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OBJECTIVE: Video-based eye tracking was used to investigate saccade, pupil, and blink abnormalities among patients with Huntington's disease (HD) who watched sequences of short videos. HD, an autosomal dominant neurodegenerative disorder resulting from a CAG mutation on chromosome 4, produces motor and cognitive impairments including slow or irregular eye movements, which have been studied using structured tasks. METHODS: To explore how HD affects eye movements under instruction free conditions, we assessed 22 HD patients and their age matched controls in a 10-minute video-based free viewing task. RESULTS: Patients with HD experienced a significant reduction in saccade exploration rate following video clip transitions, an increase in pupil reactions to luminance changes after clip transitions, and a significant higher blink rate throughout the task compared to the control group. CONCLUSIONS: These results show that HD has a significant impact on how patients visually explore and respond to their environment under unconstrained and ecologically natural conditions. SIGNIFICANCE: Eye tracking in HD patients revealed saccadic, pupil, and blink abnormalities in early HD patients, suggestive of brain circuitry abnormalities that probably involve brain stem deficits. Further research should explore the impact of these changes on the quality of life of the patients affected by the disease.
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Piscadela , Doença de Huntington , Pupila , Movimentos Sacádicos , Humanos , Movimentos Sacádicos/fisiologia , Doença de Huntington/fisiopatologia , Doença de Huntington/genética , Piscadela/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Pupila/fisiologia , Idoso , Estimulação Luminosa/métodos , Tecnologia de Rastreamento Ocular , Reflexo Pupilar/fisiologiaRESUMO
INTRODUCTION: The relationship between brain lesions and stroke outcomes is crucial for advancing patient prognosis and developing effective therapies. Stroke is a leading cause of disability worldwide, and it is important to understand the neurological basis of its varied symptomatology. Lesion-symptom mapping (LSM) methods provide a means to identify brain areas that are strongly associated with specific symptoms. However, inner variations in LSM methods can yield different results. To address this, our study aimed to characterize the lesion-symptom mapping variability using three different LSM methods. Specifically, we sought to determine a lesion symptom core across LSM approaches enhancing the robustness of the analysis and removing potential spatial bias. MATERIAL & METHODS: A cohort consisting of 35 patients with either right- or left-sided middle cerebral artery strokes were enrolled and evaluated using the NIHSS at 24 h post-stroke. Anatomical T1w MRI scans were also obtained 24 h post-stroke. Lesion masks were segmented manually and three distinctive LSM methods were implemented: ROI correlation-based, univariate, and multivariate approaches. RESULTS: The results of the LSM analyses showed substantial spatial differences in the extension of each of the three lesion maps. However, upon overlaying all three lesion-symptom maps, a consistent lesion core emerged, corresponding to the territory associated with elevated NIHSS scores. This finding not only enhances the spatial accuracy of the lesion map but also underscores its clinical relevance. CONCLUSION: This study underscores the significance of exploring complementary LSM approaches to investigate the association between brain lesions and stroke outcomes. By utilizing multiple methods, we can increase the robustness of our results, effectively addressing and neutralizing potential spatial bias introduced by each individual method. Such an approach holds promise for enhancing our understanding of stroke pathophysiology and optimizing patient care strategies.
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Mapeamento Encefálico , Acidente Vascular Cerebral , Humanos , Mapeamento Encefálico/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Encéfalo/patologia , Imageamento por Ressonância Magnética , Infarto da Artéria Cerebral MédiaRESUMO
Although mild cognitive impairment is a common non-motor symptom experienced by individuals with Parkinson's Disease, the changes in intrinsic resting-state networks associated with its onset in Parkinson's remain underexamined. To address the issue, our study sought to examine resting-state network alterations and their association with total performance in the Montreal Cognitive Assessment and its cognitive domains in Parkinson's by means of functional magnetic resonance imaging of 29 Parkinson's patients with normal cognition, 25 Parkinson's patients with mild cognitive impairment, and 13 healthy controls. To contrast the Parkinson's groups with each other and the controls, the images were used to estimate the Z-score coefficient between the regions of interest from the default mode network, the salience network and the central executive network. Our first finding was that default mode and salience network connectivity decreased significantly in Parkinson's patients regardless of their cognitive status. Additionally, default mode network nodes had a negative and salience network nodes a positive correlation with the global assessment in Parkinson's with normal cognition; this inverse relationship of both networks to total score was not found in the group with cognitive impairment. Finally, a positive correlation was found between executive scores and anterior and posterior cortical network connectivity and, in the group with cognitive impairment, between language scores and salience network connectivity. Our results suggest that specific resting-state networks of Parkinson's patients with cognitive impairment differ from those of Parkinson's patients with normal cognition, supporting the evidence that cognitive impairment in Parkinson's Disease displays a differentiated neurodegenerative pattern.
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Encéfalo , Disfunção Cognitiva , Imageamento por Ressonância Magnética , Testes de Estado Mental e Demência , Rede Nervosa , Doença de Parkinson , Descanso , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/diagnóstico por imagem , Masculino , Imageamento por Ressonância Magnética/métodos , Feminino , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Descanso/fisiologia , Idoso , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Função Executiva/fisiologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Mapeamento Encefálico/métodos , Cognição/fisiologiaRESUMO
BACKGROUND: Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset. METHODS: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity. RESULTS: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes (d>2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2. CONCLUSIONS: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.
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Imageamento por Ressonância Magnética , Ataxias Espinocerebelares , Humanos , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/patologia , Ataxias Espinocerebelares/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Genótipo , Idoso , Medula Espinal/patologia , Medula Espinal/diagnóstico por imagem , Medula Cervical/diagnóstico por imagem , Medula Cervical/patologia , Índice de Gravidade de Doença , Estudos de Casos e ControlesRESUMO
The aim of this study was to investigate how aging affects blood flow and structure of the brain. It was hypothesized older individuals would have lower gray matter volume (GMV), resting cerebral blood flow (CBF0), and depressed responses to isometabolic and neurometabolic stimuli. In addition, increased carotid-femoral pulse-wave velocity (PWV), carotid intima-media thickness (IMT), and decreased brachial flow-mediated dilation (FMD) would be associated with lower CBF0, cerebrovascular reactivity (CVR), and GMV. Brain scans (magnetic resonance imaging) and cardiovascular examinations were conducted in young (age = 24 ± 3 yr, range = 22-28 yr; n = 13) and old (age = 71 ± 4 yr; range = 67-82 yr, n = 14) participants, and CBF0, CVR [isometabolic % blood oxygen level-dependent (BOLD) in response to a breath hold (BH)], brain activation patterns during a working memory task (neurometabolic %BOLD response to N-back trial), GMV, PWV, IMT, and FMD were measured. CBF0 and to a lesser extent CVRBH were lower in the old group (P ≤ 0.050); however, the increase in the %BOLD response to the memory task was not blunted (P ≥ 0.2867). Age-related differential activation patterns during the working memory task were characterized by disinhibition of the default mode network in the old group (P < 0.0001). Linear regression analyses revealed PWV, and IMT were negatively correlated with CBF0, CVRBH, and GMV across age groups, but within the old group alone only the relationships between PWV-CVRBH and IMT-GMV remained significant (P ≤ 0.0183). These findings suggest the impacts of age on cerebral %BOLD responses are stimulus specific, brain aging involves alterations in cerebrovascular and possibly neurocognitive control, and arterial stiffening and wall thickening may serve a role in cerebrovascular aging.NEW & NOTEWORTHY Cerebral perfusion was lower in old versus young adults. %Blood oxygen level-dependent (BOLD) responses to an isometabolic stimulus and gray matter volume were decreased in old versus young adults and associated with arterial stiffening and wall thickening. The increased %BOLD response to a neurometabolic stimulus appeared unaffected by age; however, the old group displayed disinhibition of the default mode network during the stimulus. Thus, age-related alterations in cerebral %BOLD responses were stimulus specific and related to arterial remodeling.
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Espessura Intima-Media Carotídea , Imageamento por Ressonância Magnética , Adulto Jovem , Humanos , Adulto , Idoso , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologia , Envelhecimento , Circulação Cerebrovascular/fisiologia , AtrofiaRESUMO
BACKGROUND: COVID-19 is a disease known for its neurological involvement. SARS-CoV-2 infection triggers neuroinflammation, which could significantly contribute to the development of long-term neurological symptoms and structural alterations in the gray matter. However, the existence of a consistent pattern of cerebral atrophy remains uncertain. OBJECTIVE: Our study aimed to identify patterns of brain involvement in recovered COVID-19 patients and explore potential relationships with clinical variables during hospitalization. METHODOLOGY: In this study, we included 39 recovered patients and 39 controls from a pre-pandemic database to ensure their non-exposure to the virus. We obtained clinical data of the patients during hospitalization, and 3 months later; in addition we obtained T1-weighted magnetic resonance images and performed standard screening cognitive tests. RESULTS: We identified two groups of recovered patients based on a cluster analysis of the significant cortical thickness differences between patients and controls. Group 1 displayed significant cortical thickness differences in specific cerebral regions, while Group 2 exhibited significant differences in the cerebellum, though neither group showed cognitive deterioration at the group level. Notably, Group 1 showed a tendency of higher D-dimer values during hospitalization compared to Group 2, prior to p-value correction. CONCLUSION: This data-driven division into two groups based on the brain structural differences, and the possible link to D-dimer values may provide insights into the underlying mechanisms of SARS-COV-2 neurological disruption and its impact on the brain during and after recovery from the disease.
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COVID-19 , Humanos , COVID-19/complicações , COVID-19/patologia , SARS-CoV-2 , Encéfalo/diagnóstico por imagem , Cerebelo/patologia , Análise por ConglomeradosRESUMO
Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopaminergic neurons (DANs), and Non-human primates (NHPs) injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine develop some alterations observed in Parkinson's disease (PD) patients. Here, we obtained well-characterized DANs from hESCs and transplanted them into two parkinsonian monkeys to assess their behavioral and imaging changes. DANs from hESCs expressed dopaminergic markers, generated action potentials, and released dopamine (DA) in vitro. These neurons were transplanted bilaterally into the putamen of parkinsonian NHPs, and using magnetic resonance imaging techniques, we calculated the fractional anisotropy (FA) and mean diffusivity (MD), both employed for the first time for these purposes, to detect in vivo axonal and cellular density changes in the brain. Likewise, positron-emission tomography scans were performed to evaluate grafted DANs. Histological analyses identified grafted DANs, which were quantified stereologically. After grafting, animals showed signs of partially improved motor behavior in some of the HALLWAY motor tasks. Improvement in motor evaluations was inversely correlated with increases in bilateral FA. MD did not correlate with behavior but presented a negative correlation with FA. We also found higher 11C-DTBZ binding in positron-emission tomography scans associated with grafts. Higher DA levels measured by microdialysis after stimulation with a high-potassium solution or amphetamine were present in grafted animals after ten months, which has not been previously reported. Postmortem analysis of NHP brains showed that transplanted DANs survived in the putamen long-term, without developing tumors, in immunosuppressed animals. Although these results need to be confirmed with larger groups of NHPs, our molecular, behavioral, biochemical, and imaging findings support the integration and survival of human DANs in this pre-clinical PD model.
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Células-Tronco Embrionárias Humanas , Doença de Parkinson , Animais , Humanos , Neurônios Dopaminérgicos/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Haplorrinos/metabolismo , Mesencéfalo/metabolismo , Dopamina/metabolismo , Doença de Parkinson/terapia , Doença de Parkinson/metabolismoRESUMO
INTRODUCTION: The aim of this prospective descriptive study was to analyse the possible variables associated with marginal bone loss in rehabilitated implants (Proclinic S.A.U, Zaragoza, Spain) two years after their prosthetic loading. MATERIALS AND METHODS: Three clinical centres collaborated for a period of two years after the prosthetic rehabilitation of the implants (Proclinic S.A.U, Zaragoza, Spain), in which marginal bone loss and the possible associated variables were evaluated. The collection form comprised different variables throughout different stages of the implant procedure, from implant insertion to the subsequent prosthetic rehabilitation, over a two-year period. Data of the patients and implant characteristics were studied. Statistical analysis was performed with SPSS for qualitative (univariate logistic regressions, Chi2 test, and Haberman's corrected standardised residuals) and quantitative variables (Kolmogorov-Smirnov test). RESULTS: The total study sample consisted of 218 implants (Proclinic S.A.U, Zaragoza, Spain). The sample presented a frequency of 99 men (45.4%) and 119 women (54.6%). The mean age of the patients among the reported cases was 58.56 ± 10.12 years. A statistically significant association was found between marginal bone loss 2 years after prosthetic rehabilitation placement and several variables, including age (under 55 years, 0.25 mm ± 0.56; 55-64 years, 0.74 mm ± 0.57; over 65 years, 0.63 mm ± 0.55; p < 0.0001), gender (female, 0.74 mm ± 0.61; male, 0.34 mm ± 0.51; p < 0.0001), bone quality (D1, 0.75 mm ± 0.62; D2, 0.43 mm ± 0.57; D3, 0.65 mm ± 0.60; p < 0.01), implant diameter (up to 4 mm, 0.49 mm ± 0.58; more than 4 mm, 1.21 mm ± 0.30; p < 0.0001), prosthetic connection type (direct to implant, 0.11 mm ± 0.58; transepithelial straight, 0.67 mm ± 0.57; transepithelial angled, 0.33 mm ± 0.25; p < 0001), implant model (internal conical, 0.17 mm ± 0.24; external conical, 0.48 mm ± 0.61; external cylindrical, 1.12 mm ± 0.32; p < 0.0001), prosthetic restoration type (full denture, 0.59 mm ± 0.59; partial denture, 0.50 mm ± 0.85; unitary crown, 0.08 mm ± 0.19; p < 0.05), and insertion torque (>35 N/cm, 0.53 mm ± 0.58; <35 N/cm, 1.04 mm ± 0.63; p < 0.01). CONCLUSIONS: At 2 years, marginal bone loss following prosthetic rehabilitation was shown to be influenced by multiple factors. Correct implantological planning is of vital importance for successful rehabilitation.
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Little is known about access of rare disease carriers to health care. To increase this knowledge, the Pan American Hereditary Ataxia Network (PAHAN) conducted an exploratory survey about care for hereditary ataxias in American continents and the Caribbean. A questionnaire was sent to health professionals about the hereditary ataxias identified; access to care; and local teaching and research. The number of ataxics under current care per 100,000 inhabitants was subtracted from the expected overall prevalence of 6/100,000, to estimate the prevalence of uncovered ataxic patients. Local Human Development Indexes (HDI) were used to measure socio-economic factors. Twenty-six sites participated. Twelve sites had very high, 13 had high, and one site had medium HDI. Participants reported on 2239 and 602 patients with spinocerebellar ataxias and recessive forms under current care. The number of patients under current care per inhabitants varied between 0.14 and 12/100,000. The estimated prevalence of uncovered ataxic patients was inversely proportional to HDIs (rho = 0.665, p = 0.003). Access to diagnosis, pre-symptomatic tests, and rehabilitation were associated with HDIs. More and better molecular diagnostic tools, protocols and guidelines, and professional training for ataxia care were the top priorities common to all respondents. Evidence of inequalities was confirmed. Lower HDIs were associated with high potential numbers of uncovered ataxic subjects, and with lack of molecular diagnosis, pre-symptomatic testing, and rehabilitation. More and better diagnostic tools, guidelines, and professional training were priorities to all sites. PAHAN consortium might help with the last two tasks.
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Ataxia Cerebelar , Ataxias Espinocerebelares , Degenerações Espinocerebelares , Humanos , Ataxia , Degenerações Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Região do Caribe/epidemiologiaRESUMO
Mammalian respiratory rhythm-generating circuits in the brainstem are subject to neuromodulation by multiple peptidergic afferent inputs controlling circuit behavior and outputs. Although functionally important, actions of neuropeptide modulators have not been fully characterized. We analyzed at cellular and circuit levels two inspiratory patterns intrinsically generated by the preBötzinger complex (preBötC) and their modulation by the neuropeptides bombesin and substance P (SP) in neonatal rat medullary slices in vitro. We found that, in recordings of hypoglossal nerve and preBötC neuron inspiratory activity, some inspiratory bursts occurring spontaneously under basal conditions have a biphasic shape with longer duration than normal inspiratory bursts and occur at a lower frequency. This biphasic burst pattern has been proposed to represent inspiratory activity underling periodic sighs. Bath-applied bombesin or SP decreased the period and increased the duration of both normal inspiratory and biphasic bursts and their underlying synaptic drives. The ratio of the biphasic long-duration burst period to the normal inspiratory burst period and the ratio of their burst durations remained the same before and after peptidergic modulation. Bombesin increased the frequency of the inspiratory rhythm in a Ca2+-independent manner and the frequency of long-duration bursts in a Ca2+-dependent manner. This finding suggests that period and burst duration coupling are due to intrinsic mechanisms controlling simultaneously timing and burst termination within the inspiratory rhythm-generating network. We propose a model in which signaling cascades activated by bombesin and SP modulate mechanisms controlling inspiratory burst frequency and duration to coordinate preBötC circuit behavioral outputs.
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Bombesina , Mecânica Respiratória , Ratos , Animais , Animais Recém-Nascidos , Bombesina/farmacologia , Ratos Sprague-Dawley , Mecânica Respiratória/fisiologia , Bulbo/fisiologia , MamíferosRESUMO
Stroke is a devastating disease that results in neurological deficits and represents a leading cause of death and disability worldwide. Following a stroke, there is a degree of spontaneous recovery of function, the neural basis of which is of great interest among clinicians in their efforts to reduce disability following stroke and enhance rehabilitation. Conventionally, work on spontaneous recovery has tended to focus on the neural reorganization of motor cortical regions, with comparably little attention being paid to changes in non-motor regions and how these relate to recovery. Here we show, using structural neuroimaging in a macaque stroke model (N = 31) and by exploiting individual differences in spontaneous behavioural recovery, that the preservation of regions in the parietal and temporal cortices predict animal recovery. To characterize recovery, we performed a clustering analysis using Non-Human Primate Stroke Scale (NHPSS) scores and identified a good versus poor recovery group. By comparing the preservation of brain volumes in the two groups, we found that brain areas in integrity of brain areas in parietal, temporal and somatosensory cortex were associated with better recovery. In addition, a decoding approach performed across all subjects revealed that the preservation of specific brain regions in the parietal, somatosensory and medial frontal cortex predicted recovery. Together, these findings highlight the importance of parietal and temporal regions in spontaneous behavioural recovery.
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Spinocerebellar ataxia type 10 (SCA10) is an autosomal-dominant disorder caused by an expanded pentanucleotide repeat in the ATXN10 gene. This repeat expansion, when fully penetrant, has a size of 850-4,500 repeats. It has been shown that the repeat composition can be a modifier of disease, e.g., seizures. Here, we describe a Mexican kindred in which we identified both pure (ATTCT)n and mixed (ATTCT)n-(ATTCC)n expansions in the same family. We used amplification-free targeted sequencing and optical genome mapping to decipher the composition of these repeat expansions. We found a considerable degree of mosaicism of the repeat expansion. This mosaicism was confirmed in skin fibroblasts from individuals with ATXN10 expansions with RNAScope in situ hybridization. All affected family members with the mixed ATXN10 repeat expansion showed typical clinical signs of spinocerebellar ataxia and epilepsy. In contrast, individuals with the pure ATXN10 expansion present with Parkinson's disease or are unaffected, even in individuals more than 20 years older than the average age at onset for SCA10. Our findings suggest that the pure (ATTCT)n expansion is non-pathogenic, while repeat interruptions, e.g., (ATTCC)n, are necessary to cause SCA10. This mechanism has been recently described for several other repeat expansions including SCA31 (BEAN1), SCA37 (DAB1), and three loci for benign adult familial myoclonic epilepsy BAFME (SAMD12, TNRC6A, RAPGEF2). Therefore, long-read sequencing and optical genome mapping of the entire genomic structure of repeat expansions are critical for clinical practice and genetic counseling, as variations in the repeat can affect disease penetrance, symptoms, and disease trajectory.
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BACKGROUND: Recent resting-state functional magnetic resonance imaging studies have reported abnormal functional connectivity (FC) in the prefrontal cortex (PFC)-striatum circuit in patients with premanifest Huntington's disease (HD). However, there is a lack of evidence showing persistence of abnormal frontostriatal FC and its relation to cognitive flexibility performance in patients with clinically manifest HD. OBJECTIVE: The aim of this study was to evaluate the resting-state FC integrity of the frontostriatal circuit and its relation to cognitive flexibility in HD patients and healthy controls (HCs). METHOD: Eighteen patients with early clinical HD manifestation and 18 HCs matched for age, sex, and education participated in this study. Both groups performed the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional (IED) set-shift task, which measures cognitive flexibility. Resting-state functional magnetic resonance images were also acquired to examine the FC in specific frontostriatal circuits. Eight regions of interest were preselected based on regions previously associated with extradimensional (ED) shifting in patients with premanifest HD. RESULTS: Significant negative correlations between the number of attentional set-shifting errors and the ventral striatum-ventrolateral PFC FC were found in the HD group. This group also showed negative FC correlations between the total errors and the FC between right ventral striatum-right ventrolateral PFC, left ventral striatum-left ventrolateral PFC, and right ventral striatum-left ventrolateral PFC. Negative correlations between the ED errors and left ventral striatum-left ventrolateral PFC and right ventral striatum-right ventrolateral PFC FC were also found. Finally, a positive correlation between the number of stages completed and left ventral striatum-left ventrolateral PFC FC was found. CONCLUSIONS: Manifest HD patients show significant cognitive flexibility deficits in attentional set-shifting that are associated with FC alterations in the frontostriatal circuit. These results show that FC abnormalities found in the prodromal stage of the disease can also be associated with cognitive flexibility deficits at a later clinical stage, making them good candidates to be explored in longitudinal studies.
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Transtornos Cognitivos , Doença de Huntington , Humanos , Doença de Huntington/complicações , Doença de Huntington/diagnóstico por imagem , Doença de Huntington/patologia , Vias Neurais/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cognição , Mapeamento EncefálicoRESUMO
Huntington's Disease (HD) is an autosomal neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. Cognitive impairment develops gradually in HD patients, progressing later into a severe cognitive dysfunction. The Montreal Cognitive Assessment (MoCA) is a brief screening test commonly employed to detect mild cognitive impairment, which has also been useful to assess cognitive decline in HD patients. However, the relationship between MoCA performance and brain structural integrity in HD patients remains unclear. Therefore, to explore this relationship we analyzed if cortical thinning and subcortical nuclei volume differences correlated with HD patients' MoCA performance. Twenty-two HD patients and twenty-two healthy subjects participated in this study. T1-weighted images were acquired to analyze cortical thickness and subcortical nuclei volumes. Group comparison analysis showed a significantly lower score in the MoCA global performance of HD patients. Also, the MoCA total score correlated with cortical thinning of fronto-parietal and temporo-occipital cortices, as well as with bilateral caudate volume differences in HD patients. These results provide new insights into the effectiveness of using the MoCA test to detect cognitive impairment and the brain atrophy pattern associated with the cognitive status of prodromal/early HD patients.
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Doença de Huntington , Doenças Neurodegenerativas , Humanos , Doença de Huntington/complicações , Doenças Neurodegenerativas/complicações , Afinamento Cortical Cerebral , Testes de Estado Mental e Demência , Atrofia/complicaçõesRESUMO
BACKGROUND: A high proportion of coronavirus disease 2019 (COVID-19) survivors may develop long-term cognitive impairment. We aimed to develop a multivariate causal model exposing the links between COVID-19-associated biomarkers, illness-related variables, and their effects on cognitive performance. METHODS: In this prospective study, we assess the potential drivers for the development of cognitive impairment in patients with severe COVID-19 pneumonia aged ≥ 18 years at 6-month follow-up after hospital discharge, using the Montreal Cognitive Assessment (MoCA). Patients with pre-existing cognitive impairment were excluded. Laboratory results at hospital admission were clustered by principal component analysis (PCA) and included in a path analysis model evaluating the causal relationship between age, comorbidities, hypoxemia, invasive mechanical ventilation (IMV) requirement, in-hospital delirium, and cognitive performance. RESULTS: We studied 92 patients: 54 (58.7%) men and 38 (41.3%) women, with median age of 50 years (interquartile range 42-55), among whom 50 (54.4%) tested positive for cognitive impairment at 6-month follow-up. Path analysis revealed a direct link between the thrombo-inflammatory component of PCA (C-reactive protein, fibrinogen, and neutrophils) and hypoxemia severity at hospital admission. Our model showed that low PaO2/FiO2 ratio values, unlike the thrombo-inflammatory component, had a direct effect on cognitive performance, independent from age, in-hospital delirium, and invasive mechanical ventilation. CONCLUSION: In this study, biomarkers of thrombo-inflammation in COVID-19 and low PaO2/FiO2 had a negative effect on cognitive performance 6 months after hospital discharge. These results highlight the critical role of hypoxemia as a driver for impaired cognition in the mid-term.
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COVID-19 , Disfunção Cognitiva , Adolescente , COVID-19/complicações , Disfunção Cognitiva/etiologia , Feminino , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial , SARS-CoV-2RESUMO
The cerebellar cognitive affective syndrome (CCAS) has been consistently described in patients with acute/subacute cerebellar injuries. However, studies with chronic patients have had controversial findings that have not been explored with new cerebellar-target tests, such as the CCAS scale (CCAS-S). The objective of this research is to prove and contrast the usefulness of the CCAS-S and the Montreal Cognitive Assessment (MoCA) test to evaluate cognitive/affective impairments in patients with chronic acquired cerebellar lesions, and to map the cerebellar areas whose lesions correlated with dysfunctions in these tests. CCAS-S and MoCA were administrated to 22 patients with isolated chronic cerebellar strokes and a matched comparison group. The neural bases underpinning both tests were explored with multivariate lesion-symptom mapping (LSM) methods. MoCA and CCAS-S had an adequate test performance with efficient discrimination between patients and healthy volunteers. However, only impairments determined by the CCAS-S resulted in significant regional localization within the cerebellum. Specifically, patients with chronic cerebellar lesions in right-lateralized posterolateral regions manifested cognitive impairments inherent to CCAS. These findings concurred with the anterior-sensorimotor/posterior-cognitive dichotomy in the human cerebellum and revealed clinically intra- and cross-lobular significant regions (portions of right lobule VI, VII, Crus I-II) for verbal tasks that overlap with the "language" functional boundaries in the cerebellum. Our findings prove the usefulness of MoCA and CCAS-S to reveal cognitive impairments in patients with chronic acquired cerebellar lesions. This study extends the understanding of long-term CCAS and introduces multivariate LSM methods to identify clinically intra- and cross-lobular significant regions underpinning chronic CCAS.
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Doenças Cerebelares , Transtornos Cognitivos , Acidente Vascular Cerebral , Cerebelo , Cognição , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Humanos , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Spinocerebellar ataxia type 10 is a neurodegenerative disorder caused by the expansion of an ATTCT pentanucleotide repeat. Its clinical features include ataxia and, in some cases, epileptic seizures. There is, however, a dearth of information about its cognitive deficits and the neural bases underpinning them. OBJECTIVES: The objectives of this study were to characterize the performance of spinocerebellar ataxia type 10 patients in 2 cognitive domains typically affected in spinocerebellar ataxias, memory and executive function, and to correlate the identified cognitive impairments with ataxia severity and cerebral/cerebellar cortical thickness, as quantified by MRI. METHODS: Memory and executive function tests were administered to 17 genetically confirmed Mexican spinocerebellar ataxia type 10 patients, and their results were compared with 17 healthy matched volunteers. MRI was performed in 16 patients. RESULTS: Patients showed deficits in visual and visuospatial short-term memory, reduced storage capacity for verbal memory, and impaired monitoring, planning, and cognitive flexibility, which were ataxia independent. Patients with seizures (n = 9) and without seizures (n = 8) did not differ significantly in cognitive performance. There were significant correlations between short-term visuospatial memory impairment and posterior cerebellar lobe cortical thickness (bilateral lobule VI, IX, and right X). Cognitive flexibility deficiencies correlated with cerebral cortical thickness in the left middle frontal, cingulate, opercular, and temporal gyri. Cerebellar cortical thickness in several bilateral regions was correlated with motor impairment. CONCLUSIONS: Patients with spinocerebellar ataxia type 10 show significant memory and executive dysfunction that can be correlated with deterioration in the posterior lobe of the cerebellum and prefrontal, cingulate, and middle temporal cortices. © 2021 International Parkinson and Movement Disorder Society.
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Disfunção Cognitiva , Ataxias Espinocerebelares , Cerebelo , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Humanos , Imageamento por Ressonância Magnética , Memória de Curto Prazo , Testes Neuropsicológicos , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genéticaRESUMO
Purpose: No published research has compared patients' quality of life and satisfaction with fixed prostheses supported by zygomatic implants with those supported by all-on-four prostheses. The aim of this study was to evaluate patients' quality of life and satisfaction with fixed prostheses on zygomatic implants compared with the all-on-four concept. Materials and Methods: A total of 80 patients with atrophic edentulous maxillae were randomized into two groups: Group 1 (rehabilitated with fixed prostheses supported by 2-4 zygomatic and 2-4 conventional implants in the anterior region) and Group 2 (fixed prostheses on four implants in the anterior region following an all-on-four concept). One year after placement of the definitive prostheses, patients completed OHIP-14 and satisfaction questionnaires. Results: In all seven domains of the OHIP-14 and in the overall scores, a worse quality of life was found in Group 2 patients, with statistically significant differences between the two groups (p ≤ 0.05). Patients with zygomatic implants were more satisfied with their prostheses, with a statistically significant difference (p < 0.001). Conclusions: According to the results of this study, rehabilitation of patients with edentulous atrophic maxillae with prostheses supported by zygomatic implants combined with anterior implants provided better patient quality of life and satisfaction than prostheses supported by four implants.
Assuntos
Satisfação Pessoal , Qualidade de Vida , Seguimentos , Humanos , Satisfação do Paciente , Estudos Prospectivos , Resultado do Tratamento , Zigoma/cirurgiaRESUMO
INTRODUCTION: Early Huntington's disease (HD) patients begin to show planning deficits even before motor alterations start to manifest. Generally, planning ability is associated with the functioning of anterior brain areas such as the medial prefrontal cortex. However, early HD neuropathology involves significant atrophy in the occipital and parietal cortex, suggesting that more posterior regions could also be involved in these planning deficits. OBJECTIVE: To identify brain regions associated with planning deficits in HD patients at an early clinical stage. MATERIALS AND METHODS: Twenty-two HD-subjects genetically confirmed with incipient clinical manifestation and twenty healthy subjects were recruited. All participants underwent MRI T1 image acquisition as well as testing in the Stockings of Cambridge (SOC) task to measure planning ability. First, group comparison of SOC measures were performed. Then, correlation voxel-based morphometry analyses were done between gray matter degeneration and SOC performance in the HD group. RESULTS: Accuracy and efficiency planning scores correlated with gray matter density in right lingual gyrus, middle temporal gyrus, anterior cingulate gyrus, and paracingulate gyrus. CONCLUSIONS: Our results suggest that planning deficits exhibited by early HD-subjects are related to occipital and temporal cortical degeneration in addition to the frontal areas deterioration.