NEUROLOGIE

CENTRUM NEUROLOGIE

ARTIKELS

ABSTRACT 1

Be aware: COVID-19 the new stroke mimicker

Zuurbier SM, Verschelde HL, Vantyghem S, Vanacker P, et al. Acta Neurologica Belgica, 2021, 121(1), 309-310

ABSTRACT Er is geen abstract beschikbaar.

ABSTRACT 2

Detailed histological analysis of a thrombectomyresistant ischemic stroke thrombus: a case report

Staessens S, Francois O, Desender L, Vanacker P, et al. Thrombosis Journal, 2021, 19(11)

ABSTRACT Het abstract is na te lezen op p. 34

ABSTRACT 3

The impact of COVID-19 on acute stroke care in Belgium

Raymaekers V, Demeestere J, Bellante F, Vanacker P, et al. Acta neurologica Belgica, 121(5), 2021, 1251–1258

ABSTRACT A worldwide decline in stroke hospitalizations during the COVID-19 pandemic has been reported. Information on stroke care during the pandemic in Belgium is lacking. This study aims to analyze the impact of COVID-19 on acute stroke care in eight Belgian stroke centers.

This Belgian study is part of an international observational and retrospective study in 70 countries and 457 stroke centers. We compared volumes of COVID-19 and stroke hospitalizations, intravenous thrombolysis and endovascular treatment rates, acute treatment time intervals and functional outcome at 90 days during the first wave of the pandemic to two control intervals (March-May 2019 and December-February 2020). From March 2020 to May 2020, 860 stroke patients were hospitalized. In the same time period, 2850 COVID-19 patients were admitted, of which 37 (1.3%) were diagnosed with a stroke. Compared to the months prior to the pandemic and the same time epoch one year earlier, stroke hospitalizations were reduced (relative difference 15.9% [p = 0.03] and 14.5% [p = 0.05], respectively).

Despite a reduction in absolute volumes, there was no difference in the monthly proportion of thrombolysis or endovascular treatment provided to the overall stroke hospitalizations. Acute treatment time metrics did not change between COVID-19 pandemic and control time epochs. We found no difference in 90-day functional outcomes nor in mortality after stroke between patients admitted during the pandemic versus control periods.

We found a decline in the volume of stroke hospitalizations during the first wave of the COVID-19 pandemic in Belgium. Stroke care quality parameters remained unchanged.

ABSTRACT 4

The state of stroke services across the globe: report of world stroke organization-world health organization surveys

Owolabi MO, Thrift AG, Vanacker P, et al. International Journal of Stroke, 2021, 16(8), 889-901

ABSTRACT Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization-World Health Organization-Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries. Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019. Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p < 0.001). Acute stroke treatments were offered in ~60% of high-income countries compared to 26% of low-income countries (p = 0.009). Compared to high-income countries, LMICs provided less rehabilitation services including in-patient rehabilitation, home assessment, community rehabilitation, education, early hospital discharge program, and presence of rehabilitation protocol.

There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.

ABSTRACT 5

Global impact of COVID-19 on stroke care and IV thrombolysis

Nogueira RG, Abdelkader M, Vanacker P, et al. Neurology, 2021, 96(23), e2824-e2838

ABSTRACT To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissi.

The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

ABSTRACT 6

Characteristics of patients with atrial fibrillation prescribed edoxaban in Belgium and the Netherlands: insights from the ETNA-AF-Europe study

de Vries TAC, Hemels MEW, Cools F, Vanacker P, et al. Netherlands Heart Journal, 2021, 29(3), 158-167

ABSTRACT Studies on the use of non-vitamin K antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban.

With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), a large prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban: creatinine clearance 15-50 ml/min, weight ≤60 kg, and/or use of strong p-glycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC). Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age: 72.3 vs 73.9 years), and had lower CHA2DS2-VASc (mean: 2.8 vs 3.2) and HAS-BLED scores (mean: 2.4 vs 2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30 mg edoxaban (14.8%) than in OEC (25.4%). Overall, edoxaban was dosed according to label in 83.1% of patients. Yet, 30 mg edoxaban was prescribed in the absence of any dose reduction criteria in 36.9% of 30 mg users (5.5% of all patients) in BeNe compared with 35.5% (9.0% of all patients) in OEC.

There were several notable differences between BeNe and OEC regarding clinical characteristics and dosing practices in patients prescribed edoxaban, which are relevant for the local implementation of dose evaluation and optimisation.

ABSTRACT 7

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

Ntaios G, Huisman MV, Diener HC, Vanacker P, et al. Hellenic Journal of Cardiology, 2021, 62(2), 152-157

ABSTRACT 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 SAMeTT2R2 scores >2 than to patients with lower scores. 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 SAMe-TT2R2 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.

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 8

Sustained improvements in motor and non-motor symptoms in advanced parkinson’s disease patients treated with carbidopa levodopa enteral suspension in a ‘realworld’study: interim results of the multinational duoglobe study with at least 24 months follow-up

Aldred J, Standaert D, Kovacs N, Bourgeois P, et al. Neurology, 2021, 96 (15), 4584

ABSTRACT CLES has established benefit in reducing both motor and non-motor symptoms, but prospective long-term data on the effect of CLES on dyskinesia symptoms and associated effects on QoL and caregiver burden in a real-world setting are limited. Evaluate the effect of carbidopa levodopa enteral suspension (CLES) on motor and nonmotor symptoms in a multi-country observational study in advanced Parkinson’s disease (PD) patients treated with LCIG in routine clinical practice.

Design/Methods: DUOGLOBE is a prospective multinational observational study (including US sites) of CLES naïve patients treated as part of routine clinical practice with 3-years follow-up planned (NCT02611713). Assessments included “Off” time, Unified Dyskinesia Rating Scale (UDysRS), Non-Motor Symptoms Scale (NMSS), sleep symptoms (PD Sleep Scale-2, PDSS-2), Quality of Life (8-item PD questionnaire, PDQ-8), and Serious Adverse Events (SAEs). Interim outcomes from baseline up to month (M) 24 are presented.In this interim analysis, 196 patients were included (62% male, 78% ≥65 years old; 51% ≥10 years’ PD duration). Mean (SD) LCIG treatment duration was 711 (368) days with a median daily CLES infusion of 16.0 h/d. Significant improvements (mean change from baseline to M24) were observed in “Off” time (−3.7 h/d; 95% CI −4.3 to −3.1; p<.001), UDysRS total scores (−7.9; 95% CI −12.5 to −3.2; p=.001), NMSS total scores (−22.2; 95% CI −30.7 to −13.7; p<.001), PDSS-2 total score (−5.8; 95% CI −8.2 to −3.3; p<.001), and QoL (−5.8; 95% CI −10.0 to −1.5; p=.009).

Overall, 52% of patients experienced SAEs, 23% (n=45) of patients discontinued the study due to AEs as primary reason. This interim analysis shows sustained real-world long-term improvements with CLES in routine clinical practice on motor and non-motor symptoms in advanced PD patients. Safety was consistent with the established CLES.

ABSTRACT 9

Duoglobe: one-year outcomes in a real-world study of levodopa carbidopa intestinal gel for parkinson's disease

Standaert D, Aldred J, Anca-Herschkovitsch M, Bourgeois P, et al. Movement Disorders, 2021, 8(7), 1061-1074

ABSTRACT Levodopa-carbidopa intestinal gel (LCIG) is an established treatment for improving motor and some non-motor symptoms (NMS) in patients with advanced Parkinson's disease (PD). Prospective long-term data in routine clinical practice are limited. Assess LCIG effectiveness and safety in patients with advanced PD after 12months during real-world routine clinical practice.

Duodopa/Duopa in patients with advanced Parkinson's disease—a global observational study evaluating long-term effectiveness (DUOGLOBE) (NCT02611713) is an ongoing, prospective, multinational, observational study of LCIGnaïve patients treated as part of routine clinical practice; 3years of follow-up are planned. The primary outcome is the change in patient-reported off time.

Other assessments include the Unified Dyskinesia Rating Scale (UDysRS), Non-Motor Symptoms Scale (NMSS), Parkinson's Disease Sleep scale (PDSS-2), Epworth Sleepiness Scale (ESS), health-related quality of life (HR-QoL), caregiver burden, and serious adverse events (SAEs). Outcomes from baseline to month (M) 12 are presented. In this 12-month follow-up, patients (N = 195) had baseline characteristics similar to other LCIG studies.

Significant improvements (mean change to M12) were observed in off time (−3.9±3.6hr/day, P<0.001), dyskinesia assessed using the UDysRS (−9.6±22.5, P<0.001), NMSS (−23.1±41.4, P<0.001), sleep and sleepiness symptoms on the PDSS-2 (−6.5±12.2, P<0.001) and ESS (−1.0±5.7, P<0.05), HR-QoL (−9.0±21.6, P<0.001), and caregiver burden (−1.9±6.7, P = 0.008). Overall, 40.5% (n = 79) of patients experienced SAEs; fall (n = 6; 3.1%) and urinary tract infection (n = 6; 3.1%) were SAEs reported in ≥3% of patients.

These 12-month outcome data show sustained, long-term improvements and support the real-world effectiveness of LCIG in patients with advanced PD. Safety was consistent with previous studies. ABSTRACT 10

Efficacy and safety of ticagrelor and aspirin in patients with moderate ischemic stroke: an exploratory analysis of the thales randomized clinical trial

Wang Y, Pan Y, Li H, Vanacker P, et al. JAMA Neurology, 2021, 78(9), 1091-1098

ABSTRACT Prior trials of dual antiplatelet therapy excluded patients with moderate ischemic stroke. These patients were included in the Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial, but results have not been reported separately, raising concerns about safety and efficacy in this subgroup. To evaluate the efficacy and safety of ticagrelor plus aspirin in patients with moderate ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 4 to 5). The THALES trial was a randomized trial conducted at 414 hospitals in 28 countries in January 2018 and December 2019.

This exploratory analysis compared patients with moderate stroke (baseline NIHSS score of 4 to 5) with patients with less severe stroke (NIHSS score of 0 to 3). A total of 9983 patients with stroke were included in the present analysis, after excluding 2 patients with NIHSS scores greater than 5 and 1031 patients with transient ischemic attack. Data were analyzed from March to April 2021. Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily on days 2 to 30) or placebo within 24 hours after symptom onset. All patients received aspirin, 300 to 325 mg, on day 1 followed by aspirin, 75 to 100 mg, daily on days 2 to 30. Patients were observed for 30 additional days.

The primary outcome was time to stroke or death within 30 days. The primary safety outcome was time to severe bleeding.

In total, 3312 patients presented with moderate stroke and 6671 presented with less severe stroke. Of those in the moderate stroke group, 1293 (39.0%) were female, and the mean (SD) age was 64.5 (10.8) years; of those in the less severe stroke group, 2518 (37.7%) were female, and the mean (SD) age was 64.8 (11.2) years. The observed primary outcome event rate in patients with moderate stroke was 7.6% (129 of 1671) for those in the ticagrelor group and 9.1% (150 of 1641) for those in the placebo group (hazard ratio, 0.84; 95% CI, 0.66-1.06); the primary outcome event rate in patients with less severe stroke was 4.7% (158 of

3359) for those in the ticagrelor group and 5.7% (190 of 3312) for those in the placebo group (hazard ratio, 0.82; 95% CI, 0.66-1.01) (P for interaction = .88). Severe bleeding occurred in 8 patients (0.5%) in the ticagrelor group and in 4 patients (0.2%) in the placebo group in those with moderate stroke compared with 16 patients (0.5%) and 3 patients (0.1%), respectively, with less severe stroke (P for interaction = .26).

In this study, patients with a moderate ischemic stroke had consistent benefit from ticagrelor plus aspirin vs aspirin alone compared with patients with less severe ischemic stroke, with no further increase in the risk of intracranial bleeding or other severe bleeding event.