Publications by authors named "Franz Fazekas"

321 Publications

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

J Neurol 2021 Jul 17. Epub 2021 Jul 17.

Department of Neurology, CHU Caen Normandie, Caen, France.

Objective: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA).

Methods: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences.

Results: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31).

Conclusions: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.
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http://dx.doi.org/10.1007/s00415-021-10706-3DOI Listing
July 2021

Clinical Characteristics of Patients with Tick-Borne Encephalitis (TBE): A European Multicentre Study from 2010 to 2017.

Microorganisms 2021 Jun 30;9(7). Epub 2021 Jun 30.

Department of General Paediatrics, Medical University of Graz, 8036 Graz, Austria.

Tick-borne encephalitis (TBE) virus is a major cause of central nervous system infections in endemic countries. Here, we present clinical and laboratory characteristics of a large international cohort of patients with confirmed TBE using a uniform clinical protocol. Patients were recruited in eight centers from six European countries between 2010 and 2017. A detailed description of clinical signs and symptoms was recorded. The obtained information enabled a reliable classification in 553 of 555 patients: 207 (37.3%) had meningitis, 273 (49.2%) meningoencephalitis, 15 (2.7%) meningomyelitis, and 58 (10.5%) meningoencephalomyelitis; 41 (7.4%) patients had a peripheral paresis of extremities, 13 (2.3%) a central paresis of extremities, and 25 (4.5%) had single or multiple cranial nerve palsies. Five (0.9%) patients died during acute illness. Outcome at discharge was recorded in 298 patients. Of 176 (59.1%) patients with incomplete recovery, 80 (27%) displayed persisting symptoms or signs without recovery expectation. This study provides further evidence that TBE is a severe disease with a large proportion of patients with incomplete recovery. We suggest monitoring TBE in endemic European countries using a uniform protocol to record the full clinical spectrum of the disease.
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http://dx.doi.org/10.3390/microorganisms9071420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306415PMC
June 2021

2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis.

Lancet Neurol 2021 Aug 14;20(8):653-670. Epub 2021 Jun 14.

Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address:

The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centres guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial relevant advances in knowledge, including the 2017 revisions of the McDonald diagnostic criteria, renewed safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MRI for diagnostic, prognostic, and monitoring purposes. These developments suggest a changing role of MRI for the management of patients with multiple sclerosis. This 2021 revision of the previous guidelines on MRI use for patients with multiple sclerosis merges recommendations from the Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centres, and North American Imaging in Multiple Sclerosis Cooperative, and translates research findings into clinical practice to improve the use of MRI for diagnosis, prognosis, and monitoring of individuals with multiple sclerosis. We recommend changes in MRI acquisition protocols, such as emphasising the value of three dimensional-fluid-attenuated inversion recovery as the core brain pulse sequence to improve diagnostic accuracy and ability to identify new lesions to monitor treatment effectiveness, and we provide recommendations for the judicious use of gadolinium-based contrast agents for specific clinical purposes. Additionally, we extend the recommendations to the use of MRI in patients with multiple sclerosis in childhood, during pregnancy, and in the post-partum period. Finally, we discuss promising MRI approaches that might deserve introduction into clinical practice in the near future.
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http://dx.doi.org/10.1016/S1474-4422(21)00095-8DOI Listing
August 2021

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Lancet Neurol 2021 04 17;20(4):294-303. Epub 2021 Mar 17.

Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk.

Methods: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602.

Findings: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models.

Interpretation: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted.

Funding: British Heart Foundation and Stroke Association.
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http://dx.doi.org/10.1016/S1474-4422(21)00024-7DOI Listing
April 2021

Factors influencing daily treatment choices in multiple sclerosis: practice guidelines, biomarkers and burden of disease.

Ther Adv Neurol Disord 2020 7;13:1756286420975223. Epub 2020 Dec 7.

Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

At two meetings of a Central European board of multiple sclerosis (MS) experts in 2018 and 2019 factors influencing daily treatment choices in MS, especially practice guidelines, biomarkers and burden of disease, were discussed. The heterogeneity of MS and the complexity of the available treatment options call for informed treatment choices. However, evidence from clinical trials is generally lacking, particularly regarding sequencing, switches and escalation of drugs. Also, there is a need to identify patients who require highly efficacious treatment from the onset of their disease to prevent deterioration. The recently published European Committee for the Treatment and Research in Multiple Sclerosis/European Academy of Neurology clinical practice guidelines on pharmacological management of MS cover aspects such as treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and are based on expert consensus statements. However, the recommendations constitute an excellent framework that should be adapted to local regulations, MS center capacities and infrastructure. Further, available and emerging biomarkers for treatment guidance were discussed. Magnetic resonance imaging parameters are deemed most reliable at present, even though complex assessment including clinical evaluation and laboratory parameters besides imaging is necessary in clinical routine. Neurofilament-light chain levels appear to represent the current most promising non-imaging biomarker. Other immunological data, including issues of immunosenescence, will play an increasingly important role for future treatment algorithms. Cognitive impairment has been recognized as a major contribution to MS disease burden. Regular evaluation of cognitive function is recommended in MS patients, although no specific disease-modifying treatment has been defined to date. Finally, systematic documentation of real-life data is recognized as a great opportunity to tackle unresolved daily routine challenges, such as use of sequential therapies, but requires joint efforts across clinics, governments and pharmaceutical companies.
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http://dx.doi.org/10.1177/1756286420975223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724259PMC
December 2020

The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017.

Lancet Public Health 2020 10;5(10):e551-e567

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; National Institute for Stroke and Applied Neurosciences, Auckland University of Technology, Auckland, New Zealand; Research Center of Neurology, Moscow, Russia.

Background: Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide.

Methods: The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were Alzheimer's disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, Parkinson's disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates.

Findings: In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5-23·9) in the EU and 41·1 million (36·7-45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09-1·14) in the EU and 1·97 million (1·95-2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3-17·1) of total DALYs and 19·5% (18·0-21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80-84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs.

Interpretation: Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries.

Funding: European Academy of Neurology.
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http://dx.doi.org/10.1016/S2468-2667(20)30190-0DOI Listing
October 2020

Relationship between stroke etiology and collateral status in anterior circulation large vessel occlusion.

J Neurol 2020 Nov 25;267(11):3362-3370. Epub 2020 Jun 25.

Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria.

Background And Purpose: Clinical outcome after mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke is influenced by the intracerebral collateral status. We tested the hypothesis that patients with preexisting ipsilateral extracranial carotid artery stenosis (CAS) would have a better collateral status compared to non-CAS patients. Additionally, we evaluated MT-related adverse events and outcome for both groups.

Methods: Over a 7-year period, we identified all consecutive anterior circulation MT patients (excluding extracranial carotid artery occlusion and dissection). Patients were grouped into those with CAS ≥ 50% according to the NASCET criteria and those without significant carotid stenosis (non-CAS). Collateral status was rated on pre-treatment CT- or MR-angiography according to the Tan Score. Furthermore, we assessed postinterventional infarct size, adverse events and functional outcome at 90 days.

Results: We studied 281 LVO stroke patients, comprising 46 (16.4%) with underlying CAS ≥ 50%. Compared to non-CAS stroke patients (n = 235), patients with CAS-related stroke more often had favorable collaterals (76.1% vs. 46.0%). Recanalization rates were comparable between both groups. LVO stroke patients with underlying CAS more frequently had adverse events after MT (19.6% vs. 6.4%). Preexisting CAS was an independent predictor for favorable collateral status in multivariable models (Odds ratio: 3.3, p = 0.002), but post-interventional infarct size and functional 90-day outcome were not different between CAS and non-CAS patients.

Conclusions: Preexisting CAS ≥ 50% was associated with better collateral status in LVO stroke patients. However, functional 90-day outcome was independent from CAS, which could be related to a higher rate of adverse events.
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http://dx.doi.org/10.1007/s00415-020-10009-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578156PMC
November 2020

The influence of iron oxidation state on quantitative MRI parameters in post mortem human brain.

Neuroimage 2020 10 23;220:117080. Epub 2020 Jun 23.

UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada; Department of Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada; Department of Pediatrics (Division of Neurology), University of British Columbia, Vancouver, BC, Canada.

A variety of Magnetic Resonance Imaging (MRI) techniques are known to be sensitive to brain iron content. In principle, iron sensitive MRI techniques are based on local magnetic field variations caused by iron particles in tissue. The purpose of this study was to investigate the sensitivity of MR relaxation and magnetization transfer parameters to changes in iron oxidation state compared to changes in iron concentration. Therefore, quantitative MRI parameters including R, R, R∗, quantitative susceptibility maps (QSM) and magnetization transfer ratio (MTR) of post mortem human brain tissue were acquired prior and after chemical iron reduction to change the iron oxidation state and chemical iron extraction to decrease the total iron concentration. All assessed parameters were shown to be sensitive to changes in iron concentration whereas only R, R∗ and QSM were also sensitive to changes in iron oxidation state. Mass spectrometry confirmed that iron accumulated in the extraction solution but not in the reduction solution. R∗ and QSM are often used as markers for iron content. Changes in these parameters do not necessarily reflect variations in iron content but may also be a result of changes in the iron's oxygenation state from ferric towards more ferrous iron or vice versa.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117080DOI Listing
October 2020

Minor Structural Differences in the Cervical Spine Between Patients With Cervical Dystonia and Age-Matched Healthy Controls.

Front Neurol 2020 29;11:472. Epub 2020 May 29.

Department of Neurology, Medical University of Graz, Graz, Austria.

Cervical dystonia is the most common form of focal dystonia. The frequency and pattern of degenerative changes of the cervical spine in patients with cervical dystonia and their relation to clinical symptoms remain unclear as no direct comparison to healthy controls has been performed yet. Here, we used magnetic resonance imaging (MRI) to investigate (1) whether structural abnormalities of the cervical spine are more common in patients with cervical dystonia compared to age-matched healthy controls, (2) if there are clinical predictors for abnormalities on MRI, and (3) to calculate the inter-rater reliability of the respective radiological scales. Twenty-five consecutive patients with cervical dystonia and 20 age-matched healthy controls were included in the study. MRI scans of the cervical spine were analyzed separately by three experienced raters blinded to clinical information, applying different MRI rating scales. Structural abnormalities were compared between groups for upper, middle, and lower cervical spine segments. The associations between scores differentiating both groups and clinical parameters were assessed in dystonia patients. Additionally, inter-rater reliability of the MRI scales was calculated. Comparing structural abnormalities, we found minor differences in the middle cervical spine, indicated by a higher MRI total score in patients but no significant correlation between clinical parameters and MRI changes. Inter-rater reliability was satisfying for most of the MRI rating scales. Our results do not provide evidence for a role of MRI of the cervical spine in the routine work-up of patients with cervical dystonia in the absence of specific clinical signs or symptoms.
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http://dx.doi.org/10.3389/fneur.2020.00472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272577PMC
May 2020

Serum neurofilament light levels in normal aging and their association with morphologic brain changes.

Nat Commun 2020 02 10;11(1):812. Epub 2020 Feb 10.

Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.

Neurofilament light (NfL) protein is a marker of neuro-axonal damage and can be measured not only in cerebrospinal fluid but also in serum, which allows for repeated assessments. There is still limited knowledge regarding the association of serum NfL (sNfL) with age and subclinical morphologic brain changes and their dynamics in the normal population. We measured sNfL by a single molecule array (Simoa) assay in 335 individuals participating in a population-based cohort study and after a mean follow-up time of 5.9 years (n = 103). Detailed clinical examination, cognitive testing and 3T brain MRI were performed to assess subclinical brain damage. We show that rising and more variable sNfL in individuals >60 years indicate an acceleration of neuronal injury at higher age, which may be driven by subclinical comorbid pathologies. This is supported by a close association of sNfL with brain volume changes in a cross-sectional and especially longitudinal manner.
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http://dx.doi.org/10.1038/s41467-020-14612-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010701PMC
February 2020

Single mean arterial blood pressure drops during stroke thrombectomy under general anaesthesia are associated with poor outcome.

J Neurol 2020 May 18;267(5):1331-1339. Epub 2020 Jan 18.

Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036, Graz, Austria.

Background: We examined the influence of periprocedural blood pressure (BP), especially critical BP drops, on 3-month functional outcome in stroke patients undergoing mechanical thrombectomy (MT) under general anaesthesia (GA).

Methods: We screened all patients with anterior circulation large vessel occlusion receiving MT under GA at our centre from January 2011 to June 2016 and selected those who had continuous invasive periinterventional BP monitoring. Clinical and radiological data were prospectively collected as part of an ongoing cohort study, monitoring data were extracted from electronic anaesthesia records. We used uni- and multivariable regression to investigate the association of BP values with unfavourable outcome, defined as modified Rankin Scale scores 3-6 3 months post-stroke.

Results: 115 patients were included in this study (mean age 65.3 ± 13.0 years, 55.7% male). Periinterventional systolic, diastolic, and mean arterial BP (MAP) values averaged across MT had no effect on outcome. However, single BP drops were related to unfavourable outcome, with absolute MAP drops showing the highest association compared to both systolic and relative BP drops (with reference to pre-interventional values). The BP value with the strongest association with unfavourable outcome was identified as an MAP ever < 60 mmHg (p = 0.01) with a pronounced effect in patients with poor collaterals. An MAP < 60 mmHg remained independently associated with poor functional outcome in multivariable analysis (p < 0.01).

Conclusions: For patients undergoing MT under GA, single MAP drops < 60 mmHg are independently related to unfavourable 3-month outcome. Therefore, every effort should be made to prevent periinterventional hypotensive episodes, especially below this threshold.
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http://dx.doi.org/10.1007/s00415-020-09701-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184049PMC
May 2020

Planning of stroke care and urgent prehospital care across Europe: Results of the ESO/ESMINT/EAN/SAFE Survey.

Eur Stroke J 2019 Dec 19;4(4):329-336. Epub 2019 Mar 19.

Department of Neurology, University Hospital Bern and University of Bern, Inselspital, Bern, Switzerland.

Introduction: Adequate planning and implementation of stroke systems of care is key to guarantee a rapid healthcare response and delivery of specific reperfusion therapies among candidates. We assessed the availability of stroke care plans in Europe, and evaluated their impact on rates of reperfusion therapies for stroke.

Patients: Based on the European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN), and the Stroke Alliance for Europe (SAFE) survey, we analysed specific prespecified items in the questionnaire regarding availability and adequacy of stroke care plans, organised prehospital care and their potential impact on rates of delivery of reperfusion therapies for stroke at the country level.

Results: Of 44 participating European countries, 37 have stroke care plans that operate at national and/or regional levels. Most stroke care plans take responsibility for the organisation/implementation of stroke systems of care (86%), quality of care assessment (77%), and act as a liaison between emergency medical systems and stroke physicians (79%). As for stroke systems of care, the focus is mainly on prehospital and in-hospital acute stroke care (Code Stroke systems available in 37/44 countries). Preferred urgent transport is via non-medicalised ambulances (70%). Presence of stroke care plans, stroke registry data, transport of urgent stroke patients via non-medicalised ambulances, and drip-and-ship routing of acute patients showed higher reperfusion treatment rates.

Discussion: Availability of stroke care plans, still absent in some European countries, as well as some features of the stroke systems of care are associated with higher reperfusion treatment rates.

Conclusion: Stroke is not yet a priority everywhere in Europe, which is a barrier to the spread of reperfusion therapies for stroke.
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http://dx.doi.org/10.1177/2396987319837106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921941PMC
December 2019

Mean Platelet Volume Does Not Predict Restenosis After Carotid Artery Stenting in Whites.

Stroke 2020 03 18;51(3):986-989. Epub 2019 Dec 18.

From the Department of Neurology (M.H., M.K., K.N., S.F.-H., S.H., F.F., C.E., T.G.), Medical University of Graz, Austria.

Background and Purpose- Mean platelet volume (MPV) indicates platelet activity possibly affecting patient's risk for progressive atherosclerotic disease. A recent study identified elevated MPV as a predictor of in-stent restenosis (ISR) after carotid artery stenting (CAS) in a Chinese population. However, the role of MPV on the development of ISR following CAS in whites is yet unknown. Methods- We retrospectively identified all consecutive patients who underwent CAS for atherosclerotic disease at our center from 2005 to 2017. All patients were followed clinically and by duplex sonography at 1, 3, and 6 months and annually after CAS. ISR was defined as ≥50% stenosis (NASCET [North American Symptomatic Carotid Endarterectomy Trial] criteria) in the treated vessel. MPV was assessed before CAS, at last follow-up and at the time of ISR detection. Results- Of 392 patients with CAS (mean age 68.5±9.5 years, 26.8% women, 42.3% symptomatic stenosis), 54 had ISR after a mean follow-up time of 32 months. Baseline MPV was not different in ISR compared with non-ISR patients (10.7 versus 10.6 fL, =0.316). MPV levels did also not change from baseline to ISR detection (=0.310) and were not associated with recurrent stroke or vascular events (>0.5). Multivariable analysis identified active smoking as the sole risk factor for carotid ISR (odds ratio, 2.53 [95% CI, 1.21-5.29]). Conclusions- We did not identify MPV as a risk factor for ISR after CAS in whites. Smoking cessation is an important target to avoid this complication.
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http://dx.doi.org/10.1161/STROKEAHA.119.028180DOI Listing
March 2020

Brain atrophy in cerebral small vessel diseases: Extent, consequences, technical limitations and perspectives: The HARNESS initiative.

J Cereb Blood Flow Metab 2020 02 20;40(2):231-245. Epub 2019 Nov 20.

Department of Neurology and Referral Center for Rare Vascular Diseases of the Brain and Retina (CERVCO), APHP, Lariboisière Hospital, Paris, DHU NeuroVasc, Univ Paris Diderot, and U1141 INSERM, France.

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http://dx.doi.org/10.1177/0271678X19888967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370623PMC
February 2020

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.

BMJ Open 2019 11 14;9(11):e031144. Epub 2019 Nov 14.

Neurology Department, University of Maryland School of Medicine, Baltimore, Maryland, USA.

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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http://dx.doi.org/10.1136/bmjopen-2019-031144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887075PMC
November 2019

Predictors of Lesion Cavitation After Recent Small Subcortical Stroke.

Transl Stroke Res 2020 06 8;11(3):402-411. Epub 2019 Nov 8.

Centre for Clinical Brain Sciences, The University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.

Morphologic evolution of recent small subcortical infarcts (RSSI) ranges from lesion disappearance to lacune formation and the reasons for this variability are still poorly understood. We hypothesized that diffusion tensor imaging (DTI) and blood-brain-barrier (BBB) abnormalities early on can predict tissue damage 1 year after an RSSI. We studied prospectively recruited patients with a symptomatic MRI-defined RSSI who underwent baseline and two pre-specified MRI examinations at 1-3-month and 1-year post-stroke. We defined the extent of long-term tissue destruction, termed cavitation index, as the ratio of the 1-year T1-weighted cavity volume to the baseline RSSI volume on FLAIR. We calculated fractional anisotropy and mean diffusivity (MD) of the RSSI and normal-appearing white matter, and BBB leakage in different tissues on dynamic contrast-enhanced MRI. Amongst 60 patients, at 1-year post-stroke, 44 patients showed some degree of RSSI cavitation on FLAIR, increasing to 50 on T2- and 56 on T1-weighted high-resolution scans, with a median cavitation index of 7% (range, 1-36%). Demographic, clinical, and cerebral small vessel disease features were not associated with the cavitation index. While lower baseline MD of the RSSI (r = - 0.371; p = 0.004) and more contrast leakage into CSF (r = 0.347; p = 0.007) were associated with the cavitation index in univariable analysis, only BBB leakage in CSF remained independently associated with cavitation (beta = 0.315, p = 0.046). Increased BBB leakage into CSF may indicate worse endothelial dysfunction and increased risk of tissue destruction post RSSI. Although cavitation was common, it only affected a small proportion of the original RSSI.
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http://dx.doi.org/10.1007/s12975-019-00741-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235062PMC
June 2020

Morphological MRI phenotypes of multiple sclerosis differ in resting-state brain function.

Sci Rep 2019 11 7;9(1):16221. Epub 2019 Nov 7.

Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, Graz, Austria.

We aimed to assess differences in resting-state functional connectivity (FC) between distinct morphological MRI-phenotypes in multiple sclerosis (MS). Out of 180 MS patients, we identified those with high T2-hyperintense lesion load (T2-LL) and high normalized brain volume (NBV; a predominately white matter damage group, WMD; N = 37) and patients with low T2-LL and low NBV (N = 37; a predominately grey matter damage group; GMD). Independent component analysis of resting-state fMRI was used to test for differences in the sensorimotor network (SMN) between MS MRI-phenotypes and compared to 37 age-matched healthy controls (HC). The two MS groups did not differ regarding EDSS scores, disease duration and distribution of clinical phenotypes. WMD compared to GMD patients showed increased FC in all sub-units of the SMN (sex- and age-corrected). WMD patients had increased FC compared to HC and GMD patients in the central SMN (leg area). Only in the WMD group, higher EDSS scores and T2-LL correlated with decreased connectivity in SMN sub-units. MS patients with distinct morphological MRI-phenotypes also differ in brain function. The amount of focal white matter pathology but not global brain atrophy affects connectivity in the central SMN (leg area) of the SMN, consistent with the notion of a disconnection syndrome.
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http://dx.doi.org/10.1038/s41598-019-52757-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838050PMC
November 2019

Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline.

Stroke 2020 01 8;51(1):170-178. Epub 2019 Nov 8.

From the Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital (H.J., H.M.L., S. Melkas, T.E.), Finland.

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (<0.001 for global cognitive function, processing speed, executive functions, and memory and <0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on scores strongly predicted cognitive and functional outcomes (<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.
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http://dx.doi.org/10.1161/STROKEAHA.119.026170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924941PMC
January 2020

Early renal dysfunction and fibroblast growth factor-23 in patients with small vessel disease-related stroke.

Sci Rep 2019 10 28;9(1):15410. Epub 2019 Oct 28.

Department of Neurology, Medical University of Graz, Graz, Austria.

Interactions between cerebral small vessel disease (CSVD) and renal dysfunction (RD) have been reported, but previous studies were mostly retrospective and limited to measurements of estimated glomerular filtration rate (eGFR). In this prospective, longitudinal study of patients with CSVD-related recent small subcortical infarcts (RSSI), we aimed at a comprehensive exploration of markers of early RD and their association with microvascular brain damage. We investigated 101 stroke patients (mean age: 60.2 ± 10.7 years) with an MRI-confirmed RSSI who underwent follow-up brain MRI 15 months post-stroke. Besides serum creatinine and eGFR, we assessed urinary Albumin-Creatinine Ratio and fibroblast growth factor-23 (FGF-23). RD was classified according to recent Kidney Disease: Improving Global Outcomes criteria. We identified 24 patients with RD, only six patients revealed an eGFR <60 mL/min/1.73 m². RSSI patients with RD more often had severe white matter hyperintensities (WMH, 58% vs. 36%, p = 0.04). CSVD progression was not dependent on RD. However, patients in the highest FGF-23 quartile more frequently had new microangiopathic lesions on follow-up MRI (50% vs. 21%, p = 0.03). Early RD was found in a quarter of RSSI patients and associated with WMH severity, but not CSVD progression. High FGF-23 indicates an increased risk for ongoing microvascular brain damage, warranting further studies.
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http://dx.doi.org/10.1038/s41598-019-51965-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817845PMC
October 2019

Quantification of cortical damage in multiple sclerosis using DTI remains a challenge.

Brain 2019 07;142(7):1848-1850

Department of Neurology, Medical University of Graz, Austria.

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http://dx.doi.org/10.1093/brain/awz160DOI Listing
July 2019

Comment on: External Validation of the PREMISE Score in the Athens Stroke Registry.

J Stroke Cerebrovasc Dis 2019 11 20;28(11):104334. Epub 2019 Aug 20.

Department of Neurology, Medical University of Graz, Graz, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104334DOI Listing
November 2019

Vanishing midbrain mass lesion - A germinoma?

J Neurol Sci 2019 Sep 13;404:40-43. Epub 2019 Jun 13.

Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036 Graz, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jns.2019.06.013DOI Listing
September 2019

Blood Biomarkers of Heart Failure and Hypercoagulation to Identify Atrial Fibrillation-Related Stroke.

Stroke 2019 08 20;50(8):2223-2226. Epub 2019 Jun 20.

From the Department of Neurology (M.K., T.G., C.E., S.F.-H., S.E., C.H., B.B., B.P., K.N., F.F.).

Background and Purpose- Occult atrial fibrillation (AF) causes a relevant proportion of initially cryptogenic stroke (CS), but prolonged rhythm monitoring is difficult to apply to all such patients. We hypothesized that blood biomarkers indicating heart failure (NT-proBNP [N-terminal pro-brain natriuretic peptide]) and hypercoagulability (D-dimer, AT-III [antithrombin-III]) were associated with AF-related stroke and could serve to predict the likelihood of AF detection in CS patients early on. Methods- Over a 1-year period, we prospectively applied a defined etiologic work-up to all ischemic stroke patients admitted to our stroke unit. If no clear stroke cause was detected (CS), patients underwent extended in-hospital cardiac rhythm monitoring (≥72 hours). Blood to determine biomarker levels was drawn within 24 hours after admission. Results- Of 429 patients, 103 had AF-related stroke. Compared with noncardiac stroke patients (n=171), they had higher NT-proBNP (1867 versus 263 pg/ml) and D-dimer levels (1.1 versus 0.6 µg/ml), and lower AT-III concentration (89% versus 94%). NT-proBNP ≥505 pg/ml distinguished AF-related from noncardiac stroke with a sensitivity of 93% and a specificity of 72%. D-dimer and AT-III cutoffs had lower sensitivities (61% and 53%) and specificities (58% and 69%) for AF-related stroke. Of all initially 143 CS patients, 14 were diagnosed with AF during in-hospital monitoring. The preidentified NT-proBNP cutoff ≥505 pg/ml correctly predicted AF in 12 of them (86%, negative predictive value: 98%), while D-dimer and AT-III cutoffs were noncontributory. Conclusions- This study supports the association of NT-proBNP and to a lesser extent of hypercoagulation markers with AF-related stroke. NT-proBNP seems helpful in selecting CS patients for immediate extended cardiac rhythm monitoring to detect occult AF whereby levels <505 pg/ml seem to have a high-negative predictive value.
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http://dx.doi.org/10.1161/STROKEAHA.119.025339DOI Listing
August 2019

Access to and delivery of acute ischaemic stroke treatments: A survey of national scientific societies and stroke experts in 44 European countries.

Eur Stroke J 2019 Mar 20;4(1):13-28. Epub 2018 Jul 20.

Department of Neurology, University of Bern, Inselspital, Bern, Switzerland.

Introduction: Acute stroke unit care, intravenous thrombolysis and endovascular treatment significantly improve the outcome for patients with ischaemic stroke, but data on access and delivery throughout Europe are lacking. We assessed best available data on access and delivery of acute stroke unit care, intravenous thrombolysis and endovascular treatment throughout Europe.

Methods: A survey, drafted by stroke professionals (ESO, ESMINT, EAN) and a patient organisation (SAFE), was sent to national stroke societies and experts in 51 European countries (World Health Organization definition) requesting experts to provide national data on stroke unit, intravenous thrombolysis and endovascular treatment rates. We compared both pooled and individual national data per one million inhabitants and per 1000 annual incident ischaemic strokes with highest country rates. Population estimates were based on United Nations data, stroke incidences on the Global Burden of Disease Report.

Results: We obtained data from 44 European countries. The estimated mean number of stroke units was 2.9 per million inhabitants (95% CI 2.3-3.6) and 1.5 per 1000 annual incident strokes (95% CI 1.1-1.9), highest country rates were 9.2 and 5.8. Intravenous thrombolysis was provided in 42/44 countries. The estimated mean annual number of intravenous thrombolysis was 142.0 per million inhabitants (95% CI 107.4-176.7) and 72.7 per 1000 annual incident strokes (95% CI 54.2-91.2), highest country rates were 412.2 and 205.5. Endovascular treatment was provided in 40/44 countries. The estimated mean annual number of endovascular treatments was 37.1 per million inhabitants (95% CI 26.7-47.5) and 19.3 per 1000 annual incident strokes (95% CI 13.5-25.1), highest country rates were 111.5 and 55.9. Overall, 7.3% of incident ischaemic stroke patients received intravenous thrombolysis (95% CI 5.4-9.1) and 1.9% received endovascular treatment (95% CI 1.3-2.5), highest country rates were 20.6% and 5.6%.

Conclusion: We observed major inequalities in acute stroke treatment between and within 44 European countries. Our data will assist decision makers implementing tailored stroke care programmes for reducing stroke-related morbidity and mortality in Europe.
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http://dx.doi.org/10.1177/2396987318786023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533860PMC
March 2019

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Lancet Neurol 2019 07 23;18(7):653-665. Epub 2019 May 23.

Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke.

Methods: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602.

Findings: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years).

Interpretation: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden.

Funding: British Heart Foundation and UK Stroke Association.
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http://dx.doi.org/10.1016/S1474-4422(19)30197-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562236PMC
July 2019

Commentary on 'Spontaneous multiple cervical artery dissections after alemtuzumab'.

Mult Scler 2020 03 9;26(3):384-385. Epub 2019 May 9.

Department of Neurology, Medical University of Graz, Graz, Austria.

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http://dx.doi.org/10.1177/1352458519845110DOI Listing
March 2020

Are morphologic features of recent small subcortical infarcts related to specific etiologic aspects?

Ther Adv Neurol Disord 2019 22;12:1756286419835716. Epub 2019 Apr 22.

Department of Neurology, Medical University of Graz, Austria.

Background: Recent small subcortical infarcts (RSSIs) mostly result from the occlusion of a single, small, brain artery due to intrinsic cerebral small-vessel disease (CSVD). Some RSSIs may be attributable to other causes such as cardiac embolism or large-artery disease, and their association with coexisting CSVD and vascular risk factors may vary with morphological magnetic resonance imaging (MRI) features.

Methods: We retrospectively identified all inpatients with a single symptomatic MRI-confirmed RSSI between 2008 and 2013. RSSIs were rated for size, shape, location (i.e. anterior: basal ganglia and centrum semiovale posterior cerebral circulation: thalamus and pons) and MRI signs of concomitant CSVD. In a further step, clinical data, including detailed diagnostic workup and vascular risk factors, were analyzed with regard to RSSI features.

Results: Among 335 RSSI patients (mean age 71.1 ± 12.1 years), 131 (39%) RSSIs were >15 mm in axial diameter and 66 (20%) were tubular shaped. Atrial fibrillation (AF) was present in 44 (13.1%) and an ipsilateral vessel stenosis > 50% in 30 (9%) patients. Arterial hypertension and CSVD MRI markers were more frequent in patients with anterior-circulation RSSIs, whereas diabetes was more prevalent in posterior-circulation RSSIs. Larger RSSIs occurred more frequently in the basal ganglia and pons, and the latter were associated with signs of large-artery atherosclerosis. Patients with concomitant AF had no specific MRI profile.

Conclusion: Our findings suggest the contribution of different pathophysiological mechanisms to the occurrence of RSSIs in the anterior and posterior cerebral circulation. While there appears to be some general association of larger infarcts in the pons with large-artery disease, we found no pattern suggestive of AF in RSSIs.
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http://dx.doi.org/10.1177/1756286419835716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477767PMC
April 2019

Quantifying blood-brain barrier leakage in small vessel disease: Review and consensus recommendations.

Alzheimers Dement 2019 06 25;15(6):840-858. Epub 2019 Apr 25.

Centre for Clinical Brain Science, University of Edinburgh, Edinburgh, UK; Dementia Research Institute, University of Edinburgh, Edinburgh, UK; Edinburgh Imaging, University of Edinburgh, Edinburgh, UK.

Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance. It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology. Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature. Although dynamic contrast-enhanced magnetic resonance imaging is well established, challenges emerge in cSVD because of the subtle nature of BBB impairment. The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified. We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia.
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http://dx.doi.org/10.1016/j.jalz.2019.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565805PMC
June 2019

Postural hemodynamic parameters in older persons have a seasonal dependency : A pilot study.

Z Gerontol Geriatr 2020 Mar;53(2):145-155

Gravitational Physiology, Aging and Medicine Research Unit, Physiology Division, Otto Loewi Center of Vascular Biology, Immunity and Inflammation, Medical University of Graz, Neue Stiftingtalstrasse 6, Graz, Austria.

Aims: It is known that blood pressure regulation differs seasonally. It is unknown, however, how the cardiovascular system in patients with a stroke reacts to postural changes in different seasons. The aim was therefore to investigate how different temperatures in cold and warm seasons influence the reactions of haemodynamic mechanisms as well as heart rate variability during a sit-to-stand test in patients with stroke and a control group.

Methods: Hemodynamic responses were assessed in both groups during a sit-to-stand test (5 min sitting followed by 5 min standing) beat to beat within two different seasons. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate (HR), stroke index (SI), cardiac index (CI) and heart rate variability (HRV) were continuously monitored.

Results: During the sitting baseline period delta values of DBP (+15.1 [Standard error (SE) 3.75] mmHg, p < 0.05) and MBP (+14.35 [SE 4.18] mmHg, p < 0.05) were significantly higher in colder months compared to warmer months whereas SI (-3.86 [SE 1.43] ml/beat/m, p < 0.05) and CI (-0.4 [SE 0.11] l/min/m, p < 0.05) were lower in colder months compared to warmer months in non-stroke participants. In patients with stroke during sitting, baseline period delta values of DBP (+19.92 [SE 8.03] mmHg, p < 0.05) and MBP (+19.29 [SE 8.6] mmHg, p < 0.05) were significantly higher in colder months compared to warmer months but SI (-5.43 [SE 1.96] ml/beat/m, p < 0.05) was significantly lower in colder months compared to warmer months. After standing, there was a significant decrease in SBP in warmer months (-16.84 [SE 4.38] mmHg, p < 0.05) and a decrease in DBP in warmer months (-7.8 [SE 2.3] mmHg, p < 0.05) and colder months (-6.73 [SE 1.5] mmHg, p < 0.05) in non-stroke participants and a decrease in MBP in warmer months (-12.5 [SE 2.8] mmHg, p < 0.05) and colder months (-8.93 [SE 1.8] mmHg, p < 0.05) in non-stroke participants and in warmer months (-14.54 [SE 4.1] mmHg, p < 0.05) in patients with stroke.

Conclusion: Elderly with and without stroke respond to orthostatic stress with a greater drop in blood pressure in the warmer seasons.
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http://dx.doi.org/10.1007/s00391-019-01525-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066096PMC
March 2020

White Matter Hyperintensities in Alzheimer's Disease: A Lesion Probability Mapping Study.

J Alzheimers Dis 2019 ;68(2):789-796

Department of Neurology, Medical University of Graz, Graz, Austria.

Background/objective: Higher white matter hyperintensity (WMH) load has been reported in Alzheimer's disease (AD) patients in different brain regions when compared to controls. We aimed to assess possible differences of WMH spatial distribution between AD patients and age-matched controls by means of lesion probability maps.

Methods: The present study included MRI scans of 130 probable AD patients with a mean age of 73.4±8.2 years from the Prospective Dementia Registry Austria Study and 130 age-matched healthy controls (HC) from the Austrian Stroke Prevention Family Study. Risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and smoking were assessed. Manually segmented FLAIR WMH masks were non-linearly registered to a template and voxel-based probability mapping was performed.

Results: There were no significant between-group differences in cardiovascular risk factors and WMH volume. AD patients showed a significantly higher likelihood of having WMH in a bilateral periventricular distribution than controls before and after correcting for age, sex, cardiovascular risk factors, and ventricular volume (p≤0.05; threshold-free cluster enhancement corrected). There was no significant association between the periventricular WMH volume and cognitive decline of AD patients.

Conclusion: In AD, WMH were preferentially found in a periventricular location but the volume of lesions was unrelated to cognitive decline in our study irrespective of lesion location.
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http://dx.doi.org/10.3233/JAD-180982DOI Listing
July 2020
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