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The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder., (© 2024. The Author(s).)

Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group., Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness., Results: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (d max  = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (d max  = .47), crus I/II (d max  = .39), VIIIA (d max  = .45), and VIIIB (d max  = .40). Earlier age at seizure onset ( η ρ max 2  = .05) and longer epilepsy duration ( η ρ max 2  = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls., Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated., Objective: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group., Methods: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated., Results: Overall, people with PD had a regionally smaller posterior lobe (d max  = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (d max  = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (d max  = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17)., Conclusions: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

The last years have evinced a remarkable growth in neuroimaging studies around the world. All these studies have contributed to a better understanding of the cerebral outcomes of dementia, even in the earliest phases. In low- and middle-income countries, studies involving structural and functional neuroimaging are challenging due to low investments and heterogeneous populations. Outstanding the importance of diagnosing mild cognitive impairment and dementia, the purpose of this paper is to offer an overview of neuroimaging dementia research in Brazil. The review includes a brief scientometric analysis of quantitative information about the development of this field over the past 10 years. Besides, discusses some peculiarities and challenges that have limited neuroimaging dementia research in this big and heterogeneous country of Latin America. We systematically reviewed existing neuroimaging literature with Brazilian authors that presented outcomes related to a dementia syndrome, published from 2010 to 2020. Briefly, the main neuroimaging methods used were morphometrics, followed by fMRI, and DTI. The major diseases analyzed were Alzheimer's disease, mild cognitive impairment, and vascular dementia, respectively. Moreover, research activity in Brazil has been restricted almost entirely to a few centers in the Southeast region, and funding could be the main driver for publications. There was relative stability concerning the number of publications per year, the citation impact has historically been below the world average, and the author's gender inequalities are not relevant in this specific field. Neuroimaging research in Brazil is far from being developed and widespread across the country. Fortunately, increasingly collaborations with foreign partnerships contribute to the impact of Brazil's domestic research. Although the challenges, neuroimaging researches performed in the native population regarding regional peculiarities and adversities are of pivotal importance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rizzi, Aventurato and Balthazar.)

The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune reconstitution during combination antiretroviral therapy. We characterized the HIV-specific longitudinal host transcriptional response of peripheral blood mononuclear cells from elite controllers, rapid progressors, immune responders and non-responders using a RT-qPCR array in a cohort of recently HIV-infected Brazilian individuals. The elite controllers expressed unique transcripts early in infection that were closely associated with specialized cross-presentation between XCR1+ DCs and antigen-specific CD8+ T cells (XCL1). The natural suppression of HIV was also associated with the highly functional co-expression of cytokines and chemokines (CCL2, TNF and IL-10) concomitant with the maintenance of important anti-inflammatory and anticoagulant properties (Antithrombin III). Immune responders exhibited exclusively upregulated mRNAs possibly related to stem cell mobilization before combination antiretroviral therapy (neutrophil elastase). Our longitudinal approach to gene expression permitted us to discover previously unrecognized determinants that contribute to natural or antiretroviral-mediated HIV-1 immune control.