Improving the Performance of the Layered Nickel Manganese Oxide Cathode of Sodium-Ion Batteries by Direct Coating with Sodium Niobium Oxide.

This research highlights the efficacy of NaNbO3 as a coating for P2-Na2/3Ni1/3Mn2/3O2 cathodes in sodium-ion batteries. The coating enhances the kinetic behavior and cyclability of the electrochemical cells, as shown by electrochemical measurements. XRD analysis indicates that Nb does not incorporate into the cathode structure, implying a physical interaction between the coating and the cathode material. XRF analysis and EDX mapping confirm the actual composition and uniform dispersion of elements throughout the sample, while the electron micrographs evidence the occurrence of NaNbO3 particles modifying the surface of the layered oxide. The Ni4+/Ni3+ and Ni3+/Ni2+ redox pairs, along with the partially reversible oxidation of oxide to peroxide anions, contribute significantly to cell capacity, as revealed by XPS spectra. This last effect and the appearance of a co-intercalated phase at high voltage are positive factors to provide fast kinetics. Cyclic voltammograms show that samples coated with 2-3% NaNbO3 have superior rate capability, with high capacitive response and apparent diffusion coefficients. These samples also have low impedance at the electrode-electrolyte interface, which helps deliver a high capacity at 5C. Further cycling at 1C shows improved cyclability in the bare and 3% coated samples, due to their higher diffusion coefficients on charging. Notably, the 3% NaNbO3-coated sample exhibits excellent cyclability below 0 °C, making it a promising cathode material for sodium-ion batteries.

Impact of hemispherotomy on quality of life and burden of caregivers in children and adolescents: a retrospective observational study.

PURPOSE: To evaluate QOL and caregiver burden of children and teenagers submitted to hemispherotomy for pharmacoresistant epilepsy, by comparing pre and post-surgical intervention data. MATERIALS AND METHODS: Retrospective analysis of pediatric patients submitted to surgical hemispherotomy before intervention (preOP) and their follow-up at 6 months (6 M PO) and 2 years (2Y PO) after surgery. QOL was evaluated through the Quality of Life in Childhood Epilepsy (QVCE-50) questionnaire and caregiver burden, through the Zarit Burden Interview (ZBI) tool. RESULTS: Twenty-two patients were included in the study. Sixteen patients (72%) were classified as Engel I at 2Y PO follow-up. QVCE-50 scale showed improvement of total QOL at 2Y PO. In relation to QVCE-50-specific domains, there was an improvement in the physical domain and in the cognitive-education a decrease in psychological and a stabilization in social/familiar domain scores. The majority of caregivers classified their burden as mild to moderate, with no PO improvement. CONCLUSIONS: Hemispherotomy represents an effective seizure control treatment, as well as it contributes to improvement of QOL, particularly in the physical domain and in spite of children's physical and cognitive limitations. However, no improvement in caregiver burden was observed, probably due to the chronic condition of these patients, which might be worsened by social issues.

Vanishing white matter disease: imaging, clinical and molecular correlation in Brazilian families.

PURPOSE: To characterize Vanishing White Matter Disease (VWM) cases from a Brazilian University Tertiary hospital, focusing on brain magnetic resonance image (MRI) aspects, clinical and molecular data. METHODS: Medical records and brain MRI of 13 genetically confirmed VWM patients were reviewed. Epidemiological data such as age at symptom onset, gender and main symptoms were analyzed, along with genetic mutations and MRI characteristics, such as the distribution of white matter lesions and atrophy. RESULTS: The majority of patients were female, with the age of symptom onset ranging from 1 year and 6 months to 40 years. All mutations were identified in the EIF2B5 gene, the most prevalent being c.338G > A (p.Arg113His), and a novel mutation related to the disease was discovered, c.1051G > A (p.Gly351Ser). Trauma or infection were significant triggers. The most frequent symptoms were ataxia and limb spasticity. All MRI scans displayed deep white matter involvement, cystic degeneration, with U-fibers relatively spared and a predilection for the frontoparietal region. Lesions in the corpus callosum and posterior fossa were present in all patients. Follow-up exams revealed the evolution of white matter lesions and cerebral atrophy, which correlated with clinical deterioration. CONCLUSIONS: VWM affects various age groups, with a significant clinical and genetic variability. A novel mutation associated with the disease is highlighted. MRI reveals a typical pattern of white matter involvement, characterized by diffuse lesions in the periventricular and deep regions, with subsequent extension to the subcortical areas, accompanied by cystic degeneration, and plays a crucial role in diagnosis and follow-up.

Assessment of U-Net in the segmentation of short tracts: Transferring to clinical MRI routine.

Accurately studying structural connectivity requires precise tract segmentation strategies. The U-Net network has been widely recognized for its exceptional capacity in image segmentation tasks and provides remarkable results in large tract segmentation when high-quality diffusion-weighted imaging (DWI) data are used. However, short tracts, which are associated with various neurological diseases, pose specific challenges, particularly when high-quality DWI data acquisition within clinical settings is concerned. Here, we aimed to evaluate the U-Net network ability to segment short tracts by using DWI data acquired in different experimental conditions. To this end, we conducted three types of training experiments involving 350 healthy subjects and 11 white matter tracts, including the anterior, posterior, and hippocampal commissure, fornix, and uncinated fasciculus. In the first experiment, the model was exclusively trained with high-quality data of the Human Connectome Project (HCP) dataset. The second experiment focused on images of healthy subjects acquired from a local hospital dataset, representing a typical clinical routine acquisition. In the third experiment, a hybrid training approach was employed, combining data of the HCP and local hospital datasets. Then, the best model was also tested in unseen DWIs of 10 epilepsy patients of the local hospital and 10 healthy subjects acquired on a scanner from another company. The outcomes of the third experiment demonstrated a notable enhancement in performance when contrasted with the preceding trials. Specifically, the short tracts within the local hospital dataset achieved Dice scores ranging between 0.60 and 0.65. Similar intervals were obtained with HCP data in the first experiment, and a substantial improvement compared to the scores between 0.37 and 0.50 obtained with the local hospital dataset at the same experiment. This improvement persisted when the method was applied to diverse scenarios, including different scanner acquisitions and epilepsy patients. These results indicate that combining datasets from different sources, coupled with resolution standardization strengthens the neural network ability to generalize predictions across a spectrum of datasets. Nevertheless, short tract segmentation performance is intricately linked to the training composition, to validation, and to testing data. Moreover, curved tracts have intricate structural nature, which adds complexities to their segmenting. Although the network training approach tested herein has provided promising results, caution must be taken when extrapolating its application to datasets acquired under distinct experimental conditions, even in the case of higher-quality data or analysis of long or short tracts.

Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Symmetrical placement of bilateral percutaneous bone-anchored hearing systems via guide-marker.

Objectives: To investigate the use of a novel technique to estimate the symmetrical placement of percutaneous bone-anchored hearing systems (BAHS) with a guide-marker in patients undergoing bilateral surgery with this device. Study Design: Prospective cohort study. Methods: A guide-marker and anatomical landmarks were used to estimate the implant placement and transferred to the contralateral ear in 12 subjects eligible for bilateral BAHS surgery. To investigate the bilateral symmetry, preoperative tri-dimensional (3D) computed tomography (CT) image reconstruction was used to compare the distances between the mandibular condyle and implant placement estimation (mandible-implant distance) in both the right and left ears of the subjects. Results: The guide-marker could be used to estimate the bilateral implant placement in all subjects included in this study, simply and easily, including one subject with craniofacial malformation. The mean mandible-implant distances were 5.37 and 5.38 cm, in the right and left ears of the subjects, respectively, and no differences were observed between them, thereby indicating optimal bilateral symmetry. Conclusion: The use of the guide-marker proved to be an effective tool to provide symmetrical placement of bilateral BAHS. We propose a novel method employing a simple guide-marker and tracing based on symmetrical anatomical landmarks to achieve precise placement and optimal symmetry and which may be easily adopted in the surgical routine of BAHS. Level of Evidence: 3.

Epigenetic Control of Adamantinomatous Craniopharyngiomas.

INTRODUCTION: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking. OBJECTIVE: To identify methylation signatures in ACPs regarding clinical presentation and outcome. METHODS: Clinical and pathology data were collected from 35 patients with ACP (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multidimensional scaling. Statistical associations between clusters and clinical features were achieved using the Fisher test and global biological process interpretations were aided by Gene Ontology enrichment analyses. RESULTS: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = .0006), hypomethylated in CpG island, non-CpG Island sites, and globally (P < .001), and associated with greater tumor size (24.1 vs 9.5 cm3, P = .04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell adhesion, cytoskeleton organization, and cytokine binding, and cell type-specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. CONCLUSION: Two clusters of patients with ACP were consistently revealed by unsupervised machine learning methods, with one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment.

Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience.

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. OBJECTIVE: To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. METHODS: We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. RESULTS: Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. CONCLUSION: Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.

ANTECEDENTES: A doença associada ao anticorpo da glicoproteína da mielina de oligodendrócitos (anti-MOG; MOGAD) é uma doença neurológica imunomediada com um amplo espectro de apresentações clínicas que muitas vezes é difícil de distinguir de outras doenças desmielinizantes, como a esclerose múltipla e o distúrbio do espectro da neuromielite óptica. OBJETIVO: Descrever as características clínicas e paraclínicas da MOGAD em um centro terciário brasileiro. MéTODOS: Revisamos retrospectivamente os prontuários dos pacientes adultos e pediátricos que testaram positivos para anticorpos anti-MOG e apresentaram um quadro clínico e radiológico compatível com MOGAD. RESULTADOS: Quarenta e um pacientes (10 crianças) foram incluídos: 56% do sexo feminino, 58% caucasianos, idade média de início da doença foi 31 anos (intervalo de 6-64), com duração média da doença de 59,6 meses (intervalo de 1-264 meses). A apresentação inicial mais frequente foi neurite óptica (68%), seguida pela encefalomielite disseminada aguda (ADEM, 12%) e mielite (10%). Um curso monofásico da doença foi observado em 49%. EDSS foi de 2,1 na última visita. A maioria dos pacientes (83%) estava sob tratamento imunossupressor contínuo. Azatioprina foi o tratamento de primeira linha em 59%. Em todos os casos de ADEM, o envolvimento do cone medular e das raízes espinhais foi observado radiologicamente na ressonância magnética. CONCLUSãO: Os pacientes brasileiros com MOGAD apresentam um espectro clínico e radiológico semelhante aos fenótipos de MOGAD relatados anteriormente. O envolvimento do cone e das raízes espinhais parece estar frequentemente presente no MOGAD-ADEM e poderia servir como característica radiológica nesta entidade.

Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience / Espectro clínico de doença associada com anticorpos contra a glicoproteína de oligodendrócito de mielina no Brasil: uma experiencia de centro único

Abstract Background Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. Objective To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. Methods We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Results Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Conclusion Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.

Resumo Antecedentes A doença associada ao anticorpo da glicoproteína da mielina de oligodendrócitos (anti-MOG; MOGAD) é uma doença neurológica imunomediada com um amplo espectro de apresentações clínicas que muitas vezes é difícil de distinguir de outras doenças desmielinizantes, como a esclerose múltipla e o distúrbio do espectro da neuromielite óptica. Objetivo Descrever as características clínicas e paraclínicas da MOGAD em um centro terciário brasileiro. Métodos Revisamos retrospectivamente os prontuários dos pacientes adultos e pediátricos que testaram positivos para anticorpos anti-MOG e apresentaram um quadro clínico e radiológico compatível com MOGAD. Resultados Quarenta e um pacientes (10 crianças) foram incluídos: 56% do sexo feminino, 58% caucasianos, idade média de início da doença foi 31 anos (intervalo de 6-64), com duração média da doença de 59,6 meses (intervalo de 1-264 meses). A apresentação inicial mais frequente foi neurite óptica (68%), seguida pela encefalomielite disseminada aguda (ADEM, 12%) e mielite (10%). Um curso monofásico da doença foi observado em 49%. EDSS foi de 2,1 na última visita. A maioria dos pacientes (83%) estava sob tratamento imunossupressor contínuo. Azatioprina foi o tratamento de primeira linha em 59%. Em todos os casos de ADEM, o envolvimento do cone medular e das raízes espinhais foi observado radiologicamente na ressonância magnética. Conclusão Os pacientes brasileiros com MOGAD apresentam um espectro clínico e radiológico semelhante aos fenótipos de MOGAD relatados anteriormente. O envolvimento do cone e das raízes espinhais parece estar frequentemente presente no MOGAD-ADEM e poderia servir como característica radiológica nesta entidade.

Influence of cerebral blood flow on volumetric loss related to Alzheimer's disease.

CBF measured with Arterial Spin Labeling (ASL) obtained by Magnetic Resonance Imaging (MRI) may become an important biomarker by showing changes in early stages of AD, such as in the prodromal stage of Mild Cognitive Impairment (MCI). Objective: Verify the correlation between atrophy and CBF in patients with MCI and mild phase ADD, to demonstrate whether changes in CBF can be considered as vascular biomarkers in the diagnosis of the DA continuum. Methods: 11 healthy volunteers, 16 MCI and 15 mild ADD were evaluated. Images of the brain were acquired, including CBF measured with Arterial Spin Labeling (ASL). Results: When comparing MCI with control, a reduction in normalized CBF was observed in left posterior cingulate (estimated difference -0.38; p=0.02), right posterior cingulate (estimated difference -0.45; p=0.02) and right precuneus (estimated difference -0.28; p <0.01); also increase in normalized CBF in right upper temporal pole (estimated difference 0.22; p=0.03). It was also observed that in MCI, the smaller the gray matter volume, the smaller the CBF in the left posterior cingulate; as well as the greater the cerebrospinal fluid volume, consequent to the encephalic volumetric reduction associated with atrophy, the greater the CBF in the right superior temporal pole. When comparing controls, MCI and mild AD, in relation to the other variables, no other correlations were observed between CBF and atrophy. Conclusion: In patients with MCI, the reduction of CBF in the left posterior cingulate correlated with gray matter atrophy, as well as the increase of CBF in the right upper temporal pole correlated with an increase in cerebrospinal fluid consequent to the encephalic volumetric reduction associated with atrophy, demonstrating the influence of CBF in AD related brain atrophy. These findings position CBF as a possible vascular biomarker for early-stage AD diagnoses.

A imagem por ressonância magnética (IRM) pode se tornar um importante biomarcador ao mostrar alterações nos estágios iniciais da doença de Alzheimer (DA). Objetivo: Sendo a atrofia cerebral um importante biomarcador de neurodegeneração na DA, o presente estudo foi realizado com o objetivo de verificar se há correlação entre atrofia e fluxo sanguíneo cerebral (FSC) em pacientes com diagnóstico de CCL e demência da doença de Alzheimer (DDA) leve, com o objetivo de revelar se as alterações no FSC podem ser consideradas possíveis biomarcadores vasculares no diagnóstico do continuum da DA. Métodos: Foram avaliados 11 voluntários saudáveis, 16 CCL e 15 DDA leve. Imagens do cérebro foram adquiridas em um equipamento de 3 T, incluindo imagens ponderadas em T1 de alta resolução para avaliação anatômica e Arterial Spin Labeling (ASL) para a quantificação de FSC. Resultados: Quando comparado CCL com controle, observou-se redução no FSC normalizado em cingulado posterior esquerdo (diferença estimada de -0,38; p=0,02), cingulado posterior direito (diferença estimada de -0,45; p=0,02) e precúneo direito (diferença estimada de -0,28; p <0,01); e aumento de FSC normalizado no polo temporal superior direito (diferença estimada de 0,22; p=0,03). No CCL, quanto menor o volume da substância cinzenta, menor o FSC no cingulado posterior esquerdo; quanto maior o volume de fluido cerebroespinhal, consequente à redução volumétrica encefálica, maior o FSC no polo temporal superior direito. Conclusão: Nos pacientes com diagnóstico de CCL, a redução de FSC no cingulado posterior esquerdo apresentou correlação com atrofia da substância cinzenta, assim como o aumento de FSC no polo temporal superior direito apresentou correlação com o aumento de fluido cerebroespinhal, demonstrando a provável influência do FSC na atrofia encefálica relacionada à DA.

Clinical and Surgical Approach for Cerebral Cortical Dysplasia.

The present article describes pathophysiological and clinical aspects of congenital malformations of the cerebral tissue (cortex and white matter) that cause epilepsy and very frequently require surgical treatment. A particular emphasis is given to focal cortical dysplasias, the most common pathology among these epilepsy-related malformations. Specific radiological and surgical features are also highlighted, so a thorough overview of cortical dysplasias is provided.

Down-Regulation of Tinnitus Negative Valence via Concurrent HD-tDCS and PEI Technique: A Pilot Study.

Around 30% of the general population experience subjective tinnitus, characterized by conscious attended awareness perception of sound without an external source. Clinical distress tinnitus is more than just experiencing a phantom sound, as it can be highly disruptive and debilitating, leading those affected to seek clinical help. Effective tinnitus treatments are crucial for psychological well-being, but our limited understanding of the underlying neural mechanisms and a lack of a universal cure necessitate further treatment development. In light of the neurofunctional tinnitus model predictions and transcranial electrical stimulation, we conducted an open-label, single-arm, pilot study that utilized high-definition transcranial direct current stimulation (HD-tDCS) concurrent with positive emotion induction (PEI) techniques for ten consecutive sessions to down-regulate tinnitus negative valence in patients with clinical distress tinnitus. We acquired resting-state functional magnetic resonance imaging scans of 12 tinnitus patients (7 females, mean age = 51.25 ± 12.90 years) before and after the intervention to examine resting-state functional connectivity (rsFC) alterations in specific seed regions. The results showed reduced rsFC at post-intervention between the attention and emotion processing regions as follows: (1) bilateral amygdala and left superior parietal lobule (SPL), (2) left amygdala and right SPL, (3) bilateral dorsolateral prefrontal cortex (dlPFC) and bilateral pregenual anterior cingulate cortex (pgACC), and (4) left dlPFC and bilateral pgACC (FWE corrected p < 0.05). Furthermore, the post-intervention tinnitus handicap inventory scores were significantly lower than the pre-intervention scores (p < 0.05). We concluded that concurrent HD-tDCS and PEI might be effective in reducing tinnitus negative valence, thus alleviating tinnitus distress.

Early Positive Brain 18F-FDG PET and Negative MRI in Rasmussen Encephalitis.

ABSTRACT: A 15-year-old adolescent boy with left body epilepsia partialis continua, hemiparesis, and electroencephalogram abnormalities lateralized to the right hemisphere. MRI finding was small hyperintense signal in the left putamen. 18F-FDG PET showed focal glucose hypermetabolism in the right paracentral lobule and hypometabolism in the inferior right frontal and precentral gyri. One month later, a new MRI showed a hyperintense signal over the paracentral lobule. Biopsy on this region confirmed the diagnosis of Rasmussen encephalitis. This patient finally underwent right hemispherotomy and became seizure free. This case emphasize the PET as an important early tool for the diagnosis of Rasmussen encephalitis.

White Matter Lesions Identified by Magnetic Resonance in Women with Migraine: A Volumetric Analysis and Clinical Correlations.

BACKGROUND: Repeated migraine attacks and aura could independently cause structural changes in the central nervous system. Our research aims to study the correlation of migraine type, attack frequency, and other clinical variables with the presence, volume and localization of white matter lesions (WML), in a controlled study. METHODS: Sixty volunteers from a tertiary headache center were selected and divided equally into four groups: episodic migraine without aura (MoA), episodic migraine with aura (MA), chronic migraine (CM) and controls (CG). Voxel-based morphometry techniques were used to analyze WML. RESULTS: There were no differences in WML variables between groups. There was a positive correlation between age and the number and total volume of WMLs, which persisted in the comparison categorized by size and brain lobe. Disease duration was positively correlated with the number and total volume of WML, and when controlled by age, the correlation maintained significance only for the insular lobe. Aura frequency was associated with frontal and temporal lobe WMLs. There was no statistically significant correlation between WML and other clinical variables. CONCLUSION: Migraine overall is not a risk factor for WML. Aura frequency is, however, associated with temporal WML. Disease duration, in adjusted analyses that account for age, is associated with insular WML.

Integrating Methylome and Transcriptome Signatures Expands the Molecular Classification of the Pituitary Tumors.

OBJECTIVE: To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population. METHODS: In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo. RESULTS: Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs). CONCLUSION: This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis.

Voxel-Based Morphometry and Relaxometry Demonstrate Macro- and Microstructural Damages in Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is the most common SCA worldwide and comprises about 70% of SCA patients in Brazil. Magnetic resonance imaging (MRI) sequences have been used to describe microstructural abnormalities in many neurodegenerative diseases and helped to reveal the excessive iron accumulation in many of these conditions. This study aimed to characterize brain changes in gray matter (GM) and white matter (WM), detected by voxel-based morphometry (VBM) and relaxometry in patients with SCA3/MJD. A group of consecutive individuals, older than 18 years of age, with symptomatic and genetically proven SCA3/MJD diagnosed, and a control group, were submitted to clinical evaluation and MRI. The images were analyzed using VBM technique and relaxometry. The global assessment of brain volume by region of interest showed a significant difference in GM between SCA3/MJD and normal controls. VBM was used to locate these volumetric changes and it revealed a noticeable difference in the GM of the cerebellum and the brainstem. The global assessment of the brain by relaxometry also showed a significant difference in the comparison of GM between SCA3/MJD and normal controls, detecting noticeable prolongation of T2 time in the medulla oblongata (p < 0.001) and in the pontine tegmentum (p = 0.009) in SCA3/MJD compared to control group. Our study suggests that SCA3/MJD affects the macrostructure of the cerebellum and brainstem and microstructure of pons and medulla oblongata GM, as already demonstrated in the pathological study.

Structural and functional differences in the brains of patients with MCI with and without depressive symptoms and their relations with Alzheimer's disease: an MRI study.

Background: The mild cognitive impairment (MCI) stage among elderly individuals is very complex, and the level of diagnostic accuracy is far from ideal. Some studies have tried to improve the 'MCI due to Alzheimer's disease (AD)' classification by further stratifying these patients into subgroups. Depression-related symptoms may play an important role in helping to better define the MCI stage in elderly individuals. Objective: In this work, we explored functional and structural differences in the brains of patients with nondepressed MCI (nDMCI) and patients with MCI with depressive symptoms (DMCI), and we examined how these groups relate to AD atrophy patterns and cognitive functioning. Methods: Sixty-five participants underwent MRI exams and were divided into four groups: cognitively normal, nDMCI, DMCI, and AD. We compared the regional brain volumes, cortical thickness, and white matter microstructure measures using diffusion tensor imaging among groups. Additionally, we evaluated changes in functional connectivity using fMRI data. Results: In comparison to the nDMCI group, the DMCI patients had more pronounced atrophy in the hippocampus and amygdala. Additionally, DMCI patients had asymmetric damage in the limbic-frontal white matter connection. Furthermore, two medial posterior regions, the isthmus of cingulate gyrus and especially the lingual gyrus, had high importance in the structural and functional differentiation between the two groups. Conclusion: It is possible to differentiate nDMCI from DMCI patients using MRI techniques, which may contribute to a better characterization of subtypes of the MCI stage.

Influence of cerebral blood flow on volumetric loss related to Alzheimer's disease / Influência do fluxo sanguíneo cerebral na perda volumétrica relacionada à doença de Alzheimer

ABSTRACT: CBF measured with Arterial Spin Labeling (ASL) obtained by Magnetic Resonance Imaging (MRI) may become an important biomarker by showing changes in early stages of AD, such as in the prodromal stage of Mild Cognitive Impairment (MCI). Objective: Verify the correlation between atrophy and CBF in patients with MCI and mild phase ADD, to demonstrate whether changes in CBF can be considered as vascular biomarkers in the diagnosis of the DA continuum. Methods: 11 healthy volunteers, 16 MCI and 15 mild ADD were evaluated. Images of the brain were acquired, including CBF measured with Arterial Spin Labeling (ASL). Results: When comparing MCI with control, a reduction in normalized CBF was observed in left posterior cingulate (estimated difference -0.38; p=0.02), right posterior cingulate (estimated difference -0.45; p=0.02) and right precuneus (estimated difference -0.28; p <0.01); also increase in normalized CBF in right upper temporal pole (estimated difference 0.22; p=0.03). It was also observed that in MCI, the smaller the gray matter volume, the smaller the CBF in the left posterior cingulate; as well as the greater the cerebrospinal fluid volume, consequent to the encephalic volumetric reduction associated with atrophy, the greater the CBF in the right superior temporal pole. When comparing controls, MCI and mild AD, in relation to the other variables, no other correlations were observed between CBF and atrophy. Conclusion: In patients with MCI, the reduction of CBF in the left posterior cingulate correlated with gray matter atrophy, as well as the increase of CBF in the right upper temporal pole correlated with an increase in cerebrospinal fluid consequent to the encephalic volumetric reduction associated with atrophy, demonstrating the influence of CBF in AD related brain atrophy. These findings position CBF as a possible vascular biomarker for early-stage AD diagnoses.

RESUMO: A imagem por ressonância magnética (IRM) pode se tornar um importante biomarcador ao mostrar alterações nos estágios iniciais da doença de Alzheimer (DA). Objetivo: Sendo a atrofia cerebral um importante biomarcador de neurodegeneração na DA, o presente estudo foi realizado com o objetivo de verificar se há correlação entre atrofia e fluxo sanguíneo cerebral (FSC) em pacientes com diagnóstico de CCL e demência da doença de Alzheimer (DDA) leve, com o objetivo de revelar se as alterações no FSC podem ser consideradas possíveis biomarcadores vasculares no diagnóstico do continuum da DA. Métodos: Foram avaliados 11 voluntários saudáveis, 16 CCL e 15 DDA leve. Imagens do cérebro foram adquiridas em um equipamento de 3 T, incluindo imagens ponderadas em T1 de alta resolução para avaliação anatômica e Arterial Spin Labeling (ASL) para a quantificação de FSC. Resultados: Quando comparado CCL com controle, observou-se redução no FSC normalizado em cingulado posterior esquerdo (diferença estimada de -0,38; p=0,02), cingulado posterior direito (diferença estimada de -0,45; p=0,02) e precúneo direito (diferença estimada de -0,28; p <0,01); e aumento de FSC normalizado no polo temporal superior direito (diferença estimada de 0,22; p=0,03). No CCL, quanto menor o volume da substância cinzenta, menor o FSC no cingulado posterior esquerdo; quanto maior o volume de fluido cerebroespinhal, consequente à redução volumétrica encefálica, maior o FSC no polo temporal superior direito. Conclusão: Nos pacientes com diagnóstico de CCL, a redução de FSC no cingulado posterior esquerdo apresentou correlação com atrofia da substância cinzenta, assim como o aumento de FSC no polo temporal superior direito apresentou correlação com o aumento de fluido cerebroespinhal, demonstrando a provável influência do FSC na atrofia encefálica relacionada à DA.

Processing speed impairment in chronic inflammatory demyelinating polyneuropathy patients: a cross-sectional study.

BACKGROUND: There is a lack of evidence of cognitive involvement in chronic inflammatory demyelinating polyneuropathy (CIDP) and, the reports about the involvement of the brain and central nervous system (CNS) are few and controversial. The Five Digit Test (FDT) evaluates processing speed (PS) and executive functions orally. OBJECTIVE: To evaluate the performance on the FDT of CIDP patients with and without CNS (brain/cerebellum) alterations observed on brain Magnetic Resonance Imaging (MRI) scans. METHODS: The Hospital Anxiety and Depression Scale (HADS, to assess neuropsychiatry symptoms), the Rasch-built Overall Disability Scale (R-ODS; to assess disability), and the FDT (to assess cognition) were applied to 14 CIDP patients and 24 age-matched healthy control subjects. The patients were submitted to routine brain MRI and, according to the results, they were divided into two groups: those with abnormalities on the MRI (CIDPabnl) and those with normal parameters on the MRI (CIDPnl). The FDT data of five CIDPnl patients and nine CIDPabnl subjects were analyzed. Comparisons between the groups were performed for each task of the FDT. RESULTS: We found statistical differences for both groups of CIDP patients in terms of PS, for the patients spent more time performing the PS tasks than the controls. The PS measures were negatively associated with disability scores (reading: r = -0.47; p = 0.003; counting: r = -0.53; p = 0.001). CONCLUSIONS: Our data suggested the presence of PS impairment in CIDP patients. Disability was associated with slow PS.

ANTECEDENTES: Faltam evidências de envolvimento cognitivo na polineuropatia inflamatória desmielinizante crônica (PIDC), e há poucos e controversos estudos que tratam do envolvimento cerebral e do sistema nervoso central (SNC). O Teste dos Cinco Dígitos (Five Digit Test, FDT, em inglês) avalia a velocidade de processamento (VP) e as funções executivas oralmente. OBJETIVO: Avaliar o desempenho no FDT de pacientes com PIDC com e sem alterações no SNC (cérebro/cerebelo) de acordo com o exame de imagem cerebral por ressonância magnética (RM). MéTODOS: Ao todo, 14 pacientes e 24 controles saudáveis pareados por idade responderam a Escala Hospitalar de Ansiedade e Depressão (que avalia sintomas neuropsiquiátricos), a Escala de Incapacidade Geral elaborada pelo método Rasch (que avalia a incapacidade) e o FDT (que avalia a cognição). Os pacientes foram submetidos a RM cerebral e, de acordo com os resultados, divididos em dois grupos: aqueles com anormalidades (PIDCabnl) e aqueles sem alterações (PIDCnl) na RM. Cinco pacientes PIDCnl e nove PIDCabnl tiveram os dados analisados. Comparações entre os grupos foram realizadas para cada parte do FDT. RESULTADOS: Os dois grupos de pacientes foram estatisticamente mais lentos nas tarefas de VP comparados ao grupo controle. As medidas de VP foram negativamente associadas às pontuações de incapacidade (leitura: r = −0,47; p = 0,003; contagem: r = −0,53; p = 0,001). CONCLUSõES: Os dados indicaram a presença de prejuízo na VP em pacientes com PIDC. A incapacidade foi associada à lentidão na VP.

Peak width of skeletonized mean diffusivity in cerebral amyloid angiopathy: Spatial signature, cognitive, and neuroimaging associations.

Background: Peak width of skeletonized mean diffusivity (PSMD) is a promising diffusion tensor imaging (DTI) marker that shows consistent and strong cognitive associations in the context of different cerebral small vessel diseases (cSVD). Purpose: Investigate whether PSMD (1) is higher in patients with Cerebral Amyloid Angiopathy (CAA) than those with arteriolosclerosis; (2) can capture the anteroposterior distribution of CAA-related abnormalities; (3) shows similar neuroimaging and cognitive associations in comparison to other classical DTI markers, such as average mean diffusivity (MD) and fractional anisotropy (FA). Materials and methods: We analyzed cross-sectional neuroimaging and neuropsychological data from 90 non-demented memory-clinic subjects from a single center. Based on MRI findings, we classified them into probable-CAA (those that fulfilled the modified Boston criteria), subjects with MRI markers of cSVD not attributable to CAA (presumed arteriolosclerosis; cSVD), and subjects without evidence of cSVD on MRI (non-cSVD). We compared total and lobe-specific (frontal and occipital) DTI metrics values across the groups. We used linear regression models to investigate how PSMD, MD, and FA correlate with conventional neuroimaging markers of cSVD and cognitive scores in CAA. Results: PSMD was comparable in probable-CAA (median 4.06 × 10-4 mm2/s) and cSVD (4.07 × 10-4 mm2/s) patients, but higher than in non-cSVD (3.30 × 10-4 mm2/s; p < 0.001) subjects. Occipital-frontal PSMD gradients were higher in probable-CAA patients, and we observed a significant interaction between diagnosis and region on PSMD values [F(2, 87) = 3.887, p = 0.024]. PSMD was mainly associated with white matter hyperintensity volume, whereas MD and FA were also associated with other markers, especially with the burden of perivascular spaces. PSMD correlated with worse executive function (ß = -0.581, p < 0.001) and processing speed (ß = -0.463, p = 0.003), explaining more variance than other MRI markers. MD and FA were not associated with performance in any cognitive domain. Conclusion: PSMD is a promising biomarker of cognitive impairment in CAA that outperforms other conventional and DTI-based neuroimaging markers. Although global PSMD is similarly increased in different forms of cSVD, PSMD's spatial variations could potentially provide insights into the predominant type of underlying microvascular pathology.