Cerebral Magnetic Resonance Imaging Research Articles

Electrocardiogram properties and risk of covert brain infarction and other magnetic resonance imaging abnormalities in a stroke-free population.

This study aimed to investigate the association between electrocardiogram (ECG) abnormalities and silent vascular brain injury as defined by cerebral magnetic resonance imaging (MRI) in a stroke-free community-based population. A total of 5888 participants were studied from the Cardiovascular Health Study (CHS), a prospective cohort of community-living older adults. Standard 12-lead ECGs measured prior to MRI scan were used. MRI scans were conducted at years 4-6 and 10-11. The primary outcome was presence of incident covert brain infarcts (CBIs) on the 2nd MRI examination, excluding previous CBIs and stroke occurrence. Secondary outcomes included white matter, ventricular, and sulcal atrophy on the 1st MRI. Logistic and multiple linear regression models were used to assess the relationship between ECG findings and silent vascular brain injury. Left axis deviation before MRI scan was related to presence of incident CBIs (odds ratio [OR]: 1.45; 95% CI: 1.01-2.08, p=.047). A long QT interval was associated with severe white matter hyperintensity (OR: 1.36; 95% CI: 1.04-1.77, p=.024). Minor Q and QS waves with ST-T abnormalities were positively related to sulcal atrophy (β: 0.43, 95% CI: 0.06-0.81, p=.023). Our study found that ECG abnormalities were related to presence of CBIs, white matter hyperintensity, and sulcal atrophy on MRI in a stroke-free relderly population. Specifically, those with left axis deviation had an increased risk of presence of CBIs.

Case report: Mild leukoencephalopathy caused by a new mutation of NOTCH3 gene.

Cerebral autosomal dominant arteriosis with subcortical infarction and leukoencephalopathy (CADASIL) is a single-gene small-vessel disease of the brain characterized by migraine, recurrent ischemic stroke, psychiatric disorders, progressive cognitive decline, and occasional intracerebral hemorrhage.[1]NOTCH3 was identified as a pathogenic gene for CADASIL.[2] The NOTCH3 gene encodes a membrane-bound receptor protein, and to date, several different NOTCH3 gene mutations have been identified.[3] Here, we report a case of CADASIL with a heterozygous mutation c.931T > G (thymine > guanine) on the exon region of the NOTCH3 gene, resulting in an amino acid change p.C311G (cysteine > glycine). We report a case of a female patient with CADASIL whose genetic sequencing revealed a mutation in the NOTCH3 gene. However, this patient did not exhibit any of the typical clinical findings of CADASIL but the patient's cerebral magnetic resonance imaging was consistent with the characteristic findings of CADASIL. This case reminds us that mutations caused by different mutation sites present different clinical symptoms.

Association of regional white matter hyperintensities with hypertension and cognition in the population-based 1000BRAINS study.

White matter hyperintensities of presumed vascular origin (WMH) are frequent in cerebral magnetic resonance imaging of older people. They are promoted by vascular risk factors, especially hypertension, and are associated with cognitive deficits at the group level. It has been suggested that not only the severity, but also the location, of lesions might critically influence cognitive deficits and represent different pathologies. In 560 participants (65.2 ± 7.5 years, 51.4% males) of the population-based 1000BRAINS study, we analyzed the association of regional WMH using Fazekas scoring separately for cerebral lobes, with hypertension and cognition. WMH most often affected the frontal lobe (83.7% score >0), followed by the parietal (75.8%), temporal (32.7%), and occipital lobe (7.3%). Higher Fazekas scores in the frontal, parietal, and temporal lobe were associated with higher blood pressure and antihypertensive treatment in unadjusted ordinal regression models and in models adjusted for age, sex, and vascular risk factors (e.g., age- and sex-adjusted odds ratio=1.14, 95% confidence interval=1.03-1.25 for the association of frontal lobe WMH Fazekas score with systolic blood pressure [SBP] [per 10 mm Hg]; 1.13 [1.02-1.23] for the association of parietal lobe score with SBP; 1.72 [1.19-2.48] for the association of temporal lobe score with antihypertensive medications). In linear regressions, higher frontal lobe scores were associated with lower performance in executive function and non-verbal memory, and higher parietal lobe scores were associated with lower performance in executive function, verbal-, and non-verbal memory. Hypertension promotes WMH in the frontal, parietal, and temporal lobe. WMH in the frontal and parietal lobe are associated with reduced executive function and memory.

Brain Biometry Reveals Impaired Brain Growth in Preterm Neonates with Intraventricular Hemorrhage

Introduction: Preterm birth and cerebral hemorrhage have adverse effects on brain development. Alterations in regional brain size on magnetic resonance imaging (MRI) can be assessed using 2D biometrical analysis, an easily applicable technique showing good correlation with 3D brain volumes. Methods: This retrospective study included 74 preterm neonates with intraventricular hemorrhage (IVH) born <32+0 weeks of gestation between 2011 and 2019. Cerebral MRI was performed at term-equivalent age, and 2D measurement techniques were used for biometrical analysis and compared to normative data of two control groups. Finally, the correlation and association of brain parameters and patterns of impaired brain growth and outcome at 2 and 3 years of age were evaluated. Results: Interhemispheric distance (IHD), the 3rd ventricle, and lateral ventricles presented larger, in contrast, cerebral biparietal width (cBPW), fronto-occipital diameter (FOD), and the length of the corpus callosum were smaller in IVH patients compared to respective controls. The strongest correlations with outcome were observed for the parameters FOD, anteroposterior diameter of the vermis, transverse cerebellar diameter (tCD), corpus callosum, 3rd ventricle, and left ventricular index. Patients with the small FOD, small BPW, and increased IHD pattern reached overall lower outcome scores at follow-up. Discussion: Preterm neonates with IVH showed reduced total brain sizes and enlarged pericerebral spaces compared to neurologically healthy controls. Biometric analysis revealed that several 2D brain parameters as well as different patterns of impaired brain growth were associated with neurodevelopmental impairment in early childhood. These findings may support prediction of long-term outcome and parental counseling in patients with IVH.

Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis.

This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR]=0.52, 95% confidence interval [CI]=0.45-0.60), 46% lower risk of disability worsening (HR=0.54, 95% CI=0.41-0.71), and 32% greater chance of disability improvement (HR=1.32, 95% CI=1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

New Cerebral Microbleeds After Catheter-Based Structural Heart Interventions: An Exploratory Analysis.

Background Cerebral microbleeds (CMBs) are increasingly recognized as "covert" brain lesions indicating increased risk of future neurological events. However, data on CMBs in patients undergoing catheter-based structural heart interventions are scarce. Therefore, we assessed occurrence and predictors of new CMBs in patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Methods and Results We conducted an exploratory analysis using data derived from 2 prospective, observational studies. Eligible patients underwent cerebral magnetic resonance imaging (3 Tesla) examinations and cognitive tests (using the Montreal Cognitive Assessment) before and after catheter-based left atrial appendage closure and percutaneous mitral valve repair. Forty-seven patients (53% men; median age, 77 years) were included. New CMBs occurred in 17 of 47 patients (36%) following catheter-based structural heart interventions. Occurrences of new CMBs did not differ significantly between patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair (7/25 versus 10/22; P=0.348). In univariable analysis, longer procedure time was significantly associated with new CMBs. Adjustment for heparin attenuated this association (adjusted odds ratio [per 30 minutes]: 1.77 [95% CI, 0.92-3.83]; P=0.090). Conclusions New CMBs occur in approximately one-third of patients after catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Our data suggest that longer duration of the procedure may be a risk factor for new CMBs. Future studies in larger populations are needed to further investigate their clinical relevance. Clinical Trial Registration German Clinical Trials Register: DRKS00010300 (https://drks.de/search/en/trial/DRKS00010300); ClinicalTrials.gov : NCT03104556 (https://clinicaltrials.gov/ct2/show/NCT03104556?term=NCT03104556&draw=2&rank=1).

BRAIN METASTASES FROM PRIMARY UTERINE CERVICAL CANCER: A CASE REPORT AND A LITERATURE REVIEW

Background :Brain metastasesfromprimarycervical cancer are very rare.Wepresentthis report, to describe a case of brainmetastasesfromprimaryuterine cervical cancer and to conduct a literaturereview about clinicalpresentation, treatment, and prognosis of thisdesease. Case Presentation :A 51-year-old woman, followed since 2017 for squamous cell carcinoma of the cervix for which she had underwent surgical treatment and received radiotherapy, being asymptomatic for 4 years after completion of treatment.She is brought to the Emergency Department in February 2021 forintracranial hypertension syndrome associated with behavioral troubles, symptoms that developed progressively during the last two months before her consultation.The clinical examination found a conscious patient without sensory or motor deficit and without damage to the cranial nerves. A cerebral Magnetic Resonance Imaging (MRI) revealed a left frontal tumor process 50 mm in diameter enhanced peripherally after injection of contrast product, necrotic and surrounded by significant cerebral edema determining a mass effect on the median structures with signs of engagement under falcoriel (figure 1). The patientunderwent asurgicalresectionofthetumor, themassbeingremoved en bloc. Histopathologicalandimmunohistologicalexaminationoftheresectedtumorrevealed a metastaticoriginfrom a primarycervicalsquamoscellcarcinoma. A postoperative brain scan revealed the persistence of a left frontal tumor process 14 mm in diameter with significant perilesional edema. The patient subsequently received total brain radiotherapy at a dose of 37.5 Gy (15 fractions of 2.5 Gy) then an additional dose on the tumor residue at a total dose of 10 Gy (4 fractions of 2.5 Gy). A control scan performed one month after the end of radiotherapy showed a regression in size of the lesion of the left frontal cerebral lesion and the perilesional oedema.Twelve months after the end of radiotherapy, a CT scan revealed progression of the secondary cerebral localization.Sixteen months after the end of radiotherapy, the patient was still alive and followed in oncology. Conclusion: Brain metastases from primary uterine cervical tumors are extremely rare and generally have a poor prognosis.Multimodal therapy such as surgery and radiotherapy, depending on the clinical status of individual patients,should be recommended in patients with brain metastasis to improve survival.

A magnetic resonance imaging based radiomics model to predict mitosis cycles in intracranial meningioma

The aim of this study was to develop a magnetic resonance imaging (MRI) based radiomics model to predict mitosis cycles in intracranial meningioma grading prior to surgery. Preoperative contrast-enhanced T1-weighted (T1CE) cerebral MRI data of 167 meningioma patients between 2015 and 2020 were obtained, preprocessed and segmented using the 3D Slicer software and the PyRadiomics plugin. In total 145 radiomics features of the T1CE MRI images were computed. The criterion on the basis of which the feature selection was made is whether the number of mitoses per 10 high power field (HPF) is greater than or equal to zero. Our analyses show that machine learning algorithms can be used to make accurate predictions about whether the number of mitoses per 10 HPF is greater than or equal to zero. We obtained our best model using Ridge regression for feature pre-selection, followed by stepwise logistic regression for final model construction. Using independent test data, this model resulted in an AUC (Area under the Curve) of 0.8523, an accuracy of 0.7941, a sensitivity of 0.8182, a specificity of 0.7500 and a Cohen’s Kappa of 0.5576. We analyzed the performance of this model as a function of the number of mitoses per 10 HPF. The model performs well for cases with zero mitoses as well as for cases with more than one mitosis per 10 HPF. The worst model performance (accuracy = 0.6250) is obtained for cases with one mitosis per 10 HPF. Our results show that MRI-based radiomics may be a promising approach to predict the mitosis cycles in intracranial meningioma prior to surgery. Specifically, our approach may offer a non-invasive means of detecting the early stages of a malignant process in meningiomas prior to the onset of clinical symptoms.

Hippocampal volume and cognitive performance in children with congenital heart disease

BackgroundCongenital heart disease (CHD) is associated with an increased risk of brain abnormalities. Studies indicate a particular vulnerability of the hippocampus to hypoxia and inflammation. Yet, information regarding the hippocampus and its relation to cognitive function in school-age children with CHD remains scarce.MethodsChildren who underwent cardiopulmonary bypass surgery for CHD (N = 17) and healthy controls (N = 14) at 10 years of age underwent neurodevelopmental assessment and cerebral magnetic resonance imaging to measure IQ, working memory performance and hippocampal volume.ResultsIQ was significantly lower in children with CHD compared to controls (98 vs 112, P = 0.02). Children with CHD showed worse working memory performance with significantly lower scores in the letter-number sequencing test (P = 0.02). After adjusting for total brain volume, hippocampal volume was smaller in children with CHD compared to controls (P < 0.01). Smaller hippocampal volume was associated with lower IQ (P = 0.04), and digit span scaled score (P = 0.03), but not with other working memory tests (P > 0.1).ConclusionThis study suggests that the hippocampus may be particularly susceptible in children with CHD thereby contributing to cognitive impairments. Further research is necessary to understand the contribution of the hippocampus to cognitive impairments in children with CHD.ImpactIQ is significantly lower in school-age children with congenital heart disease compared to controls.Working memory performance seems to be worse in children with congenital heart disease.Smaller hippocampal volume is associated with lower IQ and seems to be associated with lower working memory performance.The study adds knowledge on the etiology of cognitive impairments in school-age children with congenital heart disease.

Relationship between early nutrition and deep gray matter and lateral ventricular volumes of preterm infants at term-equivalent age

BackgroundThe survival of preterm infants has improved over the last decade, but impaired brain development leading to poor neurological outcomes is still a major comorbidity associated with prematurity. The aim of this study was to evaluate the effect of nutrition on neurodevelopment in preterm infants and identify markers for improved outcomes.MethodsTotally 67 premature infants with a gestational age of 24–34 weeks and a birth weight of 450–2085 g were included. Clinical parameters and documented diet were collected from medical records. The nutritional analysis comprised the protein, fat, carbohydrate, and energy intake during different time spans. Brain development was assessed by determining deep gray matter (DGM; basal ganglia and thalamus) and lateral ventricular (LV) volumes as measured on cerebral magnetic resonance imaging scans obtained at term-equivalent age (TEA), and potential associations between nutrition and brain volumetrics were detected by regression analysis.ResultsWe observed a negative correlation between mean daily protein intake in the third postnatal week and MRI-measured DGM volume at TEA (P = 0.007). In contrast, head circumference at a corrected age of 35 weeks gestation (P < 0.001) and mean daily fat intake in the fourth postnatal week (P = 0.004) were positively correlated with DGM volume. Moreover, mean daily carbohydrate intake in the first postnatal week (P = 0.010) and intraventricular hemorrhage (P = 0.003) were revealed as independent predictors of LV volume.ConclusionThe study emphasizes the importance of nutrition for brain development following preterm birth.

Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis

Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions. The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS. Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium. Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score [Multiple Sclerosis Treatment Decision Score (MS-TDS)] through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI. Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5-20% for half of the patients if the treatment considered superior by the MS-TDS is used. Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established.

Protocolo diagnóstico y tratamiento de la trombosis venosa cerebral

In the diagnostic approach to cerebral venous thrombosis, both the topographic diagnosis (based on the patient's clinical manifestations, given that they can vary greatly depending on the affected venous sinus) and the neuroimaging diagnosis, in which cerebral magnetic resonance imaging and computed tomography venography or magnetic resonance imaging techniques are especially relevant, must be taken into account, without ignoring the importance of reaching an etiological diagnosis. The treatment strategies for cerebral venous thrombosis are based on anticoagulant treatment and treatment of the underlying causes, early detection, and treatment of possible complications such as epileptic seizures, intracranial hypertension, and hydrocephalus. Lastly, the high risk of recurrence of venous thrombosis that these patients present with must be considered. Therefore, it is necessary to perform an individualized evaluation and adaptation of the duration of anticoagulant treatment depending on the underlying cause.

Acute myocardial infarction related to coronary artery embolism: A systematic cardiac and cerebral magnetic resonance imaging study

Acute myocardial infarction related to coronary artery embolism: A systematic cardiac and cerebral magnetic resonance imaging study

PS-B10-10: MRI CEREBROVASCULAR CHARACTERIZATION IN A MOUSE MODEL OF HYPERTENSION-INDUCED BRAIN INJURY

Hypertension has been recognized as the main modifiable risk factor for vascular cognitive impairment (VCI), dementias and neurodegenerative pathologies as Alzheimer Disease (AD). As we previously demonstrated, Transverse aortic constriction (TAC) is a relevant mouse model of cerebral injury and cognitive impairment induced by vascular factors. In this work we characterize the effect of TAC procedure on cerebral injury leveraging Magnetic Resonance Imaging (MRI), and investigate the relationship between the alterations found by MRI and histological, cognitive and cardiac parameters of injury, to establish a framework of translational imaging biomarkers to be applied in human. We subjected C57Bl/6J to TAC procedure, inducing severe cerebral hypertension. Thereafter, the brain injury was characterized by macro and microstructural MRI; cerebral blood flow (CBF) was analyzed by perfusion MRI. All neuroimaging scans were performed on a small-animal dedicated 7 Tesla MRI. The cognitive phenotype was characterized by Morris Water Maze (MWM) and Novel Object Recognition (NOR), while cardiac and carotid remodeling was assessed by ultrasound imaging. Finally, brains were analyzed for histological alterations in terms of microvascular density and integrity. Structural MRI showed white matter microstructural degradation in the left Fimbria of TAC mice, evidenced by a reduction of Fractional Anisotropy, Mean Diffusivity and Radial Diffusiity, coupled with bilateral hypothalamic enlargement (Figure A). Hemodynamic alterations resulted in reduced global, cortical and hypothalamic CBF (Figure B). The histological microvascular analysis evidenced capillary rarefaction, reduced capillary-pericyte coverage and Blood-Brain Barrier leakiness in the neocortex (Figure C). Finally, we evaluated whether cerebral MRI parameters of injury were correlated with cardiac, carotid and cognitive alterations: CBF was significantly correlated with mouse performance at Probe trial of MWM test and correlated to cardiac remodeling and diastolic dysfunction. Diastolic disfunction was correlated also to hypothalamic swelling, and cardiac remodeling was significantly correlated to microstructural alterations in the fimbria. Finally, CBF was correlated to bilateral carotid remodeling. In conclusion we have developed a mouse model of hypertension-induced brain damage that recapitulates typical traits of the human pathology and a pipeline of analysis that will ease allow to appreciate findings resulting from novel molecular targeting of the brain and translate them from bench to bedside. JOURNAL/jhype/04.03/00004872-202301001-01152/figure1/v/2023-10-24T163949Z/r/image-jpeg

Single-cell profiling reveals preferential reduction of memory B cell subsets in cladribine patients that correlates with treatment response

Background: Cladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect. Objectives: Our aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients’ therapy response. Design: We performed an open-labeled, explorative, prospective, single-arm study, in which we examined the detailed lymphocyte subset development of MS patients who received cladribine treatment over 2 years. Methods: We performed in-depth profiling of the effects of cladribine on peripheral blood lymphocytes by flow cytometry, bulk RNA sequencing of sorted CD4+ T cells, CD8+ T cells, and CD19+ B cells as well as single-cell RNA sequencing of peripheral blood mononuclear cells in a total of 23 MS patients before and at different time points up to 24 months after cladribine treatment. Data were correlated with clinical and cranial magnetic resonance imaging (MRI) disease activity. Results: Flow cytometry revealed a predominant and sustained reduction of memory B cells compared to other B cell subsets after cladribine treatment, whereas T cell subsets were slightly reduced in a more uniform pattern. The overall transcriptional profile of total blood B cells exhibited reduced expression of proinflammatory and T cell activating genes, while single-cell transcriptomics revealed that gene expression within each B cell cluster did not change over time. Stable patients displayed stronger reductions of selected memory B cell clusters as compared to patients with clinical or cerebral MRI disease activity. Conclusion: We describe a pronounced and sustained effect of cladribine on the memory B cell compartment, and the resulting change in B cell subset composition causes a significant alteration of B cell transcriptional profiles resulting in reduced proinflammatory and T cell activating capacities. The extent of reduction in selected memory B cell clusters by cladribine may predict treatment response.

Fatal congenital copper transport defect caused by a homozygous likely pathogenic variant of SLC31A1.

Known hereditary human diseases featuring impaired copper trafficking across cellular membranes involve ATP7A (Menkes disease, occipital horn disease, X-linked spinal muscular atrophy type 3) and ATP7B (Wilson disease). Herein, we report a newborn infant of consanguineous parents with a homozygous pathogenic variant in a highly conserved sequence of SLC31A1, coding for the copper influx transporter 1, CTR1. This missense variant, c.236T > C, was detected by whole exome sequencing. The infant was born with pulmonary hypoplasia and suffered from severe respiratory distress immediately after birth, necessitating aggressive mechanical ventilation. At 2 weeks of age, multifocal brain hemorrhages were diagnosed by cerebral ultrasound and magnetic resonance imaging, together with increased tortuosity of cerebral arteries. Ensuing seizures were only partly controlled by antiepileptic drugs, and the infant became progressively comatose. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. No hair shaft abnormalities were detected by dermatoscopy or light microscopic analyses of embedded hair shafts obtained at 4 weeks of life. The infant died after redirection of care and elective cessation of invasive mechanical ventilation at 1 month of age. This case adds SLC31A1 to the genes implicated in severe hereditary disorders of copper transport in humans.

Acute Corticosteroid Responsive Meningoencephalitis with Cerebral Vasculitis after COVID-19 Infection in a Thirteen-Year-Old Case Report.

Various neurologic manifestations have already been described in children during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The central nervous system disorders reported in children are mainly encephalopathies during multisystem inflammatory syndrome. We present here an acute meningoencephalitis with cerebral vasculitis associated to a coronavirus disease 2019 (COVID-19) infection in a 13-year-old girl with a 1-year clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI) follow-up. A 13-year-old girl presented acute symptoms of consciousness impairment, frontal headache, hyperthermia, and aphasia, with moderate lymphopenia (900/mm3), elevated C-reactive protein (17 mg/L), cerebrospinal fluid (CSF) pleocytosis (15 cells/mm3), slow background with frontal focalization on EEG, a left frontal ischemic lesion, leptomeningeal enhancement, and bilateral limbic fluid-attenuated inversion recovery hyperintensity on cerebral MRI. Reverse transcription-polymerase chain reaction for SARS-CoV-2 was positive in nasopharyngeal swab and COVID serology was positive for immunoglobulin (Ig) M and G, whereas extensive autoimmune antibody investigation was negative except for a positive low titer of anti-myelin oligodendrocyte glycoprotein in CSF and blood. The diagnosis of probable encephalitis associated to cerebral vasculitis after COVID infection was suggested and steroids pulse were started. She recovered within a few days. Six months later, she had moderate clinical sequels including persistent intermittent headaches, an isolated spatial deficit, and focal spikes on the EEG without argument for epilepsia. A teenager without previous medical history presented with acute encephalitis with leptomeningitis and vasculitis after a recent COVID-19 infection. Steroids pulse therapy allowed clinical improvement. Cerebral MRI and EEG helped diagnosis, follow-up of the encephalitis, and evolution after treatment.

A case series of adrenoleukodystrophy in children conceived through in vitro fertilization with an egg donor

To report 3 cases of adrenoleukodystrophy (ALD) in children conceived by invitro fertilization (IVF) and egg donation. A case report. Patients aged 4-5 years old, evaluated by the University of Minnesota Leukodystrophy Center, who were diagnosed with ALD after being conceived by IVF with oocytes provided by the same donor. One patient received a hematopoietic stem cell transplant from a human leukocyte antigen-matched donor, and 1 patient received autologous lentiviral corrected hematopoietic cells. The disease state in 1 patient was unfortunately too advanced for effective treatment to be administered. Progression of disease after diagnosis or treatment was observed by cerebral magnetic resonance imaging and monitoring the development or advancement of any cognitive, adaptive, and motor deficits. Patients who received a transplant for ALD successfully experienced little to no disease progression at least 6 months to 1 year after treatment. These 3 cases of transmission of ALD through oocyte donation and IVF highlight the potential need to implement more comprehensive genetic screening of gamete donors to prevent the transfer of rare but severe genetic diseases through IVF. Further, these cases highlight limitations in carrier screening guidelines that limit reportable variants to pathogenic and likely pathogenic variants.

A single-center pilot randomized controlled trial of atorvastatin loading for preventing ischemic brain damage after carotid artery stenting.

Carotid artery stenting (CAS) performed perioperatively with high-dose atorvastatin may reduce the incidence of new ischemic brain lesions, but more high-level evidence is needed. Furthermore, the optimal dose and course of perioperative statin therapy remain uncertain. A single-center, prospective, parallel controlled, pilot randomized clinical trial was conducted at Beijing Hospital. The study includes a total of 130 patients with CAS. The patients were randomly assigned to receive a high-dose of 80 mg/day atorvastatin (n = 65) or a standard-dose of 20 mg/day atorvastatin (n = 65) 3 days before and 3 days after planned CAS. The primary endpoint event was the cumulative incidence of silent new ischemic cerebral lesions (sNICL) on post-CAS cerebral diffusion-weighted magnetic resonance imaging (DW-MRI), transient ischemic attack (TIA), or ischemic stroke within 30 days after CAS. Among the 130 patients, 123 completed the study, of which 63 were in the high-dose group and 60 were in the standard-dose group. The incidence of major endpoint events was 69.8% (44 cases) and 78.3% (46 cases) in the high-dose and standard-dose groups, respectively. There was no significant difference between the two groups (HR, 0.705; 95% CI, 0.315-1.576; p = 0.393). According to the stratified analysis results, the sNICL incidence was significantly different between the two groups in the symptomatic patients (HR, 0.263; 95% CI, 0.70-0.984; p = 0.04). Among patients with CAS, a periprocedural high-dose of atorvastatin did not reduce the rate of periprocedural ischemic brain damage. However, high-dose statins can reduce the incidence of sNICL after CAS in patients with symptomatic carotid stenosis. Clinicaltrials.gov, identifier NCT03079115.

712 INFLAMMATION, HAEMOSTASIS AND EXTRACELLULAR MATRIX IN THE STRATIFICATION OF BLEEDING AND THROMBOTIC RISK OF ATRIAL FIBRILLATION ON ORAL ANTICOAGULANT THERAPY: INSIGHTS FROM STRAT-AF STUDY

Abstract Background In anticoagulated atrial fibrillation patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that biological markers – both circulating and neuroimaging-based – and their possible interaction, might improve the prediction of bleeding risk in atrial fibrillation patients under treatment with any type of oral anticoagulant. Methods The Strat-AF study is an observational, prospective, single-center hospital-based study enrolling patients with atrial fibrillation, aged 65 years or older, and with no contraindications to undergo magnetic resonance imaging. Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcomes are the evaluation of cerebral microangiopathy using MRI (lacunar infarcts, non-lacunar infarcts, microbleeds, hyperintensity of the white matter, SVDs [small vessel disease score]) and the onset of ischemic or hemorrhagic stroke related to the levels of circulating biomarkers of inflammation (IL-6, IL-8, TNFα, IL-4, IL-10, CCL2, CXCL10, ICAM-1, VCAM-1, VEGF), haemostasis (PAI-1, CLT, vWF) and extracellular matrix remodeling (MMP-2,-7,-8,-9,-12, TIMP-1,-2,-3,-4). Starting from September 2017, 191 patients (mean age 78.1±6.7, range 65-97; 65.3% males) were enrolled. 56 patients (29.3%) were on vitamin K antagonists, and 135 (70.7%) were on direct oral anticoagulants. Follow-up clinical evaluation and brain MRI were performed at 18 months. Results At multivariate analysis, adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, independent predictors were: low levels of vWF and elevated levels of TIMP-2 for microbleeds [OR:0.62 95%CI(0.42-0.89), p=0.011and OR:1.25 (1.01-1.77), p=0.049 respectively]; elevated levels of IL-6 and TIMP-4 for hyperintensity of white matter [OR: 1.55 (1.01-2.58), p=0.049 and OR: 1.44 (1.01-2.07), p=0.047 respectively]; elevated levels of MMP-2 and of TIMP-1 and TIMP-2 for lacunar infarcts [OR: 1.33 (1.01-1.89), p=0.049, OR: 1.48(1.01-2.18), p=0.048 and 1.50 (1.05-2.16), p=0.028 respectively]; elevated levels of TIMP-1, TIMP-2, TIMP-3 for the appearance of at least 1 new lesion according to the SVD score [OR: 1.48 (1.01-2.19), p=0.046, OR:1.53 (1.05-2.23), p=0.028 and OR: 1.58 (1.09-2.31), p=0.016 respectively]. Conclusions The Strat-AF study may be an essential step towards the exploration of the role of a combined clinical biomarker or multiple biomarker models in predicting stroke risk in atrial fibrillation and might sustain the incorporation of such new markers in the existing stroke prediction schemes by the demonstration of a greater incremental value in predicting stroke risk and improvement in clinical outcomes in a cost-effective fashion.