Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
1.
Brain ; 147(7): 2357-2367, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38227807

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease (MND) that shares a common clinical, genetic and pathologic spectrum with frontotemporal dementia (FTD). It is highly heterogeneous in its presentation and features. Up to 50% of patients with MND develop cognitive-behavioural symptoms during the course of the disease, meeting criteria for FTD in 10%-15% of cases. In the absence of a precise biomarker, neuropathology is still a valuable tool to understand disease nosology, reach a definite diagnostic confirmation and help define specific subgroups of patients with common phenotypic, genetic and biomarker profiles. However, few neuropathological series have been published, and the frequency of frontotemporal lobar degeneration (FTLD) in MND is difficult to estimate. In this work we describe a large clinicopathological series of MND patients, analysing the frequency of concurrent FTLD changes and trying to define specific subgroups of patients based on their clinical, genetic and pathological characteristics. We performed an observational, retrospective, multicentre case study. We included all cases meeting neuropathological criteria for MND from the Neurological Tissue Bank of the FRCB-IDIBAPS-Hospital Clínic Barcelona Biobank between 1994 and 2022, regardless of their last clinical diagnosis. While brain donation is encouraged in all patients, it is performed in very few, and representativeness of the cohort might not be precise for all patients with MND. We retrospectively reviewed clinical and neuropathological data and describe the main clinical, genetic and pathogenic features, comparing neuropathologic groups between MND with and without FTLD changes and aiming to define specific subgroups. We included brain samples from 124 patients, 44 of whom (35.5%) had FTLD neuropathologic features (i.e. FTLD-MND). Pathologic TDP-43 aggregates were present in 93.6% of the cohort and were more extensive (higher Brettschneider stage) in those with concurrent FTLD (P < 0.001). Motor symptom onset was more frequent in the bulbar region in FTLD-MND cases than in those with isolated MND (P = 0.023), with no differences in survival. We observed a better clinicopathological correlation in the MND group than in the FTLD-MND group (93.8% versus 61.4%; P < 0.001). Pathogenic genetic variants were more common in the FTLD-MND group, especially C9orf72. We describe a frequency of FTLD of 35.5% in our series of neuropathologically confirmed cases of MND. The FTLD-MND spectrum is highly heterogeneous in all aspects, especially in patients with FTLD, in whom it is particularly difficult to define specific subgroups. In the absence of definite biomarkers, neuropathology remains a valuable tool for a definite diagnosis, increasing our knowledge in disease nosology.


Assuntos
Degeneração Lobar Frontotemporal , Doença dos Neurônios Motores , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Degeneração Lobar Frontotemporal/patologia , Degeneração Lobar Frontotemporal/genética , Estudos Retrospectivos , Doença dos Neurônios Motores/patologia , Doença dos Neurônios Motores/genética , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/genética , Demência Frontotemporal/patologia , Demência Frontotemporal/genética , Encéfalo/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo
2.
Eur J Neurol ; 28(9): 3040-3050, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34096670

RESUMO

OBJECTIVE: To characterize ocular motor function in patients with Niemann-Pick disease type C (NPC). METHODS: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from 12 countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Our study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls (HC). RESULTS: Some 98.2% of patients generated vertical saccades below the 95% CI of the controls' peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% CI of HC. The involvement in both downward and upward directions was similar (51°/s (68.9, [32.7-69.3]) downward versus 78.8°/s (65.9, [60.8-96.8]) upward). Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit correlated best to disease severity. Compensating strategies such as blinks to elicit saccades, and head and upper body movements to overcome the gaze palsy, were observed. Vertical reflexive saccades were more impaired and slower than self-paced ones. Gaze-holding was normal. Ocular-motor performance depended on the age of onset and disease duration. CONCLUSIONS: This is the largest cohort of NPC patients investigated for ocular-motor function. Vertical supranuclear saccade palsy is the hallmark of NPC. Vertical upward and downward saccades are equally impaired. Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials. Compensating strategies can contribute to establishing a diagnosis.


Assuntos
Doença de Niemann-Pick Tipo C , Estudos Transversais , Movimentos Oculares , Humanos , Estudos Prospectivos , Movimentos Sacádicos
3.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450872

RESUMO

Lewy body diseases (LBD) including dementia with Lewy bodies (DLB) and Parkinson disease (PD) are characterized by alpha-synuclein pathology. DLB is difficult to diagnose and peripheral biomarkers are urgently needed. Therefore, we analyzed the expression of five alpha-synuclein gene (SNCA) transcripts, SNCAtv1, SNCAtv2, SNCAtv3, SNCA126, and SNCA112, in 45 LBD and control temporal cortex samples and in the blood of 72 DLB, 59 PD, and 54 control subjects. The results revealed overexpression of SNCAtv1 and SNCA112 in DLB, and SNCAtv2 in PD temporal cortices. In DLB blood, diminution of all SNCA transcripts was observed. SNCAtv1 and SNCAtv2 were diminished in PD with disease onset before 70 years. SNCAtv3, driven by its own promoter, showed opposite expression in early DLB and PD, suggesting that its amount may be an early, DLB specific biomarker. Correlation between blood transcript levels and disease duration was positive in DLB and negative in PD, possibly reflecting differences in brain alpha-synuclein aggregation rates associated with differences in disease courses. In conclusion, SNCA transcripts showed a disease-specific increase in the brain and were diminished in blood of LBD patients. SNCAtv3 expression was decreased in early DLB and increased in early PD and could be a biomarker for early DLB diagnosis.


Assuntos
Demência/diagnóstico , Demência/etiologia , Expressão Gênica , Corpos de Lewy/genética , Doença de Parkinson/complicações , alfa-Sinucleína/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Encéfalo/metabolismo , Encéfalo/patologia , Demência/metabolismo , Progressão da Doença , Feminino , Humanos , Corpos de Lewy/metabolismo , Corpos de Lewy/patologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , alfa-Sinucleína/metabolismo
4.
Int J Geriatr Psychiatry ; 32(12): e72-e82, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28111798

RESUMO

OBJECTIVES: The aims of the study were to identify the clinical characteristics of three groups of caregivers: spouses, live-in adult-child or non-live-in adult-child, and their relation to the degree of perceived burden (Caregiver Burden Interview). METHODS: The sample comprised 275 Alzheimer's disease primary caregivers, with a follow-up of 24 months. Cognitive, functional and behavioural characteristics were evaluated in persons with dementia, whilst sociodemographic data, use of socio-medical resources, physical and mental health and self-perceived burden were assessed in caregivers. Generalized estimating equations were used for longitudinal data analysis. RESULTS: Spouse caregivers were 45.0% men, sole caregivers (>80%), used few external resources and had worse physical health. The number of female adult-child caregivers was higher (>75%). The live-in adult-child group, compared with the non-live-in adult-child group, was less likely to be married, had a lower level of education, was more commonly the sole caregiver and used fewer external resources. The greatest burden was observed in live-in adult-child caregivers, and the lowest in the non-live-in adult-child group, with no significant variation in the follow-up for both groups. Spouses had an intermediate level of perceived burden, which rose significantly during follow-up (p < 0.001). CONCLUSIONS: Kinship and cohabitation with the persons with dementia were associated with different scores and evolution of the burden, with an increase in the follow-up of the spouses, and with more or less burden, depending on cohabitation, in the adult-child groups. Interventions to reduce the level of burden on caregivers should consider these differences. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Doença de Alzheimer/enfermagem , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Família , Adaptação Psicológica , Adulto , Idoso , Doença de Alzheimer/psicologia , Família/psicologia , Características da Família , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Características de Residência , Cônjuges/psicologia
5.
Mov Disord ; 31(7): 1066-70, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27027900

RESUMO

BACKGROUND: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by similar pathological features. Several studies have shown a relation between alterations in the glucocerebrosidase gene (GBA) and the development of LB diseases. Here, we explored the role of GBA mutations in Spanish DLB patients. METHODS: GBA mRNA sequences were analyzed in a neuropathological (50 DLB, 43 PD, and 34 control brains) and in a clinical cohort (47 DLB patients and 131 unaffected individuals). RESULTS: Sixteen GBA mutation carriers were identified, 5 of which were brains with pure DLB. The most common mutation, E326K, was strongly associated with pure DLB and PD with dementia. GBA mutations were overrepresented in men and associated with earlier DLB onset. CONCLUSIONS: GBA mutations are also an important risk factor for DLB development in the Spanish population, are associated with earlier disease onset, and are more prevalent in men. © 2015 International Parkinson and Movement Disorder Society.


Assuntos
Glucosilceramidase/genética , Doença por Corpos de Lewy/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Espanha
6.
Int J Geriatr Psychiatry ; 31(2): 109-19, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25963296

RESUMO

OBJECTIVES: Neuropsychiatric symptoms and anosognosia are known to influence the perceived quality of life of patients (QoL-p) with Alzheimer's disease (AD). This study analysed their impact on patient and caregiver ratings of QoL-p and how these ratings changed in relation to the severity of dementia. METHODS: A baseline sample of 221 patients and caregivers was followed up over 24 months. Instruments: Neuropsychiatric Inventory (NPI), Anosognosia Questionnaire-Dementia (AQ-D), Quality of life-Alzheimer's Disease (QoL-AD) and the Global Deterioration Scale (GDS). Longitudinal data were analysed using generalized linear models. RESULTS: In the multivariate analysis, greater anosognosia was always associated with higher ratings of QoL-p among patients, especially at 24 months (p < 0.001), and with more negative ratings among caregivers, especially at baseline (p < 0.001). A higher total NPI score was associated with a more negative rating of QoL-p among caregivers (p < 0.001), and it also had a smaller negative effect on patients' self-ratings (p = 0.001). The neuropsychiatric symptoms (NPI) associated with a more negative view of QoL-p were depression, for patients' self-ratings, and apathy and agitation for caregiver ratings. The discrepancy between patient and caregiver ratings increased in line with the severity of dementia. CONCLUSION: Neuropsychiatric symptoms had a similarly negative effect on the QoL-p ratings of both patients and caregivers, whereas the effect of anosognosia differed according to the rater (positive for patients, negative for caregivers).


Assuntos
Agnosia/psicologia , Doença de Alzheimer/psicologia , Transtorno Depressivo/psicologia , Agitação Psicomotora/psicologia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Apatia , Cuidadores/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Inquéritos e Questionários
7.
Am J Geriatr Psychiatry ; 22(2): 138-47, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23567444

RESUMO

OBJECTIVE: To investigate the factors associated with discrepancies between patient and caregiver reports of the quality of life of patients (QoLp) with Alzheimer disease. METHODS: Cross-sectional analytic study of 141 patients and their caregivers. The instruments used were the Quality of Life in AD, the Global Deterioration Scale (GDS), the Geriatric Depression Scale, and the Anosognosia Questionnaire-Dementia. Differences were analyzed according to GDS stage. A linear regression analysis was conducted using the difference between the absolute QoLp scores of patients and caregivers. A cluster analysis involving patient variables was then performed. RESULTS: The discrepancy between patient and caregiver QoLp ratings increased in line with GDS stages (χ(2) (2) = 8.7, p = 0.013). In the regression model (F [7,133] = 16.6, p <0.001; R(2) = 0.477), discrepancies in QoLp reports were associated with greater anosognosia, less depression, and a better cognitive status in patients and with female gender among caregivers. The cluster analysis showed that patients with the lowest ratings of QoLp had a better cognitive status, more depression, and less anosognosia. Conversely, the highest ratings were given by patients with a poorer cognitive status, less depression, and greater anosognosia. CONCLUSIONS: The factors associated with greater discrepancies between patient and caregiver ratings of QoLp were severity of dementia, anosognosia, depression, and cognitive status in patients and female gender in caregivers. In patients with advanced dementia, greater anosognosia leads to more positive ratings in QoLp and complementary observations are required.


Assuntos
Agnosia/diagnóstico , Doença de Alzheimer/psicologia , Cuidadores , Efeitos Psicossociais da Doença , Depressão/diagnóstico , Qualidade de Vida/psicologia , Avaliação de Sintomas , Idoso , Idoso de 80 Anos ou mais , Agnosia/complicações , Doença de Alzheimer/complicações , Doença de Alzheimer/enfermagem , Cuidadores/psicologia , Análise por Conglomerados , Estudos Transversais , Depressão/complicações , Feminino , Nível de Saúde , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índice de Gravidade de Doença , Fatores Sexuais
8.
Artigo em Inglês | MEDLINE | ID: mdl-38992346

RESUMO

INTRODUCTION: The neural mechanisms underlying neurodegenerative disorders in the elderly remain elusive, despite extensive neuroimaging research in recent decades. Amnestic type mild cognitive impairment (aMCI) and late-life major depressive disorder (MDD) are two such conditions characterized by intersecting cognitive and affective symptomatology, and they are at a higher risk for Alzheimer's disease. MATERIALS AND METHODS: This study analyzed the neural underpinnings of cognitive and depressive symptoms in a cohort comprising 12 aMCI subjects, 24 late-life MDD patients, and 26 healthy controls (HCs). Participants underwent a detailed neuropsychological assessment and completed a visual attentional oddball task during functional magnetic resonance imaging (fMRI), with evaluations at baseline and at 2-year follow-up. RESULTS: Initial findings showed that aMCI subjects had reduced dACC activation during oddball (target) stimulus detection, a pattern that persisted in longitudinal analyses and correlated with cognitive functioning measures. For HCs, subsequent dACC activation was linked to depression scores. Furthermore, in the affective-cognitive altered groups, later dACC activation correlated with oddball and memory performance. CONCLUSIONS: These findings enhance our comprehension of the neurobiological basis of cognitive and depressive disturbances in aging, indicating that dACC activation in response to a visual attentional oddball task could serve as a neural marker for assessing cognitive impairment and depression in conditions predisposing to Alzheimer's disease.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38453029

RESUMO

INTRODUCTION: We compared effective connectivity from the locus coeruleus (LC) during the resting-state in patients with late-life Major Depressive Disorder (MDD), individuals with amnestic Mild Cognitive Impairment (aMCI), and Healthy Controls (HCs). PARTICIPANTS: 23 patients with late-life MDD, 22 patients with aMCI, and 28 HCs. MATERIAL AND METHODS: Participants were assessed in two time-points, 2 years apart. They underwent a resting-state functional magnetic resonance imaging and a high-resolution anatomical acquisition, as well as clinical assessments. Functional imaging data were analyzed with dynamic causal modeling, and parametric empirical Bayes model was used to map effective connectivity between 7 distinct nodes: 4 from the locus coeruleus and 3 regions displaying gray matter decreases during the two-year follow-up period. RESULTS: Longitudinal analysis of structural data identified three clusters of larger over-time gray matter volume reduction in patients (MDD+aMCI vs. HCs): the right precuneus, and the visual association and parahippocampal cortices. aMCI patients showed decreased effective connectivity from the left rostral to caudal portions of the LC, while connectivity from the left rostral LC to the parahippocampal cortex increased. In MDD, there was a decline in effective connectivity across LC caudal seeds, and increased connectivity from the left rostral to the left caudal LC seed over time. Connectivity alterations with cortical regions involved cross-hemisphere increases and same-hemisphere decreases. CONCLUSIONS: Our discoveries provide insight into the dynamic changes in effective connectivity in individuals with late-life MDD and aMCI, also shedding light on the mechanisms potentially contributing to the onset of neurodegenerative disorders.

10.
J Geriatr Psychiatry Neurol ; 26(2): 86-94, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23514974

RESUMO

BACKGROUND: Several studies have identified certain caregiver factors that can produce variability in their assessments of the capacities of patients with Alzheimer disease (AD). OBJECTIVES: To identify the caregiver variables associated with variability in their ratings of patients' capacities. METHODS: Consecutive sample of 221 outpatients with AD and their family caregivers. The capacities evaluated by caregivers were the degree of functional disability, using the Disability Assessment for Dementia (DAD); psychological and behavioral symptoms, via the Neuropsychiatric Inventory (NPI); anosognosia, with the Anosognosia Questionnaire-Dementia (AQ-D); and quality of life, using the Quality of Life in AD (QOL-AD). The relationship between these measures and caregiver's gender, burden, depression, and health was analyzed by means of a bivariate analysis, calculating the effect size (Cohen d) and subsequently by a regression analysis, calculating the contribution coefficient (CC). RESULTS: The greatest variability in caregiver assessments was observed in relation to patients with early-stage dementia, where caregiver's burden was the main factor associated with a more negative evaluation (d = 1.02-1.25). Depression in the caregiver was associated with less variability and only in the assessments of patients with moderate dementia (d = 0.38-0.69). In the regression analysis, caregiver factors were associated with greater variance in scores on the NPI (CC = 37.4%) and QOL-AD (CC = 27.2%), and lower variance in AQ-D (CC = 21.6%) and DAD (CC = 10.3%) scores. CONCLUSIONS: Caregiver's burden and depression were associated with more negative assessments of patients' psychological and behavioral symptoms and quality of life.


Assuntos
Doença de Alzheimer/diagnóstico , Cuidadores/psicologia , Atividades Cotidianas , Idoso , Cuidadores/estatística & dados numéricos , Efeitos Psicossociais da Doença , Depressão/psicologia , Avaliação da Deficiência , Feminino , Avaliação Geriátrica , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Variações Dependentes do Observador , Qualidade de Vida , Análise de Regressão , Índice de Gravidade de Doença , Inquéritos e Questionários
11.
Brain Cogn ; 80(2): 250-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22940399

RESUMO

Retrieval of proper names is a cause of concern and complaint among elderly adults and it is an early symptom of patients suffering from neurodegenerative diseases such as Alzheimer's disease (AD). While it is well established that AD patients have deficits of proper name retrieval, the nature of such impairment is not yet fully understood. Specifically, it is unknown whether this deficit is due to a degradation of the links between faces and proper names, or due to deficits in intentionally accessing and retrieving proper names from faces. Here, we aim to investigate the integrity of the links between famous faces and proper names in AD while minimizing the impact of the explicit retrieval. We compare the performances of AD patients and elderly controls in a face-name priming task. We assess the integrity of the link between faces and names at two different levels: identity level - the name and face belong to the same person; and semantic level - the name and face belong to the same category (e.g., politicians). Our results reveal that AD patients compared with controls show intact semantic priming but reduced priming for person identity. This suggests that the deficits in intentionally retrieving proper names in AD are the result of a partial disruption of the network at the identity level, i.e., the links between known faces and proper names.


Assuntos
Doença de Alzheimer/psicologia , Função Executiva/fisiologia , Idioma , Memória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Memória de Longo Prazo/fisiologia , Testes Neuropsicológicos , Estimulação Luminosa , Tempo de Reação/fisiologia , Reconhecimento Psicológico/fisiologia
12.
J Neuroophthalmol ; 32(4): 307-12, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23196944

RESUMO

We describe 5 patients with complex visual disturbances in the absence of ocular pathology who were ultimately diagnosed with posterior cortical atrophy (PCA). The presence of visual cortical symptoms, neuroimaging findings and clinical evolution led to the diagnosis 1-5 years after the onset of visual symptoms. Age of onset ranged from 50-66 years. In 3 cases, magnetic resonance imaging (MRI) of the brain demonstrated predominantly right posterior cortical atrophy. The other 2 patients had nonspecific MRI findings but the diagnosis was established given the findings on clinical examination and positron emission tomography (PET). All progressed to global dementia and an autopsy confirmed the diagnosis of Alzheimer disease in one patient. The possibility of PCA should be considered when a patient presents with complex visual symptoms in the absence of ocular pathology. Early neurological assessment may avoid diagnostic delay.


Assuntos
Encefalopatias/complicações , Córtex Cerebral/patologia , Transtornos da Visão/etiologia , Idoso , Atrofia , Encefalopatias/patologia , Córtex Cerebral/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tecnécio Tc 99m Exametazima , Tomografia Computadorizada de Emissão de Fóton Único
13.
J Neurol ; 269(3): 1651-1662, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34387740

RESUMO

OBJECTIVE: To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients. METHODS: In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments. RESULTS: 33 subjects aged 7-64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. CONCLUSIONS: NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. CLINICALTRIALS. GOV IDENTIFIER: NCT03759639.


Assuntos
Doença de Niemann-Pick Tipo C , Adolescente , Adulto , Criança , Método Duplo-Cego , Humanos , Leucina/análogos & derivados , Leucina/uso terapêutico , Pessoa de Meia-Idade , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
14.
Medicine (Baltimore) ; 101(48): e31471, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36482560

RESUMO

BACKGROUND: Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca®) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. METHODS: This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. DISCUSSION: NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz's capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression.


Assuntos
Disfunção Cognitiva , Doença de Niemann-Pick Tipo C , Humanos , Adulto , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia
15.
BMC Public Health ; 11: 176, 2011 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-21429194

RESUMO

BACKGROUND: The prevalence and predictors of functional status and disability of elderly people have been studied in several European countries including Spain. However, there has been no population-based study incorporating the International Classification of Functioning, Disability and Health (ICF) framework as the basis for assessing disability. The present study reports prevalence rates for mild, moderate, and severe/extreme disability by the domains of activities and participation of the ICF. METHODS: Nine populations surveyed in previous prevalence studies contributed probabilistic and geographically defined samples in June 2005. The study sample was composed of 503 subjects aged ≥75 years. We implemented a two-phase screening design using the MMSE and the World Health Organization-Disability Assessment Schedule 2nd edition (WHO-DAS II, 12 items) as cognitive and disability screening tools, respectively. Participants scoring within the positive range of the disability screening were administered the full WHO-DAS II (36 items; score range: 0-100) assessing the following areas: Understanding and communication, Getting along with people, Life activities, Getting around, Participation in society, and Self-care. Each disability area assessed by WHO-DAS II (36 items) was reported according to the ICF severity ranges (No problem, 0-4; Mild disability, 5-24; Moderate disability, 25-49; Severe/Extreme disability, 50-100). RESULTS: The age-adjusted disability prevalence figures were: 39.17 ± 2.18%, 15.31 ± 1.61%, and 10.14 ± 1.35% for mild, moderate, and severe/extreme disability, respectively. Severe and extreme disability prevalence in mobility and life activities was three times higher than the average, and highest among women. Sex variations were minimal, although life activities for women of 85 years and over had more severe/extreme disability as compared to men (OR = 5.15 95% CI 3.19-8.32). CONCLUSIONS: Disability is highly prevalent among the Spanish elderly. Sex- and age-specific variations of disability are associated with particular disability domains.


Assuntos
Avaliação da Deficiência , Pessoas com Deficiência/classificação , Classificação Internacional de Doenças , Programas de Rastreamento/métodos , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Pessoas com Deficiência/estatística & dados numéricos , Feminino , Humanos , Masculino , Prevalência , Espanha/epidemiologia
16.
Acta Neurol Belg ; 111(3): 245-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22141294

RESUMO

INTRODUCTION: Facial myokymias (FM) are continuous, involuntary, undulating movements of the facial muscles associated with spontaneous electromyographic activity, such as fasciculations and myokymic discharges. They may occur in healthy individuals, or be secondary to multiple sclerosis, posterior fossa tumors, or an inflammatory process. PATIENT AND RESULTS: We describe the case of a 31-year-old man who presented with headache, vomiting, low fever, and disorientation. Cerebrospinal fluid findings included low glucose and high protein content and lymphocyte pleocytosis, with positive culture for Myobacterium tuberculosis. The patient was diagnosed with tuberculous meningitis. Magnetic resonance imaging showed high contrast enhancement in the basal meninges and a left frontal tuberculoma. Over the course of the disease, he experienced FM and persistent, involuntary contraction of the facial muscles. The electromyogram recorded myokymic discharges. DISCUSSION: Tuberculous meningitis is a rare cause of FM. The presence of myokymic discharges on electromyography verified the peripheral origin of facial nerve hyperexcitability in this case, in contrast to persistent contraction of the facial muscles, which has a central origin. The phenomena were transitory and only positive symptoms were observed, with no facial nerve injury. CONCLUSION: Tuberculous meningitis is a rare cause of facial nerve hyperexcitability, which can have a peripheral, nuclear, or supranuclear origin.


Assuntos
Doenças do Nervo Facial/etiologia , Nervo Facial/fisiopatologia , Paralisia Facial/etiologia , Tuberculose Meníngea/complicações , Adulto , Músculos Faciais/fisiopatologia , Doenças do Nervo Facial/fisiopatologia , Paralisia Facial/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tuberculose Meníngea/patologia , Tuberculose Meníngea/fisiopatologia
17.
Biomedicines ; 9(9)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34572457

RESUMO

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer's disease (AD), and presents pathological and clinical overlap with both AD and Parkinson's disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.

18.
Acta Neurol Belg ; 110(1): 113-5, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20514939

RESUMO

We report a patient with Creutzfeldt-Jakob disease with somnolence as an initial manifestation and sleep apneas as a prominent sign. A respiratory polygraphy revealed the presence of a continuous Cheyne-Stokes pattern both awake and during sleep with central apneas. The neuropathology showed PrP deposition in brainstem involving respiratory nuclei. Central apnea is a rare manifestation of CJD that can be observed from early stages and may be related with PrP deposition in brainstem structures.


Assuntos
Tronco Encefálico/fisiopatologia , Síndrome de Creutzfeldt-Jakob/complicações , Síndrome de Creutzfeldt-Jakob/patologia , Apneia do Sono Tipo Central/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
19.
Seizure ; 81: 157-165, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32818871

RESUMO

OBJECTIVE: To follow prospectively a group of patients with seizures or epilepsy and suggestive clinical features of autoimmune aetiology and find out how many are finally diagnosed with acute symptomatic seizures (ASS) secondary to autoimmune encephalitis or autoimmune-related epilepsy, and how many develop epilepsy. METHODS: Consecutive patients meeting the inclusion criteria from 2010 to 2018 were identified. Patients were classified as confirmed, probable autoimmune, non-autoimmune, or unknown. RESULTS: One-hundred and nine patients were included, 64 (48.7 %) women, mean age 55.2 years (SD 17.9). ASS were reported by 61 patients (56 %), while 48 presented epilepsy (44 %). During follow-up 18 patients died (16.5 %). Final diagnosis was autoimmune-relatedepilepsy (confirmed + probable) in 22 cases and ASS secondary to autoimmune encephalitis (confirmed or probable) in 27, non-autoimmune aetiologies or other diagnosis in 49 (44 %), and unknown aetiology in 11 (10.2 %). Neuronal antibodies (ab) were found in 27 patients (24.7 %). T-lymphocyte infiltration in temporal lobes was observed in 2/8 patients (20 %). Neuronal ab were more frequent in the autoimmune groups: 17 patients (29.8 %) vs 1(2.3 %), p:0.001, and they suffered more autoimmune diseases: 37 (75.5 %) vs 12 (24.48 %), p:0.0001, and 34 (69 %) vs 22 (44.9 %) p:0.027, respectively. All patients with GAD ab 17/17 (100 %) evolved to chronic disease. Four patients (29 %) with ASS secondary to autoimmune encephalitis developed epilepsy. SIGNIFICANCE: ASS secondary to autoimmune encephalitis or autoimmune-related epilepsy will be diagnosed in nearly half of patients who have been suspected of it. The only diagnostic clue is neuronal ab. Patients who have suffered ASS secondary to autoimmune encephalitis may develop epilepsy over time.


Assuntos
Encefalite , Epilepsia , Doença de Hashimoto , Encefalite/complicações , Encefalite/epidemiologia , Epilepsia/complicações , Epilepsia/epidemiologia , Feminino , Doença de Hashimoto/complicações , Doença de Hashimoto/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Convulsões/complicações , Convulsões/epidemiologia
20.
Neuroimage Clin ; 28: 102482, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33371943

RESUMO

The Locus Coeruleus (LC) is the major source of noradrenergic neurotransmission. Structural alterations in the LC have been observed in neurodegenerative disorders and at-risk individuals, although functional connectivity studies between the LC and other brain areas have not been yet performed in these populations. Patients with late-life major depressive disorder (MDD) are indeed at increased risk for neurodegenerative disorders, and here we investigated LC connectivity in late-life MDD in comparison to individuals with amnestic type mild cognitive impairment (aMCI) and healthy controls (HCs). We assessed 20 patients with late-life MDD, 16 patients with aMCI, and 26 HCs, who underwent a functional magnetic resonance scan while performing a visual oddball task. We assessed task-related modulations of LC connectivity (i.e., Psychophysiological Interactions, PPI) with other brain areas. A T1-weighted fast spin-echo sequence for LC localization was also obtained. Patients with late-life MDD showed lower global connectivity during target detection in a cluster encompassing the right caudal LC. Specifically, we observed lower LC connectivity with the left anterior cingulate cortex (ACC), the right fusiform gyrus, and different cerebellar clusters. Moreover, alterations in LC-ACC connectivity correlated negatively with depression severity (i.e., Geriatric Depression Scale and number of recurrences). Reduced connectivity of the LC during oddball performance seems to specifically characterize patients with late-life MDD, but not other populations of aged individuals with cognitive alterations. Such alteration is associated with different measures of disease severity, such as the current presence of symptoms and the burden of disease (number of recurrences).


Assuntos
Transtorno Depressivo Maior , Idoso , Encéfalo , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Locus Cerúleo , Imageamento por Ressonância Magnética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA