Silent Cerebral Infarction Research Articles

Risk factors of Silent Cerebral Infarcts in Patients with Acute Coronary Syndrome Based on MRI Findings

Risk factors of Silent Cerebral Infarcts in Patients with Acute Coronary Syndrome Based on MRI Findings

Silent Infarcts, White Matter Integrity, and Oxygen Metabolic Stress in Young Adults With and Without Sickle Cell Trait.

Individuals with sickle cell anemia have heightened risk of stroke and cognitive dysfunction. Given its high prevalence globally, whether sickle cell trait (SCT) is a risk factor for neurological injury has been of interest; however, data have been limited. We hypothesized that young, healthy adults with SCT would show normal cerebrovascular structure and hemodynamic function. As a case-control study, young adults with (N=25, cases) and without SCT (N=24, controls) underwent brain magnetic resonance imaging to quantify brain volume, microstructural integrity (fractional anisotropy), silent cerebral infarcts (SCI), intracranial stenosis, and aneurysms. Pseudocontinuous arterial spin labeling and asymmetric spin echo sequences measured cerebral blood flow and oxygen extraction fraction, respectively, from which cerebral metabolic oxygen demand was calculated. Imaging metrics were compared between SCT cases and controls. SCI volume was correlated with baseline characteristics. Compared with controls, adults with SCT demonstrated similar normalized brain volumes (SCT 0.80 versus control 0.81, P=0.41), white matter fractional anisotropy (SCT 0.41 versus control 0.43, P=0.37), cerebral blood flow (SCT 62.04 versus control, 61.16 mL/min/100 g, P=0.67), oxygen extraction fraction (SCT 0.27 versus control 0.27, P=0.31), and cerebral metabolic oxygen demand (SCT 2.71 versus control 2.70 mL/min/100 g, P=0.96). One per cohort had an intracranial aneurysm. None had intracranial stenosis. The SCT cases and controls showed similar prevalence and volume of SCIs; however, in the subset of participants with SCIs, the SCT cases had greater SCI volume versus controls (0.29 versus 0.07 mL, P=0.008). Of baseline characteristics, creatinine was mildly elevated in the SCT cohort (0.9 versus 0.8 mg/dL, P=0.053) and correlated with SCI volume (ρ=0.49, P=0.032). In the SCT cohort, SCI distribution was similar to that of young adults with sickle cell anemia. Adults with SCT showed normal cerebrovascular structure and hemodynamic function. These findings suggest that healthy individuals with SCT are unlikely to be at increased risk for early or accelerated ischemic brain injury.

Assessment of functional shunting in patients with sickle cell disease.

Silent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and are thought to be caused by a mismatch between oxygen delivery and consumption. Functional cerebrovascular shunting is defined as reduced oxygen offloading due to the rapid transit of blood through the capillaries caused by increased flow and has been suggested as a potential mechanism underlying reduced oxygenation and SCI. We investigated the venous arterial spin labeling signal (VS) in the sagittal sinus as a proxy biomarker of cerebral functional shunting, and its association with hemodynamic imaging and hematological laboratory parameters. We included 28 children and 38 adults with SCD, and ten healthy racematched adult controls. VS, cerebral blood flow (CBF), velocity in the brain feeding arteries, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured before and after acetazolamide administration. VS was higher in patients with SCD compared to controls (P<0.01) and was increased after acetazolamide administration in all groups (P<0.01). VS was primarily predicted by CBF (P<0.01), but CBF-corrected VS was also associated with decreased CMRO2 (P<0.01). Additionally, higher disease severity defined by low hemoglobin and increased hemolysis was associated with higher CBF-corrected VS. Finally, CMRO2 was negatively correlated with fetal hemoglobin, and positively correlated with lactate dehydrogenase, which could be explained by changes in oxygen affinity. These findings provide evidence for cerebral functional shunting and encourage future studies investigating the potential link to aberrant capillary exchange in SCD.

Comparison of frequency of silent cerebral infarction as assessed by serum neuron specific enolase in patients with non-valvular atrial fibrillation: Warfarin versus direct oral anticoagulant

Background Cerebral infarction in patients with atrial fibrillation (AF) may clinically vary from being silent to catastrophic. Silent cerebral infarction (SCI) is the neuronal injury in the absence of clinically appearent stroke or transient ischaemic attack. Serum neuron specific enolase (NSE) is suggested to be a valid surrogate biomarker that allows to detect recent neuronal injury. We aimed to evaluate the incidence of recent SCI by positive NSE levels in patients with non-valvular AF (NVAF) on oral anticoagulants. Methods Blood samples for NSE were collected from 197 consecutive NVAF patients. NSE levels of greater than 12 ng/ml was considered as positive and suggestive of SCI. Results Patients were mainly female with a mean age of 69 years. Ninety-eight of them (49.7%) were taking warfarin. Mean INR level was 2.3 ± 0.9. Mean CHA2DS2-VASc score of the study population was 3.5 ± 1.5. Seventy-two patients (36.5%) were found to have NSE elevation. They were more likely to have history of chronic heart failure and previous stroke/TIA. Increased left atrial diameter and higher CHA2DS2-VASc were other factors associated with SCI. Patients on DOACs and patients taking aspirin on top of oral anticoagulant treatment were less likely to have SCI. Multivariate analysis demonstrated that increased left atrial diameter (OR: 2.5; 95% CI: 1.52–4; p < 0.001) and use of warfarin (OR: 2.8; 95% CI: 1.37–5.61; p = 0.005) were detected as independent predictors of SCI. Conclusions Our study revealed that DOACs were associated with significantly reduced SCIs compared with warfarin, probably due to more effective and consistent therapeutic level of anticoagulation.

Evolution of Extracranial Internal Carotid Artery Disease in Children With Sickle Cell Anemia.

Cerebral arteriopathy in patients with sickle cell anemia mainly affects the intracranial anterior circulation. However, the extracranial internal carotid artery (eICA) can also be stenosed and responsible for ischemic lesions. In children with sickle cell anemia, we perform routine annual Doppler ultrasound assessment of the eICA and magnetic resonance imaging with 3-dimensional time-of-flight magnetic resonance angiography of the Willis circle and neck arteries in those with abnormal velocity. Our aim was to report the evolution of eICA stenoses from 2011 to the present as a function of therapy in a retrospective case-series study. We hypothesized that chronic transfusion (CTT) would be more effective than hydroxyurea and simple observation on the evolution of eICA stenosis. Eligibility criteria were a history of eICA velocity ≥160 cm/s with a minimum Doppler and magnetic resonance imaging follow-up of 1 year. eICAs were graded for stenosis according to NASCET (The North American Symptomatic Carotid Endarterectomy Trial). Magnetic resonance imaging was investigated for ischemic lesions. Treatment with hydroxyurea and CTT were obtained from the chart review. Fifty-four patients were included. Eight patients had a stroke history. The median (range) follow-up was 4.7 years (1.1-9.2 years). On the first neck magnetic resonance angiography, stenosis was present in 48/54 (89%) patients. Kinking was found in 39/54 (72%) patients. On the last neck magnetic resonance angiography, the proportion of patients with eICA stenosis decreased to 39/54 (72%). ICA occlusion occurred in 5 patients despite CTT. Three patients had carotid webs without intracranial stenosis. The proportion of patients with improvement in stenosis score was 8% with no treatment intensification, 20% with hydroxyurea, and 48% with CTT (P=0.016). The mean (SD) change per year in stenosis score was 0.40 (0.60) without intensification, 0.20 (0.53) with hydroxyurea, and -0.18 (0.55) with CTT (P=0.006). Ischemic lesions were present initially in 46% of patients, and the incidence of progressive ischemic lesions was 2.5 events/100 patient-years. Cox regression analysis showed that the initial score for eICA stenosis was a significant predictive factor for the risk of new silent cerebral infarct events. Our study reinforces the need to assess cervical arteries for better prevention of cerebral ischemia and encourage initiation of CTT in sickle cell anemia children with eICA stenosis.

Transcranial Doppler sonography and the effect of haematopoietic stem cell transplantation in sickle cell disease

BackgroundSickle cell disease (SCD) is one of the most prevalent monogenetic diseases worldwide and one of the most serious complications is stroke. Transcranial Doppler (TCD) demonstrated to be highly predictive for an imminent stroke by measuring blood flow velocities in the basal cerebral arteries. Currently, the only curative therapy for SCD is hematopoietic stem cell transplantation (HSCT). The aim of this study is to verify the correlation between blood flow velocities and stroke including the effect of HSCT.MethodsIn our retrospective single-center study a total of 26 sickle cell patients (HbSS, HbSß+-thalassemia, HbSSα-thalassemia minima, HbSSα-thalassemia minor and HbSC) were analyzed between 2010 and 2016. The highest time averaged maximum mean blood flow velocity (TAMMV) measured was documented and evaluated with respect to SCD genotype and effect of HSCT. Acute and symptomatic as well as silent strokes were recorded as separate parameters.ResultsIn our study, ten patients had normal blood flow velocities before HSCT (six HbSS and four HbSß+-thalassemia patients) and 13 patients presented with abnormal TCD (eight HbSS, three HbSSα-thalassemia minima, one HbSSα-thalassemia minor and one HbSC). Thirteen of 26 study participants (ten HbSS and three HbSß+-thalassemia patients) received HSCT. In two patients, TAMMV in basal cerebral arteries remained “normal”, in one they remained conditional and in one TAMMV was reduced to normal. Four of 26 study participants (15.4%), including all patients with HbSS genotype, presented with a stroke, but none had “abnormal” TAMMV with TCD performed after the onset of stroke in each case. At the time we performed the TCD, the patients had already suffered the stroke.ConclusionIn our study, none of the patients with stroke displayed abnormal blood flow velocities in TCD. Yet, HSCT at this stage of the disease still had a positive effect on TAMMV. Further studies are needed whether this effect converts into reduced stroke risk at all or only selected SCD patients undergoing HSCT.

Fetal hemoglobin modulates neurocognitive performance in sickle cell anemia✰,✰✰

Fetal hemoglobin (HbF) is a modifier of the clinical and hematologic phenotype of sickle cell anemia (SCA). Three quantitative trait loci (QTL) modulate HbF expression. The neurocognitive effects of variants in these QTL have yet to be explored. We evaluated the relation between 11 SNPs in the three HbF QTL: BCL11A, MYB, the HBB gene cluster, and full-scale intelligence (IQ) in SCA. The prospective longitudinal cohort study, Sickle Cell Clinical Research and Intervention Program, was used as a discovery cohort (n=166). The genotypes for 11 SNPs were extracted through whole genome sequencing and were analyzed using an additive model. A polygenic score for HbF (PGSHbF) integrating the numbers of low HbF alleles from 11 SNPs was analyzed as a continuous variable. The Cooperative Study of Sickle Cell Disease (n=156) and the Silent Cerebral Infarction Transfusion (n=114) Trial were used as two independent replication cohorts. Benjamini and Hochberg approach was used to calculate false discovery rate adjusted p-value (pFDR). HbF was positively associated with IQ (minimum raw p=0·0018) at pFDR<0·05. HbF mediated the relationship between two BCL11A SNPs, rs1427407 and rs7606173, HBS1L-MYB: rs9494142, and PGSHbF with IQ (minimum raw p=0·0035) at pFDR<0·05. As the major modulator of the severity of SCA, HbF also influences neurocognition, which is done through mediation of its QTL. These findings have implications for early identification of neurocognitive risk and targeted intervention.

Neurofilament Light Chain Levels in Multiple Sclerosis Correlate With Lesions Containing Foamy Macrophages and With Acute Axonal Damage.

Background and ObjectivesTo investigate whether white matter lesion activity, acute axonal damage, and axonal density in MS associate with CSF neurofilament light chain (NfL) levels.MethodsOf 101 brain donors with MS (n = 92 progressive MS, n = 9 relapsing-remitting MS), ventricular CSF was collected, and NfL levels were measured. White matter lesions were classified as active, mixed, inactive, or remyelinated, and microglia/macrophage morphology in active and mixed lesions was classified as ramified, ameboid, or foamy. In addition, axonal density and acute axonal damage were assessed using Bielschowsky and amyloid precursor protein (APP) (immune)histochemistry.ResultsCSF NfL measurements of donors with recent (<1 year) or clinically silent stroke were excluded. CSF NfL levels correlated negatively with disease duration (p = 6.9e-3, r = 0.31). In donors without atrophy, CSF NfL levels correlated positively with the proportion of active and mixed lesions containing foamy microglia/macrophages (p = 9.85e-10 and p = 1.75e-3, respectively), but not with those containing ramified microglia. CSF NfL correlated negatively with proportions of inactive (p = 5.66e-3) and remyelinated lesions (p = 0.03). In the normal appearing pyramid tract, axonal density negatively correlated with CSF NfL levels (Bielschowsky, p = 0.02, r = −0.31), and the presence of acute axonal damage in lesions was related to higher NfL levels (APP, p = 1.17e-6). The amount of acute axonal damage was higher in active lesions with foamy microglia/macrophages and in the rim of mixed lesions with foamy microglia/macrophages when compared with active lesions containing ramified microglia/macrophages (p = 4.6e-3 and p = 0.02, respectively), the center and border of mixed lesions containing ramified microglia/macrophages (center: p = 4.6e-3, border, p = 4.6e-3, and n.s., p = 4.6e-3, respectively), the center of mixed lesions containing foamy microglia/macrophages (p = 4.6e-3 and p = 0.02, respectively), inactive lesions (p = 4.6e-3 and p = 4.6e-3, respectively), and remyelinated lesions (p = 0.03 and p = 0.04, respectively).DiscussionOur results demonstrated that active and mixed white matter MS lesions with foamy microglia show high acute axonal damage and correlate with elevated CSF NfL levels. Our data support the use of this biomarker to monitor inflammatory demyelinating lesion activity with axonal damage in MS.

Abstract P010: Relationship Of Pulse Pressure And Cognitive Performance In Individuals With Advanced Carotid Atherosclerosis

Introduction: Elevation in pulse pressure (PP), the difference between systolic and diastolic blood pressure, is associated with vascular remodeling, arterial stiffness, and carotid plaque instability (i.e. strain indices and ulceration), which is a risk factor for vascular cognitive decline. We have previously demonstrated that increased carotid plaque strain indices are associated with poorer cognitive performance in individuals with advanced carotid atherosclerosis. We examined the relationship between pre-operative pulse-pressure and cognition in individuals undergoing clinically indicated carotid endarterectomy. We hypothesized that higher PP will be associated with poorer cognitive performance. Methods: Patients with advanced carotid atherosclerosis (&gt;60 % stenosis NASCET, ACAS criteria) underwent neurocognitive testing, blood pressure measurements, and PP calculation (n=128). Cognition was measured using a 60-minute neuropsychological battery recommended by the National Institute of Neurological Disorders and Canadian Stroke Network (NINDS-CSN). Kendell Tau correlations were used to examine the relationship between cognitive tests, ulceration and PP. Results: Participants were a median age of 72 (IQR 13) years of age, 50 females (40%), 78 males (60%), median 70% stenosis (IQR 10.8), median systolic blood pressure of 132 (IQR 26) mmHg, median diastolic blood pressure of 71.5 (IQR 15) mmHg, and median PP of 58.5 mmHg (IQR 23.75). PP ranged from 36 mmHg to 163 mmHg. Results did demonstrate evidence of an association between PP and WAIS-IV Block Design in asymptomatic patients (τ=-0.23, p=0.02). It did not show a significant relationship between PP and other subtests (all p-values&gt;0.05). There was no significant association between PP and operative plaque ulceration scores (p=0.542). Conclusions: PP was not associated with cognitive performance in individuals with advanced carotid atherosclerosis except for the relationship between PP and WAIS-IV Block Design in asymptomatic patients. This finding is consistent with prior work that suggests visuospatial processing presenting as one of the earliest declines in patients with cerebrovascular disease. Though asymptomatic patients did not show classic signs of stroke, they likely had silent strokes due to plaque instability.

Normal-tension glaucoma: Current concepts and approaches-A review.

Normal tension glaucoma (NTG) has remained a challenging disease. We review, from an epidemiological perspective, why we should redefine normality, act earlier at lower pre-treatment intraocular pressure (IOP) level, and the role of ocular perfusion pressures, noting that perfusion is affected by defective vascular bed autoregulation and endothelial dysfunction. The correlation of silent cerebral infarcts (SCI) and NTG may indicate that NTG belongs to a wider spectrum of small vessel diseases (SVD), with its main pathology being also on vascular endothelium. Epidemiological studies also suggested that vascular geometry, such as fractal dimension, may affect perfusion efficiency, occurrence of SCI, SVD and glaucoma. Artificial intelligence with deep learning, may help predicting NTG progression from vascular geometry. Finally, we review latest evidence on the role of minimally-invasive glaucoma surgery, lasers, and newer drugs. We conclude that IOP is not the only modifiable risk factors as, many vascular risk factors are readily modifiable.

Abstract WP260: The Response Of Annexin A1 In Astrocyte Activation And White Matter Injury- A New Target For Stroke In Sickle Cell Disease

Introduction: Ischemic stroke is common in sickle cell disease (SCD). White matter injuries, incorporated into silent cerebral infarcts, are major risk factors of stroke in SCD. The pathogenesis of cerebral infarction in SCD is not known. Induced thrombogenesis may cause impaired astrocyte that stimulates demyelination leading to white matter injury. Annexin A1 (Anxa1) can regulate astrocyte function by inhibiting intracellular phospholipase A2 (PLA2). We hypothesized that astrocyte activation during thrombogenic events promotes white matter injury in SCD. We tested astrocyte dysfunction and white matter injury in a clinically relevant mouse model of SCD. Methods: Cerebral Infarctions induced by de novo thrombogenesis were identified by TTC staining in transgenic sickle (SS) and control (AA) mice with human sickle and normal hemoglobin respectively. Cerebral microvessels and astrocytes were isolated from SS and AA mice. Elisa assays were used to measure thrombin, PLA2 and Anxa1. Immunofluorescence staining was performed to determine astrocyte activation and demyelination. Results: Thrombogenesis within cerebral microvessels was elevated by ~2-fold (n=5, p&lt;0.05), and cerebral infarction became prevalent in SS mice compared to AA mice (n=7, p&lt;0.001). The infarcted brain tissue from SS mice showed neuronal cell death, whereas the brain tissue from the AA mice appeared normal. The SS mice had increased glial fibrillary acid protein positive (GFAP + ) activated astrocytes with significant increase in PLA2 accumulation. Relative abundance of non-phosphorylated neurofilament H (SMI32) and myelin basic protein (MBP) (SMI32/MBP), indicating white matter injury, was substantially induced in the SS compared to the AA. Expression of Anxa1 reduced significantly in plasma as well as within astrocytes’ end feet attached to the isolated cerebral microvessels of the SS mice. Recombinant Anxa1 prophylaxis to SS mice reduced the GFAP + astrocytes, PLA2 accumulation, demyelination and infarct score (n=6, p&lt;0.01) compared to SS mice treated with vehicle. Conclusion: White matter injury in SS mice is associated with astrocyte dysfunction and lack of Anxa1, which may be developed as potential therapeutic targets to prevent and/or treat stroke in SCD.

Sickle cell disease as an accelerated aging syndrome.

Sickle cell disease (SCD) is characterized by vaso-occlusion, hemolysis, and systemic manifestations that form the hallmark of the disease. Apart from morbidity, SCD is also associated with increased mortality and decreased quality of life. Aging is a natural phenomenon that is associated with changes at cellular, tissue, and organ levels, in addition to the loss of physical fitness, increased susceptibility to diseases, and a higher likelihood of mortality. Some of the cellular mechanisms involved in normal (or physiological) aging include abnormalities of sphingolipids (ceramides) and reduced length of the telomere. These changes have also been documented in SCD. Cellular, organs, and physical manifestations of SCD resemble an accelerated aging syndrome. Sickle erythrocytes also acquire morphological features similar to that of aged normal erythrocytes and are thus picked up early by the macrophages for destruction. Brain, kidney, heart, innate and adaptive immune system, and musculoskeletal system of patients with SCD exhibit morphological and functional changes that are ordinarily seen in the elderly in the general population. Stroke, silent cerebral infarcts, cardiomegaly, heart failure, pulmonary hypertension, nephropathy with proteinuria, osteopenia, osteoporosis, osteonecrosis, gout, and infections are exceedingly common in SCD. In this review, we have attempted to draw parallels between SCD and accelerated aging syndromes.

ЕЕГ-ознаки ризику розвитку симптомного інсульту в пацієнтів із множинними «німими» інфарктами мозку

У статті наведені дані дослідження ЕЕГ-корелятів порушення церебрального кровообігу та їх зв’язку з ризиком виникнення інсульту в пацієнтів із множинними «німими» інфарктами мозку (мНІМ). Аналіз біоелектричної активності мозку був проведений у 36 пацієнтів (середній вік 54,00 ± 3,22 року) із МРТ-ознаками поодинокого НІМ (пНІМ) та в 24 пацієнтів (середній вік 67,89 ± 1,84 року) із МРТ-ознаками мНІМ. Протягом року після ЕЕГ-дослідження в 4 пацієнтів із мНІМ стався симптомний інсульт. У пацієнтів із мНІМ числові показники ЕЕГ-корелятів порушення церебрального кровообігу значно відрізнялися від таких пацієнтів із пНІМ. Порівняно з пацієнтами з групи пНІМ для картини ЕЕГ пацієнтів із мНІМ було притаманне значне зниження спектральної потужності (за коефіцієнтом α/δ), щільності (14,87 ± 2,83 та 1,89 ± 0,49 мкВ2/Гц відповідно, р &lt; 0,001) та індексу (39,18 ± 2,96 та 11,65 ± 1,17 % відповідно, р &lt; 0,001) α-ритму на тлі зростання аналогічних показників δ-ритму. Загальна спектральна потужність ЕЕГ у пацієнтів групи мНІМ була в 2,3 раза нижчою, ніж у пацієнтів групи пНІМ (124,81 ± 18,24 та 285,03 ± 35,71 мкВ2 відповідно, р &lt; 0,001), коефіцієнт потужності α/δ — у 7 разів меншим (0,35 ± 0,05 та 2,49 ± 0,34 відповідно, р &lt; 0,001), а (δ + θ)/(α + β)-коефіцієнт — у 2,7 раза більшим (1,96 ± 0,26 та 0,71 ± 0,08 відповідно, р &lt; 0,001). Саме зниження загальної спектральної потужності ЕЕГ, α/δ-коефіцієнта та підвищення (δ + θ)/(α + β)-коефіцієнта є найбільш показовими та загрозливими ЕЕГ-ознаками з точки зору ризику симптомного інсульту в пацієнтів із мНІМ.

Predictive role of atrial fibrillation in cognitive decline: a systematic review and meta-analysis of 2.8 million individuals.

AimsTo systematic review and meta-analyse the association and mechanistic links between atrial fibrillation (AF) and cognitive impairment.Methods and resultsPubMed, EMBASE, and Cochrane Library were searched up to 27 March 2021 and yielded 4534 citations. After exclusions, 61 were analysed; 15 and 6 studies reported on the association of AF and cognitive impairment in the general population and post-stroke cohorts, respectively. Thirty-six studies reported on the neuro-pathological changes in patients with AF; of those, 13 reported on silent cerebral infarction (SCI) and 11 reported on cerebral microbleeds (CMB). Atrial fibrillation was associated with 39% increased risk of cognitive impairment in the general population [n = 15: 2 822 974 patients; hazard ratio = 1.39; 95% confidence interval (CI) 1.25–1.53, I2 = 90.3%; follow-up 3.8–25 years]. In the post-stroke cohort, AF was associated with a 2.70-fold increased risk of cognitive impairment [adjusted odds ratio (OR) 2.70; 95% CI 1.66–3.74, I2 = 0.0%; follow-up 0.25–3.78 years]. Atrial fibrillation was associated with cerebral small vessel disease, such as white matter hyperintensities and CMB (n = 8: 3698 patients; OR = 1.38; 95% CI 1.11–1.73, I2 = 0.0%), SCI (n = 13: 6188 patients; OR = 2.11; 95% CI 1.58–2.64, I2 = 0%), and decreased cerebral perfusion and cerebral volume even in the absence of clinical stroke.ConclusionAtrial fibrillation is associated with increased risk of cognitive impairment. The association with cerebral small vessel disease and cerebral atrophy secondary to cardioembolism and cerebral hypoperfusion may suggest a plausible link in the absence of clinical stroke. PROSPERO CRD42018109185.

Burden of central nervous system complications in sickle cell disease: A systematic review and meta-analysis.

Sickle cell disease (SCD) patients are at high risk of central nervous system (CNS) complications and may experience significant morbidity. The study was conducted to describe the comprehensive burden of SCD-related CNS complications and to identify patient-reported outcome (PRO) instruments for future research. The review included 32 studies published from January 2000 to 2020, evaluating humanistic and economic outcomes. Twenty-three studies reported humanistic outcomes, 16 of which measured cognitive function using Wechsler Intelligence Scales. A meta-analysis was conducted, finding full-scale intelligence quotient (IQ) was significantly lower in: overt stroke versus controls: -12.6 (p<.001); silent cerebral infarct (SCI) versus controls: -5.7 (p<.001); overt stroke versus SCI: -9.4 (p=.008); and any event versus controls: -7.6 (p<.001). This review quantified the cognitive deficits associated with CNS complications in pediatric SCD populations and highlights the need for improved prevention/treatment. As PRO evidence was limited, we discussed areas for future research.

Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia

Prior studies have described high venous signal qualitatively using arterial spin labelling (ASL) in patients with sickle cell anemia (SCA), consistent with arteriovenous shunting. We aimed to quantify the effect and explored cross-sectional associations with arterial oxygen content (CaO2), disease-modifying treatments, silent cerebral infarction (SCI), and cognitive performance. 94 patients with SCA and 42 controls underwent cognitive assessment and MRI with single- and multi- inflow time (TI) ASL sequences. Cerebral blood flow (CBF) and bolus arrival time (BAT) were examined across gray and white matter and high-signal regions of the sagittal sinus. Across gray and white matter, increases in CBF and reductions in BAT were observed in association with reduced CaO2 in patients, irrespective of sequence. Across high-signal sagittal sinus regions, CBF was also increased in association with reduced CaO2 using both sequences. However, BAT was increased rather than reduced in patients across these regions, with no association with CaO2. Using the multiTI sequence in patients, increases in CBF across white matter and high-signal sagittal sinus regions were associated with poorer cognitive performance. These novel findings highlight the utility of multiTI ASL in illuminating, and identifying objectively quantifiable and functionally significant markers of, regional hemodynamic stress in patients with SCA.

White matter changes, duration of hypertension, and age are associated with cerebral microbleeds in patients with different stages of hypertension.

We aimed to investigate risk factors for the presence and number of cerebral microbleeds (CMBs) in patients with different stages of hypertension stages, with an emphasis on the relationship between white matter changes (WMCs) and CMBs. Since 2016, participants aged 40 years or more have been evaluated for the presence of CMBs using enhanced 3D multiecho GE T2*-weighted angiography (ESWAN) sequences. The Mann-Whitney U test and Pearson χ2 test were used to compare the clinical characteristics between the CMB and no-CMB patient groups. Furthermore, we used Spearman's rank correlation analysis to examine the associations between the degree of CMB severity and other important factors. CMBs were detected in 110 (36.7%) of 300 participants. Among patients with stage 2 hypertension, the majority also had CMBs (61.8%, 68/110). CMBs were positively correlated with age, hypertension stage, duration of hypertension, WMCs, and silent cerebral infarction. Patients with grade 3 WMCs were significantly more likely to have CMBs than those without WMCs; this association was true for both patients with stage 1 and those with stage 2 hypertension. In patients with stage 1 or stage 2 hypertension lasting longer than 20 years, the majority had CMBs (69.0%, 29/42; 69.1%, 47/68). The results of binary logistic regression indicated that a more severe hypertension stage, longer duration of hypertension, aging, having silent cerebral infarction and higher values of WMC increase the likelihood of the occurrence of CMBs. CMBs detected in hypertensive patients were more likely to occur in deep structures, and the grade of WMCs and duration of hypertension were more closely associated with the CMB degree than with age.

Vascular Brain Damage in Thalassemia Syndrome: An Emerging Challenge.

Thalassemia syndromes are the most prevalent monogenic hemoglobinopathy in the world. In Iran, thalassemia is a public health problem because this country has been located on the thalassemia belt. In recent decades, considering that the life expectancy of patients with thalassemia has dramatically improved, some unrecognized complications have emerged in these individuals. One of these complications is a hypercoagulable state that may lead to thromboembolic events (TEE). The TEE may involve any organ in the body, including the central nervous system. Ischemic cerebrovascular events in thalassemic patients have been divided into two categories, namely overt stroke and silent cerebral infarcts (SCI). Overt stroke often develops in patients with beta-thalassemia major; however, patients with thalassemia intermedia usually suffer from SCI. This review article discusses brain vascular involvement.

Atrial fibrillation and cognitive impairment: a narrative review

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and its incidence and prevalence increase with age, as does cognitive impairment (CI). Prospective observational studies have shown that AF can significantly increase the risk of stroke, which is an important cause of CI, but it has also been established that the association between the two diseases may be independent of stroke and other shared risk factors. However, the pathophysiological mechanism linking the two entities is still unclear as it is likely to be a multifactorial process (cardioembolic silent strokes, proinflammatory states and cerebral hypoperfusion), with preliminary evidence of a link between atrial cardiomyopathy without AF and cognitive dysfunction. The association between AF and CI raises the possibility that therapeutic interventions aimed at managing this arrhythmia may prevent or delay the onset of CI. Anticoagulation has been shown to significantly reduce the risk of stroke in patients with AF and, with it, the risk of CI, but the effect of other therapeutic interventions such as rhythm and rate control is inconclusive. AF and CI are an important health problem worldwide and the demographic trend predicts exponential growth of both conditions in the coming years. Therefore, it seems necessary to increase our knowledge of the pathophysiological mechanisms related to them in order to establish effective preventive strategies.

Carotid Doppler as a screening tool for silent cerebral Stroke in hypertensive patients

Carotid Doppler as a screening tool for silent cerebral Stroke in hypertensive patients