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INTRODUCTION: Pathogenic variants in parkin (PRKN gene) are the second most prevalent known monogenic cause of Parkinson's disease (PD). How monoallelic or biallelic pathogenic variants in the PRKN gene may affect its transcription in patient-derived biological material has not been systematically studied. METHODS: PRKN mRNA expression levels were measured with real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs). PBMCs were derived from PRKN-mutated PD patients (PRKN-PD) (n = 12), sporadic PD (sPD) (n = 21) and healthy controls (n = 21). Six of the PRKN-PD patients were heterozygous, four were compound heterozygous, and two were homozygous for PRKN variants. RESULTS: A statistically significant decrease in PRKN expression levels was present, compared to healthy controls and sPD, in heterozygous (P = 0.019 and 0.031 respectively) and biallelic (P < 0.001 for both) PRKN-PD. PRKN expression levels in biallelic PD patients were uniformly very low and were reduced, albeit not significantly, compared to heterozygotes. Based on receiver operating characteristic analysis, low PRKN expression levels were a sensitive and extremely specific indicator for the presence of PRKN pathogenic variants. CONCLUSIONS: Assessment of PRKN mRNA levels in PBMCs may be a useful way to screen for biallelic pathogenic variants in the PRKN gene. Suspicion for certain variants in a heterozygous state may also be raised based on low PRKN mRNA levels. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Leucócitos Mononucleares , Doença de Parkinson , RNA Mensageiro , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/genética , Doença de Parkinson/genética , Doença de Parkinson/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Feminino , RNA Mensageiro/metabolismo , Pessoa de Meia-Idade , Idoso , Adulto , MutaçãoRESUMO
BACKGROUND: Functional neurological disorder (FND) is a common cause of neurological disability. Despite recent advances in pathophysiological understanding and treatments, application of this knowledge to clinical practice is variable and limited. OBJECTIVE: Our aim was to provide an expert overview of the state of affairs of FND practice across Europe, focusing on education and training, access to specialized care, reimbursement and disability policies, and academic and patient-led representation of people with FND. METHODS: We conducted a survey across Europe, featuring one expert per country. We asked experts to compare training and services for people with FND to those provided to people with multiple sclerosis (MS). RESULTS: Responses from 25 countries revealed that only five included FND as a mandatory part of neurological training, while teaching about MS was uniformly included. FND was part of final neurology examinations in 3/17 countries, unlike MS that was included in all 17. Seventeen countries reported neurologists with an interest in FND but the estimated mean ratio of FND-interested neurologists to MS neurologists was 1:20. FND coding varied, with psychiatric coding for FND impacting treatment access and disability benefits in the majority of countries. Twenty countries reported services refusing to see FND patients. Eight countries reported an FND special interest group or network; 11 reported patient-led organizations. CONCLUSIONS: FND is largely a marginal topic within European neurology training and there is limited access to specialized care and disability benefits for people with FND across Europe. We discuss how this issue can be addressed at an academic, healthcare and patient organization level.
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BACKGROUND: A better understanding of pain in adult-onset idiopathic dystonia (AOID) is needed to implement effective therapeutic strategies. OBJECTIVE: To develop a new rating instrument for pain in AOID and validate it in cervical dystonia (CD). METHODS: Development and validation of the Pain in Dystonia Scale (PIDS) comprised three phases. In phase 1, international experts and participants with AOID generated and evaluated the preliminary items for content validity. In phase 2, the PIDS was drafted and revised by the experts, followed by cognitive interviews to ensure self-administration suitability. In phase 3, the PIDS psychometric properties were assessed in 85 participants with CD and retested in 40 participants. RESULTS: The final version of PIDS evaluates pain severity (by body-part), functional impact, and external modulating factors. Test-retest reliability showed a high-correlation coefficient for the total score (0.9, P < 0.001), and intraclass correlation coefficients were 0.7 or higher for all items in all body-parts subscores. The overall PIDS severity score showed high internal consistency (Cronbach's α, 0.9). Convergent validity analysis revealed a strong correlation between the PIDS severity score and the Toronto Western Spasmodic Torticollis Rating Scale pain subscale (0.8, P < 0.001) and the Brief Pain Inventory-short form items related to pain at time of the assessment (0.7, P < 0.001) and impact of pain on daily functioning (0.7, P < 0.001). CONCLUSION: The PIDS is the first specific questionnaire developed to evaluate pain in all patients with AOID, here, demonstrating high-level psychometric properties in people with CD. Future work will validate PIDS in other forms of AOID. © 2023 International Parkinson and Movement Disorder Society.
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Distúrbios Distônicos , Torcicolo , Adulto , Humanos , Torcicolo/complicações , Medição da Dor , Reprodutibilidade dos Testes , Dor , Psicometria , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND PURPOSE: Lifestyle factors have been implicated in the long-lasting neurodegenerative process in prodromal Parkinson's disease (pPD). The aim was to investigate the associations between adherence to a Mediterranean diet (MeDi) and longitudinal changes of pPD probability and the development of Parkinson's disease (PD) or pPD in a Mediterranean older population. METHODS: Data from the Hellenic Longitudinal Investigation of Aging and Diet cohort (community-dwelling individuals, aged ≥ 65 years) were used. A detailed food frequency questionnaire was used to evaluate dietary intake and calculate MeDi adherence score, ranging from 0 to 55, with higher scores indicating higher adherence. The probability of pPD was calculated according to the updated Movement Disorder Society research criteria. RESULTS: In all, 1047 non-PD/dementia with Lewy bodies (DLB) participants were followed for 3 ± 1 years. MeDi adherence was associated with lower increase in pPD probability over time (b = -0.003, 95% confidence interval -0.006 to -0.001, p = 0.010). Forty-nine participants had incident possible/probable pPD (i.e., pPD probability ≥ 30%). Compared to the participants in the lowest quartile of MeDi adherence, those in the higher quartiles had an approximately 60%-70% lower risk for possible/probable pPD (p for trend 0.003). MeDi-pPD associations were driven by both motor and non-motor pPD markers and not from risk markers. Also, 21 participants were diagnosed with PD/DLB at follow-up. For each unit increase in the MeDi score, there was a 9%-10% lower risk for PD/DLB (hazard ratio 0.906 [95% confidence interval 0.823-0.997], p = 0.044). CONCLUSIONS: Mediterranean diet adherence is associated with lower increase in pPD probability over time and lower possible/probable pPD and PD/DLB incidence in older Mediterranean people. More studies are needed to confirm our results in other populations.
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Dieta Mediterrânea , Doença por Corpos de Lewy , Doença de Parkinson , Humanos , Idoso , Estudos Longitudinais , Doença de Parkinson/complicações , Doença por Corpos de Lewy/complicações , ProbabilidadeRESUMO
BACKGROUND: A decrease in glutathione (GSH) levels is considered one of the earliest biochemical changes in Parkinson's disease (PD). OBJECTIVE: The authors explored the potential role of plasma GSH as a risk/susceptibility biomarker for prodromal PD (pPD) by examining its longitudinal associations with pPD probability trajectories. METHODS: A total of 405 community-dwelling participants (median age [interquartile range] = 73.2 [7.41] years) without clinical features of parkinsonism were followed for a mean (standard deviation) of 3.0 (0.9) years. RESULTS: A 1 µmol/L increase in plasma GSH was associated with 0.4% (95% confidence interval [CI], 0.1%-0.7%; P = 0.017) less increase in pPD probability for 1 year of follow-up. Compared with participants in the lowest GSH tertile, participants in the highest GSH tertile had a 12.9% (95% CI, 22.4%-2.2%; P = 0.020) slower rate of increase of pPD probability for 1 year of follow-up. CONCLUSION: Plasma GSH was associated with pPD probability trajectories; therefore, it might assist in the identification of individuals who are likely to reach the threshold for pPD diagnosis more rapidly. © 2021 International Parkinson and Movement Disorder Society.
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Glutationa , Doença de Parkinson , Sintomas Prodrômicos , Idoso , Glutationa/sangue , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , ProbabilidadeRESUMO
BACKGROUND: The second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages. OBJECTIVE: To develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence-based and consensus-based methodology. METHODS: We identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference. RESULTS: The criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow. CONCLUSIONS: This set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Atrofia de Múltiplos Sistemas , Encéfalo/patologia , Consenso , Humanos , Imageamento por Ressonância Magnética , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/patologia , Estudos ProspectivosRESUMO
This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we applied an automated classification procedure via an ensemble of bootstrap-aggregated ("bagged") decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95%CI, 86.3%-86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased body weight, minimyoclonus, vertical gaze palsy, autonomic symptoms, other nonmotor symptoms, levodopa response quantification, and cognitive decline. Comparing monogenic atypical with monogenic typical parkinsonism using 2063 data sets from Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1 mutations, the age at onset was earlier in monogenic atypical parkinsonism (24 vs 40 years; P = 1.2647 × 10-12) and levodopa response less favorable than in patients with monogenic typical presentations (49% vs 93%). In addition, we compared monogenic to nonmonogenic atypical parkinsonism using data from 362 patients with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration. Although these conditions share many clinical features with the monogenic atypical forms, they can typically be distinguished based on their later median age at onset (64 years; IQR, 57-70 years). In conclusion, age at onset, presence of specific signs, and degree of levodopa response inform differential diagnostic considerations and genetic testing indications in atypical forms of parkinsonism. © 2021 International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Transtornos Parkinsonianos , Genótipo , Humanos , Levodopa , Transtornos Parkinsonianos/genética , FenótipoRESUMO
BACKGROUND: The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status. OBJECTIVE: The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones. METHODS: Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy. RESULTS: The modified scale retained 14 items (yielding 0-2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months). CONCLUSIONS: The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine. © 2021 International Parkinson and Movement Disorder Society.
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Paralisia Supranuclear Progressiva , Progressão da Doença , Humanos , Qualidade de Vida , Índice de Gravidade de Doença , Paralisia Supranuclear Progressiva/diagnósticoRESUMO
BACKGROUND AND PURPOSE: Due to the COVID-19 pandemic, scientific congresses are increasingly being organized as virtual congresses (VCs). In May 2020, the European Academy of Neurology (EAN) held a VC, free of charge. In the absence of systematic studies on this topic, the aim of this study is to evaluate the attendance and perceived quality of the 2020 EAN VC compared to the 2019 EAN face-to-face congress (FFC). METHODS: An analysis of the demographic data of participants obtained from the online registration was done. A comparison of the two congresses based on a survey with questions on the perception of speakers' performance, quality of networking and other aspects was made. RESULTS: Of 43,596 registered participants, 20,694 active participants attended the VC. Compared to 2019, the number of participants tripled (6916 in 2019) and the cumulated number of participants attending the sessions was five times higher (169,334 in 2020 vs. 33,024 in 2019). Out of active participants 55% were from outside Europe, 42% were board-certified neurologists (FFC 80%) and 21% were students (FFC 0.6%). The content of the congress was evaluated as 'above expectation' by 56% of the attendees (FFC 41%). Of the respondents who had been exposed to earlier EAN congresses 73% preferred the FFC compared to the VC (17%). CONCLUSION: The VC fulfilled the main mission of organizing high quality EAN congresses despite the restrictions of the impersonal format. The geographical distribution of the participants proves the expected higher inclusivity of a VC. The large participation of students and neurologists in training opens new educational potentials for the EAN.
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COVID-19 , Neurologia , Europa (Continente) , Humanos , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: There is currently no undisputed, validated, clinically meaningful measure for deficits in the broad spectrum of PSP phenotypes. OBJECTIVE: To develop a scale to monitor clinical deficits in patients with PSP across its broad phenotypes. METHODS: The Progressive Supranuclear Palsy Clinical Deficits Scale was conceptualized to cover seven clinical domains (Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait & balance), each scored from 0 to 3 (no, mild, moderate, or severe deficits). User guidelines were developed to standardize its application. Progressive Supranuclear Palsy Clinical Deficits Scale scores were collected in patients fulfilling the MDS-PSP diagnostic criteria in two independent, multicenter, observational studies, both cross-sectionally (exploratory DescribePSP cohort; confirmatory ProPSP cohort) and longitudinally (12-months' follow-up, both cohorts). RESULTS: Cognitive pretesting demonstrated easy scale utility. In total, 164 patients were scored (70.4 ± 7.6 years; 62% males, 35% variant phenotypes). Mean Progressive Supranuclear Palsy Clinical Deficits Scale completion time was 4 minutes. The Progressive Supranuclear Palsy Clinical Deficits Scale total score correlated with existing scales (e.g., Progressive Supranuclear Palsy Rating Scale: R = 0.88; P < 0.001). Individual Progressive Supranuclear Palsy Clinical Deficits Scale items correlated well with similar constructs in existing scales. Internal consistency (Cronbach's alpha: 0.75), inter-rater reliability (0.96), and test-retest stability (0.99) were acceptable. The PSP-CDS showed significant 12-month change (baseline, 8.6 ± 3.6; follow-up: 10.8 ± 3.6; annualized difference: 3.4 ± 3.4; n = 49; P < 0.0001). Sample sizes required per arm for a two-arm, 1-year follow-up therapeutic trial to detect 50% change in Progressive Supranuclear Palsy Clinical Deficits Scale progression was estimated to be 65 (two-sided, two-sample t test). CONCLUSION: The Progressive Supranuclear Palsy Clinical Deficits Scale is a rapidly completed, clinimetrically sound scale for clinical care and research involving PSP. © 2020 International Parkinson and Movement Disorder Society.
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Paralisia Supranuclear Progressiva , Progressão da Doença , Feminino , Dedos , Humanos , Masculino , Destreza Motora , Reprodutibilidade dos Testes , Paralisia Supranuclear Progressiva/diagnósticoRESUMO
OBJECTIVE: The objective of this study was to validate the recently updated research criteria for prodromal Parkinson's disease (pPD) proposed by the International Parkinson's Disease and Movement Disorders Society. METHODS: A total of 16 of 21 markers of pPD were ascertained in the Hellenic Longitudinal Investigation of Aging and Diet cohort composed of community-dwelling individuals aged ≥65 years. The probability of pPD was calculated for 961 individuals without Parkinson's disease (PD) or dementia with Lewy bodies at baseline who were followed-up for a median of 3 years. The ability of the criteria to predict conversion to PD/dementia with Lewy bodies was assessed by estimating their sensitivity and specificity, plotting receiver operating characteristics curves, and using logistic regression. These analyses were repeated using the original criteria. RESULTS: No incident PD/dementia with Lewy bodies case had probable pPD at baseline (ie, ≥80% pPD probability). At cut-offs of 10%, 30%, and 50% probability of pPD, the sensitivity and specificity of the criteria ranged from 4.5% to 27.3%, and 85.7% to 98.3% respectively. The area under the receiver operating characteristics curve was 0.691 (95% confidence intervals, 0.605-0.777). In logistic regression models, the criteria-derived posttest odds of pPD were a significant predictor of conversion at follow-up. The updated criteria performed similarly to the original but showed a slight increase in sensitivity. CONCLUSIONS: The new criteria demonstrated suboptimal sensitivity in our random sample of community-dwelling individuals. The absence of specialized assessments with high likelihood ratios in our cohort could be hindering the demonstration of higher sensitivities. Such assessments should be a part of future validation attempts. © 2020 International Parkinson and Movement Disorder Society.
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Doença de Alzheimer , Doença de Parkinson , Idoso , Estudos de Coortes , Humanos , Doença de Parkinson/diagnóstico , Sintomas Prodrômicos , Estudos ProspectivosRESUMO
BACKGROUND: A minimally invasive test for early detection and monitoring of Parkinson's disease (PD) is a highly unmet need for drug development and planning of patient care. Blood plasma represents an attractive source of biomarkers. MicroRNAs (miRNAs) are conserved noncoding RNA molecules that serve as posttranscriptional regulators of gene expression. As opposed to ubiquitously expressed miRNAs that control house-keeping processes, brain-enriched miRNAs regulate diverse aspects of neuron development and function. These include neuron-subtype specification, axonal growth, dendritic morphogenesis, and spine density. Backed by a large number of studies, we now know that the differential expression of neuron-enriched miRNAs leads to brain dysfunction. OBJECTIVES: The aim was to identify subsets of brain-enriched miRNAs with diagnostic potential for familial and idiopathic PD as well as specify the molecular pathways deregulated in PD. METHODS: Initially, brain-enriched miRNAs were selected based on literature review and validation studies in human tissues. Subsequently, real-time reverse transcription polymerase chain reaction was performed in the plasma of 100 healthy controls and 99 idiopathic and 53 genetic (26 alpha-synucleinA53T and 27 glucocerebrosidase) patients. Statistical and bioinformatics analyses were carried out to pinpoint the diagnostic biomarkers and deregulated pathways, respectively. RESULTS: An explicit molecular fingerprint for each of the 3 PD cohorts was generated. Although the idiopathic PD fingerprint was different from that of genetic PD, the molecular pathways deregulated converged between all PD subtypes. CONCLUSIONS: The study provides a group of brain-enriched miRNAs that may be used for the detection and differentiation of PD subtypes. It has also identified the molecular pathways deregulated in PD. © 2019 International Parkinson and Movement Disorder Society.
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MicroRNA Circulante , MicroRNAs , Doença de Parkinson , Encéfalo/metabolismo , Humanos , MicroRNAs/genética , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , alfa-Sinucleína/metabolismoRESUMO
BACKGROUND: The Movement Disorder Society diagnostic criteria for progressive supranuclear palsy introduced the diagnostic certainty level "suggestive of progressive supranuclear palsy" for clinical conditions with subtle signs, suggestive of the disease. This category aims at the early identification of patients, in whom the diagnosis may be confirmed as the disease evolves. OBJECTIVE: To assess the diagnostic performance of the defined clinical conditions suggestive of progressive supranuclear palsy in an autopsy-confirmed cohort. METHODS: Diagnostic performance of the criteria was analyzed based on retrospective clinical data of 204 autopsy-confirmed patients with progressive supranuclear palsy and 216 patients with other neurological diseases. RESULTS: The conditions suggestive of progressive supranuclear palsy strongly increased the sensitivity compared to the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria. Within the first year after symptom onset, 40% of patients with definite progressive supranuclear palsy fulfilled criteria for suggestive of progressive supranuclear palsy. Two-thirds of patients suggestive of progressive supranuclear palsy evolved into probable progressive supranuclear palsy after an average of 3.6 years. Application of the criteria for suggestive of progressive supranuclear palsy reduced the average time to diagnosis from 3.8 to 2.2 years. CONCLUSIONS: Clinical conditions suggestive of progressive supranuclear palsy allow earlier identification of patients likely to evolve into clinically possible or probable progressive supranuclear and to have underlying progressive supranuclear palsy pathology. Further work needs to establish the specificity and positive predictive value of this category in real-life clinical settings, and to develop specific biomarkers that enhance their diagnostic accuracy in early disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Transtornos dos Movimentos , Paralisia Supranuclear Progressiva , Autopsia , Humanos , National Institute of Neurological Disorders and Stroke (USA) , Estudos Retrospectivos , Paralisia Supranuclear Progressiva/diagnóstico , Estados UnidosRESUMO
Fifty-five years have passed from the first description of PSP, but it is in the last decade that there has been a revolutionary change in understanding both clinical and pathophysiological aspects of this disease. Ten years ago, our knowledge about the clinical spectrum and pathophysiology of the disease was quite limited, and there was no credible clinical study on any drug treatment for this devastating disease. Today, we have discovered the wide clinical spectrum of PSP, and this led to the development of new diagnostic criteria in 2017, aiming to diagnose the disease earlier and include more phenotypes into clinical studies. Moreover, just over the past 10 years, numerous large, double-blind, clinical trials with disease-modifying agents have been conducted that provided important novel insights into disease biomarkers and progression. These studies were possible because of gained novel insights into pathophysiological processes of the disease and pave the way for the near future. In the next decade, we dare to predict the discovery of biomarkers for PSP, improvements in diagnosis using the new criteria in combination with these biomarkers, and ultimately the development of a neuroprotective therapy that could be applied to patients in a prodromal stage and spare them from this devastating disorder. © 2019 International Parkinson and Movement Disorder Society.
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Paralisia Supranuclear Progressiva/terapia , Previsões , História do Século XXI , Humanos , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/história , Transtornos Parkinsonianos/terapia , Paralisia Supranuclear Progressiva/diagnóstico , Paralisia Supranuclear Progressiva/históriaRESUMO
BACKGROUND: The International Parkinson and Movement Disorder Society recently introduced a methodology for probability score calculation for prodromal PD. OBJECTIVES: To assess the probability of prodromal PD in an older population and investigate its possible association with Mediterranean diet adherence. METHODS: Data from a population-based cohort study of older adults (HEllenic Longitudinal Investigation of Aging and Diet) in Greece were used. Probability of prodromal PD was calculated according to International Parkinson and Movement Disorder Society research criteria. A detailed food frequency questionnaire was used to evaluate dietary intake and calculate Mediterranean diet adherence score, ranging from 0 to 55, with higher scores indicating higher adherence. RESULTS: Median probability of prodromal PD was 1.9%, ranging from 0.2 to 96.7% in 1,731 PD-free individuals aged ≥ 65 (41% male). Lower probability for prodromal PD (P < 0.001) in the higher Mediterranean diet adherence groups was noted, driven mostly by nonmotor markers of prodromal PD, depression, constipation, urinary dysfunction, and daytime somnolence. Each unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal PD (P < 0.001). Compared to participants in the lowest quartile of Mediterranean diet adherence, those in the highest quartile were associated with a â¼21% lower probability for prodromal PD. CONCLUSIONS: Adherence to the Mediterranean diet is associated with lower probability of prodromal PD in older people. Further studies are needed to elucidate the potential causality of this association, potential relation of the Mediterranean diet to delayed onset or lower incidence of PD, as well as the underlying neurobiological mechanisms. © 2018 International Parkinson and Movement Disorder Society.
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Dieta Mediterrânea , Doença de Parkinson/prevenção & controle , Idoso , Biomarcadores/análise , Estudos de Coortes , Constipação Intestinal , Depressão/etiologia , Feminino , Grécia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Sintomas Prodrômicos , Cooperação e Adesão ao TratamentoRESUMO
BACKGROUND: Identification and characterization of Parkinson's disease (PD) in its prodromal stage is crucial. OBJECTIVE: The objective of this study was to investigate the association between motor function and the probability of prodromal PD in a community-dwelling older population. METHODS: We used data from a population-based cohort of older adults (HELIAD study). Subjective motor function was evaluated with a 12-item motor symptoms questionnaire and objective motor function indirectly with a physical activity questionnaire and two gait speed tests. The probability of prodromal PD was calculated according to the Movement Disorder Society research criteria for n = 1731 without PD. Regression multiadjusted models were used to investigate the associations between each motor measure and prodromal PD probability. RESULTS: For each unit increase in motor symptoms score and for each kcal/kg/day lower energy expenditure (corresponding to 20 minutes of light walking/day for a 75-kg man) there was a 27% and 3% higher probability for prodromal PD, respectively (P < 0.001). Having at least one subjective motor symptom increased the odds of having possible/probable prodromal PD (n = 49; P < 0.05). Including subjective and indirect motor variables in the same model showed that both (symptoms and physical activity) contributed significantly to the model (P < 0.01). Excluding subthreshold parkinsonism from the calculation showed that gait speed less than 0.8 m/s was also associated with a higher prodromal PD probability score (P < 0.001). CONCLUSIONS: Subjective motor symptoms as well as simple objective motor measures of physical activity or gait speed are associated with a higher probability of prodromal PD in older adults. These data may serve to enable the early identification of prodromal PD cohorts, particularly if they are confirmed in longitudinal studies. © 2019 International Parkinson and Movement Disorder Society.
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Transtornos dos Movimentos/diagnóstico , Movimento , Doença de Parkinson/diagnóstico , Sintomas Prodrômicos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Depressão/psicologia , Metabolismo Energético , Feminino , Marcha , Grécia/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Probabilidade , Escalas de Graduação Psiquiátrica , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The Movement Disorder Society criteria for progressive supranuclear palsy define diagnostic allocations, stratified by certainty levels and clinical predominance types. We aimed to study the frequency of ambiguous multiple allocations and to develop rules to eliminate them. METHODS: We retrospectively collected standardized clinical data by chart review in a multicenter cohort of autopsy-confirmed patients with progressive supranuclear palsy, to classify them by diagnostic certainty level and predominance type and to identify multiple allocations. RESULTS: Comprehensive data were available from 195 patients. More than one diagnostic allocation occurred in 157 patients (80.5%). On average, 5.4 allocations were possible per patient. We developed four rules for Multiple Allocations eXtinction (MAX). They reduced the number of patients with multiple allocations to 22 (11.3%), and the allocations per patient to 1.1. CONCLUSIONS: The proposed MAX rules help to standardize the application of the Movement Disorder Society criteria for progressive supranuclear palsy. © 2019 International Parkinson and Movement Disorder Society.
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Disfunção Cognitiva/fisiopatologia , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos Parkinsonianos/fisiopatologia , Equilíbrio Postural , Transtornos de Sensação/fisiopatologia , Paralisia Supranuclear Progressiva/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Encéfalo/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sociedades Médicas , Paralisia Supranuclear Progressiva/classificação , Paralisia Supranuclear Progressiva/patologia , Paralisia Supranuclear Progressiva/fisiopatologiaRESUMO
Introduction: Progressive supranuclear palsy (PSP) is a common cause of atypical parkinsonism and a rapidly progressive disease that greatly burdens both patients and caregivers. Drugs with disease-modifying potential, targeting mechanisms implicated in the disease's pathogenesis are currently tested in Phase 1 and 2 trials. If proven efficacious, these compounds might provide substantial benefits not only to patients with PSP but to patients with other tauopathies as well. Areas covered: Drugs in Phase 1 and 2 trials in PSP, and Phase 2 trials in other tauopathies (Alzheimer's disease) are reviewed. Expert opinion: The rationale behind the currently tested compounds as well as the tools available to document a treatment effect offer hope for a therapeutic breakthrough in PSP. The current lack of sufficiently validated biomarkers remains a hurdle that needs to be overcome, in order to facilitate both clinical trials and the accurate prescription of future treatments.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Antiparkinsonianos/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Paralisia Supranuclear Progressiva/tratamento farmacológico , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Animais , Anticorpos Monoclonais/administração & dosagem , Antiparkinsonianos/administração & dosagem , Inibidores da Colinesterase/administração & dosagem , Descoberta de Drogas , Humanos , Camundongos , Fármacos Neuroprotetores/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Paralisia Supranuclear Progressiva/etiologia , Paralisia Supranuclear Progressiva/metabolismo , Resultado do Tratamento , Proteínas tau/metabolismoRESUMO
OBJECTIVE: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories. METHODS: Thirteen recent news stories from high-impact English-language media outlets that portrayed patients with complex symptoms either attributed to other diagnoses or presented as medical mysteries were identified using online keyword searches. All selected news stories contained video or still images displaying relevant symptoms. Cases were categorized into movement disorders or seizure disorders and were then independently assessed by 10 respective expert raters. For each category, one story of a patient whose symptoms were due to a well-recognized neurological disease was also included. Both the diagnostic category and the respective confidence level were reported by each rater for each case. The interrater agreement was calculated for each group of disorders. RESULTS: The raters confirmed almost unanimously that all presented news stories except the negative control cases portrayed misidentified functional movement or seizure disorders. The interrater agreement and average diagnostic confidence were high. CONCLUSIONS: Functional neurological disorders are often wrongly considered a rare medical curiosity of the past. However, these findings suggest that, while they are largely absent from public discourse, they often appear in the news incognito, hiding in plain sight.
Assuntos
Conscientização , Epilepsia/epidemiologia , Meios de Comunicação de Massa , Transtornos dos Movimentos/epidemiologia , Adolescente , Adulto , Epilepsia/psicologia , Feminino , Humanos , Masculino , Transtornos dos Movimentos/psicologiaRESUMO
Reports of primary isolated dystonia inherited in an autosomal-recessive (AR) manner, often lumped together as "DYT2 dystonia," have appeared in the scientific literature for several decades, but no genetic cause has been identified to date. Using a combination of homozygosity mapping and whole-exome sequencing in a consanguineous kindred affected by AR isolated dystonia, we identified homozygous mutations in HPCA, a gene encoding a neuronal calcium sensor protein found almost exclusively in the brain and at particularly high levels in the striatum, as the cause of disease in this family. Subsequently, compound-heterozygous mutations in HPCA were also identified in a second independent kindred affected by AR isolated dystonia. Functional studies suggest that hippocalcin might play a role in regulating voltage-dependent calcium channels. The identification of mutations in HPCA as a cause of AR primary isolated dystonia paves the way for further studies to assess whether "DYT2 dystonia" is a genetically homogeneous condition or not.