Browsing by Subject "ISCHEMIC-STROKE"

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  • Tolvi, Morag; Mattila, Kimmo; Haukka, Jari; Aaltonen, Leena-Maija; Lehtonen, Lasse (2020)
    Background: The weekend effect, the phenomenon of patients admitted at the weekend having a higher mortality risk, has been widely investigated and documented in both elective and emergency patients. Research on the issue is scarce in Europe, with the exception of the United Kingdom. We examined the situation in Helsinki University Hospital over a 14-year period from a specialty-specific approach. Materials and methods: We collected the data for all patient visits for 2000-2013, selecting patients with in-hospital care in the university hospital and extracting patients that died during their hospital stay or within 30 days of discharge. These patients were categorized according to urgency of care and specialty. Results: A total of 1,542,230 in-patients (853,268 emergency patients) met the study criteria, with 47,122 deaths in-hospital or within 30 days of discharge. Of 12 specialties, we found a statistically significant weekend effect for in-hospital mortality in 7 specialties (emergency admissions) and 4 specialties (elective admissions); for 30-day post-discharge mortality in 1 specialty (emergency admissions) and 2 specialties (elective admissions). Surgery, internal medicine, neurology, and gynecology and obstetrics were most sensitive to the weekend effect. Conclusions: The study confirms a weekend effect for both elective and emergency admissions in most specialties. Reducing the number of weekend elective procedures may be necessary. More disease-specific research is needed to find the diagnoses most susceptible. (C) 2020 Elsevier B.V. All rights reserved.
  • Atrial Fibrillation Genetics Conso; Int Stroke Genetics Consortium; Pulit, Sara L.; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Malik, Rainer; Sinisalo, Juha; Vlachopoulou, Efthymia; Lokki, Marja-Liisa; Tatlisumak, Turgut; Happola, Olli (2018)
    Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. Methods We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. Results We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p <4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Conclusions Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
  • Martiskainen, Mika; Oksala, Niku; Pohjasvaara, Tarja; Kaste, Markku; Oksala, Anni; Karhunen, Pekka J.; Erkinjuntti, Timo (2014)
  • Ritvonen, Juhani; Sairanen, Tiina; Silvennoinen, Heli; Virtanen, Pekka; Salonen, Oili; Lindsberg, Perttu J.; Strbian, Daniel (2021)
    Background: Around 30-60% of patients with basilar artery occlusion (BAO) present with coma, which is often considered as a hallmark of poor prognosis. Aim: To examine factors that will help predict outcomes in patients with BAO comatose on admission. Methods: A total of 312 patients with angiography-proven BAO were analyzed. Comas were assessed as Glasgow Coma Scale (GCS) of Results: In total, 103/259 (39.8%) of BAO patients were comatose on admission. Factors associated with acute coma were higher age, coronary artery disease, convulsions, extent of early ischemia by posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) < 8, absence of patent posterior collateral vasculature, and occlusion over multiple segments of BA. A total of 21/103 (20.4%) of comatose patients had a favorable outcome (mRS 0-3), and 12/103 (11.7%) had a good outcome (mRS 0-2). Factors associated with a favorable outcome in comatose BAO patients were younger age (p = 0.010), less extensive baseline ischemia (p = 0.027), recanalization (p = 0.013), and avoiding symptomatic intracranial hemorrhage (sICH) (p = 0.038). Factors associated with the poorest outcome or death (mRS 5-6) were older age (p = 0.001), diabetes (p = 0.022), atrial fibrillation (p = 0.016), lower median GCS [4 (IQR 3.6) vs. 6 (5-8); p = 0.006], pc-ASPECTS < 8 (p = 0.003), unsuccessful recanalization (p = 0.006), and sICH (p = 0.010). Futile recanalization (mRS 4-6) was significantly more common in comatose patients (49.4 vs. 18.5%, p < 0.001). Conclusions: One in five BAO patients with acute coma had a favorable outcome. Older patients with cardiovascular comorbidities and already existing ischemic lesions before reperfusion therapies tended to have a poor prognosis, especially if no recanalization is achieved and sICH occurred.
  • Matz, Karl; Tuomilehto, Jaakko; Teuschl, Yvonne; Dachenhausen, Alexandra; Brainin, Michael (2020)
    Background Diabetes is an increasingly important risk factor for ischemic stroke and worsens stroke prognosis. Yet a large proportion of stroke patients who are eventually diabetic are undiagnosed. Therefore, it is important to have sensitive assessment of unrecognized hyperglycaemia in stroke patients. Design Secondary outcome analysis of a randomized controlled trial focussing on parameters of glucose metabolism and detection of diabetes and prediabetes in patients with acute ischemic stroke (AIS). Methods A total of 130 consecutively admitted patients with AIS without previously known type 2 diabetes mellitus (T2DM) were screened for diabetes or prediabetes as part of secondary outcome analysis of a randomized controlled trial that tested lifestyle intervention to prevent post-stroke cognitive decline. Patients had the oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) measurements in the second week after stroke onset and after 1 year. The detection rates of diabetes and prediabetes based on the OGTT or HbA1c values were compared. Results By any of the applied tests at the second week after stroke onset 62 of 130 patients (48%) had prediabetes or T2DM. Seventy-five patients had results from both tests available, the OGTT and HbA1c; according to the OGTT 40 (53.3%) patients had normal glucose metabolism, 33 (44%) had prediabetes, two (2.7%) T2DM. In 50 (66.7%) patients the HbA1c results were normal, 24 (32%) in the prediabetic and one (1.3%) in the diabetic range. The detection rate for disorders of glucose metabolism was 10% higher (absolute difference; relative difference 29%) with the OGTT compared with HbA1c. After 1 year the detection rate for prediabetes or T2DM was 7% higher with the OGTT (26% relative difference). The study intervention led to a more favourable evolution of glycemic status after 1 year. Conclusion The OGTT is a more sensitive screening tool than HbA1c for the detection of previously unrecognized glycemic disorders in patients with acute stroke with an at least a 25% relative difference in detection rate. Therefore, an OGTT should be performed in all patients with stroke with no history of diabetes. Trial registration. Unique identifier: NCT01109836.
  • Pirinen, Jani; Kuusisto, Jouni; Järvinen, Vesa; Martinez-Majander, Nicolas; Sinisalo, Juha; Pöyhönen, Pauli; Putaala, Jukka (2020)
    Background Ischaemic stroke in young individuals often remains cryptogenic. In this pilot study, we investigated, whether advanced echocardiography methods could find differences in the diastolic function between young cryptogenic stroke patients and stroke-free controls. Methods We recruited 30 cryptogenic ischaemic stroke patients aged 18-49 and 30 age- and sex-matched stroke-free controls among participants of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study (NCT01934725). We measured diastolic function parameters derived from speckle tracking strain rate, Doppler techniques and 4D volumetry. We also performed statistical analyses comparing only the highest and lowest tertile of cases and controls for each parameter. Results None of our patients or controls had diastolic dysfunction according to ASE/EACVI criteria. However, compared to stroke-free controls, the stroke patient group had lower E/A ratio of mitral inflow, lower lateral and mean e', lower A/a' ratio, lower strain rate in early diastole and lower speckle tracking-derived e/a ratio. When comparing the lowest tertiles, patients also had a lower peak filling rate by 4D volumetry, a lower peak early filling fraction (fraction of left ventricular filling during early diastole), and lower velocities in a series of the tissue Doppler-derived diastolic parameters and blood flow/tissue velocity ratios. Conclusion Our study displayed subtle differences in diastolic function between patients and stroke-free controls, which may play a role in early-onset cryptogenic stroke. The differences were clearer when the lowest tertiles were compared, suggesting that there is a subgroup of young cryptogenic stroke patients with subclinical heart disease.
  • Penttilä, Tero; Lehto, Mika; Niiranen, Jussi; Mehtälä, Juha; Khanfir, Houssem; Lassila, Riitta; Raatikainen, Pekka (2019)
    Females with atrial fibrillation (AF) have been suggested to carry a higher risk for thromboembolic events than males. We compared the residual risk of stroke, bleeding events, and cardiovascular and all-cause mortality among female and male AF patients taking warfarin. Data from several nationwide registries and laboratory databases were linked with the civil registration number of the patients. A total of 54568 patients with data on the quality of warfarin treatment (time in therapeutic range) 60days prior to the events were included (TTR60). Gender differences in the endpoints were reported for the whole population, pre-specified age groups, and different TTR60 groups. During the 3.21.6years follow-up, there were no differences in the adjusted risk of stroke [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.911.03, P=0.304] between the genders. Cardiovascular mortality (HR 0.82, 95% CI 0.780.88, P <0.001) and all-cause mortality (HR 0.79, 95% CI 0.750.83, P <0.001) were lower in women when compared with men. There were no differences in the risk of stroke, cardiovascular mortality, and all-cause mortality between the genders in the TTR60 categories except for those with TTR60 <50%. Bleeding events were less frequent in females (HR 0.52, 95% CI 0.490.56, P <0.001). There were no differences in the risk of stroke between female and male AF patients taking warfarin. Cardiovascular mortality, all-cause mortality, and risk of bleeding events were lower in females. Hence, female gender was not a risk marker for adverse outcomes in AF patients with proper warfarin therapy.
  • Berberich, Anne; Finitsis, Stephanos; Strambo, Davide; Michel, Patrik; Herweh, Christian; Meyer, Lukas; Hanning, Uta; Strbian, Daniel; Abdalkader, Mohamad; Nogueira, Raul G.; Puetz, Volker; Kaiser, Daniel P. O.; Olive-Gadea, Marta; Ribo, Marc; Fragata, Isabel; Marto, Joao Pedro; Romoli, Michele; Ringleb, Peter A.; Nguyen, Thanh N.; Nagel, Simon (2022)
    Background and purpose Endovascular therapy (EVT) is increasingly reported for treatment of isolated posterior cerebral artery (PCA) occlusions although its clinical benefit remains uncertain. This study-level meta-analysis investigated the functional outcomes and safety of EVT and best medical management (BMM) compared to BMM alone for treatment of PCA occlusion stroke. Methods We conducted a literature search in PubMed, Web of Science and Embase for studies in patients with isolated PCA occlusion stroke treated with EVT + BMM or BMM including intravenous thrombolysis. There were no randomized trials and all studies were retrospective. The primary outcome was modified Rankin Scale score of 0-2 at 3 months, while safety outcomes included mortality rate and incidence of symptomatic intracranial hemorrhage (sICH). Results Twelve studies with a total of 679 patients were included in the meta-analysis: 338 patients with EVT + BMM and 341 patients receiving BMM alone. Good functional outcome at 3 months was achieved in 58.0% (95% confidence interval [CI] 43.83-70.95) of patients receiving EVT + BMM and 48.1% (95% CI 40.35-55.92) of patients who received BMM alone, with respective mortality rates of 12.6% (95% CI 7.30-20.93) and 12.3% (95% CI 8.64-17.33). sICH occurred in 4.2% (95% CI 2.47-7.03) of patients treated with EVT + BMM and 3.2% (95% CI 1.75-5.92) of patients treated with BMM alone. Comparative analyses were performed on studies that included both treatments and these demonstrated no significant differences. Conclusions Our results demonstrate that EVT represents a safe treatment for patients with isolated PCA occlusion stroke. There were no differences in clinical or safety outcomes between treatments, supporting randomization of future patients into distal vessel occlusion trials.
  • Fernandez-Alvarez, Veronica; Linares Sanchez, Miriam; Lopez Alvarez, Fernando; Suarez Nieto, Carlos; Mäkitie, Antti A.; Olsen, Kerry D.; Ferlito, Alfio (2022)
    Carotid atherosclerosis is a major and potentially preventable cause of ischemic stroke. It begins early in life and progresses silently over the years. Identification of individuals with subclinical atherosclerosis is needed to initiate early aggressive vascular prevention. Although carotid plaque appears to be a powerful predictor of cardiovascular risk, carotid intima-media thickness (CIMT) and arterial stiffness can be detected at the initial phases and, therefore, they are considered important new biomarkers of carotid atherosclerosis. There is a well-documented association between CIMT and cerebrovascular events. CIMT provides a reliable marker in young people, in whom plaque formation or calcification is not established. However, the usefulness of CIMT measurement in the improvement of risk cardiovascular models is still controversial. Carotid stiffness is also significantly associated with ischemic stroke. Carotid stiffness adds value to the existing risk prediction based on Framingham risk factors, particularly individuals at intermediate cardiovascular risk. Carotid ultrasound is used to assess carotid atherosclerosis. During the last decade, automated techniques for sophisticated analysis of vascular mechanics have evolved, such as speckle tracking, and new methods based on deep learning have been proposed with promising outcomes. Additional research is needed to investigate the imaging-based cardiovascular risk prediction of CIMT and stiffness.
  • Rostila, Mikael; Saarela, Jan; Kawachi, Ichiro (2013)
  • Helsinki Stroke, Study Dutch Parelsnoer Institute-Cerebrovascular Accident (CVA) Study Group; National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network; UK DNA Lacunar Stroke Study Investigators; International Stroke Genetics Consortium; Traylor, Matthew; Persyn, Elodie; Tomppo, Liisa; Havulinna, Aki; Strbian, Daniel; Markus, Hugh S. (2021)
    Background: The genetic basis of lacunar stroke is poorly understood, with a single locus on 16q24 identified to date. We sought to identify novel associations and provide mechanistic insights into the disease. Methods: We did a pooled analysis of data from newly recruited patients with an MRI-confirmed diagnosis of lacunar stroke and existing genome-wide association studies (GWAS). Patients were recruited from hospitals in the UK as part of the UK DNA Lacunar Stroke studies 1 and 2 and from collaborators within the International Stroke Genetics Consortium. Cases and controls were stratified by ancestry and two meta-analyses were done: a European ancestry analysis, and a transethnic analysis that included all ancestry groups. We also did a multi-trait analysis of GWAS, in a joint analysis with a study of cerebral white matter hyperintensities (an aetiologically related radiological trait), to find additional genetic associations. We did a transcriptome-wide association study (TWAS) to detect genes for which expression is associated with lacunar stroke; identified significantly enriched pathways using multi-marker analysis of genomic annotation; and evaluated cardiovascular risk factors causally associated with the disease using mendelian randomisation. Findings: Our meta-analysis comprised studies from Europe, the USA, and Australia, including 7338 cases and 254 798 controls, of which 2987 cases (matched with 29 540 controls) were confirmed using MRI. Five loci (ICA1L-WDR12-CARF-NBEAL1, ULK4, SPI1-SLC39A13-PSMC3-RAPSN, ZCCHC14, ZBTB14-EPB41L3) were found to be associated with lacunar stroke in the European or transethnic meta-analyses. A further seven loci (SLC25A44-PMF1-BGLAP, LOX-ZNF474-LOC100505841, FOXF2-FOXQ1, VTA1-GPR126, SH3PXD2A, HTRA1-ARMS2, COL4A2) were found to be associated in the multi-trait analysis with cerebral white matter hyperintensities (n=42 310). Two of the identified loci contain genes (COL4A2 and HTRA1) that are involved in monogenic lacunar stroke. The TWAS identified associations between the expression of six genes (SCL25A44, ULK4, CARF, FAM117B, ICA1L, NBEAL1) and lacunar stroke. Pathway analyses implicated disruption of the extracellular matrix, phosphatidylinositol 5 phosphate binding, and roundabout binding (false discovery rate <0·05). Mendelian randomisation analyses identified positive associations of elevated blood pressure, history of smoking, and type 2 diabetes with lacunar stroke. Interpretation: Lacunar stroke has a substantial heritable component, with 12 loci now identified that could represent future treatment targets. These loci provide insights into lacunar stroke pathogenesis, highlighting disruption of the vascular extracellular matrix (COL4A2, LOX, SH3PXD2A, GPR126, HTRA1), pericyte differentiation (FOXF2, GPR126), TGF-β signalling (HTRA1), and myelination (ULK4, GPR126) in disease risk. Funding: British Heart Foundation.
  • Soder, Birgitta; Meurman, Jukka H.; Soder, Per-Osten (2015)
    Objectives Gingival inflammation is the physiological response to poor oral hygiene. If gingivitis is not resolved the response will become an established lesion. We studied whether gingivitis associates with elevated risk for stroke. The hypothesis was based on the periodontitis-atherosclerosis paradigm. Methods In our prospective cohort study from Sweden 1676 randomly selected subjects were followed up from 1985 to 2012. All subjects underwent clinical oral examination and answered a questionnaire assessing background variables such as socio-economic status and pack-years of smoking. Cases with stroke were recorded from the Center of Epidemiology, Swedish National Board of Health and Welfare, Sweden, and classified according to the WHO International Classification of Diseases. Unpaired t-test, chi-square tests, and multiple logistic regression analyses were used. Results Of the 1676 participants, 39 subjects (2.3%) had been diagnosed with stroke. There were significant differences between the patients with stroke and subjects without in pack-years of smoking (p = 0.01), prevalence of gingival inflammation (GI) (p = 0.03), and dental calculus (p = 0.017). In a multiple regression analysis the association between GI, confounders and stroke, GI showed odds ratio 2.20 (95% confidence interval 1.02-4.74) for stroke. Conclusion Our present findings showed that gingival inflammation clearly associated with stroke in this 26-year cohort study. The results emphasize the role of oral health personnel in prevention.
  • Ekker, Merel S.; Jacob, Mina A.; van Dongen, Myrna M. E.; Aarnio, Karoliina; Annamalai, Arunkar K.; Arauz, Antonio; Arnold, Marcel; Barboza, Miguel A.; Bolognese, Manuel; Brouns, Raf; Chuluun, Batnairamdal; Chuluunbaatar, Enkhzaya; Dagvajantsan, Byambasuren; Debette, Stephanie; Don, Adi; Enzinger, Chris; Ekizoglu, Esme; Fandler-Hoefler, Simon; Fazekas, Franz; Fromm, Anette; Gattringer, Thomas; Gulli, Giosue; Hoffmann, Michael; Hora, Thiago F.; Jern, Christina; Jood, Katarina; Kamouchi, Masahiro; Kim, Young Seo; Kitazono, Takanari; Kittner, Steven J.; Kleinig, Timothy J.; Klijn, Catharina J. M.; Korv, Janika; Lee, Tsong-Hai; Leys, Didier; Maaijwee, Noortje A. M.; Martinez-Majander, Nicolas; Marto, Joao Pedro; Mehndiratta, Man M.; Mifsud, Victoria; Montanaro, Vinicius V.; Owolabi, Mayowa O.; Patel, Vinod B.; Phillips, Matthew C.; Piechowski-Iozwiak, Bartlomiej; Pikula, Aleksandra; Luis Ruiz-Sandoval, Jose; Sarnowski, Bettina; Schreuder, Floris H. B. M.; Swartz, Rick H.; Tan, K. S.; Tanne, David; Tatlisumak, T.; Thijs, Vincent; Tuladhar, Anil M.; Viana-Baptista, Miguel; Vibo, Riina; Wu, Teddy Y.; Yesilot, Nilufer; Waje-Andreassen, Ulrike; Pezzini, Alessandro; Putaala, Jukka; de Leeuw, Frank-Erik (2019)
    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.
  • Lehtonen, Arttu O.; Langen, Ville L.; Puukka, Pauli J.; Kahonen, Mika; Nieminen, Markku S.; Jula, Antti M.; Niiranen, Teemu J. (2017)
    Background: Scant data exist on incidence rates, correlates, and prognosis of electrocardiographic P-wave abnormalities in the general population. Methods: We recorded ECG and measured conventional cardiovascular risk factors in 5667 Finns who were followed up for incident atrial fibrillation (AF). We obtained repeat ECGs from 3089 individuals I I years later. Results: The incidence rates of prolonged P-wave duration, abnormal P terminal force (PTF), left P-wave axis deviation, and right P-wave axis deviation were 16.0%, 7.4%, 3.4%, and 2.2%, respectively. Older age and higher BMI were associated with incident prolonged P-wave duration and abnormal PTF (P Conclusions: Modifiable risk factors associate with P-wave abnormalities that are common and may represent intermediate steps of atrial cardiomyopathy on a pathway leading to AF. (C) 2017 Elsevier Inc. All rights reserved.
  • Zheng, Danni; Arima, Hisatomi; Sato, Shoichiro; Gasparrini, Antonio; Heeley, Emma; Delcourt, Candice; Lo, Serigne; Huang, Yining; Wang, Jiguang; Stapf, Christian; Robinson, Thompson; Lavados, Pablo; Chalmers, John; Anderson, Craig S.; INTERACT2 Investigators; Scheperjans, Filip; Kaste, Markku (2016)
    Background Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale. Methods INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH ( Results were presented as overall cumulative odds ratios (ORs) and 95% CI. Results Low ambient temperature ( Conclusions Exposure to low ambient temperature within several hours increases the risk of ICH.
  • Teppo, Jaakko; Vaikkinen, Anu; Stratoulias, Vassilis; Mätlik, Kert; Anttila, Jenni E.; Smolander, Olli-Pekka; Pöhö, Päivi; Harvey, Brandon K.; Kostiainen, Risto; Airavaara, Mikko (2020)
    The peri-infarct region after ischemic stroke is the anatomical location for many of the endogenous recovery processes, and the molecular events in the peri-infarct region remain poorly characterized. In this study, we examine the molecular profile of the peri-infarct region on post-stroke day four, time when reparative processes are ongoing. We used a multiomics approach, involving RNA sequencing, and mass spectrometry-based proteomics and metabolomics to characterize molecular changes in the peri-infarct region. We also took advantage of our previously developed method to express transgenes in the peri-infarct region where self-complementary adeno-associated virus (AAV) vectors were injected into the brain parenchyma on post-stroke day 2. We have previously used this method to show that mesencephalic astrocyte-derived neurotrophic factor (MANF) enhances functional recovery from stroke and recruits phagocytic cells to the peri-infarct region. Here, we first analyzed the effects of stroke to the peri-infarct region on post-stroke day 4 in comparison to sham-operated animals, finding that stroke induced changes in 3345 transcripts, 341 proteins, and 88 metabolites. We found that after stroke genes related to inflammation, proliferation, apoptosis, and regeneration were upregulated, whereas genes encoding neuroactive ligand receptors and calcium-binding proteins were downregulated. In proteomics, we detected upregulation of proteins related to protein synthesis and downregulation of neuronal proteins. Metabolomic studies indicated that in after stroke tissue there is increase in saccharides, sugar phosphates, ceramides and free fatty acids and decrease of adenine, hypoxantine, adenosine and guanosine. We then compared the effects of post-stroke delivery AAV1-MANF delivery to AAV1-eGFP (enhanced green fluorescent protein). MANF administration increased the expression of 77 genes, most of which were related to immune response. In proteomics, MANF administration reduced S100A8 and S100A9 protein levels. In metabolomics, no significant differences between MANF and eGFP treatment were detected, but relative to sham surgery group, most of the changes in lipids were significant in the AAV-eGFP group only. This work describes the molecular profile of the peri-infarct region during recovery from ischemic stroke, and establishes a resource for further stroke studies. These results provide further support for parenchymal MANF as a modulator of phagocytic function.
  • Nuotio, Krista; Ijäs, Petra; Heikkilä, Hanna M.; Koskinen, Suvi M.; Saksi, Jani; Vikatmaa, Pirkka; Sorto, Pia; Mäkitie, Laura; Eriksson, Henrietta; Kasari, Sonja; Silvennoinen, Heli; Valanne, Leena; Mäyränpää, Mikko I.; Kovanen, Petri T.; Soinne, Lauri; Lindsberg, Perttu J. (2018)
    Introduction: Every fifth ischemic stroke is caused by thromboembolism originating from an atherosclerotic carotid artery plaque. While prevention is the most cost-effective stroke therapy, antiplatelet and cholesterol-lowering drugs have a ceiling effect in their efficacy. Therefore, discovery of novel pathophysiologic targets are needed to improve the primary and secondary prevention of stroke. This article provides a detailed study design and protocol of HeCES2, an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.Materials and Methods: Recruitment and carotid endarterectomies of the study patients with carotid atherosclerosis were performed from October 2012 to September 2015. After brain and carotid artery imaging, endarterectomised carotid plaques (CPs) and blood samples were collected from 500 patients for detailed biochemical and molecular analyses.Findings to date: We developed a morphological grading for macroscopic characteristics within CPs. The dominant macroscopic CP characteristics were: smoothness 62%, ulceration 61%, intraplaque hemorrhage 60%, atheromatous gruel 59%, luminal coral-type calcification 34%, abundant (44%) and moderate (39%) intramural calcification, and symptom-causing hot spot area 53%.Future plans: By combining clinically oriented and basic biomedical research, this large-scale study attempts to untangle the pathophysiological perplexities of human carotid atherosclerosis.Key MessagesThis article is a rationale and design of the HeCES2 study that is an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.The HeCES2 study strives to develop diagnostic algorithms including radiologic imaging to identify carotid atherosclerosis patients who warrant surgical treatment.In addition, the study aims at finding out new tools for clinical risk stratification as well as novel molecular targets for drug development.
  • Karjalainen, Liisa; Tikkanen, Minna; Rantanen, Kirsi; Laivuori, Hannele; Gissler, Mika; Ijäs, Petra (2019)
    BackgroundPregnancy-associated stroke is a rare but life-threatening event, with an estimated incidence of 30/100000 deliveries. Data on the risk of stroke recurrence and the risk of other adverse pregnancy outcomes are essential for adequate counselling and surveillance in subsequent pregnancies. The aim of this systematic review is to describe the implications of a pregnancy-associated stroke for the future health of these women.MethodsWe searched Ovid Medline, PubMed, Cochrane Library and CINAHL for articles published in 1980-2018. Articles including women with pregnancy-associated stroke and information on at least one of the following outcomes were included: 1) recurrence of stroke during subsequent pregnancy, 2) number and course of subsequent pregnancies and their outcomes and 3) subsequent cardiovascular health.ResultsTwelve articles were included in the review, with six providing information on subsequent pregnancies, four on subsequent maternal health and two on both. The included articles varied greatly in terms of study design, length of follow up and reported outcomes. We found 252 women with pregnancy-associated stroke for whom the outcomes of interest were reported: 135 women with information on subsequent pregnancies and 123 women with information on future health. In total, 55 pregnancies after stroke were found. In the majority of studies, the incidence of pregnancy complications was comparable to that of the general population. The risk of stroke recurrence during pregnancy was 2%. Data on subsequent health of these women were limited, and the quality of the data varied between the studies.ConclusionsData on subsequent pregnancies and health of women with a history of pregnancy-associated stroke are limited. Further research on this topic is essential for adequate counselling and secondary prevention.
  • Thrombolysis Stroke Patients TriSP; Altersberger, Valerian L.; Sturzenegger, Rolf; Räty, Silja; Martinez-Majander, Nicolas; Tiainen, Marjaana; Valkonen, Kati; Curtze, Sami; Gensicke, Henrik (2020)
  • Remes, Tiina Maria; Suo-Palosaari, Maria Helena; Koskenkorva, Päivi K. T.; Sutela, Anna K.; Toiviainen-Salo, Sanna-Maria; Arikoski, Pekka M.; Arola, Mikko O.; Heikkilä, Vesa-Pekka; Kapanen, Mika; Lähteenmäki, Päivi Maria; Lönnqvist, Tuula R. I.; Niiniviita, Hannele; Pokka, Tytti M-L; Porra, Liisa; Riikonen, V. Pekka; Seppälä, Jan; Sirkiä, Kirsti H.; Vanhanen, Antti; Rantala, Heikki M. J.; Harila-Saari, Arja H.; Ojaniemi, Marja K. (2020)
    Background. Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy. Methods. Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients' files. Results. Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts. Conclusions. Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.