Large-scale neurophysiology and single-cell profiling in human neuroscience.

Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.

[Utilization of Peripheral Neuropathology Tests].

Neuropathological findings rarely lead to a definitive diagnosis of autoimmune and inflammatory peripheral nerve diseases, and indications for invasive nerve biopsy with subsequent disability should be carefully determined. In addition to disease-specific pathological findings, identifying findings that facilitate differential diagnosis in clinical practice is necessary. This article reviews the neuropathological findings that are valuable in the differential diagnosis of autoimmune and inflammatory peripheral nerve diseases.

Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies.

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.

Historical review: The golden age of the Golgi method in human neuropathology.

Golgi methods were used to study human neuropathology in the 1970s, 1980s, and 1990s of the last century. Although a relatively small number of laboratories applied these methods, their impact was crucial by increasing knowledge about: (1) the morphology, orientation, and localization of neurons in human cerebral and cerebellar malformations and ganglionic tumors, and (2) the presence of abnormal structures including large and thin spines (spine dysgenesis) in several disorders linked to mental retardation, focal enlargements of the axon hillock and dendrites (meganeurites) in neuronal storage diseases, growth cone-like appendages in Alzheimer disease, as well as abnormal structures in other dementias. Although there were initial concerns about their reliability, reduced dendritic branches and dendritic spines were identified as common alterations in mental retardation, dementia, and other pathological conditions. Similar observations in appropriate experimental models have supported many abnormalities that were first identified using Golgi methods in human material. Moreover, electron microscopy, immunohistochemistry, fluorescent tracers, and combined methods have proven the accuracy of pioneering observations uniquely visualized as 3D images of fully stained individual neurons. Although Golgi methods had their golden age many years ago, these methods may still be useful complementary tools in human neuropathology.

Oral administration of IPI549 protects mice from neuropathology and an overwhelming inflammatory response during experimental cerebral malaria.

Infection with Plasmodium falciparum is often deadly when it results in cerebral malaria, which is associated with neuropathology described as an overwhelming inflammatory response and mechanical obstruction of cerebral microvascular. PI3Kγ is a critical component of intracellular signal transduction and plays a central role in regulating cell chemotaxis, migration, and activation. The purpose of this study was to examine the relationship between inhibiting the PI3Kγ pathway and the outcome of experimental cerebral malaria (ECM) in C57BL/6J mice infected with the mouse malaria parasite, Plasmodium berghei ANKA. We observed that oral administration of the PI3Kγ inhibitor IPI549 after infection completely protected mice from ECM. IPI549 treatment significantly dampened the magnitude of inflammatory responses, with reduced production of pro-inflammatory factors, decreased T cell activation, and altered differentiation of antigen-presenting cells. IPI549 treatment protected the infected mice from neuropathology, as assessed by an observed reduction of pathogenic T cells in the brain. Treating the infected mice with IPI549 three days after parasite inoculation improved the murine blood brain barrier (BBB) integrity and helped the mice pass the onset of ECM. Together, these data indicate that oral administration of the PI3Kγ inhibitor IPI549 has a suppressive role in host inflammation and alleviates cerebral pathology, which supports IPI549 as a new malaria treatment option with potential therapeutic implications for cerebral malaria.

[Neuropathology of Idiopathic Normal Pressure Hydrocephalus: A Study of Three Autopsy Cases and a Literature Review].

We present neuropathological findings in three autopsy brains from patients diagnosed clinically with idiopathic normal pressure hydrocephalus (iNPH) in Japan; still, specific findings of iNPH remain unclear. Comorbid atherosclerosis and hypertensive microvascular diseases, including arterio- and arteriolosclerosis and ischemic changes in the brain parenchyma, are frequently (65%) observed in autopsy brain tissue from patients with iNPH, which has drawn attention to the clinicopathological similarities and differences between iNPH and Binswanger's disease. Additionally, Aß protein deposition and phosphorylated tau-positive neurofibrillary tangles and neuropil threads are observed in cerebral cortical biopsy specimens obtained during intracranial pressure monitoring or shunt surgery among a subset of patients with iNPH. These findings are as frequent as those reported in autopsy data of the age-matched general population. Alterations in aquaporin-4 expression in the cerebral cortex have also been reported, suggestive of a possible association with altered volume or composition of the interstitial fluid in the microenvironment, particularly in the vicinity of capillaries, or glymphatic system dysfunction and consequent altered interstitial fluid drainage. Greater understanding of the normal anatomical structures and pathways involved in cerebrospinal fluid circulation, particularly in absorption and drainage, in the craniospinal region is essential for better clarity regarding iNPH neuropathology.

Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists.

Although novel knowledge has been acquired on the molecular landscape of glioblastoma (GBM), a relatively few steps forward have been made regarding its therapy. With the increasing use of novel immunotherapeutic drugs capable of stimulating the antitumor inflammatory response, in the last decades numerous studies aimed to characterize the tumor-associated microenvironment (TME) and its relationship with the immunogenicity of GBM. In this regard, although the tumor-associated microglia and macrophages (TAMs) and PD-L1/PD-1 axis have been emerged as one of the most relevant components of the GBM TME and one of the potential molecular pathways targetable with immunotherapy, respectively. It has been supposed that TAMs may acquire different phenotypes, switching from M1 to M2 phenotypes, with tumor-suppressive and tumor-stimulating role depending on the different surrounding conditions. PD-L1 is a type 1 transmembrane protein ligand expressed by T-cells, B-cells and antigen-presenting cells, with a main inhibitory checkpoint role on tumor immune regulation. While PD-L1 immunohistochemical expression has been extensively investigated in many cancers, its usefulness in the evaluation of GBM response rates to immunotherapy and its standardized evaluation by immunohistochemistry are still debated. The present review paper focuses on the current "state of the art" about the relationship between TME, PD-L1/PD-1 pathway and immunotherapy in GBM, also providing neuropathologists with an updated guide about the clinical trials conducted with PD-L1 and PD-1 inhibitors.

Monomorphic epitheliotropic intestinal T-cell lymphoma involving the central nervous system: a rare case report with comprehensive autopsy neuropathological examinations.

Monomorphic epitheliotropic T-cell lymphoma (MEITL) of gastrointestinal tract is an aggressive T-cell lymphoma that can rarely involve the brain. We present detailed descriptions of clinical and autopsy neuropathological findings of a rare case of an elderly woman who had surgery and chemotherapy for MEITL of the small intestine. Following her surgery, she progressively exhibited neurologic decline towards the end of her treatment. The patient eventually succumbed to her illness and was found to have MEITL with intracranial involvement on autopsy. Brain autopsy was performed and examination of tissues with hematoxylin-eosin staining under optical microscopy with 100 X magnification. Immunostaining for CD3, CD4, CD5, CD7, CD8, CD56, CD20, beta-amyloid, c-Myc, TCR-beta, TCR-delta, and EBER-ish was conducted on the formalin-fixed paraffin-embedded (FFPE) brain tissues. A neuropathological exam revealed multifocal friable necrotic and hemorrhagic areas in the supratentorial region. Histologically, monotonous small to medium-sized atypical lymphocytes infiltrated the brain parenchyma, prominently around the vessels. The immunophenotype of the atypical lymphocytes was positive for CD-3, CD-7, and CD-56 and negative for CD-5, CD-4, CD-8, CD-20, and c-Myc. EBER-ish was negative. The histology and immunophenotype confirmed the MEITL brain involvement. Neurologic decline and cognitive changes in patients with known MEITL can be the first clue of brain involvement upon which prompt evaluation is warranted.

Inspection of infant motor development: importance of the insertion of a physical therapist in childcare / Vigilância do desenvolvimento motor de bebês: importância da inserção do fisioterapeuta na puericultura

Abstract Introduction: The Childcare Program aims at the health promotion, prevention and early diagnosis of diseases and recovery from diseases in childhood through programmed monitoring of the child's growth and development. A physical therapist can contribute to the early identification of neuropsychomotor developmental disorders. Objective: To characterize the motor development (DM) of infants during childcare consultations and to discuss the importance of a professional physical therapist in primary health care teams. Methods: The sample comprised 91 infants aged 0-6 months attended in childcare consultations. Infants with musculoskeletal disorders, neuropathology, and those who cried bitterly, thereby preventing the evaluation were excluded. DM was evaluated using the Alberta Infant Motor Scale. Results: Of the infants aged 0-3 months, 11.76% had atypical DM, 23.62% were at risk for motor delay, and 64.07% had typical DM. Among the infants aged 4-6 months (25.3%), less than half of the children (39.13%) had typical DM. Among the infants aged 4-6 months who did not have typical DM, 40% belonged to the group of premature infants. Conclusion: As the child grows, the motor experiences should be more challenging for DM to constantly evolve. The insertion of a physical therapist in childcare, together with the Family Health Strategy team, can expand care and guarantee the assessment, monitoring, and promotion of early stimulation of childhood DM, in addition to the recognition of its importance in primary care.

Resumo Introdução: O Programa de Puericultura tem por intuito a promoção, prevenção, diagnóstico precoce e recuperação dos agravos na infância através do acompanhamento programado do crescimento e desenvolvimento da criança. O profissional fisioterapeuta pode contribuir na identificação precoce de desordens do desenvolvimento neuropsicomotor. Objetivo: Caracterizar o desenvolvimento motor (DM) dos bebês atendidos durante as consultas de puericultura e discutir a importância do profissional fisioterapeuta na equipe de atenção básica à saúde. Métodos: A amostra foi composta por 91 bebês de 0 a 6 meses de idade, atendidos em consultas de puericultura. Foram excluídos os bebês com afecções osteomioarticulares, neuropatologia e choro intenso que impedisse a avaliação. Foi realizada avaliação do DM com a Escala Motora Infantil de Alberta. Resultados: Dos bebês de 0 a 3 meses de idade, 11,76% estavam com DM atípico, 23,62% com risco para o atraso motor, e 64,07% com DM típico. Já as crianças de 4 a 6 meses (25,3%), menos da metade das crianças (39,13%) atingiram o DM típico. Desses que não atingiram o DM típico no segundo trimestre de vida, 40% pertencem ao grupo de prematuros. Conclusão: À medida que a criança cresce, suas vivências motoras devem ser mais desafiadoras para que o DM mantenha evolução constante. A inserção do fisioterapeuta na puericultura, junto à equipe de Estratégia de Saúde da família, pode ampliar o cuidado e garantir a avaliação, acompanhamento e promoção da estimulação precoce do DM infantil, além do reconhecimento de sua importância na atenção básica.

Promotores de reserva cognitiva en adultos mayores con alto riesgo de demencia cortical / Promoters of Cognitive Reserve in the Elderly with High Risk of Cortical Dementia

Introducción: La reserva cognitiva constituye un elemento central para entender cómo responde el cerebro a la neuropatología durante el ciclo vital. Objetivo: Comprender los factores promotores de reserva cognitiva desde la experiencia de vida de adultos mayores sin deterioro cognitivo y con alto riesgo de demencia cortical. Métodos: Estudio cualitativo, con base en método Grounded Theory. Se realizan entrevistas semiestructuradas en profundidad a siete adultos mayores. En el análisis, se aplica la técnica de comparación constante según modelo de Glasser y Straus, utilizando Atlas ti/7. Resultados: Desde el análisis axial surgen cinco categorías interrelacionadas: actividad mental, experiencias gratificantes, cuidados, eventos traumáticos y características de personalidad. Se aprecia un patrón constante de experiencias vitales mentalmente estimulantes, relacionado principalmente a actividades de cuidado y experiencias gratificantes, no asociadas a educación formal. Conclusiones: Se distingue un proceso dinámico que involucra experiencias y eventos de vida cotidiana, tanto personales como ambientales, ocupacionales y del estilo de vida, que operan secuencialmente durante el ciclo vital; estos factores podrían incidir significativamente en los mecanismos neurobiológicos y actuar como promotores de reserva cognitiva. Se obtiene un modelo de promotores de reserva cognitiva que podría utilizarse en programas de salud cognitiva para contrarrestar la neuropatología(AU)

Introduction: Cognitive reserve constitutes an element central to understanding how the brain responds to neuropathology during the life cycle. Objective: To understand the factors that promote cognitive reserve from the life experience of the elderly without cognitive deterioration and with high risk of cortical dementia. Methods: Qualitative study, methodologically based on grounded theory. In-depth semi-structured interviews are conducted on seven elderlies. In the analysis, the constant comparison technique is applied according to the model by Glaser and Strauss, using ATLAS-Ti 7. Results: Five interrelated categories emerge from the axial analysis: mental activity, gratifying experiences, care, traumatic events, and personality traits. There is a constant pattern of mentally-stimulating life experiences, mainly related to care activities and gratifying experiences, not associated with formal education. Conclusions: A dynamic process is distinguished that involves experiences and events of daily life, both personal and environmental, occupational and related to lifestyle, which operate sequentially during the life cycle. These factors could significantly influence neurobiological mechanisms and act as promoters of cognitive reserve. A model of cognitive reserve promoters is obtained that could be used in cognitive health programs to counteract neuropathology(AU)

Franz Nissl (1860-1919), noted neuropsychiatrist and neuropathologist, staining the neuron, but not limiting it / Franz nissl (1860-1919), notável neuropsiquiatra e neuropatologista, tingindo o neurônio, mas não o limitando

ABSTRACT Franz Alexander Nissl carried out studies on mental and nervous disorders, as a clinician, but mainly as a pathologist, probably the most important of his time. He recognized changes in glial cells, blood elements, blood vessels and brain tissue in general, achieving this by using a special blue stain he himself developed - Nissl staining, while still a medical student. However, he did not accept the neuron theory supported by the new staining methods developed by Camillo Golgi and Santiago Ramón y Cajal. Nissl had worked with the crème de la crème of German neuropsychiatry, including Alois Alzheimer, besides Emil Kraepelin, Korbinian Brodmann and Walther Spielmeyer. He became (1904), Kraepelin's successor as Professor of Psychiatry and Director of the Psychiatric Clinic, in Heidelberg. Moreover, in 1918, the year before Nissl´s death, Kraepelin offered him a research position as head of the Histopathology Department of the newly founded "Deutsche Forschungsanstalt fur Psychiatrie" of the Max Planck Institute for Psychiatry, in Munich.

RESUMO Franz Alexander Nissl realizou estudos sobre transtornos mentais e nervosos, como clínico, mas principalmente como patologista, provavelmente o mais importante de seu tempo. Ele reconheceu mudanças nas células gliais, elementos sangüíneos, vasos sangüíneos e tecido cerebral em geral, realizando-o por meio de um corante azul especial desenvolvida por ele mesmo - coloração de Nissl, ainda como estudante de medicina. No entanto, ele não aceitou a teoria do neurônio esclarecida pelos novos métodos de coloração desenvolvidos por Camillo Golgi e Santiago Ramón y Cajal. Nissl havia trabalhado com o crème de la crème da neuropsiquiatria alemã, como Alois Alzheimer, além de Emil Kraepelin, Korbinian Brodmann e Walther Spielmeyer. Ele se tornou (1904), o sucessor de Kraepelin como professor de psiquiatria e diretor da Clínica Psiquiátrica, em Heidelberg. Além disso, em 1918, um ano antes da morte de Nissl, Kraepelin o convidou para um cargo de pesquisador, como chefe do departamento de histopatologia da recém-fundada "Deutsche Forschungsanstalt fur Psychiatrie" do Instituto Max Planck de Psiquiatria, em Munique.

The first central nervous system autopsy in Southern Brazil / Primeira autópsia do sistema nervoso central no sul do Brasil

ABSTRACT Objective: The history of Anatomical Pathology in the state of Paraná, in southern Brazil, is closely linked with the foundation of the Universidade Federal do Paraná (UFPR). This study identified the first central nervous system (CNS) clinical autopsy performed by the Department of Anatomical Pathology of the UFPR. Methods: This study reviewed the autopsy report archives of the Hospital de Clínicas-UFPR from 1951 onward. The clinical anatomy interpretations of the autopsy report and possible etiologic agents were discussed. Result: The first adult clinical autopsy with CNS study was performed on April 23, 1952 on a 45-year-old man with lobar pneumonia with abscesses complicated by bacterial meningitis. Conclusion: This case was the first CNS clinical autopsy performed in the state of Paraná and, possibly, in southern Brazil. The death was due to an infectious disease, which was the main cause of death in Brazil in the 1950s.

RESUMO Objetivo: A história da Anatomia Patológica no Estado do Paraná, sul do Brasil, está ligada com a fundação da Universidade Federal do Paraná (UFPR). Este estudo identificou a primeira autópsia clínica do sistema nervoso central (SNC) realizada pelo Departamento de Anatomia Patológica da UFPR. Métodos: Foi realizada revisão dos arquivos dos relatórios de autópsia do HC-UFPR, desde 1951. As interpretações anátomo-clínicas do laudo da autópsia e os possíveis agentes etiológicos foram discutidas. Resultado: A primeira autópsia clínica em adulto com estudo do SNC foi realizada em 23 de abril de 1952. Um homem de 45 anos com pneumonia lobar com abscessos pulmonares, complicada com meningite bacteriana. Conclusão: Este caso é a primeira autópsia clínica em adulto com estudo do SNC do estado do Paraná e possivelmente do Sul do Brasil. A causa da morte foi devido a uma doença infecciosa, as principais causas de óbito no Brasil nos anos 50.

The remarkable pioneering contribution of Gaspar Vianna to the study of the neuropathology of Chagas disease / A notável contribuição pioneira de Gaspar Vianna para o estudo da neuropatologia da doença de Chagas

ABSTRACT Gaspar Vianna is considered one of the great names in Medicine and Science in Brazil. Yet, little prominence has been given to his studies in Neuropathology. He was the first to describe, in 1911, the histopathology and pathogenesis of chagasic encephalitis in the acute phase of Chagas disease, as well as the intracellular life cycle of Trypanosoma cruzi. Over 100 years have elapsed and Gaspar Vianna's pioneering study remains an example of a meticulous and still up-to-date description of central nervous system involvement in the acute phase of Chagas disease.

RESUMO Gaspar Vianna é considerado um dos grandes nomes da Medicina e da Ciência no Brasil. Contudo, pouco destaque tem sido dado aos seus estudos em Neuropatologia. Ele foi o primeiro a descrever a histopatologia e a patogênese da encefalite chagásica na fase aguda da doença de Chagas, bem como o ciclo evolutivo intracelular do Trypanosoma cruzi, em 1911. Passados mais de 100 anos, o estudo pioneiro de Gaspar Vianna permanece como exemplo de descrição minuciosa e ainda atual do envolvimento do sistema nervoso central na fase aguda da doença de Chagas.

Neurological diseases of cattle in the state of Goiás, Brazil (2010-2017) / Doenças neurológicas de bovinos no estado de Goiás (2010-2017)

A retrospective study was conducted on neurological diseases of cattle in the state of Goiás, Brazil, from March 2010 to August 2017. Samples of three veterinary diagnostic laboratories were analyzed. Diagnosis was established in 170 out of 407 cattle with neurological signs. Epidemiological, clinical, and anatomic pathology features of each case were researched in the files. Main disorders included diseases caused by viruses (rabies 29.41%, meningoencephalitis by bovine herpesvirus 15.88%, and malignant catarrhal fever 1.76%), by bacteria (botulism 5.88%, suppurative meningitis 3.53%, encephalic abscesses 2.94%, listeriosis 1.76%, and thrombotic meningoencephalitis 1.76%), of metabolic origin (polioencephalomalacia 17.06%), of indefinite cause (lymphoplasmacytic meningoencephalitis 11.18%, traumatic hemorrhages 3.53%, and multifocal malacia with gliosis 1.18%), congenital (hydrocephaly 1.18% and multiple malformations 0.59%), toxic (urea poisoning 1.18% and insecticide poisoning 0.59%), and parasitic (meningoencephalitis associated with infection by Trypanosoma sp. 0.59%).(AU)

Foi realizado um estudo retrospectivo de doenças neurológicas de bovinos no estado de Goiás durante o período de março de 2010 a agosto de 2017, analisando amostras de três laboratórios de diagnóstico veterinário. De 407 bovinos que apresentaram sinais clínicos neurológicos, o diagnóstico foi estabelecido em 170 casos. Desses casos, foram pesquisadas nas fichas as características epidemiológicas, clínicas e anatomopatológicas. As principais doenças diagnosticadas foram causadas por vírus (raiva 29,41%, meningoencefalite por herpesvírus bovino 15,88% e febre catarral maligna 1,76%), de origem metabólica (polioencefalomalacia 17,06%), por bactérias (botulismo 5,88%, meningite supurativa 3,53%, abscessos encefálicos 2,94%, listeriose 1,76% e meningoencefalite trombótica 1,76%), sem causa definida (meningoencefalite linfoplasmocítica 11,18%, hemorragias traumáticas 3,53% e malacia multifocal com gliose 1,18%), congênitas (hidrocefalia 1,18% e malformações múltiplas 0,59%), tóxicas (intoxicação por ureia 1,18% e intoxicação por inseticida 0,59%), e parasitária (meningoencefalite associada à infecção por Trypanosoma sp. 0,59%).(AU)

Association between diabetes and causes of dementia: Evidence from a clinicopathological study / Associação entre diabetes e causas de demência: evidência de um estudo clínico-patológico

ABSTRACT.Background: Diabetes mellitus is a risk factor for dementia, especially for vascular dementia (VaD), but there is no consensus on diabetes as a risk factor for Alzheimer's disease (AD) and other causes of dementia. Objective: To explore the association between diabetes and the neuropathological etiology of dementia in a large autopsy study. Methods: Data were collected from the participants of the Brain Bank of the Brazilian Aging Brain Study Group between 2004 and 2015. Diagnosis of diabetes was reported by the deceased's next-of-kin. Clinical dementia was established when CDR ≥ 1 and IQCODE > 3.41. Dementia etiology was determined by neuropathological examination using immunohistochemistry. The association of diabetes with odds of dementia was investigated using multivariate logistic regression. Results: We included 1,037 subjects and diabetes was present in 279 participants (27%). The prevalence of dementia diagnosis was similar in diabetics (29%) and non-diabetics (27%). We found no association between diabetes and dementia (OR = 1.22; 95%CI = 0.81-1.82; p = 0.34) on the multivariate analysis. AD was the main cause of dementia in both groups, while VaD was the second-most-frequent cause in diabetics. Other mixed dementia was the second-most-common cause of dementia and more frequent among non-diabetics (p = 0.03). Conclusion: Diabetes was not associated with dementia in this large clinicopathological study.

RESUMO. Introdução: Diabetes mellitus é um fator de risco para a demência, especialmente para a demência vascular (DV), mas ainda não há consenso sobre diabetes como fator de risco para a doença de Alzheimer (DA) e outras causas de demência. Objetivo: Verificar a associação entre diabetes e demência e sua etiologia neuropatológica em um grande estudo de autópsia. Métodos: Os dados foram coletados do Banco de Encéfalos Humanos do Grupo de Estudos em Envelhecimento Cerebral da FMUSP entre 2004 e 2015. O diagnóstico de diabetes foi relatado por pelos parentes do falecido. A demência clínica foi estabelecida quando CDR ≥ 1 e IQCODE > 3,41. A etiologia da demência foi determinada pelo exame neuropatológico com imuno-histoquímica. A associação de diabetes com probabilidades de demência foi investigada usando regressão logística multivariada. Resultados: Foram incluídos 1.037 sujeitos, diabetes esteve presente em 279 participantes (27%). A frequência de diagnóstico de demência foi semelhante entre diabéticos (29%) e não diabéticos (27%). Não encontramos associação entre diabetes e demência (OR = 1,22; IC 95% = 0,81-1,82; p = 0,34) na análise multivariada. DA foi a principal causa de demência em ambos os grupos, DV foi a segunda causa em diabéticos. A frequência de outra demência mista foi a segunda causa de demência e mais frequente entre os não diabéticos (p = 0,03). Conclusão: A diabetes não foi associada à demência neste grande estudo clínico-patológico.

Distinct Phospho-TDP-43 brain distribution in two cases of FTD, one associated with ALS / Distribuição cerebral distinta de fosfo-tdp-43 em dois casos de dft, um associado com ela

ABSTRACT. INTRODUCTION: TDP-43 is an intranuclear protein involved in many cellular processes. When altered, it shows a change in pattern of distribution, as well as in functioning, throughout the Central Nervous System structures. Frontotemporal Lobar Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS) are examples of TDP-43 proteinopathy. These disorders form a clinical spectrum, with some patients having a pure cognitive disorder while others also exhibit motor features. METHODS: We studied two donated brains from patients with a diagnosis of Frontotemporal Dementia (FTD), one of which was associated with ALS (ALS-FTD). After fixation and macroscopic examinations, sample analyses were performed. Specific regions were chosen for the application of immunohistochemistry (IHC) with anti-Aß, AT8, anti-α-synuclein and anti-phospho-TDP-43. RESULTS: Both brains presented anti-phospho-TDP-43 positivity, but this was not equally distributed throughout the encephalic zones. In the FTD case, the studied brain presented phosphorylated TDP-43- in the frontal cortex, hippocampus, entorhinal cortex and mesencephalon; in the ALS-FTD case, the abnormal protein was also seen in the pons and medulla oblongata. The brain in the ALS-FTD case presented Aß and AT8 positivity in the hippocampus and entorhinal cortex (Braak I and II). DISCUSSION: The hypothesis supported by scientific literature that these neurodegenerative diseases can have the same etiology with distinct encephalic region involvement is corroborated by the present study.

RESUMO. INTRODUÇÃO: TDP-43 é uma proteína intranuclear envolvida em vários processos celulares. Essa molécula, quando alterada, mostra padrões de distribuição modificados, assim como de funcionamento, ao longo das estruturas do Sistema Nervoso Central. A Degeneração Lobar Frontotemporal (DLFT) e a Esclerose Lateral Amiotrófica (ELA) são dois exemplos de proteinopatia de TDP-43. Esses transtornos formam um espectro clínico, com alguns pacientes apresentando um transtorno cognitivo puro enquanto outros também apresentam disfunções motoras. MÉTODOS: Nós estudamos dois cérebros doados de pacientes com diagnóstico de Demência Frontotemporal (DFT), um dos quais se associava com ELA (ELA-DFT). Após fixação e exame macroscópico, foram realizadas análises de amostras. Regiões específicas foram escolhidas para aplicação de imunohistoquímica (IHQ) com anti-Aß, AT8, anti-α-sinucleina e anti-fosfo-TDP-43. RESULTADOS: Ambos os cérebros foram positivos para anti-fosfo-TDP-43, mas de forma não igualmente distribuida pelas regiões encefálicas. No caso DFT, o cérebro estudado apresentou TDP-43-fosforilada no córtex frontal, hipocampo, córtex entorrinal e mesencéfalo; no caso ELA-DFT, a proteína anormal também foi vista na ponte e no bulbo. O cérebro do caso ELA-DFT foi positivo para Aß e AT8 no hipocampo e no córtex entorrinal (Braak I e II). DISCUSSÃO: O presente estudo corrobora a hipótese atualmente sustentada pela literatura científica de que essas duas doenças neurodegenerativas possuem a mesma etiologia, mas acometem regiões encefálicas distintas.

Arterial spin labeling in patients with schizophrenia: a systematic review

Abstract Background: Neuroimaging studies are an invaluable source of information about the physiopathology of schizophrenia. Arterial spin labeling (ASL) is a new magnetic resonance technique (MRI) that is able to effectively evaluate brain function without the use of radiation. Objective: To make a systematic review of studies using ASL to compare resting-state regional cerebral blood flow (rCBF) patterns in patients with schizophrenia and healthy controls. Methods: Original articles were searched for on PubMed, Scopus, Web of Science and PsycINFO electronic databases. The search terms used were 'arterial', 'spin', 'labeling', and 'schizophrenia'. Only studies comparing resting-state rCBF were included, a qualitative synthesis was then performed. Results: Ten articles were included in the review among a total of 22. Decreased rCBF in schizophrenia patients was described in the anterior cingulate, cuneus, fusiform gyrus, frontal lobe, left middle frontal gyrus, inferior frontal gyrus, lingual gyrus, middle occipital gyrus, and parietal lobe. The putamen was the only region with increased rCBF in schizophrenia. Discussion: The evidence of the studies reviewed lends support to the concept of hipofrontality in schizophrenia. rCBF alterations were found in regions classically associated with schizophrenia. ASL seems to be valid, and reliable tool to assess schizophrenia.