Browsing by Subject "ischemic stroke"

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  • Muhammad, Sajjad; Chaudhry, Shafqat Rasul; Kahlert, Ulf Dietrich; Niemelä, Mika; Hänggi, Daniel (2021)
    Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain-immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain-immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.
  • Woock, Malin; Martinez-Majander, Nicolas; Seiffge, David J.; Selvik, Henriette Aurora; Nordanstig, Annika; Redfors, Petra; Lindgren, Erik; Sanchez van Kammen, Mayte; Rentzos, Alexandros; Coutinho, Jonathan M.; Doyle, Karen; Naess, Halvor; Putaala, Jukka; Jood, Katarina; Tatlisumak, Turgut (2022)
    The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.
  • Bivard, Andrew; Churilov, Leonid; Ma, Henry; Levi, Christopher; Campbell, Bruce; Yassi, Nawaf; Meretoja, Atte; Zhao, Henry; Sharma, Gagan; Chen, Chushuang; Davis, Stephen; Donnan, Geoffrey; Yan, Bernard; Parsons, Mark (2022)
    Aims We reprocessed the Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) perfusion imaging with a different automated software with the aim of comparing mismatch eligibility and outcomes. Methods EXTEND baseline perfusion imaging data were reprocessed using autoMIStar software to identify patients who were eligible based on the same target mismatch criteria as per the original trial. Results From the 225 patients fulfilling RAPID-based mismatch criteria randomized in the EXTEND study, 196 (87%) patients met the revised mismatch criteria. Most common reasons for not meeting revised criteria were core >70 ml (n = 9), and no perfusion lesion/lack of penumbral tissue (n = 20). The revised perfusion lesion volumes were significantly smaller compared to the original RAPID volumes (median 68 ml IQR 34-102 ml vs. 42 ml 16-92 ml, p = 0.036). Of the patients who met the revised mismatch criteria, 40% receiving alteplase had modified Rankin Scale (mRS) 0-1 at 3-month compared to 28% with placebo (Adjusted Odds Ratio (OR) = 2.23, CI 1.08-4.58, p = 0.028). In contrast, in the original mismatch cohort, 35% receiving alteplase had mRS 0-1 at 3-month compared to 30% with placebo (adjusted OR = 1.88, p = 0.056). Conclusions These data reinforce the benefit of alteplase in the later time window, and suggest that differences in automated perfusion imaging software outputs may be clinically relevant.
  • Martinez-Majander, Nicolas; Gordin, Daniel; Joutsi-Korhonen, Lotta; Salopuro, Titta; Adeshara, Krishna; Sibolt, Gerli; Curtze, Sami; Pirinen, Jani; Liebkind, Ron; Soinne, Lauri; Sairanen, Tiina; Sinisalo, Juha; Lehto, Mika; Groop, Per-Henrik; Tatlisumak, Turgut; Putaala, Jukka (2021)
    Background The aim of this study was to assess the association between endothelial function and early-onset cryptogenic ischemic stroke (CIS), with subgroup analyses stratified by sex and age groups. Methods and Results We prospectively enrolled 136 consecutive patients aged 18 to 49 years (median age, 41 years; 44% women) with a recent CIS and 136 age- and sex-matched (+/- 5 years) stroke-free controls. Endothelial function was measured with an EndoPAT 2000 device and analyzed as tertiles of natural logarithm of reactive hyperemia index with lower values reflecting dysfunction. We used conditional logistic regression adjusting for age, education, hypertension, diabetes mellitus, dyslipidemia, current smoking, heavy drinking, obesity, and diet score to assess the independent association between endothelial function and CIS. Patients in the lowest tertile of natural logarithm of reactive hyperemia index were more often men and they more frequently had a history of dyslipidemia; they were also more often obese, had a lower diet score, and lower high-density lipoprotein cholesterol. In the entire cohort, we found no association in patients with endothelial function and CIS compared with stroke-free controls. In sex- and age-specific analyses, endothelial dysfunction was associated with CIS in men (adjusted odds ratio [OR], 3.50 for lowest versus highest natural logarithm of reactive hyperemia index tertile; 95% CI, 1.22-10.07) and in patients >= 41 years (OR, 5.78; 95% CI, 1.52-21.95). These associations remained significant when dyslipidemia was replaced with the ratio of total to high-density lipoprotein cholesterol. Conclusions Endothelial dysfunction appears to be an independent player in early-onset CIS in men and patients approaching middle age.
  • Campbell, Bruce C. V.; Mitchell, Peter J.; Churilov, Leonid; Keshtkaran, Mahsa; Hong, Keun-Sik; Kleinig, Timothy J.; Dewey, Helen M.; Yassi, Nawaf; Yan, Bernard; Dowling, Richard J.; Parsons, Mark W.; Wu, Teddy Y.; Brooks, Mark; Simpson, Marion A.; Miteff, Ferdinand; Levi, Christopher R.; Krause, Martin; Harrington, Timothy J.; Faulder, Kenneth C.; Steinfort, Brendan S.; Ang, Timothy; Scroop, Rebecca; Barber, P. Alan; McGuinness, Ben; Wijeratne, Tissa; Phan, Thanh G.; Chong, Winston; Chandra, Ronil V.; Bladin, Christopher F.; Rice, Henry; de Villiers, Laetitia; Ma, Henry; Desmond, Patricia M.; Meretoja, Atte; Cadilhac, Dominique A.; Donnan, Geoffrey A.; Davis, Stephen M.; EXTEND-IA Investigators (2017)
    Background: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. Methods: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014). Results: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplaseonly group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. c Conclusion: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.
  • Pirinen, Jani; Kuusisto, Jouni; Martinez-Majander, Nicolas; Sinisalo, Juha; Pöyhönen, Pauli; Putaala, Jukka; Järvinen, Vesa (2021)
    Introduction: Ischemic stroke in young patients often remains cryptogenic, that is, no underlying reason can be found. Some of these strokes may originate in the heart. Left ventricular (LV) dynamic volumetry and strain analysis are relatively new and promising methods for evaluating LV function. Methods: In this pilot study, we recruited 30 young (18-50 years) patients with cryptogenic ischemic stroke and 30 age- and sex-matched controls from the SECRETO study (NCT01934725). The LV systolic function was assessed by LV volumetry (ejection fraction, peak emptying rate, and time to peak emptying rate). The longitudinal systolic function was assessed by speckle tracking strain and strain rate imaging, and by tissue velocity imaging derived MAD (mitral annular displacement) and septal S'. Results: Stroke patients had less vigorous global longitudinal strain (median -18.9, interquartile range 3.3), compared to healthy controls (median -20.0, interquartile range 2.8), P = .010. There was no statistically significant differences in septal S', MAD, global longitudinal strain rate, or dynamic volumetry-derived parameters between the two groups. Conclusions: Young cryptogenic stroke patients have subtly altered systolic function compared to healthy controls, found merely with longitudinal strain analysis. This infers that the heart may play a role in the pathogenesis of cryptogenic ischemic stroke.
  • Suomalainen, Olli P.; Abou, Ahmed Elseoud; Martinez-Majander, Nicolas; Tiainen, Marjaana; Valkonen, Kati; Virtanen, Pekka; Forss, Nina; Curtze, Sami (2022)
    Objectives Current guidelines for recanalization treatment are based on the time elapsed between symptom onset and treatment and visualization of existing penumbra in computed tomography perfusion (CTP) imaging. The time window for treatment options relies on linear growth of infarction although individual infarct growth rate may vary. We aimed to test how accurately the estimated follow-up infarct volume (eFIV) can be approximated by using a linear growth model based on CTP baseline imaging. If eFIV did not fall within the margins of +/- 19% of the follow-up infarct volume (FIV) measured at 24 h from non-enhanced computed tomography images, the results would imply that the infarct growth is not linear. Materials and Methods All consecutive endovascularly treated (EVT) patients from 11/2015 to 9/2019 at the Helsinki University Hospital with large vessel occlusion (LVO), CTP imaging, and known time of symptom onset were included. Infarct growth rate was assumed to be linear and calculated by dividing the ischemic core volume (CTPcore) by the time from symptom onset to baseline imaging. eFIV was calculated by multiplying the infarct growth rate with the time from baseline imaging to recanalization or in case of futile recanalization to follow-up imaging at 24 h, limited to the penumbra. Collateral flow was estimated by calculating hypoperfusion intensity ratio (HIR). Results Of 5234 patients, 48 had LVO, EVT, CTP imaging, and known time of symptom onset. In 40/48 patients (87%), infarct growth was not linear. HIR did not differ between patients with linear and nonlinear growth (p > .05). As expected, in over half of the patients with successful recanalization eFIV exceeded FIV. Conclusions Infarct growth was not linear in most patients and thus time elapsed from symptom onset and CTPcore appear to be insufficient parameters for clinical decision-making in EVT candidates.
  • Järvinen, Elli Katariina (Helsingin yliopisto, 2021)
    Ischemic stroke is a complex disease involving multiple pathophysiological mechanisms. To date, many therapeutic intervention strategies such as anti-inflammatory treatments have been tested, but none of them has been successful. Previous studies have shown that mesencephalic astrocyte-derived neurotrophic factor (MANF) improves stroke recovery and increases the expression of phagocytosis related genes. In this study, the phagocytic and inflammatory effect of monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), complement component 3 (C3), adhesion G protein-coupled receptor E1 (ADGRE1), MER receptor tyrosine kinase (MerTK) and mesencephalic astrocyte-derived neurotrophic factor (MANF) on microglia were studied simultaneously for the first time. The phagocytosis related genes were transiently transfected into a microglial cell line and studied in vitro utilizing phagocytosis assay, fluorescence-activated cell sorting, Western blot and enzyme-linked immunosorbent assay. MCP-1, M-CSF and C3a were shown to enhance microglial phagocytosis without inducing a pro-inflammatory response. In addition, MerTK induces phagocytosis and the synthesis of pro-inflammatory cytokines. In conclusion, the real therapeutic potential of MCP-1, M-CSF, C3a and MerTK in stroke treatment should be further characterized and tested in vivo.
  • Saarela, Marika; Mustanoja, Satu; Pekkola, Johanna; Tyni, Tiina; Hernesniemi, Juha; Kivipelto, Leena; Tatlisumak, Turgut (2017)
    Background and purpose Moyamoya vasculopathy, a rare steno-occlusive progressive cerebrovascular disorder, has not been thoroughly studied in Caucasian populations. We established a registry of Finnish patients treated at the Helsinki University Hospital, to collect and report demographic and clinical data. Methods We collected data both retrospectively and prospectively from all the patients with a moyamoya vasculopathy referred to our hospital between January 1987 and December 2014. All patients underwent a neurological outpatient clinic visit. Results We diagnosed 61 patients (50 females, 10 children) with moyamoya vasculopathy. The mean age at the disease-onset was 31.517.9 years. The two most common presenting symptoms were ischemic stroke (n=31) and hemorrhage (n=8). Forty-four percent underwent revascularization surgery, and 70% were prescribed antithrombotic treatment. Conclusions The results support in part the Western phenotype of the disease considering the later presentation and larger female predominance compared to the Asian moyamoya vasculopathy reports. However, the proportion of ischemic strokes and hemorrhagic strokes is closer to Japanese population than German population. The absence of familial cases points to a different genetic profile in the Finnish patients.
  • Tolppanen, Heli (Helsingfors universitet, 2010)
    Ischemic stroke in young adults with patent foramen ovale (PFO) and/or atrial septal aneurysm is underinvestigated. Methods: We investigated 86 such patients (age 16-49 years) with long-term follow-up. Results: Most patients recovered well, one died and 15 retired prematurely due to the index stroke. Seven patients underwent PFO closure. Few stroke recurrences occurred (4%) either on aspirin or warfarin during the 6.5 years of follow-up. Conclusions: Our data suggest good outcome, low morbidity, and low recurrence. Finding the best secondary prevention measures requires randomized trials.
  • Haula, Tuuli-Maria; Puustinen, Juha; Takala, Mari; Holm, Anu (2020)
    Objectives Presence of sleep-disordered breathing (SDB) affects negatively recovery from stroke. The aim of this study is to evaluate the relationships between sleep-disordered breathing (SDB) and outcome measures in Finnish stroke unit cohort: mRS, need of rehabilitation and hospitalization time. Material and Methods An observational longitudinal study consisted of 95 patients referred to the Stroke Unit of Satakunta Hospital District over a period of November 2013 to March 2016. Patients were tested for SDB within 72 hr from the hospital admission because of ischemic stroke or TIA. The patients underwent polysomnography with NOX T3 wireless recorder. Results There are 37% (n = 35) non-OSA patients, 20% (n = 19) of patients have mild obstructive sleep apnea (OSA) and 39% (n = 37) have moderate/severe OSA and 4% (n = 4) have CSA. Patients with OSA have higher proportion of disability scores of mRS 3-5 (38%) compared to non-OSA (11%) and mild OSA (5%) patients on registration day (mRS0), and the same trend is seen at hospital discharge 35% versus 9% and 5%. (p = .009). Proportion of patients with OSA who needed rehabilitation is 65% (n = 19) versus non-OSA patients 17.5% (n = 4) and mild OSA patients 17.5% (n = 4;p = .039). We observed longer duration of hospitalization (5-15 days) in 29% of OSA patients compared to mild OSA patients 47% and OSA patients 54%. (p = .045). Conclusion Ischemic stroke patients with OSA have higher disability, higher need of rehabilitation, and longer hospitalization length. Prescreening tools for recognizing these stroke patients in acute phase could be valuable. That could result in earlier initiation of treatment and might prevent worse recovery from stroke.
  • NAVIGATE ESUS Investigators; Martinez-Majander, Nicolas; Ntaios, George; Liu, Yan Yun; Ylikotila, Pauli; Joensuu, Heikki; Saarinen, Jukka; Tiainen, Marjaana; Tatlisumak, Turgut (2020)
    Abstract Background Cancer is a frequent finding in ischemic stroke patients. We investigated the frequency of cancer among participants in NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban. Methods Trial participation required a recent embolic stroke of undetermined source (ESUS). Patients? history of cancer was recorded at time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischemic stroke, major bleeding, and all-cause mortality were compared between patients with cancer and without cancer. Results Among 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban (254[7.0%] with cancer) and 3604 patients to aspirin (289[8.0%] with cancer). The annual rate of recurrent ischemic stroke was 4.5% in non-cancer patients in rivaroxaban arm and 4.6% in the aspirin arm (hazard ratio, HR 0.98 [95% CI 0.78-1.24]). In cancer patients, the rate of recurrent ischemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43 [95% CI 0.71-2.87]). Among cancer patients, the annual rate of major bleeds was nonsignificantly higher for rivaroxaban than aspirin (2.9% versus 1.1%; HR 2.57 [95% CI 0.67-9.96], P for interaction 0.95). All-cause mortality was similar in both groups. Conclusions Our exploratory analyses show that patients with ESUS and a history of cancer had similar rates of recurrent ischemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds.
  • Anttila, Jenni E.; Pöyhönen, Suvi; Airavaara, Mikko (2019)
    A stroke affecting the somatosensory pathway can trigger central post-stroke pain syndrome (CPSP). The symptoms often include hyperalgesia, which has also been described in rodents after the direct damage of the thalamus. Previous studies have shown that hemorrhagic stroke or ischemia caused by vasoconstriction in the thalamus induces increased pain sensitivity. We investigated whether inducing secondary damage in the thalamus by a cortical stroke causes similar pain hypersensitivity as has previously been reported with direct ischemic injury. We induced a focal cortical ischemia-reperfusion injury in male rats, quantified the amount of secondary neurodegeneration in the thalamus, and measured whether the thalamic neurodegeneration is associated with thermal or mechanical hypersensitivity. After one month, we observed extensive neuronal degeneration and found approximately 40% decrease in the number of NeuN+ cells in the ipsilateral thalamus. At the same time, there was a massive accumulation-a 30-fold increase-of phagocytic cells in the ipsilateral thalamus. However, despite the evident damage in the thalamus, we did not observe thermal or mechanical sensitization. Thus, thalamic neurodegeneration after cortical ischemia-reperfusion does not induce CPSP-like symptoms in rats, and these results suggest that direct ischemic damage is needed for CPSP induction. Despite not observing hyperalgesia, we investigated whether administration of cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) into the ipsilateral thalamus would reduce the secondary damage. We gave a single injection (10 mu g) of recombinant CDNF or MANF protein into the thalamus at 7 days post-stroke. Both CDNF and MANF treatment promoted the functional recovery but had no effect on the neuronal loss or the amount of phagocytic cells in the thalamus.
  • Haula, Tuuli-Maria; Puustinen, Juha; Takala, Mari; Holm, Anu (2021)
    Background and Aims Presence of sleep-disordered breathing (SDB) and especially obstructive sleep apnea (OSA) is a known risk factor for ischemic stroke. Additionally, SDB effects negatively on recovery after stroke. Up to one fourth of strokes are present on awakening. The link between OSA and wake-up stroke (WUS) has been suggested. We aim to determine the association between OSA and WUS in a Finnish stroke unit cohort. Material and Methods An observational prospective longitudinal study consisted of 95 TIA (transient ischemic attack) and mild to moderate stroke patients referred to a Stroke Unit in Finland. Respiratory polygraphy was performed within 72 h of hospital admission. Patients were classified into WUS and non-WUS, and functional outcome measures (mRS, rehabilitation, hospitalization time) were collected. Functional outcomes and prevalence of OSA were compared between non-WUS and WUS. Results OSA (AHI > 15/h) was more frequent among WUS than non-WUS (71% and 36%, respectively, p = 0.009). Functional outcome measured with mRS was worse in patients with WUS than non-WUS on registration day and at hospital discharge (p = 0.001). Need for rehabilitation in WUS was 43% of cases compared to 23% of non-WUS (p = 0.067). Hospitalization time was longer (5-15days) in 55% of WUS and 41% of non-WUS patients (p = 0.261). Conclusion Moderate-to-severe OSA is related to WUS compared to non-WUS. In addition, WUS have worse short-term outcomes measured in mRS. Further studies are needed to determine if OSA is causally linked to WUS.