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The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper., Competing Interests: LFP: have served as advisory board and speakers for continuous education programs for the companies UCB, ABBOTT, ADIUM, LIBBS, TORRENT, BIOLAB and EUROFARMA; CLY: have served as advisory board and speakers for continuous education programs for the companies UCB, ABBOTT, ADIUM, LIBBS, TORRENT; FC: have served as advisory board and speaker for continuous education programs for the companies UCB, ABBOTT, ADIUM, LIBBS, TORRENT, EUROFARMA, PRATI- DONADUZZI and TAKEDA; RBJ: has served as a guest speaker for the company LIBBS; LSS, VB: without conflict of interest., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

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.

Background: Although several studies have emphasized the association between epilepsy and psychiatric disorders, fewer have investigated the impact of epilepsy on caregivers' emotional status, mainly in adult people with epilepsy (PWE). Here we investigated depressive symptoms, suicidal ideation, and anxiety symptoms in a large group of adult PWE and their caregivers., Methods: We analyzed symptoms of depression [with the Beck Depression Inventory-II (BDI-II)], suicidal ideation (with BDI-II item 9), and anxiety symptoms (with the Beck Anxiety Inventory) in a large group of adult PWE [ N = 548 (60% women; median age 41)] and caregivers [ N = 191 (72% women; median age 47)] from a Brazilian tertiary center, considering sociodemographic and clinical aspects. We also applied the Liverpool Adverse Events Profile to assess anti-seizure drugs adverse events., Results: While the presence ( p = 0.026) (and intensity, p = 0.007) of depressive symptoms and suicidal ideation ( p = 0.02) were higher in PWE compared to caregivers, the proportion of clinical anxiety symptoms ( p = 0.32) (and the intensity, p = 0.13) was similar in both groups. Although the rates of suicidal ideation were higher in focal epilepsy (20%), both generalized genetic epilepsy and caregivers also presented elevated frequencies (11%) of suicidal ideation. The analyses of 120 patient-caregiver dyads revealed that the intensity of depressive symptoms in PWE (but not anxiety) correlated with the intensity of depressive ( r = 0.35; p < 0.001) and anxiety ( r = 0.25; p = 0.01) symptoms in their caregivers. In the multivariate analyses of PWE, focal epilepsy (compared to GGE) was associated with clinical depressive symptoms (odds ratio, OR 2.1) and suicidal ideation (OR 3.2), while recurrent seizures (compared to the seizure-free group) were associated with suicidal ideation (OR 2.6) and anxiety symptoms (OR 2.1). Also, caregivers with anxiety symptoms were 8 times more likely to exhibit depressive symptoms, and those with depressive symptoms were 8 times more likely to present anxiety symptoms., Conclusion: Our study suggests that specific attention for the caregivers' mental health is as essential as PWE. There is an urgent need for more studies involving caregivers to identify their emotional distress and provide adequate treatment., 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 © 2022 João, Nogueira, Morita-Sherman, Alvim, Johnny, Pereira, Pinheiro, Cendes and Yasuda.)