RESUMEN
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder resulting from a CAG expansion in the huntingtin (HTT) gene, which leads to the production and accumulation of mutant huntingtin (mHTT). While primarily considered a disorder of the central nervous system, multiple changes have been described to occur throughout the body, including activation of the immune system. In other neurodegenerative disorders, activation of the immune system has been shown to include the production of antibodies against disease-associated pathological proteins. However, the existence of mHTT-targeted antibodies has never been reported. In this study, we assessed the presence and titer of antibodies recognizing HTT/mHTT in patients with HD (n = 66) and age- and gender-matched healthy controls (n = 66) using a combination of Western blotting and ELISA. Together, these analyses revealed that antibodies capable of recognizing HTT/mHTT were detectable in the plasma samples of all participants, including healthy controls. When antibody levels were monitored at different disease stages, it was observed that antibodies against full-length mHTT were highest in patients with severe disease while antibodies against HTTExon1 were elevated in patients with mild disease. Combined, these results suggest that antibodies detecting different forms of mHTT peak at different disease stages.
Asunto(s)
Enfermedad de Huntington , Enfermedades Neurodegenerativas , Humanos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Enfermedad de Huntington/metabolismo , AnticuerposRESUMEN
OBJECTIVES: Disease-modifying therapies in development for Huntington's disease (HD) may require specialised administration and additional resource capacity. We sought to understand current and future capacity for HD management in Canada considering the possible introduction of an intrathecal (IT) disease-modifying treatment (DMT). DESIGN, SETTING AND PARTICIPANTS: Using a case study, mixed methods framework, online surveys followed by semistructured interviews were conducted in late 2020 and early 2021. Neurologists from Canadian HD (n=16) and community (n=11) centres and social workers (n=16) were invited to complete online surveys assessing current HD management and potential capacity to support administration of an IT DMT. OUTCOME MEASURES: Survey responses, anticipated demand and assumed resource requirements were modelled to reveal capacity to treat (ie, % of eligible patients) by centre. Resource bottlenecks and incremental support required (full-time equivalent, FTE) were also determined. RESULTS: Neurologists from 15/16 HD centres and 5/11 community centres, plus 16/16 social workers participated. HD centres manage 94% of patients with HD currently seeking care in Canada, however, only 20% of IT DMT-eligible patients are currently seen by neurologists. One-third of centres have no access to nursing support. The average national incremental nursing, room, neurologist and social worker support required to provide IT DMT to all eligible patients is 0.73, 0.36, 0.30 and 0.21 FTE per HD centre, respectively. At peak demand, current capacity would support the treatment of 6% of IT DMT-eligible patients. If frequency of administration is halved, capacity for IT-DMT administration only increases to 11%. CONCLUSIONS: In Canada, there is little to no capacity to support the administration of an IT DMT for HD. Current inequitable and inadequate resourcing will require solutions that consider regional gaps and patient needs.
Asunto(s)
Enfermedad de Huntington , Canadá , Atención a la Salud , Capacidad de Camas en Hospitales , Humanos , Enfermedad de Huntington/tratamiento farmacológico , Encuestas y CuestionariosRESUMEN
Importance: Essential tremor (ET) is one of the most common movement disorders, affecting 5% of the general population older than 65 years. Common variants are thought to contribute toward susceptibility to ET, but no variants have been robustly identified. Objective: To identify common genetic factors associated with risk of ET. Design, Setting, and Participants: Case-control genome-wide association study. Inverse-variance meta-analysis was used to combine cohorts. Multicenter samples collected from European populations were collected from January 2010 to September 2019 as part of an ongoing study. Included patients were clinically diagnosed with or reported having ET. Control individuals were not diagnosed with or reported to have ET. Of 485â¯250 individuals, data for 483â¯054 passed data quality control and were used. Main Outcomes and Measures: Genotypes of common variants associated with risk of ET. Results: Of the 483â¯054 individuals included, there were 7177 with ET (3693 [51.46%] female; mean [SD] age, 62.66 [15.12] years), and 475â¯877 control individuals (253â¯785 [53.33%] female; mean [SD] age, 56.40 [17.6] years). Five independent genome-wide significant loci and were identified and were associated with approximately 18% of ET heritability. Functional analyses found significant enrichment in the cerebellar hemisphere, cerebellum, and axonogenesis pathways. Genetic correlation (r), which measures the degree of genetic overlap, revealed significant common variant overlap with Parkinson disease (r, 0.28; P = 2.38 × 10-8) and depression (r, 0.12; P = 9.78 × 10-4). A separate fine-mapping of transcriptome-wide association hits identified genes such as BACE2, LRRN2, DHRS13, and LINC00323 in disease-relevant brain regions, such as the cerebellum. Conclusions and Relevance: The results of this genome-wide association study suggest that a portion of ET heritability can be explained by common genetic variation and can help identify new common genetic risk factors for ET.
Asunto(s)
Temblor Esencial/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , TranscriptomaRESUMEN
BACKGROUND: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility. OBJECTIVE: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach. METHODS: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal. RESULTS: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10-8 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10-6 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10-8 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823). CONCLUSION: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.
Asunto(s)
Estudio de Asociación del Genoma Completo , Tortícolis , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Factores de Intercambio de Guanina Nucleótido/genética , Humanos , Polimorfismo de Nucleótido Simple/genética , Reproducibilidad de los Resultados , Tortícolis/genéticaRESUMEN
The visualization of the human body has frequently been groundbreaking in medicine. In the last few years, the use of ultrasound (US) imaging has become a well-established procedure for botulinum toxin therapy in people with cervical dystonia (CD). It is now undisputed among experts that some of the most relevant muscles in this indication can be safely injected under visual US guidance. This review will explore the method from basic technical considerations, current evidence to conceptual developments of the phenomenology of cervical dystonia. We will review the implications of introducing US to our understanding of muscle function and anatomy of common cervical dystonic patterns. We suggest a flow chart for the use of US to achieve a personalized treatment of people with CD. Thus, we hope to contribute a resource that is useful in clinical practice and that stimulates the ongoing development of this valuable technique.
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Toxinas Botulínicas/administración & dosificación , Tortícolis/tratamiento farmacológico , Ultrasonografía Intervencional/métodos , Humanos , Fármacos Neuromusculares/administración & dosificación , Medicina de Precisión , Tortícolis/diagnóstico por imagenRESUMEN
OBJECTIVE: To assess the clinical manifestations and predictors of different types of tremors in individuals with different types of isolated dystonia. METHODS: Clinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2,362 individuals with all types of isolated dystonia (focal, segmental, multifocal, and generalized) recruited through the Dystonia Coalition. RESULTS: Methodical and standardized assessments of all participants in this cohort revealed the overall prevalence of any type of tremor was 53.3%. The prevalence of dystonic tremor varied from 36.9% to 48.4%, depending on criteria used to define it. To identify the factors associated with tremors in dystonia, the data were analyzed by generalized linear modeling and cluster analyses. Generalized linear modeling indicated 2 of the strongest factors associated with tremor included body region affected by dystonia and recruitment center. Tremor was also associated with severity of dystonia and duration of dystonia, but not with sex or race. The cluster analysis distinguished 8 subgroups within the whole cohort; defined largely by body region with dystonia, and secondarily by other clinical characteristics. CONCLUSION: The large number of cases evaluated by an international team of movement disorder experts facilitated the dissection of several important factors that influence the apparent prevalence and phenomenology of tremor in dystonia. These results are valuable for understanding the many differences reported in prior studies, and for guiding future studies of the nosology of tremor and dystonia.
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Distonía/diagnóstico , Distonía/epidemiología , Internacionalidad , Temblor/diagnóstico , Temblor/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: More than 75% of Parkinson's disease (PD) patients will develop dementia. Previous studies on the cognitive predictors of dementia in PD had some methodological limitations and the cognitive tests identified as good predictors vary greatly. OBJECTIVE: This prospective cohort study aims to identify the optimal cognitive predictors of dementia in PD using complementary statistical methods. METHODS: Eighty PD patients without dementia underwent polysomnographic recording, a neurological examination, and a complete neuropsychological assessment at baseline. They were then followed for a mean of 4.3 years. Baseline group comparisons and survival analyses were used to identify optimal cognitive predictors. Moreover, patients who developed dementia were pair-matched at baseline according to age, sex, and education to healthy controls (2â:â1), and receiver operating characteristic curves were calculated for cognitive tests. RESULTS: At follow-up, 23 patients (29%) developed dementia. PD patients who developed dementia had poorer baseline performance and a higher proportion of clinically impaired performance on several cognitive tests. Impaired baseline performance on the Block Design subtest was the best independent predictor of dementia (HRâ=â8). Moreover, the Trail Making Test part B (time) and Verbal Fluency (semantic) had the best psychometric properties (area under the curve >0.90) for identifying PD patients at risk of dementia. CONCLUSION: The present study identified three cognitive tests as the most accurate to detect individuals with PD at high risk of developing dementia.
Asunto(s)
Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Pruebas Neuropsicológicas/normas , Enfermedad de Parkinson/diagnóstico , Síntomas Prodrómicos , Anciano , Disfunción Cognitiva/etiología , Demencia/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Enfermedad de Parkinson/complicaciones , Psicometría/normas , Psicometría/estadística & datos numéricos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Genetic, biologic and clinical data suggest that Parkinson's disease (PD) is an umbrella for multiple disorders with clinical and pathological overlap, yet with different underlying mechanisms. To better understand these and to move towards neuroprotective treatment, we have established the Quebec Parkinson Network (QPN), an open-access patient registry, and data and bio-samples repository. OBJECTIVE: To present the QPN and to perform preliminary analysis of the QPN data. METHODS: A total of 1,070 consecutively recruited PD patients were included in the analysis. Demographic and clinical data were analyzed, including comparisons between males and females, PD patients with and without RBD, and stratified analyses comparing early and late-onset PD and different age groups. RESULTS: QPN patients exhibit a male:female ratio of 1.8:1, an average age-at-onset of 58.6 years, an age-at-diagnosis of 60.4 years, and average disease duration of 8.9 years. REM-sleep behavior disorder (RBD) was more common among men, and RBD was associated with other motor and non-motor symptoms including dyskinesia, fluctuations, postural hypotension and hallucinations. Older patients had significantly higher rates of constipation and cognitive impairment, and longer disease duration was associated with higher rates of dyskinesia, fluctuations, freezing of gait, falls, hallucinations and cognitive impairment. Since QPN's creation, over 60 studies and 30 publications have included patients and data from the QPN. CONCLUSIONS: The QPN cohort displays typical PD demographics and clinical features. These data are open-access upon application (http://rpq-qpn.ca/en/), and will soon include genetic, imaging and bio-samples. We encourage clinicians and researchers to perform studies using these resources.
Asunto(s)
Bancos de Muestras Biológicas , Disfunción Cognitiva , Trastornos Neurológicos de la Marcha , Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Sistema de Registros , Edad de Inicio , Anciano , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Estudios de Cohortes , Femenino , Trastornos Neurológicos de la Marcha/epidemiología , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/fisiopatología , Quebec/epidemiología , Trastorno de la Conducta del Sueño REM/epidemiología , Trastorno de la Conducta del Sueño REM/etiología , Trastorno de la Conducta del Sueño REM/fisiopatologíaRESUMEN
OBJECTIVES: To identify the prevalence of dystonia in a RNA Polymerase III (POLR3)-related leukodystrophy patient cohort and to further characterize their dystonic features. BACKGROUND: POLR3-related leukodystrophy is a hypomyelinating leukodystrophy characterized by neurological and non-neurological features. Dystonia remains a challenging and under-recognized feature. METHODS: A retrospective chart review was performed in a cohort of 20 patients for whom videos of a standardized neurological examination were available. Patients were recruited at the Montreal Children's Hospital of the McGill University Health Center and the Myelin Disorders Bioregistry Project. Families were consented at the initial assessment and the following data was recorded: age and symptoms at clinical presentation, investigations, causal gene and mutation(s), type and severity of dystonia, and treatment response when needed. Standardized examination videos were reviewed by three independent reviewers and scored using the Global Dystonia Scale. RESULTS: 10 males and 10 females were included in this study; 12/20 had POLR3A mutations, while 8/20 had POLR3B mutations; 19/20 patients had documented dystonia, with 3/19 requiring therapy. There was a good response in two patients to a single agent, and a poor response in one patient to three agents; the majority had mild-to-moderate multifocal dystonia without a functional impact. CONCLUSIONS: Dystonia is a common, yet underdiagnosed, slowly progressive manifestation of POLR3-related leukodystrophy, and in most cases has limited-to-no functional impact. When treatment is needed, good response to typically used medication may occur. Further studies are needed to assess evolution of dystonia over time, patients' functional outcome, and response to therapy (when needed).
RESUMEN
We aimed to investigate cortical and subcortical brain alterations in people with Parkinson's disease with polysomnography-confirmed rapid eye movement (REM) sleep behavior disorder (RBD). Thirty people with Parkinson's disease, including 15 people with RBD, were recruited and compared with 41 healthy controls. Surface-based cortical and subcortical analyses were performed on T1-weighted images to investigate thickness and shape abnormalities between groups, and voxel-based and deformation-based morphometry were performed to investigate local volume. Correlations were performed in patients to investigate the structural correlates of motor activity during REM sleep. People with RBD showed cortical thinning in the right perisylvian and inferior temporal cortices and shape contraction in the putamen compared with people without RBD. Compared with controls, people with RBD had extensive cortical thinning and volume loss, brainstem volume was reduced, and shape contraction was found in the basal ganglia and hippocampus. In comparison to controls, people without RBD showed more restricted thinning in the sensorimotor, parietal, and occipital cortices, reduced volume in the brainstem, temporal and more posterior areas, and shape contraction in the pallidum and hippocampus. In Parkinson's disease, higher tonic and phasic REM sleep motor activity was associated with contraction of the thalamic surface, extensive cortical thinning, and subtle volume reduction in the middle temporal gyrus. In Parkinson's disease, the presence of RBD is associated with extensive cortical and subcortical abnormalities, suggesting more severe neurodegeneration in people with RBD. This provides potential neuroanatomical correlates for the more severe clinical phenotype reported in people with Parkinson's disease with RBD.
Asunto(s)
Encéfalo/patología , Enfermedad de Parkinson/patología , Trastorno de la Conducta del Sueño REM/fisiopatología , Sueño REM/fisiología , Anciano , Atrofia/patología , Ganglios Basales/patología , Tronco Encefálico/patología , Femenino , Hipocampo/patología , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora/fisiología , Enfermedad de Parkinson/complicaciones , Polisomnografía , Trastorno de la Conducta del Sueño REM/complicaciones , Tálamo/patologíaRESUMEN
The production of extracellular vesicles (EV) is a ubiquitous feature of eukaryotic cells but pathological events can affect their formation and constituents. We sought to characterize the nature, profile and protein signature of EV in the plasma of Parkinson's disease (PD) patients and how they correlate to clinical measures of the disease. EV were initially collected from cohorts of PD (nâ¯=â¯60; Controls, nâ¯=â¯37) and Huntington's disease (HD) patients (Pre-manifest, nâ¯=â¯11; manifest, nâ¯=â¯52; Controls, nâ¯=â¯55) - for comparative purposes in individuals with another chronic neurodegenerative condition - and exhaustively analyzed using flow cytometry, electron microscopy and proteomics. We then collected 42 samples from an additional independent cohort of PD patients to confirm our initial results. Through a series of iterative steps, we optimized an approach for defining the EV signature in PD. We found that the number of EV derived specifically from erythrocytes segregated with UPDRS scores corresponding to different disease stages. Proteomic analysis further revealed that there is a specific signature of proteins that could reliably differentiate control subjects from mild and moderate PD patients. Taken together, we have developed/identified an EV blood-based assay that has the potential to be used as a biomarker for PD.
Asunto(s)
Eritrocitos/metabolismo , Vesículas Extracelulares/metabolismo , Enfermedad de Parkinson/sangre , Anciano , Biomarcadores/sangre , Recuento de Células Sanguíneas , Eritrocitos/ultraestructura , Vesículas Extracelulares/ultraestructura , Femenino , Humanos , Enfermedad de Huntington/sangre , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/patología , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/patología , ProteómicaRESUMEN
Essential Tremor is a prevalent neurological disorder of unknown etiology. Studies suggest that genetic factors contribute to this pathology. To date, no causative mutations in a gene have been reproducibly reported. All three structures of the olivocerebellar motor circuitry have been linked to Essential Tremor. We postulated that genes enriched for their expression in the olivocerebellar circuitry would be more susceptible to harbor mutations in Essential Tremor patients. A list of 11 candidate genes, enriched for their expression in the olivocerebellar circuitry, was assessed for their variation spectrum and frequency in a cohort of Canadian Essential Tremor cases. Our results from this list of 11 candidate genes do not support an association for Essential Tremor in our cohort of Canadian cases. The heterogenic nature of ET and modest size of the cohort used in this study are two confounding factors that could explain these results.
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Cerebelo/patología , Secuencia Conservada , Temblor Esencial/genética , Corteza Motora/patología , Mutación Missense/genética , Filogenia , Anciano , Canadá , Estudios de Asociación Genética , Humanos , Persona de Mediana EdadRESUMEN
Huntington's disease (HD) is a hereditary disorder that typically manifests in adulthood with a combination of motor, cognitive and psychiatric problems. The pathology is caused by a mutation in the huntingtin gene which results in the production of an abnormal protein, mutant huntingtin (mHtt). This protein is ubiquitously expressed and known to confer toxicity to multiple cell types. We have recently reported that HD brains are also characterised by vascular abnormalities, which include changes in blood vessel density/diameter as well as increased blood-brain barrier (BBB) leakage. OBJECTIVES: Seeking to elucidate the origin of these vascular and BBB abnormalities, we studied platelets that are known to play a role in maintaining the integrity of the vasculature and thrombotic pathways linked to this, given they surprisingly contain the highest concentration of mHtt of all blood cells. METHODS: We assessed the functional status of platelets by performing ELISA, western blot and RNA sequencing in a cohort of 71 patients and 68 age- and sex-matched healthy control subjects. We further performed haemostasis and platelet depletion tests in the R6/2 HD mouse model. RESULTS: Our findings indicate that the platelets in HD are dysfunctional with respect to the release of angiogenic factors and functions including thrombosis, angiogenesis and vascular haemostasis. CONCLUSION: Taken together, our results provide a better understanding for the impact of mHtt on platelet function.
Asunto(s)
Barrera Hematoencefálica/fisiopatología , Proteína Huntingtina/sangre , Enfermedad de Huntington/sangre , Activación Plaquetaria/fisiología , Adulto , Anciano , Proteínas Angiogénicas/sangre , Animales , Factores de Coagulación Sanguínea/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Modelos Animales de Enfermedad , Femenino , Factor 2 de Crecimiento de Fibroblastos/sangre , Humanos , Enfermedad de Huntington/complicaciones , Masculino , Ratones , Persona de Mediana Edad , Recuento de PlaquetasRESUMEN
The production and release of extracellular vesicles (EV) is a property shared by all eukaryotic cells and a phenomenon frequently exacerbated in pathological conditions. The protein cargo of EV, their cell type signature and availability in bodily fluids make them particularly appealing as biomarkers. We recently demonstrated that platelets, among all types of blood cells, contain the highest concentrations of the mutant huntingtin protein (mHtt)-the genetic product of Huntington's disease (HD), a neurodegenerative disorder which manifests in adulthood with a complex combination of motor, cognitive and psychiatric deficits. Herein, we used a cohort of 59 HD patients at all stages of the disease, including individuals in pre-manifest stages, and 54 healthy age- and sex-matched controls, to evaluate the potential of EV derived from platelets as a biomarker. We found that platelets of pre-manifest and manifest HD patients do not release more EV even if they are activated. Importantly, mHtt was not found within EV derived from platelets, despite them containing high levels of this protein. Correlation analyses also failed to reveal an association between the number of platelet-derived EV and the age of the patients, the number of CAG repeats, the Unified Huntington Disease Rating Scale total motor score, the Total Functional Capacity score or the Burden of Disease score. Our data would, therefore, suggest that EV derived from platelets with HD is not a valuable biomarker in HD.
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Biomarcadores/sangre , Plaquetas/metabolismo , Vesículas Extracelulares/metabolismo , Enfermedad de Huntington/sangre , Adulto , Anciano , Femenino , Humanos , Proteína Huntingtina/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: In Parkinson's disease cognitive impairment is an early nonmotor feature, but it is still unclear why some patients are able to maintain their cognitive performance at normal levels, as quantified by neuropsychological tests, whereas others cannot. The objectives of this study were to perform a cross-sectional study and analyze the white matter changes in the cognitive and motor bundles in patients with Parkinson's disease. METHODS: Sixteen Parkinson's disease patients with normal cognitive performance, 19 with mild cognitive impairment (based on their performance of 1.5 standard deviations below the healthy population mean), and 16 healthy controls were compared with respect to their tractography patterns between the cortical cognitive / motor regions and subcortical structures, using high angular resolution diffusion imaging and constrained spherical deconvolution computation. RESULTS: Motor bundles showed decreased apparent fiber density in both PD groups, associated with a significant increase in diffusivity metrics, number of reconstructed streamlines, and track volumes, compared with healthy controls. By contrast, in the cognitive bundles, decreased fiber density in both Parkinson's groups was compounded by the absence of changes in diffusivity in patients with normal cognition, whereas patients with cognitive impairment had increased diffusivity metrics, lower numbers of reconstructed streamlines, and lower track volumes. CONCLUSIONS: Both PD groups showed similar patterns of white matter neurodegeneration in the motor bundles, whereas cognitive bundles showed a distinct pattern: Parkinson's patients with normal cognition had white matter diffusivity metrics similar to healthy controls, whereas in patients with cognitive impairment white matter showed a neurodegeneration pattern. © 2018 International Parkinson and Movement Disorder Society.
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Trastornos del Conocimiento/etiología , Leucoencefalopatías/complicaciones , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Anciano , Mapeo Encefálico , Estudios Transversales , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Leucoencefalopatías/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Pruebas NeuropsicológicasRESUMEN
Chronic tic disorders (TD) are associated with a number of psychological problems such as attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive behavior (OCB), oppositional-defiant disorder (ODD) as well as anxious and depressive symptoms. ODD is often considered a risk factor for many psychological symptoms and recent work suggests that different ODD dimensions show independent predictions of later psychological problems. This study examined the longitudinal predictions between ODD dimensions of Irritability and Defiance and the most frequent comorbidities in TD from childhood to early adulthood. From an initial sample of 135, parent reports were obtained on 58 participants with TD using standard clinical questionnaires and semi-structured interviews. Defiance symptoms decreased from baseline to follow-up whereas Irritability symptoms were more stable over time. In multiple regressions, Irritability in childhood predicted anxiety and OCB in early adulthood while Defiance in childhood predicted ADHD and conduct disorder symptoms in early adulthood. No developmental link was found for depressive symptoms. Results indicate that ODD dimensions are developmentally linked to both internalizing and externalizing adult mental health symptoms in TD.
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Déficit de la Atención y Trastornos de Conducta Disruptiva/psicología , Trastornos de Tic/psicología , Adolescente , Adulto , Ansiedad/psicología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Enfermedad Crónica , Comorbilidad , Trastorno de la Conducta/psicología , Depresión/psicología , Femenino , Estudios de Seguimiento , Humanos , Genio Irritable , Estudios Longitudinales , Masculino , Trastorno Obsesivo Compulsivo/psicología , Encuestas y Cuestionarios , Adulto JovenAsunto(s)
Atetosis/tratamiento farmacológico , Atetosis/fisiopatología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Corea/tratamiento farmacológico , Corea/fisiopatología , Hipotiroidismo Congénito/tratamiento farmacológico , Hipotiroidismo Congénito/fisiopatología , Metilfenidato/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatología , Atetosis/genética , Niño , Corea/genética , Hipotiroidismo Congénito/genética , Femenino , Humanos , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Factor Nuclear Tiroideo 1/genéticaRESUMEN
BACKGROUND: Individuals with Parkinson's disease (PD) often present with visual symptoms (e.g., difficulty in reading, double vision) that can also be found in convergence insufficiency (CI). Our objective was to estimate the prevalence of CI-type visual symptomatology in individuals with PD, in comparison with controls. METHODS: Participants ≥50 years with (n=300) and without (n=300) PD were recruited. They were administered the Convergence Insufficiency Symptom Survey (CISS-15) over the phone. A score of ≥21 on the CISS-15, considered positive for CI-type symptomatology, served as the cutoff. Data from individuals (n=87 with, n=94 without PD) who were approached but who reported having a known oculovisual condition were analysed separately. Student's t test and chi-square at the 0.05 level were employed for statistical significance. RESULTS: A total of 29.3% of participants with versus 7.3% without PD presented with a score of ≥21 on the CISS-15 (p=0.001). Of the participants having a known oculovisual condition, 39.1% with versus 19.1% without PD presented with a score of ≥21 on the CISS-15 (p=0.01). CONCLUSIONS: The prevalence of CI-type visual symptoms is higher in individuals with versus without PD whether or not they have a coexisting oculovisual condition. These results suggest that PD per se places individuals with the disease at greater risk of visual symptomatology. These results further underline the importance of providing regular eye exams for individuals with PD.
Asunto(s)
Trastornos de la Motilidad Ocular/epidemiología , Enfermedad de Parkinson/epidemiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Motilidad Ocular/diagnóstico , Trastornos de la Motilidad Ocular/etiología , Enfermedad de Parkinson/complicaciones , Prevalencia , Riesgo , Encuestas y Cuestionarios , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiologíaRESUMEN
Study Objectives: REM sleep behavior disorder (RBD) is a parasomnia affecting 33% to 46% of patients with Parkinson's disease (PD). The existence of a unique and specific impaired cognitive profile in PD patients with RBD is still controversial. We extensively assessed cognitive functions to identify whether RBD is associated with more severe cognitive deficits in nondemented patients with PD. Methods: One hundred sixty-two participants, including 53 PD patients with RBD, 40 PD patients without RBD, and 69 healthy subjects, underwent polysomnography, a neurological assessment and an extensive neuropsychological exam to assess attention, executive functions, episodic learning and memory, visuospatial abilities, and language. Results: PD patients with RBD had poorer and clinically impaired performance in several cognitive tests compared to PD patients without RBD and healthy subjects. These two latter groups were similar on all cognitive measures. Mild cognitive impairment (MCI) diagnosis frequency was almost threefold higher in PD patients with RBD compared to PD patients without RBD (66% vs. 23%, p < .001). Moreover, subjective cognitive decline was reported in 89% of PD patients with RBD compared to 58% of PD patients without RBD (p = .024). Conclusions: RBD in PD is associated with a more impaired cognitive profile and higher MCI diagnosis frequency, suggesting more severe and widespread neurodegeneration. This patient subgroup and their caregivers should receive targeted medical attention to better detect and monitor impairment and to enable the development of management interventions for cognitive decline and its consequences.