Montreal cognitive assessment in Brazilian adults with sickle cell disease: The burdens of poor sociocultural background.

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients (n = 124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/ß0, 7 S/ß+) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8-30); 70% had a 25-or-less score, suggesting some level of cognitive impairment. There were no significant associations between MoCA results and any clinical or laboratory data in SS and SC patients; however, a significant correlation (P = 0.03) with stroke was found in HbS/ß-thalassemic patients. Correlations were further detected according to sociodemographic conditions, such as age (r = -0.316; P < 0.001), age at first job (r = 0.221; P = 0.018), personal (r = 0.23; P = 0.012) and per capita familiar incomes (r = 0.303; P = 0.001), personal (r = 0.61; P = 0), maternal (r = 0.536; P = 0), and paternal educational status (r = 0.441; P = 0). We further sought independent predictors of performance using multivariable regressions and increased education was an independent predictor of better scores in MoCA (0.8099, 95% confidence interval [CI]: 0.509-1.111). Brain imaging analysis showed significant and progressive atrophy in important cerebral areas related to memory, learning, and executive function. These data point to the high prevalence and impact of cognitive decline in adult SCD patients, mirrored in brain atrophic areas. It is also possible to observe the influence of sociodemographic conditions on patients' cognitive performances and the need for creating focused therapeutic plans that address these deficiencies. Moreover, the absence of a significant correlation of MoCA values with stroke in the SS and SC groups may be related to the worst sociocultural and economic conditions of the Brazilian African descent population, in which the impact of low educational stimulation on cognitive function can outweigh even the anatomical damage caused by the disease.

A case of non-bacterial thrombotic endocarditis on the aortic valve following coronary angiography.

Nonbacterial thrombotic endocarditis (NBTE) on the aortic valve involves fibrin and platelet aggregate formation, potentially leading to embolic events. We present a case of NBTE on the aortic valve following coronary angiography (CAG) in a 54-year-old man with multiple comorbidities. Surgical thrombectomy was performed owing to acute cerebral infarcts. This case highlights the significance of considering that mechanical trauma from catheterization during CAG can trigger thrombus formation.

Atrial Fibrillation and Dementia: Focus on Shared Pathophysiological Mechanisms and Therapeutic Implications.

OBJECTIVES: Atrial fibrillation (AF) and dementia are highly prevalent chronic and debilitating conditions, especially affecting the older population. This review focuses on possible common pathophysiological mechanisms that could explain the association between the 2 conditions. DESIGN: Narrative review. SETTING AND PARTICIPANTS: Evidence from epidemiologic, observational, and interventional studies evaluating prevalence and incidence of cognitive impairment in patients with AF. METHODS: Broad literature search between December 2022 and May 2023. Eligible categories for inclusion comprised interventional studies, observational studies, systematic reviews, and meta-analysis. RESULTS: Evidence from different cohorts has shown that AF increases the risk of dementia, although the association with dementia subtypes is not always unequivocal. According to recent evidence, common pathophysiological mechanisms include thromboembolism and hypercoagulable states, proinflammatory state, infection, cerebral hypoperfusion, and brain atrophy. Moreover, we reviewed the evidence on therapeutic measures to prevent dementia in patients with AF. CONCLUSIONS AND IMPLICATIONS: Screening for cognition in patients with AF is of paramount importance, given the shared risk factors and common pathophysiological mechanisms. More evidence is needed to clarify whether antiarrhythmic and anticoagulant therapy have an impact on cognitive outcomes in AF patients.

Personality predictors of dementia diagnosis and neuropathological burden: An individual participant data meta-analysis.

INTRODUCTION: The extent to which the Big Five personality traits and subjective well-being (SWB) are discriminatory predictors of clinical manifestation of dementia versus dementia-related neuropathology is unclear. METHODS: Using data from eight independent studies (Ntotal = 44,531; Ndementia = 1703; baseline Mage = 49 to 81 years, 26 to 61% female; Mfollow-up range = 3.53 to 21.00 years), Bayesian multilevel models tested whether personality traits and SWB differentially predicted neuropsychological and neuropathological characteristics of dementia. RESULTS: Synthesized and individual study results indicate that high neuroticism and negative affect and low conscientiousness, extraversion, and positive affect were associated with increased risk of long-term dementia diagnosis. There were no consistent associations with neuropathology. DISCUSSION: This multistudy project provides robust, conceptually replicated and extended evidence that psychosocial factors are strong predictors of dementia diagnosis but not consistently associated with neuropathology at autopsy. HIGHLIGHTS: N(+), C(-), E(-), PA(-), and NA(+) were associated with incident diagnosis. Results were consistent despite self-report versus clinical diagnosis of dementia. Psychological factors were not associated with neuropathology at autopsy. Individuals with higher conscientiousness and no diagnosis had less neuropathology. High C individuals may withstand neuropathology for longer before death.

The Role of Extracellular Matrix and Inflammation in the Stratification of Bleeding and Thrombotic Risk of Atrial Fibrillation on Oral Anticoagulant Therapy: Insights from Strat-Af Study.

In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.

Silent Cerebral Infarcts in Iraqi Patients with Sickle Cell Disease.

Silent ischemic infarcts have been reported to be the most frequent neurological abnormalities in sickle cell disease (SCD) in several studies worldwide. However, no previous studies investigated this neurological disorder in Iraqi SCD patients. To address this issue, a total of 52 patients with a median age of 20 years (range 10-46) and including 46.2% males were enrolled. Patients were clinically evaluated and their records were reviewed. They had full blood and reticulocyte counts, hemoglobin F estimation, serum lactic dehydrogenase and bilirubin assayed, as well as brain magnetic resonance imaging (MRI) to screen for silent cerebral infarcts. Six out of the 52 patients (11.5%) had silent cerebral infarcts, all of which were in the deep white matter, ranging from 6 to 10 mm in their largest diameters. There were no significant differences in age, sex, or sickle cell genotype between those with silent cerebral infarcts and those without it. Those with silent cerebral infarcts had lower median hemoglobin, higher reticulocytes and lower pain frequencies than those without it, yet again this was not significant. Follow up MRI in four out of the six silent infarct patients showed no additional lesions and no increase in size of the original ones after six to eight months. In conclusion, it appears that the frequency of silent cerebral infarcts in Iraqi SCD patients is lower than the bulk of the literature from other populations. Further studies to screen for genetic polymorphisms that may explain this lower rate may be informative.

Comorbidities in Early-Onset Sporadic versus Presenilin-1 Mutation-Associated Alzheimer's Disease Dementia: Evidence for Dependency on Alzheimer's Disease Neuropathological Changes.

Autopsy studies have demonstrated that comorbid neurodegenerative and cerebrovascular disease occur in the great majority of subjects with Alzheimer disease dementia (ADD), and are likely to additively alter the rate of decline or severity of cognitive impairment. The most important of these are Lewy body disease (LBD), TDP-43 proteinopathy and cerebrovascular disease, including white matter rarefaction (WMR) and cerebral infarcts. Comorbidities may interfere with ADD therapeutic trials evaluation of ADD clinical trials as they may not respond to AD-specific molecular therapeutics. It is possible, however, that at least some comorbidities may be, to some degree, secondary consequences of AD pathology, and if this were true then effective AD-specific therapeutics might also reduce the extent or severity of comorbid pathology. Comorbidities in ADD caused by autosomal dominant mutations such as those in the presenilin-1 (PSEN1) gene may provide an advantageous perspective on their pathogenesis, and deserve attention because these subjects are increasingly being entered into clinical trials. As ADD associated with PSEN1 mutations has a presumed single-cause etiology, and the average age at death is under 60, any comorbidities in this setting may be considered as at least partially secondary to the causative AD mechanisms rather than aging, and thus indicate whether effective ADD therapeutics may also be effective for comorbidities. In this study, we sought to compare the rates and types of ADD comorbidities between subjects with early-onset sporadic ADD (EOSADD; subjects dying under age 60) versus ADD associated with different types of PSEN1 mutations, the most common cause of early-onset autosomal dominant ADD. In particular, we were able to ascertain, for the first time, the prevalences of a fairly complete set of ADD comorbidities in United States (US) PSEN1 cases as well as the Colombian E280A PSEN1 kindred. Data for EOSADD and US PSEN1 subjects (with multiple different mutation types) was obtained from the National Alzheimer Coordinating Center (NACC). Colombian cases all had the E280A mutation and had a set of neuropathological observations classified, like the US cases according to the NACC NP10 definitions. Confirmatory of earlier reports, NACC-defined Alzheimer Disease Neuropathological Changes (ADNC) were consistently very severe in early-onset cases, whether sporadic or in PSEN1 cases, but were slightly less severe in EOSADD. Amyloid angiopathy was the only AD-associated pathology type with widely-differing severity scores between the 3 groups, with median scores of 3, 2 and 1 in the PSEN1 Colombia, PSEN1 US and EOSADD cases, respectively. Apoliprotein E genotype did not show significant proportional group differences for the possession of an E-4 or E-2 allele. Of ADD comorbidities, LBD was most common, being present in more than half of all cases in all 3 groups. For TDP-43 co-pathology, the Colombian PSEN1 group was the most affected, at about 27%, vs 16% and 11% for the US PSEN1 and sporadic US cases, respectively. Notably, hippocampal sclerosis and non-AD tau pathological conditions were not present in any of the US or Colombian PSEN1 cases, and was seen in only 3% of the EOSADD cases. Significant large-vessel atherosclerosis was present in a much larger percentage of Colombian PSEN1 cases, at almost 20% as compared to 0% and 3% of the US PSEN1 and EOSADD cases, respectively. Small-vessel disease, or arteriolosclerosis, was much more common than large vessel disease, being present in all groups between 18% and 37%. Gross and microscopic infarcts, however, as well as gross or microscopic hemorrhages, were generally absent or present at very low percentages in all groups. White matter rarefaction (WMR) was remarkably common, at almost 60%, in the US PSEN1 group, as compared to about 18% in the EOSADD cases, a significant difference. White matter rarefaction was not assessed in the Colombian PSEN1 cases. The results presented here, as well as other evidence, indicates that LBD, TDP-43 pathology and WMR, as common comorbidities with autosomal dominant and early-onset sporadic ADD, should be considered when planning clinical trials with such subjects as they may increase variability in response rates. However, they may be at least partially dependent on ADNC and thus potentially addressable by anti-amyloid or and/anti-tau therapies.

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia.

Cerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI-MRA) in sub-Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood-based brain biomarkers of cerebral infarcts have been identified in non-SCA adults. Using plasma samples from a well-characterized cross-sectional sample of Ugandan children with SCA, we explored relationships between biomarker levels and MRI-detected cerebral infarcts and transcranial Doppler (TCD) arterial velocity. Testing was performed using a 4-plex panel of brain injury biomarkers, including neurofilament light chain (NfL), a central nervous system neuron-specific protein. Mean biomarker levels from the SCA group (n = 81) were similar to those from non-SCA sibling controls (n = 54). Within the SCA group, NfL levels were significantly higher in those with MRI-detected infarcts compared to no infarcts, and higher with elevated TCD velocity versus normal velocity. Elevated NfL remained strongly associated with MRI-detected infarcts after adjusting for sex and age. All non-SCA controls and SCA participants lacking MRI-detected infarcts had low NfL levels. These data suggest potential utility of plasma-based NfL levels to identify children with SCA cerebrovascular injury. Replication and prospective studies are needed to confirm these novel findings and the clinical utility of NfL versus MRI imaging.

Characteristics of Multiple Acute Concomitant Cerebral Infarcts Involving Different Arterial Territories.

(1) Background: Multiple acute concomitant cerebral infarcts (MACCI) are relatively uncommon. Data regarding the characteristics and outcomes of patients with MACCI are lacking. We, therefore, aimed to characterize the clinical features of MACCI. (2) Methods: Patients with MACCI were identified from a prospective registry of stroke patients admitted to a tertiary teaching center. Patients with an acute single embolic stroke (ASES) involving only one vascular bed served as controls. (3) Results: MACCI was diagnosed in 103 patients who were compared to 150 patients with ASES. MACCI patients were significantly older (p = 0.010), more often had a history of diabetes (p = 0.011) and had lower rates of ischemic heart disease (p = 0.022). On admission, MACCI patients had significantly higher rates of focal signs (p < 0.001), an altered mental state (p < 0.001) and seizures (p = 0.036). The favorable functional outcome was significantly less common in patients with MACCI (p = 0.006). In the multivariable analysis, MACCI was associated with lower chances of achieving favorable outcomes (odds ratio: 0.190, 95% CI: 0.070-0.502). (4) Conclusions: There are important differences in clinical presentation, comorbidities and outcomes between MACCI and ASES. MACCI is less often associated with favorable outcomes and could represent a more severe form of a stroke compared with a single embolic stroke.

Survey on antiphospholipid syndrome diagnosis and antithrombotic treatment in patients with ischemic stroke, other brain ischemic injury, or arterial thromboembolism in other sites: communication from ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

BACKGROUND: The optimal strategy for diagnosis and antithrombotic treatment of patients with antiphospholipid syndrome (APS)-associated acute ischemic stroke (AIS), transient ischemic attack (TIA), or other brain ischemic injury is poorly defined. OBJECTIVES: The survey goal was to capture variations in diagnosis and antithrombotic treatment of APS-associated ischemic stroke and related disorders to inform guidance and clinical trials to define optimal management. METHODS: Professional colleagues, including key opinion leaders, were invited to complete a REDCap survey questionnaire initiated by the International Society on Thrombosis and Haemostasis Scientific and Standardisation Committee Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. The survey data were tallied using simple descriptive statistics. RESULTS: There was generally good agreement on several aspects, including which patients to test for antiphospholipid antibodies (aPL), use of a lifelong vitamin K antagonist for AIS or recurrent TIA, and formal cognitive assessment for suspected cognitive impairment. There was less agreement on other aspects, including aPL testing for brain ischemic injury other than AIS/TIA or if an alternative cause for AIS or TIA exists; choice of aPL tests, their timing, and age cutoff; the aPL phenotype to trigger antithrombotic treatment; management for patent foramen ovale; antithrombotic treatment for first TIA or white matter hyperintensities; head magnetic resonance imaging specifications; and low-molecular-weight heparin dosing/anti-Xa monitoring in pregnancy. The survey highlighted that approximately 25% practice at dedicated APS clinics and <50% have a multidisciplinary team structure for patients with APS. CONCLUSION: Much of the variation in practice reflects the lack of evidence-based recommendations. The survey results should inform the development of a more uniform multidisciplinary consensus approach to diagnosis and antithrombotic treatment.

Pathogenic Mechanisms in Thalassemia I: Ineffective Erythropoiesis and Hypercoagulability.

Erythropoiesis is the physiological process that results in the production of red blood cells (RBCs). In conditions of pathologically altered erythropoiesis or ineffective erythropoiesis, as in the case of ß-thalassemia, the reduced ability of erythrocytes to differentiate, survive and deliver oxygen stimulates a state of stress that leads to the ineffective production of RBCs. We herein describe the main features of erythropoiesis and its regulation in addition to the mechanisms behind ineffective erythropoiesis development in ß-thalassemia. Finally, we review the pathophysiology of hypercoagulability and vascular disease development in ß-thalassemia and the currently available prevention and treatment modalities.

Recurrent ischemic stroke from reversible extracranial internal carotid artery and middle cerebral artery vasospasm: A case report.

Idiopathic internal carotid artery (ICA) vasospasm is a rare cause of ischemic stroke. Its pathophysiology remains unclear and diagnostic and treatment protocols are yet to be defined. A 45-year-old male, presenting with recurrent transient dizziness, blurred vision, and speech disturbances, was diagnosed with recurrent ischemic stroke caused by bilateral ICA and middle cerebral artery (MCA) vasospasm, and the vascular ultrasound and imaging techniques have grabbed the reversible changes in a short time. This case underscores the importance of considering idiopathic ICA vasospasm as a potential cause of recurrent ischemic stroke, even in the absence of common diagnostic markers. The case also indicates the possible, albeit rare, involvement of the MCA in this condition. Therefore, it is crucial to maintain a high index of suspicion for idiopathic ICA vasospasm in similar clinical presentations and to explore more inclusive diagnostic criteria.

The Development of Neuroimaging Biomarkers for Cognitive Decline in Sickle Cell Disease.

Sickle cell disease (SCD) is complicated by neurologic complications including vasculopathy, hemorrhagic or ischemic overt stroke, silent cerebral infarcts and cognitive dysfunction. Patients with SCD, even in the absence of vasculopathy or stroke, have experience cognitive dysfunction that progresses with age. Transcranial Doppler ultrasound and structural brain MRI are currently used for primary and secondary stroke prevention, but laboratory or imaging biomarkers do not currently exist that are specific to the risk of cognitive dysfunction in patients with SCD. Recent investigations have used advanced MR sequences assessing cerebral hemodynamics, white matter microstructure and functional connectivity to better understand the pathophysiology of cognitive decline in SCD, with the long-term goal of developing neuroimaging biomarkers to be used in risk prediction algorithms and to assess the efficacy of treatment options for patients with SCD.

SARS-CoV-19-associated Rhino-orbital and cerebral mucormycosis: clinical and radiological presentations.

We describe presenting clinical and imaging manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated Rhino-oculo-cerebral mucormycosis (ROCM) in a hospital setting during the second wave of SARS-CoV-2 pandemic in India. Data on the presenting manifestations were collected from 1 March to 31 May 2021. Associations between clinical and imaging findings were explored, specifically: (1) the presence or absence of orbital pain and infiltration of a superior orbital fissure on imaging; (2) the presence of unilateral facial nerve palsy and pterygopalatine fossa infiltration and geniculate ganglion signal on contrast magnetic resonance imaging, and (3) vision loss and optic nerve findings on imaging. Orbital pain was reported by 6/36 subjects. A fixed, frozen eye with proptosis and congestion was documented in 26 (72%), complete vision loss in 23 (64%), and a unilateral lower motor neuron facial nerve palsy in 18 (50%). No association was found between the presence of orbital pain and superior orbital fissure infiltration on imaging. The ipsilateral geniculate ganglion was found to enhance more profoundly in 7/11 subjects with facial palsy and available magnetic resonance (MR) imaging, and the ipsilateral pterygopalatine fossa was found infiltrated in 14. Among 23 subjects with complete loss of vision, 9 (39%) demonstrated long-segment bright signal in the posterior optic nerve on diffusion MR images. We conclude that orbital pain might be absent in SARS-CoV-2-associated ROCM. Facial nerve palsy is more common than previously appreciated and ischemic lesions of the posterior portion of the optic nerve underlie complete vision loss.

Unique clinical and radiological manifestations identified in the outbreak of Rhino-oculo-cerebral mucormycosis (ROCM) during the second epidemic wave of coronavirus disease 2019 (COVID-19) infection included the common occurrence of facial paralysis, frequent absence of ocular pain, and long segments of optic nerve damage.

Silent cerebral infarcts following pulmonary vein isolation with different atrial fibrillation ablation techniques - incidence and risk factors.

Introduction: Silent cerebral infarcts (SCIs) detected by diffusion-weighted magnetic resonance (DW-MRI) following atrial fibrillation (AF) ablation have been reported, with the incidence of 1-38%. We aimed to compare the incidence of SCIs following AF ablation with four different technologies and analyze the risk factors. Material and methods: A total of 104 patients (mean age: 59.9 ±9.5 years, 68 males) with symptomatic AF, referred for ablation, were included in the study. The AF ablation was performed with irrigated radiofrequency point-by-point technique (RF group) in 24 patients, and with 3 different single-shot techniques: phased-RF (PVAC) in 46, second-generation cryoballoon (CB) in 24 and irrigated multipolar RF catheter (nMARQ) in 10 patients. In all patients DW-MRI was performed pre- and post-procedurally to evaluate the incidence of SCIs. Procedural parameters, complication rate and post-procedural SCI incidence were compared between the groups. Results: Procedure (167.1 vs. 110.5 vs. 106.0 vs. 141.5 min, p < 0.001), fluoroscopy (22.7 vs. 15.9 vs. 16.3 vs. 15.3 min, p = 0.048) and LA dwell (101.5 vs. 53.9 vs. 56.0 vs. 97.0 min, p < 0.001) times compared respectively between RF, PVAC, CB and nMARQ groups were significantly shorter with single-shot techniques. The number of new-onset SCIs was 4/24 (16.7%) in RF, 7/46 (15.2%) in PVAC, 1/24 (4.2%) in CB and 1/10 (10%) in the nMARQ group. Univariate analysis identified procedure duration (p = 0.02), lower LV ejection fraction (p = 0.03), persistent form of arrhythmia (p = 0.007) and intraprocedural cardioversion (p = 0.002) as risk factors of new-onset SCIs. Conclusions: Silent cerebral infarcts can be detected following AF ablation regardless of the technology used. Prolonged procedure time, lower ejection fraction, persistent form of arrhythmia and intraprocedural cardioversion increase the risk of SCIs.

Moyamoya syndrome in a child with HbEß-thalassemia.

Moyamoya is a progressive cerebrovascular disease associated with stenosis or occlusion of the arteries of the Circle of Willis. It is uncommon in thalassemia. We present a 9-year-old girl with HbEß-thalassemia who presented with headache, vomiting, and episodes of transient hemiparesis with complete occlusion internal carotid arteries.

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.

Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease.

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric patients with SCD. Using voxel-based morphometry methodology, high-resolution T1 structural scans were preprocessed using SPM and further analyzed in SPSS. The whole brain multiple regression analysis identified that perigenual anterior cingulate cortex (ACC) GMV was negatively associated with the frequency of pain crises (r = -0.656, P = 0.003). A two-group t-test analysis showed that the subgroup having pain crisis/crises in the past year also showed significantly lower GMV at left supratemporal gyrus than the group without any pain crisis (p=0.024). The further 21 pain-related regions of interest (ROI) analyses identified a negative correlation between pregenual ACC (r = -0.551, P = 0.001), subgenual ACC (r = -0.540, P = 0.001) and the frequency of pain crises. Additionally, the subgroup with poorer QOL displayed significantly reduced GMV in the parahippocampus (left: P = 0.047; right: P = 0.024). The correlations between the cerebral structural alterations and the accentuated pain experience and QOL suggests a possible role of central mechanisms in SCD pain.

Recurrent Cerebral Infarcts Associated with Uterine Adenomyosis: Successful Prevention by Surgical Removal.

Hypercoagulability associated with malignant tumors causes thrombosis, termed Trousseau's syndrome, but is rarely associated with benign gynecological tumors, such as myoma and adenomyosis. We herein report a 47-year-old Japanese woman with uterine adenomyosis who developed multiple cerebral infarcts during menstruation. Edoxaban was initially used for prevention but failed to prevent recurrence of thrombosis. However, hysterectomy and bilateral salpingo-oophorectomy resulted in the successful prevention of recurrence of cerebral infarct for five years without antiplatelet or anticoagulant agents. In our patient, the surgical removal of adenomyosis was highly effective for preventing thrombosis in a patient with adenomyosis.

Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review).

Stroke is the leading cause of disabilities and cognitive deficits, accounting for 5.2% of all mortalities worldwide. Transient or permanent occlusion of cerebral vessels leads to ischemic strokes, which constitutes the majority of strokes. Ischemic strokes induce brain infarcts, along with cerebral tissue death and focal neuronal damage. The infarct size and neurological severity after ischemic stroke episodes depends on the time period since occurrence, the severity of ischemia, systemic blood pressure, vein systems and location of infarcts, amongst others. Ischemic stroke is a complex disease, and neuronal injuries after ischemic strokes have been the focus of current studies. The present review will provide a basic pathological background of ischemic stroke and cerebral infarcts. Moreover, the major mechanisms underlying ischemic stroke and neuronal injuries are summarized. This review will also briefly summarize some representative clinical trials and up­to­date treatments that have been applied to stroke and brain infarcts.