Florey Department of Neuroscience and Mental Health - Research Publications

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    Small vessel disease and clinical outcomes after IV rt-PA treatment
    Arba, F ; Inzitari, D ; Ali, M ; Warach, SJ ; Luby, M ; Lees, KR (WILEY, 2017-07)
    INTRODUCTION: Cerebral small vessel disease (SVD) contributes to dementia and disability in the elderly, and may negatively affect stroke outcomes. We aimed to evaluate to what extent single features and global burden of SVD detected with magnetic resonance (MR) are associated with worse outcomes in patients with ischaemic stroke treated with intravenous thrombolysis. METHODS: We accessed anonymized data and MR images from the Stroke Imaging Repository (STIR) and the Virtual International Stroke Trials Archive (VISTA) Imaging. We described SVD features using validated scales and quantified the global burden of SVD with a combined score. Our mainoutcome was the modified Rankin Scale (mRS) at 90 days after stroke. We used logistic regression and ordinal regression models (adjusted for age, sex, stroke severity, onset to treatment time) to examine the associations between each SVD feature, SVD global burden and clinical outcomes. RESULTS: A total of 259 patients had MR scans available at baseline (mean age±SD=68.7±15.5 years; 131 [49%] males). After adjustment for confounders, severe white matter changes were associated with disability (OR=5.14; 95%CI=2.30-11.48), functional dependency (OR=4.38; 95%CI=2.10-9.13) and worse outcomes in ordinal analysis (OR=2.71; 95%CI=1.25-5.85). SVD score was associated with disability (OR=1.66; 95%CI=1.03-2.66) and functional dependency (OR=1.47; 95%CI=1.00-2.45). Lacunes, enlarged perivascular spaces and brain atrophy showed no association with clinical outcomes. CONCLUSION: Our results suggest that SVD negatively affects stroke outcomes after intravenous thrombolysis. Although white matter changes seem to be the major driver in relation to worse outcomes, global estimation of SVD is feasible and may provide helpful information.
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    Prognostic significance of pulsatile tinnitus in cervical artery dissection
    Kellert, L ; Kloss, M ; Pezzini, A ; Debette, S ; Leys, D ; Caso, V ; Thijs, VN ; Bersano, A ; Touze, E ; Tatlisumak, T ; Traenka, C ; Lyrer, PA ; Engelter, ST ; Metso, TM ; Grond-Ginsbach, C (WILEY, 2016-07)
    BACKGROUND AND PURPOSE: Our aim was to investigate whether pulsatile tinnitus (PT) in cervical artery dissection (CeAD) has prognostic significance. METHODS: All CeAD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale (NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0-1. RESULTS: Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.22-12.87] adjusted to significant outcome predictors NIHSS on admission (OR 0.82, 95% CI 0.79-0.86), Horner syndrome (OR 1.95, 95% CI 1.16-3.29) and vessel occlusion (OR 0.62, 95% CI 0.40-0.94) and to non-significant predictors age, sex, pain and location of CeAD. CONCLUSION: The presence of PT in CeAD is associated with a benign clinical course and predicts a favourable outcome.
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    Frequency and predictors of acute ischaemic lesions on brain magnetic resonance imaging in young patients with a clinical diagnosis of transient ischaemic attack
    Tanislav, C ; Grittner, U ; Fazekas, F ; Thijs, V ; Tatlisumak, T ; Huber, R ; von Sarnowski, B ; Putaala, J ; Schmidt, R ; Kropp, P ; Norrving, B ; Martus, P ; Gramsch, C ; Giese, AK ; Rolfs, A ; Enzinger, C (WILEY, 2016-07)
    BACKGROUND AND PURPOSE: Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. METHODS: The sifap1 study prospectively recruited a multinational European cohort (n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. RESULTS: The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas (n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27-2.91], dysarthria (OR 2.17, 95% CI 1.38-3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42-4.15; OR 2.41, 95% CI 1.02-5.69, respectively). CONCLUSIONS: In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA.
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    Language processing in bilingual aphasia: a new insight into the problem
    Khachatryan, E ; Vanhoof, G ; Beyens, H ; Goeleven, A ; Thijs, V ; Van Hulle, MM (WILEY, 2016)
    There is increasing evidence that a bilingual person should not be considered as two monolinguals in a single body, a view that has gradually been adopted in the diagnosis and treatment of bilingual aphasia. However, its investigation is complicated due to the large variety in possible language combinations, pre- and postmorbid language proficiencies, and age of second language acquisition. Furthermore, the tests and tasks used to assess linguistic capabilities differ in almost every study, hindering a direct comparison of their outcomes. Behavioral, electrophysiological, and neuroimaging data from healthy population show that the processing of second language domains (semantics, syntax, morphology) depends on factors such as age and method of acquisition, proficiency level and environment in which the second language was acquired. A number of single and multiple case reports that rely on behavioral testing of bilingual aphasics replicate these results. Additionally, they show that the patient's performance depends on the size and location of the lesion, as well as language typology and morphological characteristics. Furthermore, the impairment and recovery patterns and recovery generalization from treated to untreated language depend on the lexical and orthographic distances between the two languages. For healthy bilinguals, language processing is usually studied in comparison to monolinguals. We advocate that a good starting point for identifying patterns specific for bilingual aphasia is to compare patient studies of bilinguals and monolinguals.
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    Outcomes of endovascular thrombectomy with and without bridging thrombolysis for acute large vessel occlusion ischaemic stroke
    Maingard, J ; Shvarts, Y ; Motyer, R ; Thijs, V ; Brennan, P ; O'Hare, A ; Looby, S ; Thornton, J ; Hirsch, JA ; Barras, CD ; Chandra, R ; Brooks, M ; Asadi, H ; Kok, HK (WILEY, 2019-03)
    BACKGROUND: Endovascular thrombectomy (EVT) for management of large vessel occlusion (LVO) acute ischaemic stroke is now current best practice. AIM: To determine if bridging intravenous (i.v.) alteplase therapy confers any clinical benefit. METHODS: A retrospective study of patients treated with EVT for LVO was performed. Outcomes were compared between patients receiving thrombolysis and EVT with EVT alone. Primary end-points were reperfusion rate, 90-day functional outcome and mortality using the modified Rankin Scale (mRS) and symptomatic intracranial haemorrhage (sICH). RESULTS: A total of 355 patients who underwent EVT was included: 210 with thrombolysis (59%) and 145 without (41%). The reperfusion rate was higher in the group receiving i.v. tissue plasminogen activator (tPA) (unadjusted odds ratio (OR) 2.2, 95% confidence interval (CI): 1.29-3.73, P = 0.004), although this effect was attenuated when all variables were considered (adjusted OR (AOR) 1.22, 95% CI: 0.60-2.5, P = 0.580). The percentage achieving functional independence (mRS 0-2) at 90 days was higher in patients who received bridging i.v. tPA (AOR 2.17, 95% CI: 1.06-4.44, P = 0.033). There was no significant difference in major complications, including sICH (AOR 1.4, 95% CI: 0.51-3.83, P = 0.512). There was lower 90-day mortality in the bridging i.v. tPA group (AOR 0.79, 95% CI: 0.36-1.74, P = 0.551). Fewer thrombectomy passes (2 versus 3, P = 0.012) were required to achieve successful reperfusion in the i.v. tPA group. Successful reperfusion (modified thrombolysis in cerebral infarction ≥2b) was the strongest predictor for 90-day functional independence (AOR 10.4, 95% CI:3.6-29.7, P < 0.001). CONCLUSION: Our study supports the current practice of administering i.v. alteplase before endovascular therapy.
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    Carotid artery stenting: Current state of evidence and future directions
    Lamanna, A ; Maingard, J ; Barras, CD ; Kok, HK ; Handelman, G ; Chandra, RV ; Thijs, V ; Brooks, DM ; Asadi, H (WILEY, 2019-04)
    Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for carotid artery stenosis. Several randomized controlled trials (RCTs) have compared CEA to CAS in the treatment of carotid artery stenosis. These studies have suggested that CAS is more strongly associated with periprocedural stroke; however, CEA is more strongly associated with myocardial infarction. Published long-term outcomes report that CAS and CEA are similar. A reduction in complications associated with CAS has also been demonstrated over time. The symptomatic status of the patient and history of previous CEA or cervical radiotherapy are significant factors when deciding between CEA or CAS. Numerous carotid artery stents are available, varying in material, shape and design but with minimal evidence comparing stent types. The role of cerebral protection devices is unclear. Dual antiplatelet therapy is typically prescribed to prevent in-stent thrombosis, and however, evidence comparing periprocedural and postprocedural antiplatelet therapy is scarce, resulting in inconsistent guidelines. Several RCTs are underway that will aim to clarify some of these uncertainties. In this review, we summarize the development of varying techniques of CAS and studies comparing CAS to CEA as treatment options for carotid artery stenosis.
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    Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis
    Ekker, MS ; Jacob, MA ; van Dongen, MME ; Aarnio, K ; Annamalai, AK ; Arauz, A ; Arnold, M ; Barboza, MA ; Bolognese, M ; Brouns, R ; Chuluun, B ; Chuluunbaatar, E ; Dagvajantsan, B ; Debette, S ; Don, A ; Enzinger, C ; Ekizoglu, E ; Fandler-Hoefler, S ; Fazekas, F ; Fromm, A ; Gattringer, T ; Gulli, G ; Hoffmann, M ; Hora, TF ; Jern, C ; Jood, K ; Kamouchi, M ; Kim, YS ; Kitazono, T ; Kittner, SJ ; Kleinig, TJ ; Klijn, CJM ; Korv, J ; Lee, T-H ; Leys, D ; Maaijwee, NAM ; Martinez-Majander, N ; Marto, JP ; Mehndiratta, MM ; Mifsud, V ; Montanaro, VV ; Owolabi, MO ; Patel, VB ; Phillips, MC ; Piechowski-Iozwiak, B ; Pikula, A ; Luis Ruiz-Sandoval, J ; Sarnowski, B ; Schreuder, FHBM ; Swartz, RH ; Tan, KS ; Tanne, D ; Tatlisumak, T ; Thijs, V ; Tuladhar, AM ; Viana-Baptista, M ; Vibo, R ; Wu, TY ; Yesilot, N ; Waje-Andreassen, U ; Pezzini, A ; Putaala, J ; de Leeuw, F-E (BMJ PUBLISHING GROUP, 2019-11)
    INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.
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    Contact Aspiration versus Stent-Retriever Thrombectomy for Distal Middle Cerebral Artery Occlusions in Acute Ischemic Stroke: Meta-Analysis.
    Phan, K ; Maingard, J ; Kok, HK ; Dmytriw, AA ; Goyal, S ; Chandra, R ; Brooks, DM ; Thijs, V ; Asadi, H (Korean Society of Interventional Neuroradiology, 2018-09)
    PURPOSE: The evidence for endovascular therapy and choice of technique in distal middle cerebral artery (MCA) M2 segment occlusions in acute ischemic stroke remains controversial. We aimed to conduct a systematic review and meta-analysis primarily comparing reperfusion rates of stent-retrieval versus contact aspiration for M2 occlusions. MATERIALS AND METHODS: Study selection included cohorts of patients with distal MCA occlusions in acute ischemic strokes treated with an endovascular approach including stent-retrieval or contact aspiration. Twelve studies were selected for meta-analysis for a total of 835 cases. Meta-analysis by proportions was conducted on parameters including baseline and procedural characteristics, thrombolysis in cerebral infarction (TICI) 2b-3 outcomes, and 90-day modified Rankin scale (mRS) outcomes. RESULTS: Hypertension and hyperlipidemia were more prevalent in stent-retriever patients. Pooled baseline National Institute of Health Stroke Scale scores and Alberta Stroke Program Early Computed Tomography Score imaging scores were similar. Pooled time onset of symptoms to door arrival was higher for the stent-retrieval group (154 vs. 97.4 minutes, P=0.01), as was time to groin puncture (259.9 vs. 156.2 minutes, P=0.02), but there was no difference in procedure time. The TICI 2b-3 recanalization rate was similar (80.5% vs. 86.8%, P=0.168). The frequency of mRS 0-2 at 90-day was also similar (74.5% vs. 59.9%, P=0.120), and an excellent mRS 0-1 was lower for stent-retrievers (39.9% vs. 65.6%, P=0.003). A significant negative correlation was found between onset to groin puncture time and the proportion of patients with a good mRS (r=-0.71, P=0.048). CONCLUSION: Both endovascular techniques achieved recanalization rates greater than 80% and 90-day outcomes of minimal disability with similar complication rates. The literature is skewed by aspiration cases being performed sooner after onset of stroke compared to stent-retriever cases.
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    Electrocardiographic RR Interval Dynamic Analysis to Identify Acute Stroke Patients at High Risk for Atrial Fibrillation Episodes During Stroke Unit Admission
    Adami, A ; Gentile, C ; Hepp, T ; Molon, G ; Gigli, GL ; Valente, M ; Thijs, V (SPRINGER, 2019-06)
    Patients at short-term risk of paroxysmal atrial fibrillation (PAF) often exhibit increased RR interval variability during sinus rhythm. We studied if RR dynamic analysis, applied in the first hours after stroke unit (SU) admission, identified acute ischemic stroke patients at higher risk for subsequent PAF episodes detected within the SU hospitalization. Acute ischemic stroke patients underwent continuous cardiac monitoring (CCM) using standard bedside monitors immediately after SU admission. The CCM tracks from the first 48 h were analyzed using a telemedicine service (SRA clinic, Apoplex Medical, Germany). Based on the RR dynamics, the stroke risk analysis (SRA) algorithm stratified the risk for PAF as follows: low risk for PAF, high risk for PAF, presence of manifest AF. The subsequent presence/absence of PAF during the whole SU hospitalization was ruled out using all available CCMs, standard ECGs, or 24-h Holter ECGs. Two hundred patients (40% females, mean age 71 ± 16 years) were included. According to the initial SRA analysis, 111 patients (56%) were considered as low risk for PAF, 52 (26%) as high risk while 37 patients (18%) had manifest AF. A low-risk level SRA was associated with a reduced probability for subsequent PAF detection (1/111, 0.9%, 95% CI 0-4.3%) while a high-risk level SRA predicted an increased probability (20/52, 38.5% (95% CI 25-52%). RR dynamic analysis performed in the first hours after ischemic stroke may stratify patients into categories at low or high risk for forthcoming paroxysmal AF episodes detected within the SU hospitalization.
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    Development of an electronic health message system to support recovery after stroke: Inspiring Virtual Enabled Resources following following Vascular Events (iVERVE)
    Cadilhac, DA ; Busingye, D ; Li, JC ; Andrew, NE ; Kilkenny, MF ; Thrift, AG ; Thijs, V ; Hackett, ML ; Kneebone, I ; Lannin, NA ; Stewart, A ; Dempsey, I ; Cameron, J (DOVE MEDICAL PRESS LTD, 2018)
    PURPOSE: Worldwide, stroke is a leading cause of disease burden. Many survivors have unmet needs after discharge from hospital. Electronic communication technology to support post-discharge care has not been used for patients with stroke. In this paper, we describe the development of a novel electronic messaging system designed for survivors of stroke to support their goals of recovery and secondary prevention after hospital discharge. PARTICIPANTS AND METHODS: This was a formative evaluation study. The design was informed by a literature search, existing data from survivors of stroke, and behavior change theories. We established two working groups; one for developing the electronic infrastructure and the other (comprising researchers, clinical experts and consumer representatives) for establishing the patient-centered program. Following agreement on the categories for the goal-setting menu, we drafted relevant messages to support and educate patients. These messages were then independently reviewed by multiple topic experts. Concurrently, we established an online database to capture participant characteristics and then integrated this database with a purpose-built messaging system. We conducted alpha testing of the approach using the first 60 messages. RESULTS: The initial goal-setting menu comprised 26 subcategories. Following expert review, another 8 goal subcategories were added to the secondary prevention category: managing cholesterol; smoking; physical activity; alcohol consumption; weight management; medication management; access to health professionals, and self-care. Initially, 455 health messages were created by members of working group 2. Following refinement and mapping to different goals by the project team, 980 health messages across the health goals and 69 general motivational messages were formulated. Seventeen independent reviewers assessed the messages and suggested adding 73 messages and removing 16 (2%). Overall, 1,233 messages (18 administrative, 69 general motivation and 1,146 health-related) were created. CONCLUSION: This novel electronic self-management support system is ready to be pilot tested in a randomized controlled trial in patients with stroke.