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 ACP patients (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 multi-dimensional scaling. Statistical associations between clusters and clinical features were achieved using Fisher's 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 = 0.0006), hypomethylated in CpG Island (CGI), non-CGI sites, and globally (P < 0.001), and associated with greater tumor size (24.1 vs 9.5cm3, P = 0.04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell-adhesion, cytoskeleton organization, and cytokine binding, and also cell-type specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. CONCLUSION: Two clusters of ACP patients were consistently revealed by unsupervised machine learning methods, being 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.

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.

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.

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.

Processing speed impairment in chronic inflammatory demyelinating polyneuropathy patients: a cross-sectional study / Prejuízo na velocidade de processamento em pacientes com polineuropatia inflamatória desmielinizante crônica: um estudo transversal

Abstract 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.

Resumo 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.

Incidence and lethality by COVID-19 in the population of the Federal District: an ecological study / Incidência e letalidade por COVID-19 na população do Distrito Federal: um estudo ecológico / Incidencia y letalidad por COVID-19 en la población del Distrito Federal: un estudio ecológico

Background and objectives: understanding the social situation of COVID-19 in poor and less developed countries is still doubtful. Thus, this study aimed to estimate the incidence and lethality by COVID-19, according to the per capita income of the administrative regions of the Federal District (FD). Methods: this is a descriptive ecological study, based on secondary data. Thirty-one administrative regions of the FD were included, and the population consisted of 382,488 individuals. The variables considered were sex, incidence, mortality, lethality, age group, population estimate and education. Results: despite the greater contamination by women, in terms of total mortality, more men died, representing 57.3% of the total deaths in the period. Regarding the influence of the level of education and income on the incidence, it appears that the highest rates of confirmed cases occurred in groups with higher levels of education and income. Despite this higher incidence, it is the group that exhibits the lowest lethality and the third lowest mortality per 100,000 inhabitants. Conclusion: the highest incidence rates were observed in regions with higher per capita income. On the other hand, lethality occurred more incisively in regions with lower purchasing power. In view of this, it is necessary to apply long-term preventive measures in unequal regions.(AU)

Justificativa e objetivos: o entendimento da situação social da COVID-19 em países pobres e menos desenvolvidos ainda é dubitável. Desse modo, o objetivo deste estudo é estimar a incidência e letalidade por COVID-19, de acordo com a renda per capita das regiões administrativas do Distrito Federal (DF). Métodos: trata-se de um estudo ecológico descritivo, baseado em dados secundários. Foram incluídas 31 regiões administrativas do DF, e a população foi composta por 382.488 indivíduos. Consideraram-se como variáveis sexo, incidência, mortalidade, letalidade, faixa etária, estimativa populacional e escolaridade. Resultados: apesar da contaminação maior por parte das mulheres, em termos de mortalidade total, mais homens foram a óbito, representando 57,3% do total de mortos no período. A respeito da influência do grau de escolaridade e da renda na incidência, verifica-se que os maiores índices de casos confirmados aconteceram em grupos com maior nível de escolaridade e de renda. Apesar dessa maior incidência, é o grupo que exibe a menor letalidade e a terceira menor mortalidade por 100.000 habitantes. Conclusão: as mais altas taxas de incidência foram observadas nas regiões com maior renda per capita. Por outro lado, a letalidade ocorreu, de forma mais incisiva, nas regiões de menor poder aquisitivo. Diante disso, é necessário aplicar medidas preventivas de longo prazo em regiões desiguais.(AU)

Justificación y objetivos: la comprensión de la situación social del COVID-19 en los países pobres y menos desarrollados aún es dudosa. Así, el objetivo de este estudio es estimar la incidencia y letalidad por COVID-19, según el ingreso per cápita de las regiones administrativas del Distrito Federal (DF). Métodos: se trata de un estudio ecológico descriptivo, basado en datos secundarios. Se incluyeron 31 regiones administrativas del DF, la población estuvo conformada por 382,488 individuos. Se consideraron como variables el sexo, la incidencia, la mortalidad, la letalidad, el grupo de edad, la población estimada y la escolaridad. Resultados: a pesar de la mayor contaminación por mujeres, en términos de mortalidad total, fallecieron más hombres, representando el 57,3% del total de defunciones en el período. En cuanto a la influencia del nivel de educación e ingresos en la incidencia, parece que las tasas más altas de casos confirmados ocurrieron en grupos con mayores niveles de educación e ingresos. A pesar de esta mayor incidencia, es el grupo que presenta la menor letalidad y la tercera mortalidad más baja por 100.000 habitantes. Conclusión: las tasas de incidencia más altas se observaron en las regiones con mayor ingreso per cápita. Por otro lado, la letalidad se produjo de forma más incisiva en las regiones de menor poder adquisitivo. Ante esto, es necesario aplicar medidas preventivas a largo plazo en regiones desiguales.(AU)

Long-Term Outcome of Temporal Lobe Epilepsy Surgery in 621 Patients With Hippocampal Sclerosis: Clinical and Surgical Prognostic Factors.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and is frequently drug-resistant (DR) to antiseizure medication (ASM), corresponding to approximately one-third of the cases. When left inadequately treated, it can worsen the quality of life, cognitive deficits, and risk of death. The standard treatment for drug-resistant TLE is the surgical removal of the structures involved, with good long-term outcome rates of 60-70 % and a low rate of adverse effects. The goal of successful treatment is sustained seizure freedom. In our study, we evaluated sustained long-term (up to 23 years) surgical outcomes in 621 patients with DR-TLE associated with hippocampal sclerosis, who underwent a temporal lobectomy. We analyzed the main predictive factors that influence the surgical outcome related to seizure control, through a longitudinal and retrospective study, using a multivariable regression model. We found that 73.6% of the patients were free from disabling seizures (Engel Class I), maintained over time in 65% of patients followed up to 23 years after surgery. We found that four independent variables predicted seizure outcomes. The presence of dysmnesic and olfactory aura predicted a less favorable outcome. The history of febrile seizure and the surgical technique predicted a good outcome. Regarding the type of surgical technique, the standard anteromesial temporal lobectomy (ATL) led to significantly better outcomes (78.6% Engel Class I) when compared to the selective amygdalohippocampectomy via subtemporal approach (67.2% Engel Class I; p = 0.002), suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial temporal structures. The multivariable regression model with the above-mentioned predictor variables revealed an ExpB = 3.627 (N = 621, p < 0.001), indicating that the model was able to distinguish between patients with a seizure-free. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.

Telomere length and Wnt/ß-catenin pathway in adamantinomatous craniopharyngiomas.

Objectives: To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations. Design: Retrospective cross-sectional study enrolling 42 aCP patients from 2 tertiary institutions. Methods: Clinicopathological features were retrieved from the patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths. Results: Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1 mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; P = 0.04) and a trend to recurrent disease (76% vs 24%; P = 0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597vs 0.607, IQR: 0.445-0.778; P = 0.04), but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomeres and CTNNB1-mutated aCPs. Conclusions: CTNNB1: mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres, demonstrating a relationship between the Wnt/ß-catenin pathway and telomere biology in the pathogenesis of aCPs.

Contrast agent-free state-of-the-art magnetic resonance imaging on cerebral small vessel disease - Part 2: Diffusion tensor imaging and functional magnetic resonance imaging.

Cerebral small vessel disease (cSVD) has been widely studied using conventional magnetic resonance imaging (MRI) methods, although the association between MRI findings and clinical features of cSVD is not always concordant. We assessed the additional contribution of contrast agent-free, state-of-the-art MRI techniques, particularly diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI), to understand brain damage and structural and functional connectivity impairment related to cSVD. We performed a review following the PICOS worksheet and Search Strategy, including 152 original papers in English, published from 2000 to 2022. For each MRI method, we extracted information about their contributions regarding the origins, pathology, markers, and clinical outcomes in cSVD. In general, DTI studies have shown that changes in mean, radial, and axial diffusivity measures are related to the presence of cSVD. In addition to the classical deficit in executive functions and processing speed, fMRI studies indicate connectivity dysfunctions in other domains, such as sensorimotor, memory, and attention. Neuroimaging metrics have been correlated with the diagnosis, prognosis, and rehabilitation of patients with cSVD. In short, the application of contrast agent-free, state-of-the-art MRI techniques has provided a complete picture of cSVD markers and tools to explore questions that have not yet been clarified about this clinical condition. Longitudinal studies are desirable to look for causal relationships between image biomarkers and clinical outcomes.