Stroke in childhood neurofibromatosis type 2

This commentary is on the case series by Lascelles et al. on pages 1285–1288 of this issue

MRI detection of brain abnormality in sickle cell disease

Introduction: Over the past decades, neuroimaging studies have clarified that a significant proportion of patients with sickle cell disease (SCD) have functionally significant brain abnormalities. Clinically, structural magnetic resonance imaging (MRI) sequences (T2, FLAIR, diffusion-weighted imaging) have been used by radiologists to diagnose chronic and acute cerebral infarction (both overt and clinically silent), while magnetic resonance angiography and venography have been used to diagnose arteriopathy and venous thrombosis. In research settings, imaging scientists are increasingly applying quantitative techniques to shine further light on underlying mechanisms. Areas covered: From a June 2020 PubMed search of ‘magnetic’ or ‘MRI’ and ‘sickle’ over the previous 5 years, we selected manuscripts on T1-based morphometric analysis, diffusion tensor imaging, arterial spin labeling, T2-oximetry, quantitative susceptibility, and connectivity. Expert Opinion: Quantitative MRI techniques are identifying structural and hemodynamic biomarkers associated with risk of neurological and neurocognitive complications. A growing body of evidence suggests that these biomarkers are sensitive to change with treatments, such as blood transfusion and hydroxyurea, indicating that they may hold promise as endpoints in future randomized clinical trials of novel approaches including hemoglobin F upregulation, reduction of polymerization, and gene therapy. With further validation, such techniques may eventually also improve neurological and neurocognitive risk stratification in this vulnerable population

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies

Cerebral Infarcts and Vasculopathy in Tanzanian Children With Sickle Cell Anemia

BACKGROUND: Cerebral infarcts and vasculopathy in neurologically asymptomatic children with sickle cell anemia (SCA) have received little attention in African settings. This study aimed to establish the prevalence of silent cerebral infarcts (SCI) and vasculopathy and determine associations with exposure to chronic hemolysis, anemia, and hypoxia. METHODS: We prospectively studied 224 children with SCA with transcranial Doppler (TCD), and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Regressions were undertaken with contemporaneous hemoglobin, reticulocyte count, mean prior hemoglobin, oxygen content, reticulocyte count, and indirect bilirubin. RESULTS: Prevalence of SCI was 27% (61 of 224); cerebral blood flow velocity was abnormal (>200 cm/s) in three and conditional (>170<200 cm/s) in one. Vasculopathy grades 2 (stenosis) and 3 (occlusion) occurred in 16 (7%) and two (1%), respectively; none had grade 4 (moyamoya). SCI was associated with vasculopathy on MRA (odds ratio 2.68; 95% confidence intervals [95% CI] 1.32 to 5.46; P = 0.007) and mean prior indirect bilirubin (odds ratio 1.02, 95% CI 1.00 to 1.03, P = 0.024; n = 83) but not age, sex, non-normal TCD, or contemporaneous hemoglobin. Vasculopathy was associated with mean prior values for hemoglobin (odds ratio 0.33, 95% CI 0.16 to 0.69, P = 0.003; n = 87), oxygen content (odds ratio 0.43, 95% CI 0.25 to 0.74, P = 0.003), reticulocytes (odds ratio 1.20, 95% CI 1.01-1.42, P = 0.041; n = 77), and indirect bilirubin (odds ratio 1.02, 95% CI 1.01 to 1.04, P = 0.009). CONCLUSIONS: SCI and vasculopathy on MRA are common in neurologically asymptomatic children with SCA living in Africa, even when TCD is normal. Children with vasculopathy on MRA are at increased risk of SCI. Longitudinal exposure to anemia, hypoxia, and hemolysis appear to be risk factors for vasculopathy

Nocturnal oxyhemoglobin desaturation and arteriopathy in a pediatric sickle cell disease cohort

OBJECTIVE: The purpose of this study of sickle cell disease (SCD) was to determine whether arteriopathy, measurable as intracranial vessel signal loss on magnetic resonance angiography (MRA), was associated with low nocturnal hemoglobin oxygen saturation (SpO2) or hemolytic rate, measurable as reticulocytosis or unconjugated hyperbilirubinemia. METHODS: Ninety-five East London children with SCD without prior stroke had overnight pulse oximetry, of whom 47 (26 boys, 39 hemoglobin SS; mean age 9.1 ± 3.1 years) also had MRA, transcranial Doppler (TCD), steady-state hemoglobin, and reticulocytes within 34 months. Two radiologists blinded to the other data graded arteriopathy on MRA as 0 (none) or as increasing severity grades 1, 2, or 3. RESULTS: Grades 2 or 3 arteriopathy (n = 24; 2 with abnormal TCD) predicted stroke/TIA compared with grades 0 and 1 (log-rank χ(2) [1, n = 47] = 8.1, p = 0.004). Mean overnight SpO2 correlated negatively with reticulocyte percentage (r = -0.387; p = 0.007). Despite no significant differences across the degrees of arteriopathy in genotype, mean overnight SpO2 was higher (p < 0.01) in those with grade 0 (97.0% ± 1.6%) than those with grades 2 (93.9 ± 3.7%) or 3 (93.5% ± 3.0%) arteriopathy. Unconjugated bilirubin was not associated but reticulocyte percentage was lower (p < 0.001) in those with grade 0 than those with grades 2 and 3 arteriopathy. In multivariable logistic regression, lower mean overnight SpO2 (odds ratio 0.50, 95% confidence interval 0.26-0.96; p < 0.01) predicted arteriopathy independent of reticulocyte percentage (odds ratio 1.47, 95% confidence interval 1.15-1.87; p = 0.003). CONCLUSION: Low nocturnal SpO2 and reticulocytosis are associated with intracranial arteriopathy in children with SCD. Preventative strategies might reduce stroke risk

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

High-temperature performance of ferritic steels in fireside corrosion regimes: temperature and deposits

The paper reports high temperature resistance of ferritic steels in fireside corrosion regime in terms of temperature and deposits aggressiveness. Four candidate power plant steels: 15Mo3, T22, T23 and T91 were exposed under simulated air-fired combustion environment for 1000 h. The tests were conducted at 600, 650 and 700 °C according to deposit-recoat test method. Post-exposed samples were examined via dimensional metrology (the main route to quantify metal loss), and mass change data were recorded to perform the study of kinetic behavior at elevated temperatures. Microstructural investigations using ESEM-EDX were performed in order to investigate corrosion degradation and thickness of the scales. The ranking of the steels from most to the least damage was 15Mo3 > T22 > T23 > T91 in all three temperatures. The highest rate of corrosion in all temperatures occurred under the screening deposit

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Alcohol use among amateur sportsmen in Ireland

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to establish baseline data on alcohol consumption patterns, behaviours and harms among amateur sportsmen in the Republic of Ireland.</p> <p>Findings</p> <p>The study presents findings from the baseline survey for a cluster randomised controlled trial to evaluate the effectiveness of a community intervention programme to reduce problem alcohol use among a representative sample of Gaelic Athletic Association (GAA) clubs in two counties in the Republic of Ireland. Self reported alcohol use, prevalence of binge drinking, AUDIT scores and alcohol-related harms were assessed in amateur GAA sportsmen aged 16 years and over.</p> <p>Nine hundred and sixty (960) players completed questionnaires (72% response rate). Mean age was 24.0 years (S.D. 5.2). Of those aged 18 years or over, 75% had post-primary education; most (864, 90%) were current drinkers and 8.2% were regular smokers. The self-reported average yearly alcohol consumption was 12.5 litres. Almost one third (31%) of current drinkers reported drinking over the recommended limit of 21 standard drinks per week and just over half (54.3%) reported drinking 6 or more standard drinks in a row at least once a week (regular binge drinking). Of those who (self) completed the Alcohol Use Disorder Identification Test (AUDIT) questionnaire, three-quarters (74.7%) had a score of 8 or more; 11.5% had a score of 20 or above warranting referral for diagnostic evaluation and treatment. Almost all (87.6%) of the 864 drinkers reported experiencing at least one harm due to their drinking. These alcohol misuse outcomes were higher than those found in a nationally representative sample of males of a similar age. There were strong associations between regular binge drinking and reporting harms such as being in a fight (adjusted odds ratio (OR) 2.02, p < 0.001), missing time from work or college (adjusted OR 1.39, p = 0.04) or being in an accident (adjusted OR 1.78, p = 0.04).</p> <p>Conclusions</p> <p>These male amateur sportsmen reported high rates of alcohol consumption and alcohol-related harm.</p

Corneal topographic changes in premenopausal and postmenopausal women

<p>Abstract</p> <p>Background</p> <p>To asses the effect of menopause on the corneal curvature changes using corneal computerized videokeratography (CVK) in premenopausal and postmenopausal healthy women.</p> <p>Methods</p> <p>Thirty-six postmenopausal women with mean ages of 49.2 (range 39 to 57) were enrolled in this randomized, prospective study, comparing with 26 healthy controls with mean ages of 38.5 +/- 4.9 (range 32 to 49). Subjects were determined to be postmenopausal, by the Gynecology and Obstetrics Department, based on blood Follicular Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol, Progesterone levels and clinical complaints. Complete ophthalmic examination and CVK using Haag-Streit System was performed in both premenopausal and postmenopausal women.</p> <p>Results</p> <p>Mean horizontal curvature and vertical curvature of central corneal power in premenopausal women were 43.5 +/- 1.25 Diopter (D), and 44.1 +/- 1.53 D. Mean horizontal curvature and vertical curvature of central corneal power in postmenopausal women were 43.9 +/- 1.4 D, and 44.6 +/- 1.3 D. The mean keratometric astigmatisms of premenopausal and postmenopausal women were 0.81 +/- 0.57 D (4–179 degrees), 0.74 degrees +/- 0.5 D (1–180 degrees) respectively. No significant corneal curvature changes were detected between premenopausal and postmenopausal groups (P > 0.05). On the other hand, we only found negative but significant correlation between horizontal corneal curvature and estrogen level of postmenopausal women (r = -0.346, p = 0.038).</p> <p>Conclusion</p> <p>Menopause is physiologic process and may also affect corneal topographic changes. In postmenopausal women, corneal steeping was observed minimally compared to premenopausal women. The results suggest that changes in estrogen level of women with menopause are associated with slightly alteration of horizontal curvature of cornea.</p