Intravenous thrombolysis in stroke with admission NIHSS score 0 or 1

Background Up to 30% of stroke patients initially presenting with non-disabling or mild deficits may experience poor functional outcome. Despite, intravenous thrombolysis remains controversial in this subgroup of stroke patients due to its uncertain risk benefit ratio. Aim We aimed to analyze the real-world experience with intravenous thrombolysis in stroke patients presenting with very low NIHSS. Methods Data of stroke patients presenting with mild initial stroke severity (NIHSS 0–5) including vascular risk factors, stroke syndrome and etiology, early neurological deterioration, symptomatic intracerebral haemorrhage (sICH), and functional outcome by modified Rankin Scale were extracted from a large nationwide stroke registry and analysed. Patients were categorized and compared according to admission severity NIHSS 0–1 versus NIHSS 2–5 and intravenous thrombolysis use. Results Seven hundred and three (2%) of 35,113 patients presenting with NIHSS 0–1 and 6316 (13.9%) of 45,521 of patients presenting with NIHSS 2–5 underwent intravenous thrombolysis. In the NIHSS 0–1 group, intravenous thrombolysis was associated with early neurological deterioration (adjusted OR 8.84, CI 6.61–11.83), sICH (adjusted OR 9.32, CI 4.53–19.15) and lower rate of excellent outcome (mRS 0–1) at three months (adjusted OR 0.67, CI 0.5–0.9). In stroke patients with NIHSS 2–5, intravenous thrombolysis was associated with early neurological deterioration (adjusted OR 1.7, 1.47–1.98), sICH (adjusted OR 5.75, CI 4.45–7.45), and higher rate of excellent outcome (mRS 0–1) at three months (adjusted OR 1.21, CI 1.08–1.34). Conclusions Among patients with NIHSS 0–1, intravenous thrombolysis did not increase the likelihood of excellent outcome. Moreover, potential signals of harm were observed. Further research seems to be warranted.

Impact of hyperglycaemia on complications in patients who had a stroke after thrombolysis

BackgroundWe sought to investigate whether admission hyperglycaemia is associated with complications in patients who had an acute ischaemic stroke (AIS) treated with intravenous recombinant tissue plasminogen activator and, if so, whether complications during hospitalisation modify the effect of hyperglycaemia on 3-month poor outcome after thrombolysis.MethodsPatients who were diagnosed with AIS after thrombolysis between July 2016 and January 2019 were enrolled in this study. Five prespecified complications, including infections, brain oedema, deep vein thrombosis (DVT), haemorrhagic transformation (HT) and gastrointestinal bleeding, were recorded during hospitalisation.ResultsOf 388 patients, 143 (36.86%) presented with hyperglycaemia. Patients with hyperglycaemia were more likely to experience one or more complications than patients without hyperglycaemia. After adjustment for potential confounders, hyperglycaemia was associated with brain oedema (OR 2.39; 95% CI 1.08 to 5.30), HT (OR 2.16, 95% CI 1.06 to 4.41), symptomatic intracerebral haemorrhage (sICH) (OR 7.32, 95% CI 2.35 to 22.80) and gastrointestinal bleeding (OR 3.62; 95% CI 1.93 to 6.80), but was not linked to infections (OR 1.48, 95% CI 0.76 to 2.9) and DVT (OR 0.60, 95% CI 0.23 to 1.5). Additional adjustment for the complications in the clinical outcome analysis, done to assess these complications as an intermediate in the pathway from admission hyperglycaemia to clinical outcome, did not substantially change the model (all p for interaction >0.05).ConclusionHyperglycaemia is an independent predictor of complications following stroke after thrombolysis, especially for brain oedema, gastrointestinal bleeding, HT and sICH. Complications during hospitalisation did not modify the effect of hyperglycaemia on the poor outcome at 3 months in ischaemic stroke.

Intravenous thrombolysis with 0.9 mg/kg alteplase for acute ischaemic stroke: a network meta-analysis of treatment delay

ObjectivesThe aim of this study was to evaluate the effect of alteplase in intravenous thrombolysis of acute ischaemic stroke (AIS) regarding the different time windows of treatment (<3 hours, 3–4.5 hours, >4.5 hours).MethodsA systematic literature search was conducted from PubMed, Cochrane Library and Embase. 12 clinical randomised controlled trials with 3402 patients with AIS met the inclusion criteria. The primary, secondary and tertiary outcomes were modified Rankin Scale (mRS) scores 0–1, mortality at 90th day after treatment and symptomatic intracerebral haemorrhage within 36 hours, respectively. Network meta-analysis and conventional meta-analysis were carried out for calculating odds ratio (OR), the surface under cumulative ranking curve (SUCRA) and the probabilities of being the best.ResultsFor mRS, alteplase regardless of time delay was significantly more effective than placebo (OR 1.33–2.17). However, alteplase used within 3 hours after AIS occurrence (SUCRA=98.3%) was significantly more effective (OR=1.64) than that at 3–4.5 hours (SUCRA=43%) and showed the trend of priority (OR=1.47) compared with that beyond 4.5 hours (SUCRA=58%). For the mortality, compared with placebo (SUCRA=64.7%), alteplase within 3 hours was similar to that of 3–4.5 hours whereas alteplase beyond 4.5 hours (SUCRA=7.3%) showed the trend of significantly increasing 85% mortality. For the tertiary outcome, alteplase within 3 hours (SUCRA=19.0%) was comparable with placebo (SUCRA=99.9%) whereas alteplase beyond 3 hours significantly increased (OR 5.89–6.67) the symptomatic intracerebral haemorrhage.ConclusionsAlteplase within 3 hours should be recommended as the best treatment delay for its best efficacy among all the intervention and equivalent safety compared with placebo. Alteplase beyond 3 hours was less effective compared with that within 3 hours and increased the risk of mortality on 3 months as well as symptomatic intracerebral haemorrhage at 36 hours. More head-to-head clinical trials are needed to confirm those findings.

Endovascular therapy for anterior circulation large vessel occlusion in telestroke

Introduction Recent exploratory analysis suggested comparable outcomes among stroke patients undergoing endovascular therapy (EVT) for anterior circulation large vessel occlusion, whether selected via the telestroke network or admitted directly to an EVT-capable centre. We further studied the role of telemedicine in selection of ischaemic stroke patients potentially eligible for EVT. Methods We prospectively included consecutive ischaemic stroke patients with anterior circulation large vessel occlusion who underwent EVT at our neurovascular centre (January 2016 to March 2018). We compared safety and efficacy including symptomatic intracerebral haemorrhage (sICH), successful reperfusion (mTICI 2b/3), 90-day favourable outcome (mRS ≤ 2) and 90-day survival between patients transferred from telestroke hospitals and patients directly admitted. Results Of 280 potentially EVT-eligible patients, 72/129 (56%) telestroke and 91/151 (60%) direct admissions eventually underwent EVT (age 76 (66–82) years, median (interquartile range), 46% men, NIHSS score 17 (13–20)). Telestroke patients had larger pre-EVT infarct cores (ASPECTS: 7 (6–8) vs. 8 (7–9); p < 0.0001) and shorter door-to-groin puncture times (71 (56–84) vs. 101 (79–133) min; p < 0.0001) than directly admitted patients. sICH (2.8% vs. 1.1%; p = 0.58), successful reperfusion (81% vs. 77%; p = 0.56), 90-day favourable outcome (25% vs. 29%; p = 0.65) and 90-day survival (73% vs. 67%; p = 0.39) rates were comparable among telestroke and direct admissions. Discussion Our data underpins the important role of telemedicine in identifying acute ischaemic stroke patients lacking immediate access to EVT-capable stroke centres. Stroke patients selected via telemedicine and those directly admitted had comparable chances of favourable outcomes after EVT for large vessel occlusion.

Door to needle time and functional outcome for mild ischemic stroke over telestroke

Introduction Faster intravenous alteplase (tPA) administration from time of symptom onset is associated with better functional outcome. Lack of recognition of mild ischemic stroke (MIS) might result in delay in treatment with tPA. We hypothesise that patients with MIS have a longer door to needle (DTN) time when compared to patients with severe stroke symptoms. Methods Data on all patients who received tPA at spoke hospitals through the Medical University of South Carolina (MUSC) telestroke network were analysed. Collected data included baseline characteristics, stroke severity on presentation measured by the National Institute of Health Stroke Scale (NIHSS), the rate of symptomatic intracerebral haemorrhage, discharge location, and discharge functional outcome measured by the modified Rankin scale. Results and Discussion Of the 454 patients treated with tPA through the MUSC telestroke network in the period from January 2013 to April 2017, 98 (22%) had MIS defined as NIHSS ≤ 5 on presentation; the remaining 356 (78%) patients were found to have severe stroke defined as NIHSS > 5 on presentation. Patients presenting with MIS were found to have a delay in receiving intravenous tPA by ∼10 min ( p = 0.007) and approximately 15% of them had poor functional outcome at discharge. Patients with a MIS on presentation have significantly more prolonged DTN time. Nearly 15% of low severity strokes had poor outcome even after receiving tPA.

Outcomes following telestroke-assisted thrombolysis for stroke in Ontario, Canada

Introduction Since 2002, the Ontario Telestroke Program has provided hospitals in under-served regions of the province the opportunity to offer intravenous thrombolysis with tissue plasminogen activator (IV tPA) to eligible patients. The purpose of this study was to determine whether telestroke-assisted IV tPA patients had similar risks of 7- and 90-day mortality, symptomatic intracerebral haemorrhage (sICH), and poor functional outcome compared to patients who received IV tPA with on-site expertise. Methods Data from two audits of patients with acute ischaemic stroke hospitalized in Ontario, Canada in 2010 and 2012 were analysed. We modelled the risk of all-cause death within 7 and 90 days of receiving IV tPA using proportional hazards adjusting for hospital type, patient characteristics, and whether IV tPA was administered as part of a telestroke consultation. Outcomes of sICH and modified Rankin Scale ≥ 3 at discharge were modelled using generalized estimating equations adjusting for the same variables used in the mortality model. Results There was no difference in 7- or 90-day mortality among those who received IV tPA with telestroke ( n = 214) compared to those without ( n = 1885) (7-day adjusted hazard ratio (aHR) 1.29 (95% confidence interval (CI) 0.68, 2.44); 90-day aHR 1.01 (95% CI 0.67, 1.50)). Complications were similar between groups, with an adjusted odds ratio (aOR) for sICH of 0.71 (95% CI 0.29, 1.71) and an aOR of 0.75 (95% CI 0.46, 1.23) for poor functional ability at discharge. Discussion Patients receiving IV tPA supported by telestroke had similar outcomes to those managed with on-site expertise.

Abstract TMP23: Intravenous Thrombolysis in Unknown-onset Stroke

Background and Purpose: Unknown onset (UKO) stroke patients are at present excluded from thrombolytic therapy thrombolysis according to approval criteria and guideline recommendations. However, a number of them might benefit from the treatment. We aim to study the safety and efficacy of intravenous (IV) tissue plasminogen activator (tPA) in ischemic stroke patients with UKO of symptoms compared to those treated within 4.5 hours in a large cohort. Methods: Data were analyzed from 47,237 patients with acute ischemic stroke receiving IV-tPA in hospitals participating in the SITS International Stroke Thrombolysis Registry between 2010 and 2014. Two groups were defined: 1) patients with UKO, (n=502) and 2) patients treated within 4.5 hours of stroke onset, (n=44,875). Outcome measures were symptomatic intracerebral haemorrhage (SICH)-SITS, mortality at 3 months and functional independency as a score in the modified Rankin Scale (mRS) of 0-2 at 3 months. Results: Patients in UKO group were older (74 [65-82] vs. 72 [62-79] years, p<0.001), and had more severe stroke at baseline as measured by NIH Stroke Scale (12 [7-18] vs. 11 [6-17], p<0.001) than ≤4.5h. SICH-SITS occurred in 2.7% vs. 1.6% (p=0.052). At 3 months, mortality was higher (22%vs.16.9%, p=0.01) and functional independency was lower (46.8% vs. 56.2%, p<0.001) in the UKO group than ≤4.5h. In the multivariate analysis, these differences disappeared after adjustment baseline imbalances; SICH-SITS (OR0.98; 95% CI [0.43-2.21], p=0.962), mortality (OR0.88; 95% CI [0.64-1.20], p=0.435) and functional independency (OR 0.71; 95% CI [0.48-1.04], p=0.083). Conclusions: Our data suggest no excess risk of SICH in patients with UKO stroke treated with tPA and similar rate of functional independency and mortality than patients treated within 4.5 hours.