NEUROLOGIE

CENTRUM NEUROLOGIE

ARTIKELS

ABSTRACT 1

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

Paciaroni M, Agnelli G, Gastuzzi M, Vanacker P, et al. European Stroke Journal, 2020, 5(4), 374-383

INTRODUCTION The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing.

MATERIALS/METHODS Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke.

RESULTS A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80).

CONCLUSION Our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. ABSTRACT 2

Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance.

Staessens S, Denorme F, François O, Vanacker P, et al. Haematologica, 2020, 105(2), 498-507

Zie Medische beeldvorming pagina 34.

ABSTRACT 3

Quantitative signal intensity in fluid-attenuated inversion recovery and treatment effect in the WAKE-UP trial.

Cheng B, Boutitie F, Nickel A, Vanacker P, et al. Stroke, 2020, 51(1), 209-215

INTRODUCTION Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase.

MATERIALS/METHODS FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume.

RESULTS FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKEUP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI.

CONCLUSION In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.

ABSTRACT 4

Stroke coach: a pilot study of a personal digital coaching program for patients after ischemic stroke.

Kamoen O, Maqueda V, Yperzeele L, Vanacker P, et al. Acta Neurologica Belgica, 2020, 120(1), 91-97

INTRODUCTION Despite recent advances in acute stroke care, the risk of recurrent stroke remains high. On behalf of the Belgian Stroke Council (BSC), a nurse-led self-management program was developed, using a personal coach and digital platform with the aim of improving cardiovascular risk factor control in patients after ischemic stroke.

MATERIALS/METHODS The program was implemented in four Belgian hospitals. The stroke coach provided one educational session during hospitalization. After discharge, the patient received tips and tricks concerning a healthy lifestyle through the customized platform. The stroke coach set up video appointments through the platform at regular intervals. Primary endpoint of our study was the change in SCORE (Systematic COronary Risk Evaluation: High and Low cardiovascular Risk Charts) risk at baseline and 6 months compared with a historical control group who received standard care. RESULTS A total of 147 patients were included for a follow-up period of 6 months. The mean SCORE in the intervention group showed a statistically significant reduction of 3.2 (p < 0.001) at 6 months. However, comparison between control and intervention groups was non-significant (p = 0.55). Secondary endpoints are promising with a medication adherence of 96%. Reported quality of life also improved (p < 0.001). No significant improvement in the modified Rankin scale (mRS) was observed (p = 0.720). Five percent of patients suffered a recurrent stroke.

CONCLUSION Our project consisting of a coached lifestyle intervention and digital platform shows promise in improving stroke recurrence rates, therapeutic adherence and quality of life in a Belgian healthcare setting.

ABSTRACT 5

Eligibility for late endovascular treatment using DAWN, DEFUSE-3, and more liberal selection criteria in a stroke center.

Nannoni S, Strambo D, Sirimarco G, Vanacker P, et al. Journal of Neurointerventional Surgery, 2020, 12(9), 842-847

INTRODUCTION The real-life application of DAWN and DEFUSE-3 trials has been poorly investigated. We aimed to identify the proportion of patients with acute ischemic stroke (AIS) eligible for late endovascular treatment (EVT) in our stroke center based on trial and more liberal selection criteria.

MATERIALS/METHODS All consecutive patients in our stroke registry (2003-2017) admitted within 5-23 hours of last proof of good health were selected if they had complete clinical and radiological datasets. We calculated the proportion of patients eligible for late EVT according to trial (DAWN and/or DEFUSE-3) and more liberal clinical/imaging mismatch criteria (including lower admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score for core estimation).

RESULTS Of 1705 patients with AIS admitted to our comprehensive stroke center in the late time window, we identified 925 patients with complete clinical and radiological data. Among them, the proportions of late EVT eligibility were

2.5% (n=23) with DAWN, 5.1% (n=47) with DEFUSE-3, and 11.1% (n=103) with more liberal criteria. Considering late-arriving patients with large vessel occlusion (n=221), the percentages of eligible patients were 10.4%, 21.3%, and 46.6%, respectively. A favorable outcome was observed at comparable rates in treated patients selected by trial or liberal criteria (67% vs 58%, p=0.49).

CONCLUSION In a long-term stroke registry, the proportion of late EVT eligibility varied greatly according to selection criteria and referral pattern. Among late-arriving patients referred to our comprehensive stroke center, we found 5.6% eligible according to trial (DAWN/DEFUSE-3) and 11.1% according to liberal criteria. These data indicate that late EVT could be offered to a larger population of patients if more liberal criteria are applied.

ABSTRACT 6

Safety of anticoagulation in patients treated with urgent reperfusion for ischemic stroke related to atrial fibrillation.

Giustozzi M, Acciarresi M, Agnelli G, Vanacker P, et al. Stroke, 2020, 51(8), 2347-2354

INTRODUCTION The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention.

MATERIALS/METHODS We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features.

RESULTS A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]).

CONCLUSION Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.

ABSTRACT 7

Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA.

Johnston C, Amarenco P, Denison H, Vanacker P, et al. The New England Journal of Medicine, 2020, 383, 207-217

INTRODUCTION Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.

MATERIALS/METHODS We conducted a randomized, placebo-controlled, doubleblind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis

or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.

RESULTS A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001).

CONCLUSION Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429).

ABSTRACT 8

Multicenter, retrospective analysis of endovascular treatment for acute ischemic stroke in nonagenarians.

Jannsen H, Nannoni S, François O, Vanacker P, et al.

Zie Medische beeldvorming pagina 42. ABSTRACT 9

Ticagrelor added to aspirin in acute ischemic stroke or transient ischemic attack in prevention of disabling stroke: a randomized clinical trial.

Amarenco P, Densison H, Evans S, Vanacker P, et al. JAMA Neurology, 2020, 78(2), 1-9

INTRODUCTION Reduction of subsequent disabling stroke is the main goal of preventive treatment in the acute setting after transient ischemic attack (TIA) or minor ischemic stroke.

MATERIALS/METHODS The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) was a randomized clinical trial conducted between January 22, 2018, and December 13, 2019, with a 30-day follow-up, at 414 hospitals in 28 countries. The trial included 11 016 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk TIA, including 10 803 with modified Rankin Scale score (mRS) recorded at 30 days. Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo within 24 hours of symptom onset. All patients received aspirin, 300 to 325 mg on day 1 followed by 75 to 100 mg daily for days 2 to 30.

RESULTS Among participants with 30-day mRS greater than 1, mean age was 68.1 years, 1098 were female (42.6%), and 2670 had an ischemic stroke (95.8%) as a qualifying event. Among 11 016 patients, a primary end point with mRS greater than 1 at 30 days occurred in 221 of 5511 patients (4.0%) randomized to ticagrelor and in 260 of 5478 patients (4.7%) randomized to placebo (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99, P = .04). A primary end point with mRS 0 or 1 at 30 days occurred in 70 of 5511 patients (1.3%) and 87 of 5478 patients (1.6%) (HR, 0.79; 95% CI, 0.57-1.08; P = .14). The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; 95% CI, 0.65-0.91; P = .002). Factors associated with disability were baseline National Institutes of Health Stroke Scale score 4 to 5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure, while treatment with ticagrelor was associated with less disability.

CONCLUSION In patients with TIA and minor ischemic stroke, ticagrelor added to aspirin was superior to aspirin alone in preventing

disabling stroke or death at 30 days and reduced the total burden of disability owing to ischemic stroke recurrence.

ABSTRACT 10

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Thomalla G, Boutitie F, Ma H, Vanacker P, et al. Lancet, 2020, 396(10262), 1574-1584

INTRODUCTION Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

MATERIALS/METHODS We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

RESULTS Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·034·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

CONCLUSION In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

ABSTRACT 11

Ticagrelor added to aspirin in acute nonsevere ischemic stroke or transient ischemic attack of atherosclerotic origin.

Amarenco P, Denison H, Evans S, Vanacker P, et al. Stroke, 2020, 51(12), 3504-3513

INTRODUCTION Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events.

MATERIALS/METHODS In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo added to aspirin (300-325 mg on day 1 followed by 75-100 mg daily for days 2-30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days.

RESULTS Of 11,016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56-0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19-171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74-1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04-16.9], P=0.001).

CONCLUSION In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19-171).

ABSTRACT 12

Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial.

Frey B, Boutitie F, Cheng B, Vanacker P, et al. Neurological Research and Practice, 2020, 2, 40

INTRODUCTION One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial.

MATERIALS/METHODS WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0-1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase.

RESULTS Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p < 0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%, p = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome (p = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047-4.236).

CONCLUSION Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.

ABSTRACT 13

Anticoagulant selection in relation to the SAMe-TT 2 R 2 score in patients with atrial fibrillation: the GLORIA-AF registry.

Ntaios G, Huisman M, Diener H, Vanacker P, et al. Hellenic Journal of Cardiology, 2020, 15, DOI: 10.1016/j. hjc.2020.11.009

INTRODUCTION The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a

target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores.

MATERIALS/METHODS We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMeTT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2.

RESULTS The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial.

ABSTRACT 14

Improvements in dyskinesia with levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients in a "real-world" study: interim results of the multinational DUOGLOBE study with up to 24 months follow-up.

Aldred J, Kovacs N, Pontieri F, Bourgeois P, et al. Neurology, 2020, 94 (15 supplement)

INTRODUCTION Evaluate effect of levodopa-carbidopa intestinal gel (LCIG) on dyskinesia symptoms, quality of life (QoL) and caregiver burden in advanced Parkinson’s disease (aPD) patients treated with LCIG in routine clinical practice.

BACKGROUND LCIG has established benefit in reducing “Off” time, but prospective long-term data on the effect of LCIG on dyskinesia symptoms and associated effects on QoL and caregiver burden in a real-world setting are limited.

MATERIALS/METHODS DUOGLOBE is a multinational observational study (including US sites) of LCIG naïve patients treated during routine clinical practice with 3-years follow-up planned (NCT02611713). This is the first multinational LCIG study using the Unified Dyskinesia Rating Scale (UDysRS). Other assessments included the UPDRS Part IV, “Off” time, Non-Motor Symptoms Scale (NMSS), QoL (8-item PD questionnaire [PDQ-8]), caregiver burden (MCSI), and Serious Adverse Events (SAEs). Interim outcomes from baseline to month (M) 24 are presented.

RESULTS In this interim analysis, 196 patients were included (62% male, 78% ≥65 years old; 51% ≥10 years’ PD duration. Median daily duration of LCIG infusion was 16.0 h/d LCIG through M24, with up to 9% of patients on 24h LCIG infusion. Significant improvements (mean change from baseline to M24) were observed in “Off” time (−3.6 h/d) and NMSS total scores (−27.0). LCIG treatment significantly improved dyskinesia symptoms and signs assessed by the UDysRS and UPDRS Part IV items 33 and 34 through M18. QoL and caregiver burden were improved through M18. Overall, 41% of patients experienced SAEs; 31% (n=60) discontinued participation in DUOGLOBE with 13 patients continuing LCIG outside the study.

CONCLUSION This interim analysis shows sustained improvements of dyskinesia symptoms and signs, measured using the UDysRS, with LCIG in routine clinical practice and supports real-world effectiveness of LCIG on “Off” time, NMS, QoL, and caregiver burden in aPD patients. Safety was consistent with the established LCIG profile.

ABSTRACT 15

Application of the '5-2-1' screening criteria in advanced Parkinson's disease: interim analysis of DUOGLOBEaldres.

Aldred J, Anca-Herschkovitsch M, Bourgeois P, et al. Neurodegenerative Disease Management, 2020, 10(5), 309-323

OBJECTIVE A Delphi expert consensus panel proposed that fulfilling >1 of the '5-2-1' criteria suggests advanced Parkinson's disease (PD).

MATERIALS/METHODS DUOdopa/Duopa in Patients weth Advanced PD - a Global OBservational Sudy Evaluating >Long-Term Effectiveness (DUOGLOBE) - is a single-arm, postmarketing, observational, long-term effectiveness levodopa-carbidopa intestinal gel (LCIG) for advance PD.

RESULTS This 6-month interim analysis(n= 139) affirms tha most (98%) enrolled patients fulfill > of the 5-2-1 criteria. These patients responded favorably to LCIG treatment. Safety was consistent with other LCIG studies.

CONCLUSION In advanced PD patients, the 5-2-1 criteria generally aligns with clinician assessment. Clinical Trial Resgistration: NCT02611713 ( ClinicalTrials.gov).

PRESENTATIES

ABSTRACT 16

Correlation between dyskinesia and quality of life at baseline and after 12 months of treatment with LCIG in patients with advanced Parkinson’s disease.

Aldred J, Pontieri F, Bergmann L, Bourgeois P, et al. International Parkinson and Movement Disorder Society, Virtual Congress, 2020

INTRODUCTION To provide optimal treatment regimens for patients in advanced stages of PD, it is important to understand how changes in dyskinesia affect patients’ quality of life.

OBJECTIVE Evaluate the correlation between dyskinesia and quality of life (QoL) at baseline and after 12 months of treatment with levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson’s disease (PD).

MATERIALS/METHODS DUOdopa/Duopa in Patients with Advanced Parkinson’s Disease—a GLobal OBservational Study Evaluating Long-Term Effectiveness (DUOGLOBE)—is an ongoing multi-country, single-arm, post-marketing observational study assessing the long-term effectiveness of LCIG in patients with advanced PD (NCT02611713). Assessments included the Unified Dyskinesia Rating Scale (UDysRS) and Parkinson’s Disease Questionnaire (PDQ-8) prior to and at 12 months LCIG therapy. Patients who were followed up for 12 months and completed all 4 assessments were included in this post hoc analysis of an interim dataset.

RESULTS For this dataset, the baseline UDysRS score was 33.7 ± 21.1 points (n = 152), and the baseline PDQ-8 score was 45.1 ± 18.1 points (n = 171) with a Pearson correlation coefficient between the 2 measures of 0.2732 (P < .001), indicating a weak, yet significant correlation. After 12 months of receiving LCIG treatment, patients’ UDysRS scores reduced by an average of 9.6 ± 22.5 points (n = 117) and PDQ-8 scores reduced by 9.0 ± 21.6 points (n = 135) with a Pearson correlation coefficient of 0.2345, indicating a significant positive correlation between the improvements (P = .011).

CONCLUSION In this cohort of patients with advanced PD, UDysRS and PDQ-8 scores were significantly correlated at baseline, suggesting that dyskinesia negatively impacts patients’ QoL. After 12 months of LCIG treatment, improvement in QoL was positively correlated with improvement of dyskinesia.

ABSTRACT 17

Detailed histological analysis of ischemic stroke thrombi reveals a platelet-dominant thrombus composition in patients with cardioembolic etiology.

Staessens S, François O, Desender L, Dewaele T, Vanacker P, et al. November 2020, BSTH congress, Brussel - België

ABSTRACT 18

Occurrence of ischemic stroke in patients treated with NOAC: a neglected population group.

Vanacker P, Simons S, Verhaeghe A, Geebels A, Meeus G November 2020, ESO-WSO Conference 2020, Wenen - Oostenrijk

ABSTRACT 19

Concordance between guidelines on perioperative management of NOACS and ITS implementation: preventable cause of ischemic stroke.

Vanacker P, Simons S, Verhaeghe A, Geebels A, Meeus G November 2020, ESO-WSO Conference 2020, Wenen - Oostenrijk

ABSTRACT 20

Intravenous thrombolysis in acute spinal cord ischaemia syndrome: a retrospective analysis of registry data.

Rosner J, Vanacker P, Heldner M, et al. November 2020, ESO-WSO 2020, Wenen - Oostenrijk

ABSTRACT 21

Histological analysis of a thrombectomy-resistant ischemic stroke thrombus: a case report.

Staessens S, François O, Dewaele T, Vanacker P, Andersson T, et al. November 2020, ESO-WSO Conference 2020, Wenen - Oostenrijk

ABSTRACT 22

DIGITAL AF: impact of smartphone-based atrial fibrillation screening in the general population for primary stroke prevention.

Proesmans T, Vanacker P, et al. February 2020, International Stroke Conference 2020, Los Angeles - USA (Published in Stroke 2020 Suppl. 1)

INTRODUCTION Opportunistic AF screening for primary stroke prevention is recommended in patients aged above 65 based on stroke risk models. Logistics hamper uniform screening with 12-lead ECG. Novel technologies, e.g. photoplethysmography-based (PPG) apps, may overcome this, providing readily available screening at low cost. We assessed the feasibility of smartphone screening and the impact on subsequent clinical care.

MATERIALS/METHODS A media campaign educated on AF, recruited subjects, and gave access to a PPG-based app to assess the heart rhythm. Subjects were instructed to measure twice daily for 8 days. An algorithm classified the traces as regular, possible AF, non-AF irregularity, or insufficient quality. PPGs of possible irregularities or AF were reviewed by medical technicians and cardiologists. If AF was confirmed, a physician visit was recommended. Questionnaires collected data on clinical care.

RESULTS In 2 weeks, 62,821 subjects onboarded, resulting in 588,336 60-second PPG traces. The screened population was 49±15 years, 58% was male. In 791 subjects (1.3%), AF was diagnosed by the algorithm and offline confirmed. This group was older (62±11 years, p<0.001), more frequently male (76%, p<0.001) and had a higher CHA2DS2-VASc score (1.00±1.00 vs 2.00±2.00, p<0.001). The proportion with CHA2DS2-VASc ≥ 1 is 81.3% for the AF cohort vs 64.3% in non-AF cohort. The AF yield increased from 0.52% with 1 recording to 1.84% after 8 days. Of the AF patients, 335 (42%) were known, 373 (47%) newly identified, and 83 (11%) did not give this information. A physician was consulted by 138 (17%) newly identified patients, findings were confirmed in 71 (9%), 46 (6%) received antithrombotic therapy.

CONCLUSION This digital screening, targeting the general population and using only smartphones, demonstrates the feasibility to collect data in a scalable and low-cost way. Next to single timepoint ECG, twice-daily PPG may detect a significant number of asymptomatic AF patients.