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BACKGROUND AND PURPOSE: Our objective was to define phenotypes of non-lesional late-onset epilepsy (NLLOE) depending on its presumed aetiology and to determine their seizure and cognitive outcomes at 12 months. METHODS: In all, 146 newly diagnosed NLLOE patients, >50 years old, were prospectively included and categorized by four presumed aetiological subtypes: neurodegenerative subtype (patients with a diagnosis of neurodegenerative disease) (n = 31), microvascular subtype (patients with three or more cardiovascular risk factors and two or more vascular lesions on MRI) (n = 39), inflammatory subtype (patient meeting international criteria for encephalitis) (n = 9) and unlabelled subtype (all individuals who did not meet the criteria for other subtypes) (n = 67). Cognitive outcome was determined by comparing for each patient the proportion of preserved/altered scores between initial and second neuropsychological assessment. RESULTS: The neurodegenerative subtype had the most severe cognitive profile at diagnosis with cognitive complaint dating back several years. The microvascular subtype was mainly evaluated through the neurovascular emergency pathway. Their seizures were characterized by transient phasic disorders. Inflammatory subtype patients were the youngest. They presented an acute epilepsy onset with high rate of focal status epilepticus. The unlabelled subtype presented fewer comorbidities with fewer lesions on brain imaging. The neurodegenerative subtype had the worst seizure and cognitive outcomes. In other groups, seizure control was good under antiseizure medication (94.7% seizure-free) and cognitive performance was stabilized or even improved. CONCLUSION: This new characterization of NLLOE phenotypes raises questions regarding the current International League Against Epilepsy aetiological classification which does not individualize neurodegenerative and microvascular aetiology per se.
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OBJECTIVE: To determine whether it is the magnitude of early postnatal catch-up growth (CUG) in response to fetal growth restriction (FGR) or the FGR itself that negatively impacts cognitive outcome in a model of monochorionic twins discordant for fetal growth. STUDY DESIGN: This analysis is part of the LEMON study, a cohort study including all monochorionic twins with selective FGR aged 3 through 17 years. Growth measurements as documented by our primary care system were collected retrospectively. An age-appropriate neurodevelopmental test was performed generating a full-scale IQ (FSIQ). CUG at 2 years was calculated as (weight [kg] at 2 years-birth weight [kg]). We used a multivariable regression model investigating the association between FSIQ (outcome) and birth weight zscore, gestational age at birth and CUG at 2 years (predictors). Generalized estimating equations accounted for the fact that observations between cotwins are not independent. RESULTS: Median age at follow-up of the 46 included twin pairs was 11 (IQR 8-13) years. Birth weight z score and gestational age at birth were significantly associated with FSIQ, with ß-coefficients of 5.897 (95% CI 3.382-8.411), and 2.589 (95% CI 1.227-3.951), respectively (P < .0001). Adjusted for birth weight z score and gestational age, CUG in the first 2 years after birth was not significantly associated with FSIQ (ß-coefficient 0.108 [95% CI -1.373 to 1.590], P = .886). CONCLUSIONS: Our results, combining detailed growth measurements and neurodevelopmental follow-up in a discordant identical twin model, demonstrate that FGR itself rather than early postnatal CUG has negative consequences for cognitive development.
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BACKGROUND: Endoscopic ventricular surgery (EVS) shows overall reduced morbidity compared to open craniotomy, but carries, however, the risk for neurocognitive impairment caused by fornix-, hypothalamus-, and injuries other structures adjacent to the ventricular system. Objective or subjective neurocognitive impairment after EVS is rarely reported. The aim of this study was to assess the subjective neurocognitive outcome in patients undergoing EVS for various pathologies. METHODS: We conducted a retrospective cohort study in adult patients undergoing EVS at our institution between 2010 and 2021. The primary outcome was subjective neurocognitive outcome after EVS measured by patient-reported outcomes (PROs). Secondary outcomes were objective neurocognitive outcome, return-to-work rate, subjective quality of life and satisfaction with surgery. Descriptive and comparative statistics were conducted for all outcome parameters. RESULTS: Fifty-one patients (median age 48 years, 62.7% female) were included. Patients commonly presented with subjective neurocognitive impairment (54.9%) and hydrocephalus was the most common indication for surgery (54.9%). Worse long-term subjective neurocognitive outcome was observed in 5 (21.7%) patients while 18 (78.3%) patients improved. Worse long-term objective neurocognitive outcome was seen in 2 cases (10.5%), of which 1 patient became worse trough surgery while 15 (78.9%) patients improved. Improved subjective and objective neurocognitive outcome correlated in 73.8% of the cases (r = 0.363, P = 0.018). Return to work was possible for 70% of the patients and subjective quality of life was improved or unchanged in 88.1% of the patients. CONCLUSIONS: Subjective neurocognitive outcome and quality of life improvement are often achieved after EVS and permanent neurocognitive impairment is rare. Further well-designed trials on subjective and objective neurocognitive outcome after EVS are warranted.
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BACKGROUND: Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS) is the most common cause of drug-resistant focal seizures and surgical resection is the primary treatment option, with seizure-free rates ranging from 60 to 80%. However, data on postsurgical seizure outcomes in patients ≥ 50 years of age are limited. This study aimed to assess the efficacy and safety of surgery in this age group compared to younger patients. METHODS: We performed a retrospective analysis of data from resective surgeries conducted in patients with MTLE/HS between 1990 and 2022. We focused on patients aged ≥ 50 years and compared the surgical safety and efficacy variables between this group and a control group of patients aged < 50 years through a case-control study. RESULTS: Among the 450 MTLE/HS patients who underwent surgery during the inclusion period, 61 (13.6%) were aged ≥ 50 years and matched with 183 younger patients, totaling 244 study participants. The two groups had similar characteristics. At the last follow-up (median 5.7 years), Engel I outcomes were achieved in 80.3% of the older patients and 81.4% of the younger patients, with no significant difference (p = 0.85). Postoperative cognitive and psychiatric outcomes did not differ between the groups. Major complication rates were also comparable, at 3.3% in the older group and 2.7% in the younger group (p = 0.83). The extratemporal ictal abnormalities observed on video-EEG were the only variable that demonstrated a significant association with an unfavorable seizure outcome in the older group (OR 9.3, 95% CI [1.8-47.6], p = 0.005). CONCLUSIONS: This study provides grade 3 evidence that resective surgery for MTLE/HS patients aged ≥ 50 years is as effective and safe as it is for younger patients, and thus should be considered as the primary treatment option for drug-resistant cases.
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Epilepsia do Lobo Temporal , Hipocampo , Esclerose , Humanos , Epilepsia do Lobo Temporal/cirurgia , Pessoa de Meia-Idade , Masculino , Feminino , Esclerose/cirurgia , Hipocampo/cirurgia , Hipocampo/patologia , Estudos de Casos e Controles , Adulto , Estudos Retrospectivos , Idoso , Adulto Jovem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/etiologia , Fatores Etários , Procedimentos Neurocirúrgicos/efeitos adversos , Adolescente , Seguimentos , Resultado do Tratamento , Esclerose HipocampalRESUMO
We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.
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Imagem de Tensor de Difusão , Esclerose Múltipla , Substância Branca , Humanos , Feminino , Masculino , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Anisotropia , Adulto , Imagem de Tensor de Difusão/métodos , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/etiologiaRESUMO
Rasmussen's encephalitis is a rare neurological pathology affecting one cerebral hemisphere, therefore, posing unique challenges. Patients may undergo hemispherectomy, a surgical procedure after which cognitive development occurs in the isolated contralateral hemisphere. This rare situation provides an excellent opportunity to evaluate brain plasticity and cognitive recovery at a hemispheric level. This literature review synthesizes the existing body of research on cognitive recovery following hemispherectomy in Rasmussen patients, considering cognitive domains and modulatory factors that influence cognitive outcomes. While language function has traditionally been the focus of postoperative assessments, there is a growing acknowledgment of the need to broaden the scope of language investigation in interaction with other cognitive domains and to consider cognitive scaffolding in development and recovery. By synthesizing findings reported in the literature, we delineate how language functions may find support from the right hemisphere after left hemispherectomy, but also how, beyond language, global cognitive functioning is affected. We highlight the critical influence of several factors on postoperative cognitive outcomes, including the timing of hemispherectomy and the baseline preoperative cognitive status, pointing to early surgical intervention as predictive of better cognitive outcomes. However, further specific studies are needed to confirm this correlation. This review aims to emphasize a better understanding of mechanisms underlying hemispheric specialization and plasticity in humans, which are particularly important for both clinical and research advancements. This narrative review underscores the need for an integrative approach based on cognitive scaffolding to provide a comprehensive understanding of mechanisms underlying the reorganization in Rasmussen patients after hemispherectomy.
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BACKGROUND: Approximately half of cardiac arrest survivors have persistent cognitive impairment. Guidelines recommend early screening to identify patients at risk for cognitive impairment, but there is no consensus on the best screening method. We aimed to identify quantitative EEG measures relating with short- and long-term cognitive function after cardiac arrest for potential to cognitive outcome prediction. METHODS: We analyzed data from a prospective longitudinal multicenter cohort study designed to develop a prediction model for cognitive outcome after cardiac arrest. For the current analysis, we used twenty-minute EEG registrations from 80 patients around one week after cardiac arrest. We calculated power spectral density, normalized alpha-to-theta ratio (nATR), peak frequency, and center of gravity (CoG) of this peak frequency. We related these with global cognitive functioning (scores on the Montreal Cognitive Assessment (MoCA)) at one week, three and twelve months follow-up with multivariate mixed effect models, and with performance on standard neuropsychological examination at twelve months using Pearson correlation coefficients. RESULTS: Each individual EEG parameter related to MoCA at one week (ßnATR = 7.36; P < 0.01; ßpeak frequency = 1.73, P < 0.01; ßCoG = -9.88, P < 0.01). The nATR also related with the MoCA at three months ((ßnATR = 2.49; P 0.01). No EEG metrics significantly related to the MoCA score at twelve months. nATR and peak frequency related with memory performance at twelve months. Results were consistent in sensitivity analyses. CONCLUSION: Early resting-state EEG parameters relate with short-term global cognitive functioning and with memory function at one year after cardiac arrest. Additional predictive values in multimodal prediction models need further study.
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Disfunção Cognitiva , Eletroencefalografia , Parada Cardíaca , Humanos , Masculino , Feminino , Eletroencefalografia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Parada Cardíaca/complicações , Parada Cardíaca/fisiopatologia , Idoso , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Cognição/fisiologia , Estudos Longitudinais , Testes Neuropsicológicos , Fatores de TempoRESUMO
OBJECTIVE: We aimed to explore the clinical characteristics and functional network properties of patients with late-onset Lennox-Gastaut syndrome (LGS). METHODS: Late-onset LGS was defined by the appearance of LGS features after 8 years of age. We reviewed the medical charts of 9 patients with late-onset LGS, and performed electroencephalography connectivity analysis using graph theory. We assessed the clustering coefficient (CC) and characteristic path length (CPL), which are common basic measures of functional networks that represent local segregation and global integration. The characteristics and brain parameters of late-onset LGS were compared with a typical age-onset LGS group. RESULTS: Late onset LGS subjects were older than typical age onset LGS at the time of testing, but otherwise there were no significant differences in clinical characteristics. The late-onset group showed higher median CC values in the alpha (p = 0.045) and beta (p < 0.001) bands over brain regions implicated in cognitive processing. There were no significant differences in CPL between the LGS groups. CONCLUSIONS: Higher clustering coefficient values, in alpha/beta bands over brain regions implicated in cognitive processing, are consistent with increased cognitive network segregation in late onset LGS compared to typical age-onset LGS. Given network segregation is a normal aspect of brain maturation, these results imply that this process is less disturbed when the LGS process begins later in childhood.
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Encéfalo , Eletroencefalografia , Síndrome de Lennox-Gastaut , Humanos , Síndrome de Lennox-Gastaut/fisiopatologia , Masculino , Feminino , Eletroencefalografia/métodos , Encéfalo/fisiopatologia , Adolescente , Criança , Adulto Jovem , Idade de Início , Adulto , Vias Neurais/fisiopatologia , Mapeamento Encefálico/métodosRESUMO
OBJECTIVE: Infantile seizures cause great concern for both doctors and parents. In addition to modern neuroimaging and genetics, clinical tools helpful in predicting the course of the disease are needed. We prospectively studied the incidence, electroclinical characteristics and etiologies of epilepsy syndromes with onset before the age of 12 months and looked for prognostic determinants of outcome by age 24 months. METHODS: From February 2017 through May 2019, we recruited all eligible infants diagnosed with epilepsy at our unit. Data on electroclinical studies, genetic investigations and drug response were gathered prospectively. The infants were given a structured neurological examination (Hammersmith Infantile Neurological examination [HINE] and Griffiths scales) at predetermined intervals until age 24 months at which age neurocognitive evaluation with Bayley scales was performed. RESULTS: Included were 60 infants (27 female). The mean onset age of epilepsy was 5.3 (±2.5 standard deviation) months. The incidence of epilepsy in the population-based cohort was 131 (95% confidence interval 99-172)/100 000. Epilepsy syndrome was identified in 80% and etiology in 58% of infants. Self-limited infantile epilepsy was the second most common syndrome (incidence 18/100 000) after infantile epileptic spasms syndrome. PRRT2 was the most common monogenic cause. At age 24 months, 37% of the infants had drug-resistant epilepsy (DRE) and half had a global developmental delay (GDD). Abnormal first HINE was the strongest predictor of GDD, followed by DRE and identified etiology. DRE was associated with structural etiology and GDD. Those with normal first HINE and good response to treatment had favorable outcomes, irrespective of the identified etiology. SIGNIFICANCE: Our results support a high incidence of self-limited epilepsy in infancy and PRRT2 as the genetic cause in the first year of life. Notwithstanding the advances in etiological discovery, we want to highlight the importance of clinical evaluation as standardized neurological examination with HINE proved a valuable tool in prognostication. PLAIN LANGUAGE SUMMARY: One in every 700-800 babies develop epilepsy within the first year after birth. Our study identified an epilepsy syndrome in 80% and the cause of epilepsy in 60% of the participants. By age 2 years, over one-third of the children still experienced seizures, and almost half faced significant developmental delay. Structural brain abnormalities increased the likelihood of difficult epilepsy and developmental challenges. Babies whose epilepsy was caused by a gene defect varied widely in development and response to medications. Babies with normal neurological examination at first visit, especially if their seizures stopped quickly, had favorable development.
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Epilepsia , Humanos , Feminino , Masculino , Lactente , Estudos Prospectivos , Pré-Escolar , Idade de Início , Síndromes Epilépticas , Incidência , Espasmos Infantis/epidemiologia , Eletroencefalografia , Recém-Nascido , Prognóstico , Anticonvulsivantes/uso terapêuticoRESUMO
Determining preoperatively the maximal extent of resection that would preserve cognitive functions is the core challenge of brain tumour surgery. Over the past decade, the methodological framework to achieve this goal has been thoroughly renewed: the population-level topographically-focused voxel-based lesion-symptom mapping has been progressively overshadowed by machine learning (ML) algorithmics, in which the problem is framed as predicting cognitive outcomes in a patient-specific manner from a typically large set of variables. However, the choice of these predictors is of utmost importance, as they should be both informative and parsimonious. In this perspective, we first introduce the concept of connectotomy: instead of parameterizing resection topography through the status (intact/resected) of a huge number of voxels (or parcels) paving the whole brain in the Cartesian 3D-space, the connectotomy models the resection in the connectivity space, by computing a handful number of networks disconnection indices, measuring how the structural connectivity sustaining each network of interest was hit by the resection. This connectivity-informed reduction of dimensionality is a necessary step for efficiently implementing ML tools, given the relatively small number of patient-examples in available training datasets. We further argue that two other major sources of interindividual variability must be considered to improve the accuracy with which outcomes are predicted: the underlying structure-function phenotype and neuroplasticity, for which we provide an in-depth review and propose new ways of determining relevant predictors. We finally discuss the benefits of our approach for precision surgery of glioma.
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Neoplasias Encefálicas , Glioma , Plasticidade Neuronal , Humanos , Glioma/cirurgia , Neoplasias Encefálicas/cirurgia , Plasticidade Neuronal/fisiologia , Fenótipo , Cognição/fisiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Aprendizado de Máquina , Encéfalo/cirurgia , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
Background: Ischemic stroke and heavy alcohol consumption are both known risk factors for cognitive impairment. The issue gains importance because the prevalence of stroke and binge drinking have both increased among working-aged adults. Alarmingly, a recent cross-sectional study suggests the additive negative effects of binge drinking and comorbid brain disease on cognition. However, the long-term cognitive prognosis of the additive effects of stroke and binge drinking on adults remains unknown. Methods: In this prospective, two-center cohort study, we recruited consecutive 18-65-year-old patients with first-ever ischemic stroke along with demographically matched stroke-free controls. Patients participated in neuropsychological assessment at 6 months, 2 years, and 9 years after stroke, and in neurological assessment at acute care and at 9-year follow-up. Controls participated in a similar follow-up procedure. We examined the association between binge drinking, follow-up time, and long-term cognitive outcomes using repeated-measures analysis of variance. Results: We included 85 patients who had had their first-ever and only ischemic stroke (mean age 53 years at the incident stroke). Patients were divided into binge-drinking (n = 22) and non-binge-drinking groups (n = 63) based on the shortened version of the Alcohol Use Disorders Identification Test. Follow-up data in healthy controls (n = 31) was used to normalize the patients' test scores for effects of age, sex, and education. We compared cognitive changes between binge-drinking and non-binge-drinking patients over a 9-year follow-up. Non-binge-drinking patients outperformed binge-drinking patients across all follow-up points on most of the executive function tests and in one memory test: binge drinking had a significant main effect both on executive function (the phonemic fluency task, p = 0.002; the Trail Making Test, p = 0.013) and memory (the list learning task, p = 0.002). Conclusion: Binge drinking was associated with executive and memory dysfunction at three time points over a decade after a first-ever ischemic stroke. Subdiagnostic binge drinking might increase the adverse effects of a first-ever ischemic stroke on executive function and memory, evident over a decade poststroke.
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The purpose of this study was to systematically examine three different surgical approaches in treating left medial temporal lobe epilepsy (mTLE) (viz., subtemporal selective amygdalohippocampectomy [subSAH], stereotactic laser amygdalohippocampotomy [SLAH], and anterior temporal lobectomy [ATL]), to determine which procedures are most favorable in terms of visual confrontation naming and seizure relief outcome. This was a retrospective study of 33 adults with intractable mTLE who underwent left temporal lobe surgery at three different epilepsy surgery centers who also underwent pre-, and at least 6-month post-surgical neuropsychological testing. Measures included the Boston Naming Test (BNT) and the Engel Epilepsy Surgery Outcome Scale. Fisher's exact tests revealed a statistically significant decline in naming in ATLs compared to SLAHs, but no other significant group differences. 82% of ATL and 36% of subSAH patients showed a significant naming decline whereas no SLAH patient (0%) had a significant naming decline. Significant postoperative naming improvement was seen in 36% of SLAH patients in contrast to 9% improvement in subSAH patients and 0% improvement in ATLs. Finally, there were no statistically significant differences between surgical approaches with regard to seizure freedom outcome, although there was a trend towards better seizure relief outcome among the ATL patients. Results support a possible benefit of SLAH in preserving visual confrontation naming after left TLE surgery. While result interpretation is limited by the small sample size, findings suggest outcome is likely to differ by surgical approach, and that further research on cognitive and seizure freedom outcomes is needed to inform patients and providers of potential risks and benefits with each.
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Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal , Testes Neuropsicológicos , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Epilepsia do Lobo Temporal/cirurgia , Estudos Retrospectivos , Lobectomia Temporal Anterior/métodos , Lobectomia Temporal Anterior/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto Jovem , Convulsões/cirurgia , Procedimentos Neurocirúrgicos/métodos , Lobo Temporal/cirurgiaRESUMO
Background: The effect of cholinesterase inhibitor (ChEI) on mild cognitive impairment (MCI) is controversial. Brain age has been shown to predict Alzheimer's disease conversion from MCI. Objective: The study aimed to show that brain age is related to cognitive outcomes of ChEI treatment in MCI. Methods: Brain MRI, the Clinical Dementia Rating (CDR) and Mini-Mental State Exam (MMSE) scores were retrospectively retrieved from a ChEI treatment database. Patients who presented baseline CDR of 0.5 and received ChEI treatment for at least 2 years were selected. Patients with stationary or improved cognition as verified by the CDR and MMSE were categorized to the ChEI-responsive group, and those with worsened cognition were assigned to the ChEI-unresponsive group. A gray matter brain age model was built with a machine learning algorithm by training T1-weighted MRI data of 362 healthy participants. The model was applied to each patient to compute predicted age difference (PAD), i.e. the difference between brain age and chronological age. The PADs were compared between the two groups. Results: 58 patients were found to fit the ChEI-responsive criteria in the patient data, and 58 matched patients that fit the ChEI-unresponsive criteria were compared. ChEI-unresponsive patients showed significantly larger PAD than ChEI-responsive patients (8.44±8.78 years versus 3.87±9.02 years, pâ=â0.0067). Conclusions: Gray matter brain age is associated with cognitive outcomes after 2 years of ChEI treatment in patients with the CDR of 0.5. It might facilitate the clinical trials of novel therapeutics for MCI.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Inibidores da Colinesterase/uso terapêutico , Estudos Retrospectivos , Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/complicações , Encéfalo/diagnóstico por imagem , CogniçãoRESUMO
Background: Composite scores have been increasingly used in trials for Alzheimer's disease (AD) to detect disease progression, such as the AD Composite Score (ADCOMS) in the lecanemab trial. Objective: To develop a new composite score to improve the prediction of outcome change. Methods: We proposed to develop a new composite score based on the statistical model in the ADCOMS, by removing duplicated sub-scales and adding the model selection in the partial least squares (PLS) regression. Results: The new AD composite Score with variable Selection (ADSS) includes 7 cognitive sub-scales. ADSS can increase the sensitivity to detect disease progression as compared to the existing total scores, which leads to smaller sample sizes using the ADSS in trial designs. Conclusions: ADSS can be utilized in AD trials to improve the success rate of drug development with a high sensitivity to detect disease progression in early stages.
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While socioeconomic status (SES) is associated with a variety of health outcomes, the literature on the association between SES and traumatic brain injury (TBI) outcomes has not been formally summarized. This study aims to review existing literature to ascertain whether patients with low SES pre-injury have worse clinical outcomes after TBI compared with those with high SES, in high-income countries. A systematic search was conducted using the MEDLINE, Embase, and PsychINFO databases. Observational studies addressing the association between SES and TBI outcomes (mortality, functional, cognitive, and vocational outcomes) were included (published from 2000, written in English). Both pediatric and adult TBI groups were included. Thirty-two studies met the inclusion criteria. Measures of SES varied across studies. Mortality was assessed in seven studies; five reported an association between low SES and higher mortality. Five of eight studies showed an association between low SES and worse functional outcomes; results for cognitive (n = 13) and vocational outcomes (n = 10) were mixed. The results of this review suggest that SES is a variable of interest in the context of TBI outcomes and should be assessed at time of admission to assist in social work discharge planning and early mobilization of available community resources. Further work is required to better understand the impact of SES on TBI outcomes.
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Lesões Encefálicas Traumáticas , Classe Social , Humanos , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/economiaRESUMO
AIM: To investigate how the aetiology of very preterm birth/very low birth weight is associated with mortality and later neurodevelopmental outcomes. METHODS: Very preterm/very low-birth weight singletons were categorised based on the aetiology of preterm birth: spontaneous preterm birth (n = 47, 28.1%), preterm premature rupture of membranes (n = 56, 33.5%) or placental vascular pathology (n = 64, 38.3%). Mortality, cerebral palsy, severe cognitive impairment by 11 years of age (<2SD) and mean full-scale intelligence quotient at 11 years were studied in association with birth aetiology. RESULTS: There was no difference in mortality or rate of cerebral palsy according to birth aetiologies. The rate of severe cognitive impairment was lower (4.9% vs. 15.3%) in the preterm premature rupture of the membrane group in comparison to the placental vascular pathology group (OR 0.2, 95% CI 0.03-0.9, adjusted for gestational age). At 11 years, there was no statistically significant difference in the mean full-scale intelligence quotient. CONCLUSION: Placental vascular pathology, as the aetiology of very preterm birth/very low birth weight, is associated with a higher rate of severe cognitive impairments in comparison to preterm premature rupture of membranes, although there was no difference in the mean full-scale intelligence quotient at 11 years. The aetiology of very preterm birth/very low birth weight was not associated with mortality or the rate of cerebral palsy.
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Paralisia Cerebral , Ruptura Prematura de Membranas Fetais , Nascimento Prematuro , Recém-Nascido , Humanos , Gravidez , Feminino , Criança , Paralisia Cerebral/etiologia , Placenta , Recém-Nascido de muito Baixo Peso , Idade GestacionalRESUMO
Epilepsy is a common condition that affects approximately 1% of the world's population, with about one-third being refractory epilepsy. Temporal lobe epilepsy is the most common type of drug-resistant epilepsy, and laser interstitial thermal therapy (LITT) is an innovative treatment. In this systematic review and meta-analysis, we aimed to summarize the current evidence on outcomes after LITT, including seizure freedom rate, complication rate, and neurocognitive outcome. PubMed and OVID Medline search engines were systematically searched for all indexed publications in the English language up to July15, 2023. The search was limited to human studies. Proportions and 95% confidence interval (CI) values were calculated for seizure, neurocognitive outcome, and complication rate. A total of 836 patients were included. Overall seizure outcomes, regardless of the pathology, included Engel I outcome in 56% (95% CI, 52.4-59.5%), Engel II outcome in 19.2% (95% CI, 15.4-23.6%), Engel III outcome in 17.3% (95% CI, 13.5-21.8%), and Engel IV outcome in 10.5% (95% CI 6.3-17%) of the patients. The overall decline in verbal and visual memory regardless of laterality was 24.2 (95% CI 8.6-52%) and 25.2% (8.3-55.8%). For naming, the decline was 13.4% (6.6-25.4%). The results of the pooled analysis in comparison with available data in the literature showed that seizure outcomes after LITT were slightly inferior to published data after temporal lobectomy. Data on cognitive outcomes after LITT are scarce and heterogeneous.
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Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Epilepsia , Terapia a Laser , Humanos , Epilepsia do Lobo Temporal/cirurgia , Resultado do Tratamento , Terapia a Laser/métodos , Convulsões/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/cirurgia , Imageamento por Ressonância Magnética/métodos , LasersRESUMO
BACKGROUND: The purpose of this study was to evaluate the long-term functional and neurodevelopmental outcomes in pediatric patients who underwent neurosurgical intervention following suspected abusive head trauma (AHT). METHODS: We performed a single-center retrospective review (January 1, 2007, to December 31, 2019) of patients aged less than three years who had intracranial injury suspicious for AHT and received a neurosurgical procedure. Long-term functional outcome was measured using the Pediatric Cerebral Performance Category (PCPC), Pediatric Overall Performance Category (POPC), and the Mullen Scales of Early Learning (MSEL). RESULTS: Seventy-seven patients were identified; 53 survived to discharge and had at least one-year follow-up. To examine long-term functional outcome, PCPC at the last available visit was examined and found to be 1 or 2 (normal to mild disability) for 64% of patients and 3 or 4 (moderate to severe disability) for 36%. The last available MSEL composite score for neurodevelopmental assessment also demonstrated that 13% of patients scored in the "average" range, 17% in the "below average" range, and 70% in the "very low" range. There was no statistical difference in the last available PCPC or POPC score or the last available MSEL score for patients who received a craniotomy when compared with those who received an intracranial shunt. CONCLUSIONS: For patients with AHT who survived to discharge, functional improvements over time were noted in both patients who received craniotomy or who simply required shunt placement. These results suggest that, for patients who survive to discharge, operative management of AHT can lead to reasonable long-term functional outcomes.
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Maus-Tratos Infantis , Traumatismos Craniocerebrais , Criança , Humanos , Lactente , Traumatismos Craniocerebrais/cirurgia , Estudos Retrospectivos , Maus-Tratos Infantis/diagnóstico , CraniotomiaRESUMO
Cardiac arrest survivors develop a variety of neuropsychological impairments and neuroanatomical lesions. The goal of this study is to evaluate if brain voxel-based morphometry and lesional Magnetic Resonance Imaging (MRI) analyses performed in the acute phase of an Out-of-Hospital Cardiac Arrest (OHCA) can be sensitive enough to predict the persistence of neuropsychological disorders beyond 3 months. Survivors underwent a prospective brain MRI during the first month after an OHCA and performed neuropsychological assessments at 1 and 3 months. According to the second neuropsychological assessment, survivors were separated into two subgroups, a deficit subgroup with persistent memory, executive functions, attention and/or praxis disorders (n = 11) and a preserved subgroup, disorders free (n = 14). Brain vascular lesion images were investigated, and volumetric changes were compared with healthy controls. Correlations were discussed between brain MRI results, OHCA data and the second neuropsychological assessment. Analyses of acute ischemic lesions did not reveal significant differences between the two subgroups (p = .35), and correlations with cognitive impairments could not be assessed. voxel-based morphometry analyses revealed a global cerebral volume reduction for the two subgroups and a clear decrease of the right thalamic volume for the deficit subgroup. It was associated with a cognitive dysexecutive syndrome represented by four executive indexes according to the 'Groupe de Réflexion pour l'Evaluation des Fonctions EXécutives' criteria. The right thalamus atrophy seems to be more predictive than the vascular lesions and more specific than a global cerebral volume reduction of post-OHCA neuropsychological executive disorders.
Assuntos
Disfunção Cognitiva , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/patologia , Estudos Prospectivos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Testes Neuropsicológicos , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagem , Tálamo/patologia , CogniçãoRESUMO
Contaminated water and food are the main sources of lead, cadmium, and mercury in the human body. Long-term and low-level ingestion of these toxic heavy metals may affect brain development and cognition. However, the neurotoxic effects of exposure to lead, cadmium, and mercury mixture (Pb + Cd + Hg) at different stages of brain development are rarely elucidated. In this study, different doses of low-level Pb + Cd + Hg were administered to Sprague-Dawley rats via drinking water during the critical stage of brain development, late stage, and after maturation, respectively. Our findings showed that Pb + Cd + Hg exposure decreased the density of memory- and learning-related dendritic spines in the hippocampus during the critical period of brain development, resulting in hippocampus-dependent spatial memory deficits. Only the density of learning-related dendritic spines was reduced during the late phase of brain development and a higher-dose of Pb + Cd + Hg exposure was required, which led to hippocampus-independent spatial memory abnormalities. Exposure to Pb + Cd + Hg after brain maturation revealed no significant change in dendritic spines or cognitive function. Further molecular analysis indicated that morphological and functional changes caused by Pb + Cd + Hg exposure during the critical phase were associated with PSD95 and GluA1 dysregulation. Collectively, the effects of Pb + Cd + Hg on cognition varied depending on the brain development stages.