Cause Of Cerebral Ischemia Research Articles

Premature newborns with intraventricular hemorrhage do not have vasospasm pattern by cranial Doppler ultrasound: A pilot study.

Preterm neonates are at risk for neurodevelopmental impairment, especially those with intraventricular hemorrhage (IVH). Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH) in adult population, but it is unknown if preterm neonates with IVH may develop it. We prospectively enrolled premature newborns < 32weeks with IVH and without IVH. All patients received serial transcranial sonography through the temporal window of the middle cerebral artery, anterior cerebral artery, posterior cerebral artery, and the internal carotid artery with transcranial Doppler sonography days 2, 4, and 10 of life. Cerebral blood velocities (CBFVs) were measured including median velocity flow (MV), peak systolic velocity (PSV), and maximum end-diastolic velocity (EDV). Resistance index and pulsatility index were calculated. VSP was defined as an increase of 50% in the baseline velocity per day and/or a Lindegaard ratio higher than 3. Fifty subjects were enrolled. None of the patients with IVH showed elevation of MV or a Lindegaard ratio > 3. There were no differences between IVH and without IVH groups regarding resistance index and pulsatility index. Conclusion: Preterm infants with IVH do not present a pattern of VSP analyzed by Doppler transcranial ultrasound in this pilot study. What is Known: • In adult population with subarachnoid hemorrhage the most treatable cause of cerebral ischemia is due cerebral vasospasm but is unknown if premature newborn may have vasospasm due the extravasation of blood in the context of intraventricular hemorrhage What is New: •In this pilot study we did not find in premature newborn with intraventricular hemorrhage signs of vasoespam measured by transcranial color doppler ultrasound.

The Effects of IRL-1620 in Post-ischemic Brain Injury: A Systematic Review and Meta-analysis of Experimental Studies.

Sovateltide (IRL-1620), an endothelin B receptor agonist, has previously demonstrated neuroprotective and neuroregenerative effects in animal models of acute ischemic stroke. Recently, clinical trials indicated that it could also be effective in humans with stroke. Here, we systematically investigate whether IRL-1620 may be used for the treatment of ischemia-induced brain injury. A systematic review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. MEDLINE (PubMed) and Scopus databases were searched for eligible studies up to December 2022. The databases ClinicalTrials.gov and Pharmazz Inc. were screened for unpublished or ongoing trials. Only studies in English were evaluated for eligibility. Meta-analysis of the included studies was also conducted. Finally, seven studies were included in the review, all in animal rat models because of scarcity of clinical trials. Six studies, all in middle cerebral artery occlusion (MCAO) models, were selected for meta-analysis. In the two studies assessing mortality, no deaths were reported in the IRL-1620 group 24h after MCAO, whereas the vehicle group had almost a five times higher mortality risk (risk ratio 5.3, 95% confidence interval 0.7-40.1, I2 = 0%). In all five studies evaluating outcome on day 7 after MCAO, IRL-1620 was associated with statistically significantly lower neurological deficit and improved motor performance compared with the vehicle. Infract volume, differentiation potential of neuronal progenitor cells, and mitochondrial fate also improved with IRL-1620 administration. According to the above, in animal MCAO models, IRL-1620 enhanced neurogenesis and neuroprotection and improved outcome. Future studies are needed to expand our understanding of its effects in human study participants with acute ischemic stroke as well as in other common causes of cerebral ischemia including cardiac arrest.

Coarctation of the aorta, carotid artery stenosis and aberrant right subclavian artery as a rare cause of cerebral ischemia in a primigravid woman.

Coarctation of the aorta, carotid artery stenosis and aberrant right subclavian artery as a rare cause of cerebral ischemia in a primigravid woman.

Enhanced external counter pulsation therapy in patients with symptomatic and severe intracranial steno-occlusive disease: a randomized clinical trial protocol.

ClinicalTrials.gov, Identifier: NCT03921827.

Update on Management of Symptomatic Carotid Stenosis

Carotid artery stenosis (CAS) is one of the leading causes of cerebral ischemia and stroke.7 When plaque builds up in the internal carotid artery, it blocks blood flow to the brain. Oftentimes, this condition only comes to light after a patient experiences a stroke or stroke-like symptoms. When this occurs, cholesterol-lowering medications and blood thinners can help to increase blood flow to the brain. However, if the plaque is so large that it severely narrows the lumen of the artery, surgery may be required to restore blood flow to the brain. Patients with severe stenosis can undergo procedures such as carotid endarterectomies (CEA), stenting, and transcarotid artery revascularization (TCAR) for this purpose. In this review, we discuss these procedures and which patients warrant which type of intervention. We look at the pathophysiology of internal carotid artery stenosis and current treatment options while highlighting emerging treatment options. This review aims to increase understanding of the management of symptomatic carotid artery stenosis as well as provide a groundwork for more innovative treatments.

Abstract WP198: Microatherosclerosis Is A Common But Often Overlooked Cause Of Ischemic Stroke

Background: Clinicians frequently ascribe lacunar strokes to lipohyalinosis/arteriosclerosis, but classic neurovascular pathology studies lacunar infarcts are more often due to “microatherosclerosis” (small atheromatous plaque within penetrating arteries). The proportion of lacunar infarcts in clinical practice due to microatherosclerosis has not been previously quantified. Methods: The findings in all reported neuropathologic studies were catalogued for the 4 lacunar syndromes of pure motor hemiparesis (PMH), pure sensory stroke (PSS), dysarthria-clumsy hand (DCH), and ataxic hemiparesis (AH). Systematic meta-analyses, per PRISMA guidelines, were performed of large clinical series of consecutive ischemic stroke patients to delineate: 1) the proportion of all ischemic strokes due to lacunar infarcts, and 2) among the lacunar events, the relative frequencies of PMH, PSS, DCH, and AH. Results: Neuropathology showed: PMH caused by microatherosclerosis in 64%, parent artery ostial atherosclerosis in 7%, lipohyalinosis in 14%, and embolism in 14%; PSS caused by lipohyalinosis in 100%; DCH caused by embolism in 100%; and AH caused by microatherosclerosis in 100%. In the systematic review, among 22 large ischemic stroke series enrolling 25,260 patients, frequency of lacunar infarct was 18.8% (±5.1%). Among 5 large series enrolling 838 lacunar infarct patients, subtype frequencies were: PMH 45.5%, PSS 17.7%, DCH 7.4%, and AH 2.9% (with the remainder sensorimotor stroke and less common lacunar syndromes). Quantitative synthesis indicated that, among lacunar strokes, microatherosclerosis is the most common cause (44%), followed by lipohyalinosis (33%), and parent artery athero or embolism (combined 23%). Among all ischemic strokes, microatherosclerosis is the cause in 6%. Conclusion: Microatherosclerotic plaque within a penetrating artery is a common cause of cerebral ischemia, accounting for 6% of all ischemic strokes. This substantial burden of microatherosclerosis is the likely pathophysiologic basis for the benefits of thrombolytic and statin therapy in lacunar ischemic stroke.

Screening for atrial fibrillation in the general population: experience from a cardiovascular risk campaign in the Emilia-Romagna Region

Atrial fibrillation (AF) is a major cause of cerebral ischemia, and its early detection may impact on health. Both invasive and non-invasive devices can be used for the diagnosis of AF. The aim of our study was to estimate the prevalence of AF using a single-lead ECG device (MyDiagnostickTM) on an adult, asymptomatic population during a screening campaign. A total of 2547 subjects underwent AF screening. The device detected an arrhythmia in 42 subjects (1.65%), and AF was confirmed on 12-lead ECG in 14 (0.55%) of them. The prevalence of confirmed AF increased in subjects over 65 years of age (1.21%) or with a CHA2DS2-VASc score ≥2 in males or ≥3 in females (1.33%). Furthermore, heart failure (odds ratio [OR] 8.62, 95% confidence interval [CI] 1.87-39.6, p=0.006) and diabetes (OR 4.55, 95% CI 1.25-16.5, p=0.021) significantly increased the risk of AF. During a screening campaign, the diagnosis of AF increases when subjects with a high thromboembolic risk are selected.

Prevalence, risk factors, and long-term outcomes of cerebral ischemia in hospitalized COVID-19 patients - study rationale and protocol of the CORONIS study: A multicentre prospective cohort study.

Background:COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown.Patients and methods:CORONavirus and Ischemic Stroke (CORONIS) is a multicentre prospective cohort study investigating the prevalence, risk factors and long-term incidence of (silent) cerebral ischemia, and the long-term functional outcome among patients with COVID-19. We aim to include 200 adult patients hospitalized with COVID-19 without symptomatic ischemic stroke to investigate the prevalence of silent cerebral ischemia compared with 60 (matched) controls with MRI. In addition, we will identify potential risk factors and/or causes of cerebral ischemia in COVID-19 patients with (n = 70) or without symptomatic stroke (n = 200) by means of blood sampling, cardiac workup and brain MRI. We will measure functional outcome and cognitive function after 3 and 12 months with standardized questionnaires in all patients with COVID-19. Finally, the long-term incidence of (new) silent cerebral ischemia in patients with COVID-19 will be assessed with follow up MRI (n = 120).Summary:The CORONIS study is designed to add further insight into the prevalence, long-term incidence and risk factors of cerebral ischemia, and the long-term functional outcome in hospitalized adult patients with COVID-19.

Outcomes of Carotid Endarterectomy with Primary Closure

Background: Cerebrovascular ischemic cases are 3rd leading cause of fatality and neurologic dysfunction in adults. Atherosclerotic lesions outside the carotid cranial circulation are main cause of cerebral ischemia in almost 10-20 percent cases and carotid endarterectomy (CEA) has been proved beneficial for patients with severe carotid artery stenosis to prevent acute cerebrovascular events. Current study is conducted to assess the short-term outcomes of carotid endarterectomy among patients in terms of morbidities and mortalities at our institution during the study period. Material and Methods: This cross-sectional analytical study was carried out at Combined Military Hospital, Rawalpindi during August 2019 to July 2021 to analyze the short-term outcomes of carotid endarterectomy (CEA) with primary closure. All the patients who underwent carotid endarterectomy (CEA) with primary closure during study duration were included in the study. Patients who received selective shunting if Electro Encephalogram (EEG) changes noted were excluded from study. Data was collected after taking verbal consent by using preformed questionnaire. Frequency of morbidities like bleeding, infection, stroke, transient ischemic attacks (TIA), myocardial infarction, repeat operation and revision with stent were noted within postoperative period of one month. Frequency of mortalities in one-month postoperative period among patients undergoing carotid endarterectomy was also calculated. Data was entered and analyzed by using SPSS version 22. Results: Total 198 patients who underwent carotid endarterectomy with primary closure during study duration were included in the study. Age range of the study participants was between 35 to 80 years. Male patients were 107 (54.04%). The comorbidities evaluated in the study participants showed that 172 (86.87%) patients were hypertensive and 73 (36.87%) has diabetes mellitus. The most frequent postoperative morbidities among patients were bleeding and repeat operation. Conclusion: It is concluded that carotid endarterectomy with primary closure is a safe and effective surgical means of stroke prevention.

Clinical Study of Cerebral Ischemia in Moyamoya Disease from the View of Development of the Anterior Choroidal Artery

ObjectivesThe anterior choroidal artery (AchA) is one of the collateral vessels in moyamoya disease (MMD). The incidence of cerebral ischemia in MMD was analyzed through the association between development of the AchA and advancement of MMD stage. Materials and MethodsTwelve patients of MMD with cerebral ischemia (infarction; 9 patients, transient ischemic attack; 3 patients) were enrolled. Advancement of MMD was evaluated using Suzuki's stage. The grades in Suzuki's stage were subclassified into a non-progressive stage for grades 1 and 2, and a progressive stage for grades 4 and 5. Dilatation of the AchA was judged as the presence of development of this artery. Development of the AchA was grouped into proximal type and proximal and distal type. ResultsMost frequent locations of infarcts were the anterior and parietal lobes in 6 patients each. Development of the AchA was confirmed on the ischemic side in all patients and on the non-ischemic side in 9 patients. Development of the AchA in the progressive stage was limited in the proximal and distal type on both sides. Development of the AchA in the non-progressive stage was the proximal type on the ischemic side. ConclusionsThe cause of cerebral ischemia was possibly associated with inadequate blood supply of the AchA in the non-progressive stage, and the lower blood flow from the internal carotid artery (ICA) in the progressive stage. Disparity between collateral blood flow from the AchA and the blood flow from the ICA was considered to relate to incidence of cerebral ischemia in MMD.

Internal carotid and vertebral artery dissections - a comparison of clinical, radiological and prognostic characteristics.

To examine whether baseline characteristics, potential risk factors, clinical symptoms, radiological presentation, and long-term outcomes differ between internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD). Cervical artery dissection (CeAD) is a major cause of cerebral ischaemia in young adults. Its clinical course is highly variable, resulting in challenges in making a proper diagnosis. We performed a retrospective analysis of 31 patients (mean age 42.2 years) with CeAD (18 with ICAD, 13 with VAD) treated in our neurology department from 2008 to 2018. Appropriate imaging confirmed the diagnosis of CeAD. Patients with ICAD presented Horner syndrome significantly more often (44.4% vs 7.6%; p = 0.04). Patients with VAD more often had ischaemic events (ischaemic stroke, TIA or transient blindness) (84.6% vs 44.6%; p = 0.0032). Ischaemic stroke was more severe in patients with ICAD [(median NIHSS 6, interquartile range 4-12) vs VAD (median NIHSS 4, interquartile range 1.5-5.5), p = 0,03]. Occlusion occurred more often in patients with VAD (69.2% vs 22.2%; p = 0.013). Most patients had a favourable outcome (mRS 0-2). In a series of patients with CeAD, we observed significant differences between VAD and ICAD in terms of clinical symptoms and radiological features.

Primary involvement of neurovascular coupling in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent monogenic cause of cerebral ischemia, but reliable biomarkers to monitor the disease are lacking. To evaluate cerebral autoregulation (CA), vasoreactivity (VR), and neurovascular coupling (NVC) in CADASIL patients through a battery of dynamic transcranial Doppler tests. We screened our database for all pre-dementia CADASIL cases. We monitored cerebral blood flow velocity (CBFV) with transcranial Doppler, blood pressure, and expiratory carbon dioxide (CO2) non-invasively. CA was assessed by transfer function from the spontaneous oscillations of blood pressure to CBFV, VR with inhalation of CO2 at 5%, and hyperventilation and NVC by the CBFV response to visual stimulation. We included 27 CADASIL patients and 20 healthy controls with similar age and sexes. CA and VR were similar between groups. However, NVC was significantly affected in CADASIL patients, with lower magnitudes of CBFV upsurge (overshoot 19 ± 5 vs 26 ± 6%, p = 0.013; gain 12 ± 7 vs 17 ± 5%, p = 0.003) and altered time behavior during visual stimulation (natural frequency 0.18 ± 0.06 vs 0.24 ± 0.06Hz, p = 0.005; rate time 0.7 ± 1.7 vs 2.7 ± 3.5s, p = 0.025). Our results express a primary and selective involvement of the neurovascular unit in CADASIL rather than a generalized cerebral vasomotor disturbance. Functional cerebrovascular testing could be useful in patient evaluation and monitoring.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Low Cerebral Oxygenation Is Associated with Cognitive Impairment in Chronic Hemodialysis Patients

Background/Aims: High rates of cognitive impairment (CI) are an alarming problem in patients undergoing chronic hemodialysis (HD). Its pathophysiology remains unclear and there are indications that brain ischemia might be one of the key causes. Cerebral tissue oxygenation, as measured by near-infrared spectroscopy, is known to be decreased in HD patients. However, it is unknown whether CI is associated or not associated with lower cerebral oxygenation in these patients. The primary aim of our study was to probe this possible association. Our secondary aim was to assess other factors possibly related to cerebral ischemia and CI. Methods: Thirty-nine patients treated by chronic HD were included in this cross-sectional study. All measurements were performed before the initiation of an HD session. The Montreal Cognitive Assessment (MoCA) was administered according to published recommendations. Regional saturation of oxygen (rSO2) of the left frontal lobe was measured using the INVOS 5100C device. Basic medical history and laboratory data were recorded, and handgrip strength was analyzed. We used the unpaired t test to compare the rSO2 and other variables between cognitively normal patients (MoCA score ≥26) and those who displayed CI (MoCA score <26). Multiple linear regression analysis was used to adjust for principal confounders. Results: Cognitively impaired patients had lower brain rSO2 values compared to cognitively normal patients (48 ± 9 vs. 57 ± 10%, p = 0.01). Among other variables, higher red cell distribution width (15.8 ± 1.9 vs. 13.8 ± 1.6%, p = 0.01) and lower hand grip strength (49.2 ± 23.3 vs. 99.3 ± 31.4 lbs, p < 0.001) also displayed a significant association with CI. The relation between rSO2 and MoCA score was significant after adjustment for age and gender (p = 0.007). Conclusion: Decreased brain oxygenation is associated with weaker cognitive performance in patients undergoing chronic HD. Further understanding the causes of cerebral ischemia in HD patients could lead to the prevention of cognitive decline in this population.

Cerebral Ischemia in Active Giant Cell Arteritis: Clinical and Diagnostic Aspects in 36 Patients

Abstract Background: Cerebral ischemia (CI) is an uncommon, sometimes life-threatening complication of active giant cell arteritis (aGCA) due to affection of the precerebral arteries. Aim of the Study: To analyze and describe clinical findings and results of multimodal vascular imaging of the craniocervical arteries. Patients and Methods: Out of 317 aGCA patients, 36 (11%) presented with CI. All patients underwent vascular imaging including ultrasonography (US) of the temporal arteries (TA) and precerebral arteries, biopsies were taken in 27, CTA/MRA were performed in 21 and FDG-PET in 18 patients. Results: In 72% of patients, CI was located in the posterior circulation and in14% of patients, it occurred after beginning of steroid therapy. TA were normal on clinical and US examination in 10 patients (with normal biopsies in 5) but PET demonstrated GCA of the precerebral arteries in 9 of them. Abnormalities of the precerebral arteries typical of GCA were demonstrated by US as halos in 67% (in 61% halos of the vertebral arteries), CTA/MRA in 43% and PET in 72% of patients. Concurrent etiologies for CI were evident in 19% of patients (including &gt;50% ICA stenosis in 3 and atrial fibrillation in 4 patients). Conclusions: Awareness for GCA as a cause of CI requiring specific diagnostic and therapeutic steps is important. US, CTA, MRA and PET are valuable diagnostic tools for rapid detection of GCA involving the precerebral arteries in different stages of the disease even if the TA look normal.

Carotid artery stenting

### Learning objectives After reading this article the reader should: In western countries, stroke is the fourth leading cause of death, after heart disease, cancer and chronic respiratory diseases.1 Carotid...

Predicting Paroxysmal Atrial Fibrillation in Cerebrovascular Ischemia Using Tissue Doppler Imaging and Speckle Tracking Echocardiography

Often the underlying cause of cerebral ischemia (CI) cannot be found during a routine diagnostic investigation, but paroxysmal atrial fibrillation (PAF) could be the culprit. The objective of the study is to investigate whether advanced echocardiography improves the diagnostic approach for PAF in CI. The study included 286 CI patients with an echocardiogram in sinus rhythm. Patients were divided by PAF occurrence (PAF: n = 86, non-PAF: n = 200). PAF was defined as 1 or more reported episodes of atrial fibrillation. Echocardiograms consisted of conventional measures, tissue Doppler imaging (TDI), and speckle tracking. TDI was performed to acquire myocardial peak velocities during systole/ventricular contraction (global s'), early diastole/ventricular filling (global e'), and late diastole/atrial contraction (global a'). Speckle tracking was performed for myocardial strain analysis, thereby retrieving global longitudinal strain and global strain rate (s, e, a) values. Patients with PAF exhibited significantly impaired atrial contractile measures: global a' (-7.0 cm/second versus -5.7 cm/second, P < .001) and global strain rate a (.97 second(-1) versus .81 second(-1), P < .001). Both were univariable markers of PAF, and along with age remained the only independent significant determinants of PAF after multivariable logistic regression. Area under the curve (AUC) for age, global a', and global strain rate a significantly exceeded AUC for age alone (.79 versus .76, P = .032). Cutoff values with the highest sensitivity and specificity for these 3 parameters improved the diagnostic accuracy (sensitivity = 97%, specificity = 32%, negative predictive value = 95%, and positive predictive value = 38%). Atrial contractile measures by advanced echocardiography are significant determinants of PAF in CI. However, there is no discriminatory power to make them clinically useful at the current moment.

Kukoamine B, an amide alkaloid, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro

A major cause of cerebral ischemia is overactivation of the N-methyl-D-aspartate receptors (NMDARs). Therefore, NMDAR antagonists are needed for the treatment of cerebral ischemia. In our research, KuB protected the SH-SY5Y cells against NMDA-induced injury, apoptosis, LDH release and MMP loss. In addition, KuB could decrease MDA levels while increasing SOD activity. Meanwhile, KuB decreased NADPH oxidase-mediated ROS production, inhibited Ca2+ influx, and increased the Bcl-2/Bax ratio. Furthermore, KuB not only down-regulated expression of the NR2B subunit of NMDAR but also actively modulated expression of the signaling molecules downstream of NR2B, including p-ERK, p-CREB, p-AKT and SAPKs. Finally, docking results showed that KuB had a high affinity for NR2B-containing NMDARs. Therefore, we conclude that KuB protected the SH-SY5Y cells from NMDA-induced injury likely by antagonizing NMDARs and reducing oxidative stress.

Link between cerebral blood flow and autonomic function in survivors of internal carotid artery occlusion

PurposeSymptomatic internal carotid artery occlusion (ICAO) is an important cause of cerebral ischemia with poor long-term outcome. Reductions in baroreflex function is reported in carotid atherosclerosis and implicated in increased risk of recurrent cardiovascular events. A distributed network of forebrain regions can exert modulatory influences over the cardio-vagal and baroreflex functions. The successful clinical translation of these approaches offers insights into underlying modulatory mechanisms and to possible therapeutic strategy. MethodsThis study enrolled 20 symptomatic ICAO survivors, 20 patients with small vessel disease (SVD) as risk control, and 20 healthy controls. All underwent a standardized evaluation of cardiovascular autonomic function testing that included baroreflex sensitivity (BRS), Valsalva ratio (VR), and heart rate response to deep breathing (HR_DB). The regional cerebral blood flow (rCBF) of the central autonomic network (CAN) was obtained from arterial spin-labeling magnetic resonance imaging. Parameters of autonomic function between symptomatic ICAO survivors with and those without recurrent cardiovascular events were compared. ResultsValsalva ratio and HR_DB levels were significantly higher in the control group, followed by the SVD and ICAO groups (p=0.009 and p=0.007, respectively). Spontaneous BRS and BRS during the early phase II of Valsalva maneuver levels were both significantly higher in the control group, followed by the SVD and ICAO groups (p<0.001 and p=0.042, respectively). The rCBF of CAN inversely correlated with spontaneous BRS. ConclusionAutonomic dysregulation, including reduced BRS and impaired cardio-vagal function in the convalescent stage ICAO, can persist for a long time. Reduced BRS is inversely correlated with CAN activity.

Intraventricular Air Embolus Causing Ischemic Stroke after Lung Biopsy

Gas embolism is a rare potentially fatal pathology and a recognized cause of cerebral ischemia and stroke [1,2]. It is a dreaded complication following invasive medical procedures, such as transthoracic needle biopsy, traumatic lung injury and decompression accidents [3-7]. Arterial gas embolism is caused by the entry of gas into the pulmonary veins or directly into the arteries of the systemic circulation [8]. Another mechanism takes place when gas enters the arterial circulation through a right-to-left cardiac or intrapulmonary shunt or if passage of bubbles through the pulmonary capillary bed occurs. Injection of 2 ml of air into cerebral circulation can be fatal [9]. Cerebral lesion can result from intracranial artery occlusion, platelet clot development on the gas-blood interface, endothelial lesion or inflammatory activation. The purpose of this study is to report an uncommon cause of stroke following an invasive medical procedure and its management.