Cytogenomic Analysis of Long-Term Epilepsy-Associated Tumors Using an Array-Based CGH Strategy.

A palette of copy number changes in long-term epilepsy-associated tumors (LEATs) have been reported, but the data are heterogeneous. To better understand the molecular basis underlying the development of LEATs, we performed array-comparative genomic hybridization analysis to investigate chromosomal imbalances across the entire genome in 8 cases of LEATs. A high number of aberrations were found in 4 patients, among which deletions predominated. Both whole-chromosome and regional abnormalities were observed, including monosomy 19, deletion of 1p, deletions of 4p, 12p, and 22q, and gain of 20p. The common altered regions are located mainly on chromosomes 19 and 4p, identifying genes potentially involved in biological processes and cellular mechanisms related to tumorigenesis. Our study highlights new genomic alterations and reinforces others previously reported, offering new molecular insights that may help in diagnosis and therapeutic decision-making.

The landscape of common genetic drivers and DNA methylation in low-grade (epilepsy-associated) neuroepithelial tumors: A review.

Low-grade neuroepithelial tumors (LNETs) represent an important group of central nervous system neoplasms, some of which may be associated to epilepsy. The concept of long-term epilepsy-associated tumors (LEATs) includes a heterogenous group of low-grade, cortically based tumors, associated to drug-resistant epilepsy, often requiring surgical treatment. LEATs entities can sometimes be poorly discriminated by histological features, precluding a confident classification in the absence of additional diagnostic tools. This study aimed to provide an updated review on the genomic findings and DNA methylation profiling advances in LNETs, including histological entities of LEATs. A comprehensive search strategy was conducted on PubMed, Embase, and Web of Science Core Collection. High-quality peer-reviewed original manuscripts and review articles with full-text in English, published between 2003 and 2022, were included. Results were screened based on titles and abstracts to determine suitability for inclusion, and when addressed the topic of the review was screened by full-text reading. Data extraction was performed through a qualitative content analysis approach. Most LNETs appear to be driven mainly by a single genomic abnormality and respective affected signaling pathway, including BRAF p.V600E mutations in ganglioglioma, FGFR1 abnormalities in dysembryoplastic neuroepithelial tumor, MYB alterations in angiocentric glioma, BRAF fusions in pilocytic astrocytoma, PRKCA fusions in papillary glioneuronal tumor, between others. However, these molecular alterations are not exclusive, with some overlap amongst different tumor histologies. Also, clustering analysis of DNA methylation profiles allowed the identification of biologically similar molecular groups that sometimes transcend conventional histopathological classification. The exciting developments on the molecular basis of these tumors reinforce the importance of an integrative histopathological and (epi)genetic classification, which can be translated into precision medicine approaches.

Analysis of the energy balance and CO2 flow under the influence of the seasonality of climatic elements in a mangrove ecosystem in Eastern Amazon.

An unprecedented study was carried out in a mangrove ecosystem in the northeastern coast of the Brazilian Amazon to understand the behavior of climatic elements in a year with the occurrence of El Niño (2015), associated with the seasonal function source/sink of CO2 by the ecosystem. Global radiation (Rg), net radiation (Rn), temperature, relative humidity, precipitation, horizontal wind speed and direction, as well as turbulent flows of sensible heat (H), latent heat (LE), and carbon (f_CO2) were recorded using eddy covariance, a system for studying turbulent flows of heat and gases in the atmosphere. We observed a drastic reduction in rainfall volumes, which accounts for 63.7% of the expected total according to the region's climatology. Regarding f_ CO2, the highest values of photosynthesis, autotrophic, and heterotrophic respiration of the ecosystem occurred in the wet season due to precipitation, ideal photosynthetically active radiation, lower soil salinity, and higher NDVI of the ecosystem. In the 2nd semester of the year, we observed that the decrease in cloudiness, causing a higher radiation supply in the forest canopy, accompanied by a reduction in precipitation and an increase in the value of H and soil salinity, favored the increase of foliar abscission by the dominant genus Rhizophora and Avicennia, thus influencing the reduction of magnitudes of carbon source/sink functions in the ecosystem during this season, even on high tide days.

Apathy Profile in Parkinson's and Huntington's Disease: A Comparative Cross-Sectional Study.

BACKGROUND/AIMS: Apathy is one of the most frequent, disabling and difficult-to-treat symptoms that show up in many neurodegenerative disorders. The aim of this study was to assess and compare apathy profile in Parkinson's and Huntington's patients using the same comprehensive instruments to measure apathy, cognition and depressive symptoms. MATERIALS AND METHODS: We consecutively assessed Parkinson's disease (PD) and Huntington's disease (HD) patients recruited from a Movement Disorders Unit. In all patients, information related to demographics, clinical data, motor score (Movement Disorders Society-Unified Parkinson Disease Rating Scale; Unified Huntington Disease Rating Scale), cognition (Montreal Cognitive Assessment scale), depressive symptoms (Beck Depression Inventory II) and apathy (Apathy Evaluation Scale - clinical version) was collected. Patients with dementia or major depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised criteria were excluded from the study. RESULTS: Seventy-five patients were enrolled, 45 with PD and 30 with HD. Apathy was present in 42.5% of PD patients and 51.7% of HD patients. In PD patients, apathy was associated with motor score, shorter duration of disease, lower dose of levodopa equivalent daily dose and depressive symptomatology, whereas in HD patients, apathy was related to disease duration, motor score and cognitive impairment. CONCLUSIONS: We found a similar prevalence of apathy in PD and HD patients but with different clinical correlations and different apathy domains involved, and this may warrant the development of different therapeutic approaches.

Anxiety and Depression as Longitudinal Predictors of Mild Cognitive Impairment in Older Adults.

INTRODUCTION: Few studies have dealt with the potential correlation between anxiety, depression, and cognitive impairment in community-dwelling older adults. METHOD: This longitudinal study was conducted in the city of Montreal, Canada, with 352 older adults aged 55 years or more. The participants were interviewed at baseline and again 2 years later. The Montreal Cognitive Assessment (MoCA) score was estimated and compared between the 2 time points, the Composite International Diagnostic Interview (CIDI) was used to assess major depression and anxiety, and the K10 measured high psychological distress. Likewise, major depression, anxiety disorders, and psychological distress were evaluated at the 2 study time points. RESULTS: In older adults with a diagnosis of depression or anxiety at baseline, no significant reduction in the MoCA score indicating deterioration in cognitive function was found 2 years later. Nevertheless, in individuals with a high level of psychological distress at baseline, there was a significant reduction in MoCA scores 2 years later, indicating deterioration in cognition. The findings of the present study suggest that a high level of psychological distress in addition to environmental factors may constitute important predictors for cognitive health.

Transcranial Sonography and DaTSCAN in Early Stage Parkinson's Disease and Essential Tremor.

BACKGROUND: The diagnosis of Parkinson's disease (PD) can sometimes be a challenge in the early stages of the disease. Both transcranial sonography (TCS) and DaTSCAN are recommended as auxiliary examinations for the differential diagnosis of PD; however, only few data exist regarding their diagnostic accuracy in the early stage of PD and essential tremor (ET). METHODS: We evaluated patients with clinically suspected diagnosis of PD at early stages (Hoehn and Yahr ≤2) or ET. All patients underwent DaTSCAN and TCS with a maximum interval of 6 months. Final diagnosis was established after 1-year follow-up. RESULTS: From the 63 patients recruited, 3 were excluded due to transcranial insonability and 2 for uncertain clinical diagnosis. The final clinical diagnosis was ET in 44.8% and PD in 55.2%. Compared to clinical diagnosis of PD, TCS had a sensitivity of 87.5% and specificity of 96.2%; DaTSCAN sensitivity was 84.4% and specificity was 96.2%. Both diagnostic tests demonstrated a substantial level of agreement (Cohen's kappa coefficient: 0.83, 95% CI 0.68-0.97, p < 0.001). CONCLUSION: TCS and DaTSCAN have similar diagnostic accuracy for the diagnosis of early stage PD versus ET.

Assessment of effectiveness of acoustic analysis of voice for monitoring the evolution of vocal nodules after vocal treatment.

In the present study, we report the results of acoustic analysis of voice in 97 patients diagnosed with vocal nodules before and after the vocal logopedic treatment, to evaluate its effectiveness in monitoring the evolution. We analyzed five parameters: the mean fundamental frequency (F0) and its standard deviation, jitter, shimmer, and normalized noise energy (NNE). Our results indicate that most patients showed a reduction of fundamental frequency, an increase of perturbation (jitter and shimmer), and an increase of NNE before the treatment. We did not find any statistically significant relationship between previous values of the five parameters analyzed and the clinical course. We did not find significant differences between the two groups (with and without clinical improvement) in the evolution of any of the five parameters, although these differences were greater in the case of jitter. We conclude that the acoustic analysis of voice can be useful as a complementary tool in the diagnosis of vocal nodules, but the parameter values analyzed before treatment did not correlate with the clinical course and we believe that its usefulness in the evaluation of results after the vocal treatment is limited.

Chemotherapy-related trigeminal and glossopharyngeal nerves neurotoxicity: a cohort study.

BACKGROUND AND OBJECTIVES: The association between orofacial neurotoxicity and chemotherapy treatment is still unclear. In this context, the purpose of this study is to relate the orofacial alterations that manifest during antineoplastic pharmacological treatment, highlighting the drugs commonly related to orofacial neuropathy and the adequate instrument to verify the alterations at clinical levels. METHODS: This prospective cohort study, addressed patients who would start therapy with taxanes, platinum, or related therapy. The collection of signs and symptoms was divided into 3 different times (baseline, second or third cycle of antineoplastic chemotherapy treatment, and sixth cycle). A total of 40 patients were submitted to the application of the Short McGill pain questionnaire and Neutoxicity Induced by Antineoplastics questionnaire (QNIA). To verify sensory alterations in the face, a clinical evaluation was performed with the help of Semmes-Weinstein monofilaments. RESULTS: Taxanes show greater orofacial neurotoxic potential, being associated with sensory alterations assessed by monofilaments (P = .003) and the presence of orofacial pain analyzed by the Short McGill pain questionnaire (P = .001). These medications related to neuropathy in the orofacial region measured through the QNIA, demonstrating a predominantly acute nature (P < .001). CONCLUSION: It is suggested that chemotherapy may induce neurotoxicity in the orofacial region.

The Challenge of Somatic Variants in Focal Cortical Dysplasia.

Objective: The advent of next-generation sequencing (NGS) enabled the detection of low-level brain somatic variants in postsurgical tissue of focal cortical dysplasia (FCD). The genetic background of FCD Type I remains elusive, while the mammalian target of rapamycin (mTOR) pathway seems to have a relevant role in the pathogenesis of FCD Type II. Our goal was to uncover information on the molecular basis of FCD, performing whole genome sequencing (WGS) in postsurgical tissue to detect candidate brain-specific somatic variants, and evaluate their clinical significance. Design: WGS was performed using paired peripheral venous blood and postsurgical pathological brain deoxyribonucleic acid (DNA) samples. Libraries were prepared using the Roche KAPA HyperPrep polymerase chain reaction (PCR) free library preparation kit. Paired-end 150bp reads were generated on the Illumina NovaSeq platform. The FASTQ files were processed using the nf-core sarek pipeline (version 3.0) to call somatic variants, which were then annotated with ANNOVAR. A screening strategy was applied to obtain relevant variants. Results: Two female patients with drug-resistant epilepsy due to FCD who underwent surgical treatment were included. Regarding neuropathological diagnosis, one patient had FCD Type Ia and the other had FCD Type IIa. Five somatic nonsynonymous single nucleotide variants (SNVs) were detected using WGS, three in FCD Ia tissue (WDR24 p.Trp259Gly; MICAL1 p.Lys1036Arg; and KATNB1 p.Leu566Ile) and two in FCD IIa tissue (MATN4 p.Phe91Val and ANKRD6 p.His386Gln). All variants were predicted to be potentially pathogenic by at least two different tools. However, they were classified as variants of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) criteria. Conclusion: Brain-specific somatic missense variants were identified by NGS in new candidate genes (WDR24, MICAL1, KATNB1, MATN4, and ANKRD6) using postsurgical FCD tissue, which may contribute to further understanding of the genetic background of FCD. All the reported genes were previously related to epilepsy and/or malformations of central nervous system (CNS) and cortical development. However, the pathogenicity assessment of these variants and, consequently, their impact on clinical practice still poses an important challenge.

Resective Epilepsy Surgery and Respective Histopathological Diagnoses: A Retrospective Cohort Study.

INTRODUCTION: Over recent decades, brain resection for drug-resistant epilepsy has proven to be a valuable treatment option. The histopathological classification was of paramount value for patient management. The aims of this study were to characterize our resective epilepsy surgical series including the histopathological diagnoses and to understand the differences in clinical practice between two different periods of our epilepsy surgical programme. MATERIAL AND METHODS: We performed a retrospective cohort study, including patients with drug-resistant epilepsy that underwent resective surgery between 1997 and 2021 in the Coimbra University Hospital Centre. Histopathological diagnoses were classified into seven major conventional categories. For comparison purposes, the cohort was divided into two consecutive periods of 12 years. RESULTS: A total of 259 patients were included, from which 228 (88%) were adults at the time of surgery. The median disease duration prior to surgery was 14 (interquartile range 23) years. Fifty-five (21%) patients performed pre-surgical invasive work-up. The temporal lobe was the most frequently operated region (73%). Major and minor post-surgical complications were identified in 21 (8%) patients. A reduction in the number of antiepileptic drugs was possible in 96 (37%) patients after surgery. The most common histopathological diagnosis was hippocampal sclerosis, but among children it was long-term epilepsy associated tumour. Long-term epilepsy associated tumours, hippocampal sclerosis and vascular malformations had the best post-operative outcomes. Malformations of cortical development and glial scars had the worst outcomes. Regarding differences between the two periods, the absolute number of operated patients increased (119 versus 140), and the age at surgery was higher in the second period (p = 0.04). The number of malformations of cortical development increased (p = 0.01), but the number of other tumours (p = 0.01) and specimens with no lesion (p = 0.03) decreased in the same period. CONCLUSION: This study is in line with contemporaneous research, reinforcing the previous knowledge on the underlying structural aetiologies, clinical practice, and surgical outcomes over more than two decades of experience. Our data provide realistic expectations about epilepsy surgery and highlight the need for further improvements in diagnosis and treatment paradigm for people with chronic epilepsy.

Introdução: Nas últimas décadas, a cirurgia ressectiva demonstrou ser uma opção valiosa no tratamento da epilepsia farmacorresistente. A classificação histopatológica foi de grande importância na orientação do doente. Os objetivos deste estudo foram caracterizar a nossa série de cirurgia de epilepsia ressectiva incluindo os diagnósticos histopatológicos, e compreender as diferenças na prática clínica entre dois períodos diferentes do programa de cirurgia da epilepsia. Material e Métodos: Realizou-se um estudo de coorte retrospetivo, incluindo doentes com epilepsia farmacorresistente submetidos a cirurgia ressectiva entre 1997 e 2021 no Centro Hospitalar e Universitário de Coimbra. Os diagnósticos histopatológicos foram classificados em sete categorias. Para análise comparativa, a coorte foi dividida em dois períodos consecutivos de 12 anos. Resultados: Um total de 259 doentes foram incluídos, sendo 228 (88%) adultos aquando da cirurgia. A mediana da duração da doença antes da cirurgia foi de 14 (amplitude interquartil 23) anos. Cinquenta e cinco (21%) doentes realizaram investigação invasiva pré-cirúrgica. O lobo temporal foi a região mais frequentemente operada (73%). Complicações pós-cirúrgicas major e minor foram identificadas em 21 (8%) doentes. Uma redução no número de antiepiléticos foi observada em 96 (37%) doentes após a cirurgia. O diagnóstico histopatológico mais comum foi a esclerose do hipocampo, mas nas crianças foi o tumor associado a epilepsia de longa duração. Tumores associados a epilepsia de longa duração, esclerose do hipocampo e malformações vasculares tiveram os melhores resultados pós-operatórios. Malformações do desenvolvimento cortical e cicatrizes gliais tiveram os piores resultados. Relativamente às diferenças entre os dois períodos, o número absoluto de doentes operados aumentou (119 versus 140), e a idade aquando da cirurgia foi maior no segundo período (p = 0,04). O número de malformações do desenvolvimento cortical aumentou (p = 0,01), mas o número de outros tumores (p = 0,01) e amostras sem lesão (p = 0,03) diminuiu no mesmo período. Conclusão: Este estudo está de acordo com a literatura atual, reforçando o conhecimento prévio sobre as etiologias estruturais, prática clínica e resultados cirúrgicos ao longo de mais de duas décadas de experiência. Os dados analisados fornecem expectativas realistas sobre a cirurgia de epilepsia e destacam a necessidade de melhorias no paradigma de diagnóstico e tratamento destes doentes.

Non-contrast transcatheter aortic valve implantation for patients with aortic stenosis and chronic kidney disease: a pilot study.

Background: Acute kidney injury (AKI) is frequently observed after transcatheter aortic valve implantation (TAVI). Of note, it is associated with a threefold increase in all-cause and cardiac death. We propose a new non-contrast strategy for evaluating and performing the TAVI procedure that can be especially valuable for patients with aortic stenosis (AS) and chronic kidney disease (CKD) to prevent AKI. Methods: Patients with severe symptomatic AS and CKD stage ≥3a were evaluated for TAVI using four non-contrast imaging modalities for procedural planning: transesophageal echocardiogram (TEE), cardiac magnetic resonance, multidetector computed tomography (MDCT), and aortoiliac CO2 angiography. Patients underwent transfemoral (TF) TAVI using the self-expandable Evolut R/Pro, and the procedures were guided by fluoroscopy and TEE. Contrast MDCT and contrast injection at certain checkpoints during the procedure were used in a blinded fashion to guarantee patient safety. Results: A total of 25 patients underwent TF-TAVI with the zero-contrast technique. The mean age was 79.9 ± 6.1 years, 72% in NYHA class III/IV, with a mean STS-PROM of 3.0% ± 1.5%, and creatinine clearance of 49 ± 7 ml/min. The self-expandable Evolut R and Pro were implanted in 80% and 20% of patients, respectively. In 36% of the cases, the transcatheter heart valve (THV) chosen was one size larger than the one by contrast MDCT, but none of these cases presented adverse events. Device success and the combined safety endpoint (at 30 days) both achieved 92%. Pacemaker implantation was needed in 17%. Conclusion: This pilot study demonstrated that the zero-contrast technique for procedural planning and THV implantation was feasible and safe and might become the preferable strategy for a significant population of CKD patients undergoing TAVR. Future studies with a larger number of patients are still needed to confirm such interesting findings.

Percutaneous Strategies in Structural Heart Diseases: Focus on Chronic Heart Failure. / Estratégias Percutâneas em Doenças Estruturais: Foco em Insuficiência Cardíaca Crônica.

BACKGROUND: Central Illustration : Percutaneous Strategies in Structural Heart Diseases: Focus on Chronic Heart Failure Transcatheter devices for monitoring and treating advanced chronic heart failure patients. PA: pulmonary artery; LA: left atrium; AFR: atrial flow regulator; TASS: Transcatheter Atrial Shunt System; VNS: vagus nerve stimulation; BAT: baroreceptor activation therapy; RDN: renal sympathetic denervation; F: approval by the American regulatory agency (FDA); E: approval by the European regulatory agency (CE Mark). BACKGROUND: Innovations in devices during the last decade contributed to enhanced diagnosis and treatment of patients with cardiac insufficiency. These tools progressively adapted to minimally invasive strategies with rapid, widespread use. The present article focuses on actual and future directions of device-related diagnosis and treatment of chronic heart failure.

Post-Endomyocardial Biopsy Fistula Between Left Anterior Descending Artery and Right Ventricle.

The image in this vignette helps to illustrate a rare, albeit reported, complication of endomyocardial biopsy. The case was discussed by the heart team. Fistula occlusion with microcoils was considered; however, the patient was asymptomatic and presented no reduction of left ventricular ejection fraction, and the documented ischemia was minor. Therefore, the patient received conservative treatment.

Combined transcatheter aortic valve replacement and left atrial appendage occlusion in patients ineligible for oral anticoagulation: A case series.

Patients presenting with aortic stenosis and atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) are commonly at increased risk for stroke and bleeding complications. Concomitant left atrial appendage occlusion (LAAO) after TAVR may be an alternative to oral anticoagulation (OAC).Between 2018 and 2022, 7 consecutive patients who were ineligible for OAC underwent simultaneous TAVR and LAAO. The mean age was 84.9 ±â€¯4.9 years. The mean CHA2DS2-VASc, HAS-BLED, and STS predicted risk of mortality scores were 5.9 ±â€¯0.7, 3.9 ±â€¯1.1, and 8.8 ±â€¯3.4%, respectively. The median follow-up time was 23 (1 to 27) months. All procedures achieved technical success and no adverse events were observed during follow-up. This case series shows that concomitant TAVR and LAAO is feasible and safe among patients with severe aortic stenosis and AF who are deemed ineligible for OAC. Learning objectives: Atrial fibrillation is the most common arrhythmia in the transcatheter aortic valve replacement (TAVR) population. In those who experience major or life-threatening bleeding, mortality is doubled. We report a case series of 7 concomitant left atrial appendage occlusions (LAAO) after TAVR in patients ineligible for oral anticoagulation. All procedures achieved technical success and no adverse events were observed. The simultaneous approach with TAVR and LAAO was feasible and safe in this case series.

DEPDC5 variant in focal cortical dysplasia: a case report and review of the literature.

Germline and 2-hit brain somatic variants in DEPDC5 gene, a negative regulator of the mammalian target of rapamycin (mTOR) pathway, are increasingly recognized in patients with focal cortical dysplasia (FCD). Next-generation targeted sequencing identified a heterozygous germline variant in DEPDC5 gene (c.3241A>C, p.Thr1081Pro), classified as of unknown significance, in a patient with clinical features compatible with DEPDC5 phenotype (FCD, focal epilepsy, attention-deficit/hyperactivity disorder and borderline intellectual functioning). This missense variant has previously been reported in two other epileptic patients. Although interpretation of missense variants remains a challenge, DEPDC5 variants in patients with FCD and epilepsy cannot be neglected. Null variants were the most frequently reported in FCD patients, but missense variants have been described as well. The recognition of DEPDC5 phenotype and the appropriate interpretation of the detected variants are essential, since it may have important treatment implications in the near future, namely the use of mTOR inhibitors.

Impact of Post-Stroke Recanalization on General and Upper Limb Functioning: A Prospective, Observational Study.

The objective of this study is to assess the impact of recanalization (spontaneous and therapeutic) on upper limb functioning and general patient functioning after stroke. This is a prospective, observational study of patients hospitalized due to acute ischemic stroke in the territory of the middle cerebral artery (n = 98). Patients completed a comprehensive rehabilitation program and were followed-up for 24 weeks. The impact of recanalization on patient functioning was evaluated using the modified Rankin Scale (mRS) and Stroke Upper Limb Capacity Scale (SULCS). General and upper limb functioning improved markedly in the first three weeks after stroke. Age, gender, and National Institutes of Health Stroke Scale (NIHSS) score at admission were associated with general and upper limb functioning at 12 weeks. Successful recanalization was associated with better functioning. Among patients who underwent therapeutic recanalization, NIHSS scores ≥16.5 indicate lower general functioning at 12 weeks (sensibility = 72.4%; specificity = 78.6%) and NIHSS scores ≥13.5 indicate no hand functioning at 12 weeks (sensibility = 83.8%; specificity = 76.5%). Recanalization, either spontaneous or therapeutic, has a positive impact on patient functioning after acute ischemic stroke. Functional recovery occurs mostly within the first 12 weeks after stroke, with greater functional gains among patients with successful recanalization. Higher NIHSS scores at admission are associated with worse functional recovery.

Natural History of Adapted Leaman Score Assessing Coronary Artery Disease Progression by Computed Tomography Angiography: A 7-Year Follow-Up Report.

BACKGROUND: Coronary computed tomographic angiography (CCTA) provides a non-invasive assessment of the coronary artery tree. Computed Tomography - adapted Leaman Score (CT-LeSc) has been shown to be an independent predictor of cardiac events in coronary artery disease (CAD) patients with a score greater than 5 (high). PURPOSE: To investigate the relationship between CT-LeSc and the progression of CAD and to provide vessel- and segment-level CAD qualification and quantification at baseline and 7-year follow-up. METHODS: Patients with multivessel CAD and CCTA assessments at baseline and follow-up were included. The CT-LeSc analysis was performed in a paired fashion. The patient-level scores and the differences between each phase were assessed by 2 analysts in an independent core laboratory. RESULTS: This study analyzed 248 coronary segments from 17 patients with a mean follow-up interval of 7.5 ± 0.6 years. The mean CT-LeSc at baseline and follow-up were 14.6 ± 4.2 and 16.9 ± 1.5, respectively, with an absolute increase of 2.3 ± 1.8. The mean cumulative increase of new lesions was 0.2 ± 0.2 per year. Over time, 14.6% of the non-obstructive lesions became obstructive, and 15.0% of the non-calcified plaques became calcified. There were 29 new lesions found at follow-up, and out of these, 16 were obstructive and 19 were non-calcified. CONCLUSION: In patients at high risk for cardiac events, as determined by CT-LeSc, there was an increase in CT-LeSc, obstructive lesions, and calcified plaques over the 7-year follow-up period. Most of the new lesions were obstructive and non-calcified. This is the first report showing long-term serial imaging CCTA changes in a high-risk population.

Genomic and Epigenetic Advances in Focal Cortical Dysplasia Types I and II: A Scoping Review.

Introduction: Focal cortical dysplasias (FCDs) are a group of malformations of cortical development that constitute a common cause of drug-resistant epilepsy, often subjected to neurosurgery, with a suboptimal long-term outcome. The past few years have witnessed a dramatic leap in our understanding of the molecular basis of FCD. This study aimed to provide an updated review on the genomic and epigenetic advances underlying FCD etiology, to understand a genotype-phenotype correlation and identify priorities to lead future translational research. Methods: A scoping review of the literature was conducted, according to previously described methods. A comprehensive search strategy was applied in PubMed, Embase, and Web of Science from inception to 07 May 2020. References were screened based on title and abstract, and posteriorly full-text articles were assessed for inclusion according to eligibility criteria. Studies with novel gene variants or epigenetic regulatory mechanisms in patients that underwent epilepsy surgery, with histopathological diagnosis of FCD type I or II according to Palmini's or the ILAE classification system, were included. Data were extracted and summarized for an overview of evidence. Results: Of 1,156 candidate papers, 39 met the study criteria and were included in this review. The advent of next-generation sequencing enabled the detection in resected FCD tissue of low-level brain somatic mutations that occurred during embryonic corticogenesis. The mammalian target of rapamycin (mTOR) signaling pathway, involved in neuronal growth and migration, is the key player in the pathogenesis of FCD II. Somatic gain-of-function variants in MTOR and its activators as well as germline, somatic, and second-hit mosaic loss-of-function variants in its related repressors have been reported. However, the genetic background of FCD type I remains elusive, with a pleomorphic repertoire of genes affected. DNA methylation and microRNAs were the two epigenetic mechanisms that proved to have a functional role in FCD and may represent molecular biomarkers. Conclusion: Further research into the possible pathogenic causes of both FCD subtypes is required, incorporating single-cell DNA/RNA sequencing as well as methylome and proteomic analysis. The collected data call for an integrated clinicopathologic and molecular genetic diagnosis in current practice not only to improve diagnostic accuracy but also to guide the development of future targeted treatments.

Correlation between computed tomography adapted leaman score and computed tomography liver and spleen attenuation parameters for non-alcoholic fatty liver disease as well as respective inflammatory mediators.

Metabolic syndrome is a primary driver of vascular inflammation, plaque development, and atherosclerotic disease. The Computed Tomography-adapted Leaman Score (CT-LeSc) has been shown to be an independent predictor of cardiac events in coronary artery disease (CAD) patients but has never been studied for broader applicability. Non-alcoholic fatty liver disease (NAFLD) is associated with similar systemic inflammatory processes as CAD, and its presence as assessed by Computed Tomography Liver and Spleen Attenuation (CT-LSA) may impact on the extension of the CT-LeSc. The purpose of this study was to investigate the association between the CT-LeSc and NAFLD and to characterize and compare the inflammatory processes of each disease state. This was an exploratory study in which patients with known multivessel CAD who were scheduled to undergo percutaneous coronary intervention were included. CT-LeSc were graded on pre-existing criteria by two independent CoreLab analysts. CT-LSA parameters analyzed included the liver absolute attenuation value, liver and spleen attenuation difference and liver-to-spleen attenuation ratio and were scored by two independent CoreLab analysts as well. Inflammatory mediator analysis included routine laboratory draws for a variety of known signal molecules. The overall liver absolute attenuation value did not correlate significantly with the CT-LeSc, but the subgroup 50 to 65 HU showed moderately negative correlation (R = - 0.629; p = 0.008). The overall liver and spleen attenuation difference did not correlate significantly with the CT-LeSc, but the subgroup 1 to 18 HU showed moderately positive correlation (R = 0.513; p = 0.017). The overall and subgroup liver-to-spleen attenuation ratio did not correlate with the CT-LeSc. The eosinophil and leukocyte ratio showed weakly negative correlation with the overall CT-LeSc (R = - 0.4602; p = 0.008), and VCAM-1 showed moderately negative correlation with CT-LeSc < 16.0 (R = - 0.5678; p = 0.022). Some CT-LSA parameters correlate with high risk CT-LeSc and may both provide complementary information for cardiovascular risk stratification. The significant metrics of liver absolute attenuation value and liver and spleen attenuation difference can be quickly completed in the clinical setting and may support a suspicion of CAD.

Motion integration deficits are independent of magnocellular impairment in Parkinson's disease.

Motion processing involves multiple hierarchical steps, from the magnocellular pathway, sensitive to high temporal frequency modulations, to subsequent motion integration within the visual cortical dorsal stream. We have tested whether motion integration deficits in mild Parkinson disease (PD) can be explained by visual deficits in earlier processing nodes. Contrast sensitivity deficits in the magnocellular pathway, were compared with speed discrimination of local dots moving in random directions, speed and direction discrimination of moving surfaces and motion integration as measured by 2D coherence thresholds (n=27). We have found that low-level magnocellular impairment in PD does not explain deficits in subsequent steps in motion processing. High-level performance was abnormal in particular for tasks requiring perception of coherently moving surfaces. Motion coherence deficits were predictive of visuomotor impairment, corroborating a previous magnetic stimulation study in normal subjects. We conclude that dorsal stream deficits in PD have a high-level visual cortical basis independent of low-level magnocellular damage.