation, diagnostic challenges, and possible treatment options for pICAOs.
A 67-year-old male photographer who used traditional cameras that necessitated monocular focusing developed intermittent blepharospasms, evident only during and shortly after the voluntary ...contraction of the left eyelids while using the camera, a form of a task-specific blepharospasm. The spasms gradually progressed to involve the entire hemiface resulting in a task-specific hemifacial spasm that eventually evolved into a persistent hemifacial spasm. Our case report highlights the fact that focal dystonia may also develop in the facial muscles following chronic and repetitive muscle contractions, such as those performed by an older photographer who used traditional cameras that necessitated monocular focusing. To our knowledge, hemifacial spasm has not yet been recognized as a form of focal, task-specific dystonia. Moreover, occupational, focal dystonia has not been described in photographers.
Background and aims:
Tenecteplase has recently emerged as an alternative thrombolytic agent in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO), possibly superior in achieving ...early reperfusion compared with alteplase. We aimed to compare the safety and efficacy of intravenous tenecteplase with intravenous alteplase for AIS patients with LVO in everyday clinical practice settings.
Methods:
We prospectively evaluated patients with AIS due to LVO, treated with intravenous thrombolysis (IVT) with or without mechanical thrombectomy in two tertiary stroke centers. Patients were treated with standard-dose alteplase (0.9 mg/kg) or 0.25 mg/kg tenecteplase. Safety outcomes included prevalence of symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes included averted thrombectomy, major neurological improvement at 24 h (defined as decrease in baseline NIHSS score of 8 points or greater) and functional status on discharge and on 3 months assessed by modified Rankin Scale (mRS).
Results:
Nineteen AIS patients with LVO received tenecteplase and 39 received alteplase. We observed a non-significant higher rate of averted thrombectomies (32% versus 18%, p = 0.243) and a non-significant higher rate of sICH (16% versus 5%, p = 0.201) in the tenecteplase group. The rate of 24 h major neurological improvement was higher in the tenecteplase group (64% versus 33%, p = 0.046) but this was marginally attenuated in multivariable analyses (adjusted OR 10.22, 95% CI: 0.73–142.98; p = 0.084). Discharge mRS, 3-months mRS, and 3-month functional independence (mRS scores of 0–2) did not differ (p > 0.2) between the two groups. The rates of 3-month mortality (11% versus 18%, p = 0.703) were similar in the two groups. No independent association between thrombolytic agent and safety or efficacy outcomes emerged in multivariable regression analyses.
Conclusion:
The present pilot observational study highlights that AIS patients with LVO treated with 0.25 mg/kg bolus administration of tenecteplase had increased likelihood to achieve early neurological improvement compared with AIS patients treated with alteplase, but this association was attenuated after adjustment for potential confounders. There were no significant differences in 3-month functional or safety outcomes between the two groups. This preliminary real-world observation requires independent confirmation in larger, multicenter studies.
Purpose
Recent randomized-controlled clinical trials have provided preliminary evidence for expanding the time window of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients by ...applying certain neuroimaging criteria. We prospectively assessed the potential eligibility for IVT in the extended time window (4.5–9 h) among consecutive AIS patients treated in a comprehensive stroke center during a nine-month period.
Methods
Potential eligibility for IVT in the extended time window was evaluated by using inclusion criteria from the EXTEND trial. All patients were underwent baseline emergent neurovascular imaging using either computed tomography angiography/computed tomography perfusion (CTA/CTP) or magnetic resonance angiography/magnetic resonance perfusion (MRA/MRP). Images were post processed by the automated software RAPID.
Results
Our study population consisted of 317 AIS patients, and, among them, 31 (9.8 %) patients were presented in the time window of 4.5–9 h. Seven patients (2.2 %) fulfilled the EXTEND neuroimaging criteria. Four patients (1.3 %) were treated with IVT because they fulfilled both clinical and neuroimaging EXTEND criteria. Patients eligible for EXTEND neuroimaging criteria had no ischemic core lesion, whereas the mean volume of critical hypoperfusion was relatively small (17.0 ± 11.8 ml). There was no hemorrhagic complication in any of the patients treated with IVT. The median mRS score at three months was 0 (range: 0–3) among patients who were eligible for EXTEND neuroimaging criteria.
Conclusion
Our everyday clinical practice experience suggests 9.8 % of consecutive AIS patients present in the 4.5–9 h window and 2.2 % adhere to EXTEND neuroimaging eligibility criteria for IVT. Only 1.3% of AIS is eligible for IVT according to EXTEND neuroimaging and clinical eligibility criteria.
Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time ...windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.
The literature on endovascular treatment (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) has been rapidly increasing after the publication of positive randomized-controlled ...clinical trials (RCTs) and a plethora of systematic reviews (SRs) showing benefit compared to best medical therapy (BMT) for LVO.
An overview of SRs (umbrella review) and meta-analysis of primary RCTs were performed to summarize the literature and present efficacy and safety of EVT.
MEDLINE
Pubmed, Embase and Epistemonikos databases were searched from January 2015 until 15 October 2023. All SRs of RCTs comparing EVT to BMT were included. Quality was assessed using Risk of Bias in Systematic Reviews scores and the RoB 2 Cochrane Collaboration tool, as appropriate. GRADE approach was used to evaluate the strength of evidence. Data were presented according to the Preferred Reporting Items for Overviews of Reviews statement. The primary outcome was 3-month good functional outcome modified Rankin scale (mRS) score 0-2.
Three eligible SRs and 4 additional RCTs were included in the overview, comprising a total of 24 RCTs, corresponding to 5968 AIS patients with LVO (3044 randomized to EVT
2924 patients randomized to BMT). High-quality evidence shows that EVT is associated with an increased likelihood of good functional outcome risk ratio (RR) 1.78 (95% confidence interval (CI): 1.54-2.06); 166 more per 1000 patients, independent ambulation mRS-scores 0-3; RR 1.50 (95% CI: 1.37-1.64); 174 more per 1000 patients, excellent functional outcome mRS-scores 0-1; RR 1.90 (95% CI: 1.62-2.22); 118 more per 1000 patients at 3 months. EVT was associated with reduced 3-month mortality RR 0.81 (95% CI: 0.74-0.88); 61 less per 1000 patients despite an increase in symptomatic intracranial haemorrhage sICH; RR 1.65 (95% CI: 1.23-2.21); 22 more per 1000 patients.
In patients with AIS due to LVO in the anterior or posterior circulation, within 24 h from symptom onset, EVT improves functional outcomes and increases the chance of survival despite increased sICH risk.
PROSPERO Registration Number CRD42023461138.
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