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.

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.

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.

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.

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.

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.

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.