IV Thrombolysis in Basilar Artery Occlusion: Outcomes and Comparison With Endovascular Thrombectomy.

BACKGROUND AND OBJECTIVES: Recanalization is considered a prerequisite for favorable outcome in basilar artery occlusion (BAO). Intravenous thrombolysis (IVT) has been successfully used for eligible patients with BAO well beyond the 4.5-hour time window but has been largely underrepresented in the best medical management arms in recent randomized controlled trials of recanalization therapy in BAO. We aimed to analyze the outcomes of patients with BAO treated with IVT only and to compare IVT with endovascular thrombectomy (EVT). METHODS: This observational single-center, retrospective cohort study included consecutive patients with BAO treated with IVT and/or EVT up to 48 hours of symptom onset during 1995-2022. The primary outcome was favorable functional outcome (modified Rankin Scale 0-3) at 3 months collected by a stroke physician by phone. In the first part, we described the outcomes and factors associated with functional outcome in the IVT-only cohort during 1995-2022. In the second part, we used doubly robust inverse probability-weighted regression adjustment models to compare functional outcome of patients treated with IVT vs EVT+/-IVT during 2010-2022. RESULTS: In the whole cohort of 376 patients with acute BAO treated with recanalization therapy, 245 (65.2%) received only IVT. In the IVT-only cohort, most patients had moderate-to-severe clinical presentation (median NIH Stroke Scale 18) but no extensive early ischemic changes in the posterior circulation on admission. Half of them had onset-to-treatment time over 6 hours. 46.5% of the IVT-treated patients achieved 3-month favorable functional outcome, whereas mortality was 35.9%. sICH occurred in 11.1%. In a multivariable analysis, younger age, milder symptom severity, and less baseline ischemic changes predicted favorable functional outcome. In the 2010-2022 cohort, when compared with patients treated with EVT+/-IVT (n = 121), the IVT-only cohort (n = 122) had higher odds for favorable functional outcome (IVT 58.2% vs EVT 43.0% (aOR 2.82 [95% CI 1.31-6.05]). DISCUSSION: IVT alone produced outcomes comparable with those in recent trials of endovascular BAO recanalization. Furthermore, in head-to-head comparison in our cohort, the IVT-only approach was more often associated with favorable outcome than EVT+/-IVT. Thus, it should not be overlooked as the first-line recanalization therapy in acute BAO, even in longer time windows. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that tPA is as effective as thrombectomy for basilar artery thrombosis.

Ultra-Early Differential Diagnosis of Acute Cerebral Ischemia and Hemorrhagic Stroke by Measuring the Prehospital Release Rate of GFAP.

BACKGROUND: Plasma glial fibrillary acidic protein (GFAP) and tau are promising markers for differentiating acute cerebral ischemia (ACI) and hemorrhagic stroke (HS), but their prehospital dynamics and usefulness are unknown. METHODS: We performed ultra-sensitivite single-molecule array (Simoa®) measurements of plasma GFAP and total tau in a stroke code patient cohort with cardinal stroke symptoms [National Institutes of Health Stroke Scale (NIHSS) ≥3]. Sequential sampling included 2 ultra-early samples, and a follow-up sample on the next morning. RESULTS: We included 272 cases (203 ACI, 60 HS, and 9 stroke mimics). Median (IQR) last-known-well to sampling time was 53 (35-90) minutes for initial prehospital samples, 90 (67-130) minutes for secondary acute samples, and 21 (16-24) hours for next morning samples. Plasma GFAP was significantly higher in patients with HS than ACI (P < 0.001 for <1 hour and <3 hour prehospital samples, and <3 hour secondary samples), while total tau showed no intergroup difference. The prehospital GFAP release rate (pg/mL/minute) occurring between the 2 very early samples was significantly higher in patients with HS than ACI [2.4 (0.6-14.1)] versus 0.3 (-0.3-0.9) pg/mL/minute, P < 0.001. For cases with <3 hour prehospital sampling (ACI n = 178, HS n = 59), a combined rule (prehospital GFAP >410 pg/mL, or prehospital GFAP 90-410 pg/mL together with GFAP release >0.6 pg/mL/minute) enabled ruling out HS with high certainty (NPV 98.4%) in 68% of patients with ACI (sensitivity for HS 96.6%, specificity 68%, PPV 50%). CONCLUSIONS: In comparison to single-point measurement, monitoring the prehospital GFAP release rate improves ultra-early differentiation of stroke subtypes. With serial measurement GFAP has potential to improve future prehospital stroke diagnostics.

Comatose With Basilar Artery Occlusion: Still Odds of Favorable Outcome With Recanalization Therapy.

Background: Around 30-60% of patients with basilar artery occlusion (BAO) present with coma, which is often considered as a hallmark of poor prognosis. Aim: To examine factors that will help predict outcomes in patients with BAO comatose on admission. Methods: A total of 312 patients with angiography-proven BAO were analyzed. Comas were assessed as Glasgow Coma Scale (GCS) of ≤8 or impaired level of consciousness ascertained in the medical records. Outcomes were evaluated with the modified Rankin Scale (mRS) over a phone call at 3 months. In our study, 53 patients were excluded due to inadequate data on the level of consciousness. Results: In total, 103/259 (39.8%) of BAO patients were comatose on admission. Factors associated with acute coma were higher age, coronary artery disease, convulsions, extent of early ischemia by posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) < 8, absence of patent posterior collateral vasculature, and occlusion over multiple segments of BA. A total of 21/103 (20.4%) of comatose patients had a favorable outcome (mRS 0-3), and 12/103 (11.7%) had a good outcome (mRS 0-2). Factors associated with a favorable outcome in comatose BAO patients were younger age (p = 0.010), less extensive baseline ischemia (p = 0.027), recanalization (p = 0.013), and avoiding symptomatic intracranial hemorrhage (sICH) (p = 0.038). Factors associated with the poorest outcome or death (mRS 5-6) were older age (p = 0.001), diabetes (p = 0.022), atrial fibrillation (p = 0.016), lower median GCS [4 (IQR 3.6) vs. 6 (5-8); p = 0.006], pc-ASPECTS < 8 (p = 0.003), unsuccessful recanalization (p = 0.006), and sICH (p = 0.010). Futile recanalization (mRS 4-6) was significantly more common in comatose patients (49.4 vs. 18.5%, p < 0.001). Conclusions: One in five BAO patients with acute coma had a favorable outcome. Older patients with cardiovascular comorbidities and already existing ischemic lesions before reperfusion therapies tended to have a poor prognosis, especially if no recanalization is achieved and sICH occurred.

Outcomes and long-term mortality after basilar artery occlusion-A cohort with up to 20 years' follow-up.

BACKGROUND: The data on long-term outcome after basilar artery occlusion (BAO) are scarce. Little is known about BAO survivors´ outcome over decades. AIM: We set out to investigate long-term survival and causes of death in BAO patients with up to two decades of follow-up. We also evaluated differences in outcome trends. METHODS: Two hundred and seven BAO patients treated with intravenous thrombolysis (IVT) at the Department of Neurology, Helsinki University Hospital, between 1995 and 2016, were analyzed. Short-term outcome was assessed by modified Rankin Scale (mRS) at 3 months. Long-term cumulative survival rate was analyzed using Kaplan-Meier analysis. Factors associated with mortality were analyzed with Cox regression. RESULTS: Moderate outcome (mRS 0-3) was achieved in 41.1% and good outcome (mRS 0-2) in 30.4% of patients at 3 months. Three-month mortality was 39.6%, of which 89% died within the first month. The median follow-up time in 3-month survivors was 8.9 years (maximum 21.8 years). Total mortality during follow-up was 52.2%. Cumulative mortality rate was 25.7%. Older age, coronary artery disease and more extensive ischemic changes on admission brain imaging were independently associated with long-term mortality. After the acute phase, the rate of other vascular causes of death increased in relation to stroke. CONCLUSIONS: The described evolution of a large, single-center BAO cohort shows a trend towards a higher rate of good and/or moderate outcome during later years in IVT-treated patients. Survivors showed relative longevity, and the rate of cardiac and other vascular causes of death increased in relation to stroke sequelae over the long term.

Targets for improving dispatcher identification of acute stroke.

BACKGROUND: Accurate identification of acute stroke by Emergency Medical Dispatchers (EMD) is essential for timely and purposeful deployment of Emergency Medical Services (EMS), and a prerequisite for operating mobile stroke units. However, precision of EMD stroke recognition is currently modest. AIMS: We sought to identify targets for improving dispatcher stroke identification. METHODS: Dispatch codes and EMS patient records were cross-linked to investigate factors associated with an incorrect dispatch code in a prospective observational cohort of 625 patients with a final diagnosis of acute stroke or transient ischemic attack (TIA), transported to our stroke center as candidates for recanalization therapies. Call recordings were analyzed in a subgroup that received an incorrect low-priority dispatch code indicating a fall or unknown acute illness (n = 46). RESULTS: Out of 625 acute stroke/TIA patients, 450 received a high-priority stroke dispatch code (sensitivity 72.0%; 95% CI, 68.5-75.5). Independent predictors of dispatcher missed acute stroke included a bystander caller (aOR, 3.72; 1.48-9.34), confusion (aOR, 2.62; 1.59-4.31), fall at onset (aOR, 1.86; 1.24-2.78), and older age (aOR [per year], 1.02; 1.01-1.04). Of the analyzed call recordings, 71.7% revealed targets for improvement, including failure to recognize a Face Arm Speech Time (FAST) test symptom (21/46 cases, 18 with speech disturbance), or failure to thoroughly evaluate symptoms (12/46 cases). CONCLUSIONS: Based on our findings, efforts to improve dispatcher stroke identification should primarily focus on improving recognition of acute speech disturbance, and implementing screening of FAST-symptoms in emergency phone calls revealing a fall or confusion. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02145663.

Should we thrombolyse prior to endovascular treatment in acute stroke?

The superiority of endovascular treatment (EVT) in acute stroke due to large vessel occlusion has been proven in recent randomized trials. Yet, there are no randomized trials which have tested the additive effect of standard treatment with intravenous thrombolysis (IVT) as pretreatment to EVT over EVT treatment alone. So far, the EVT treatment groups of RCTs most often had pretreatment with IVT. The current guidelines on acute stroke treatment rely on meta-analyses and systematic analyses from RCTs and observational studies on pretreatment with IVT + EVT. Clinicians also apply their clinical experience and local "in-house" protocols. We performed literature search on randomized controlled trials, systematic and meta-analyses and observational studies on recanalization therapies including intravenous thrombolysis and endovascular treatment or thrombectomy in acute stroke. Here we present a review and an opinion on the current choice of treatment modalities.

Diagnosing cerebral ischemia with door-to-thrombolysis times below 20 minutes.

OBJECTIVES: To clarify diagnostic accuracy and consequences of misdiagnosis in the admission evaluation of stroke-code patients in a neurologic emergency department with less than 20-minute door-to-thrombolysis times. METHODS: Accuracy of admission diagnostics was studied in an observational cohort of 1,015 stroke-code patients arriving by ambulance as candidates for recanalization therapy between May 2013 and November 2015. Immediate admission evaluation was performed by a stroke neurologist or a neurology resident with dedicated stroke training, primarily utilizing CT-based imaging. RESULTS: The rate of correct admission diagnosis was 91.1% (604/663) for acute cerebral ischemia (ischemic stroke/TIA), 99.2% (117/118) for hemorrhagic stroke, and 61.5% (144/234) for stroke mimics. Of the 150 (14.8%) misdiagnosed patients, 135 (90.0%) had no acute findings on initial imaging and 100 (67.6%) presented with NIH Stroke Scale score 0 to 2. Misdiagnosis altered medical management in 70 cases, including administration of unnecessary treatments (thrombolysis n = 13, other n = 24), omission of thrombolysis (n = 5), delays to specific treatments of stroke mimics (n = 13, median 56 [31-93] hours), and delays to antiplatelet medication (n = 14, median 1 [1-2] day). Misdiagnosis extended emergency department stay (median 6.6 [4.7-10.4] vs 5.8 [3.7-9.2] hours; p = 0.001) and led to unnecessary stroke unit stay (n = 10). Detailed review revealed 8 cases (0.8%) in which misdiagnosis was possible or likely to have worsened outcomes, but no death occurred as a result of misdiagnosis. CONCLUSIONS: Our findings support the safety of highly optimized door-to-needle times, built on thorough training in a large-volume, centralized stroke service with long-standing experience. Augmented imaging and front-loaded specialist engagement are warranted to further improve rapid stroke diagnostics.