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BACKGROUND: Latin America has played a crucial role in advancing our understanding of Huntington's disease (HD). However, previous global reviews include limited data from Latin America. It is possible that English-based medical search engines may not capture all the relevant studies. METHODS: We searched databases in Spanish, Portuguese, and English. The names of every country in Latin America in English-based search engines were used to ensure we found any study that had molecular ascertainment and provided general epidemiological information or subpopulation data. Additionally, we contacted experts across the region. RESULTS: The search strategy yielded 791 citations; 24 studies met inclusion criteria, representing 12 of 36 countries. The overall pooled prevalence was 0.64 per 100,000 (prediction interval, 0.06-7.22); for cluster regions, it was 54 per 100,000 (95% CI, 34.79-84.92); for juvenile HD, it was 8.7% (prediction interval, 5.12-14.35), and 5.9% (prediction interval, 2.72-13.42) for late-onset HD. The prevalence was higher for Mexico, Peru, and Brazil. However, there were no significant differences between Central America and the Caribbean versus South America. CONCLUSION: The prevalence of HD appears to be similar across Latin America. However, we infer that our findings are underestimates, in part because of limited research and underdiagnosis of HD because of limited access to molecular testing and the availability of neurologists and movement disorders specialists. Future research should focus on identifying pathways to improve access to molecular testing and education and understanding differences among different ancestral groups in Latin America. © 2024 International Parkinson and Movement Disorder Society.
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BACKGROUND AND PURPOSE: Clinical correlates of fear of falling (FoF) are scarcely studied in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). This study was undertaken to evaluate the clinical correlates of FoF in PSP and MSA. METHODS: This cross-sectional study features motor, cognitive, and psychiatric assessment and longitudinal evaluation of falls and FoF at 6-month follow-up. RESULTS: Twenty-one patients with PSP-parkinsonism, 22 patients with MSA (13 parkinsonian type and nine cerebellar type), and 22 healthy controls were evaluated; 76.2% of patients with PSP and 86.4% of patients with MSA had FoF regardless of falls. Berg Balance Scale (p < 0.001), Tinetti Mobility Test (p < 0.01), Beck Anxiety Inventory (p = 0.001), and Beck Depression Inventory-II (p = 0.01) correlated with FoF in patients with PSP and MSA, whereas Timed Up and Go test (p = 0.01) and Starkstein Apathy Scale correlated only in MSA (p = 0.04). CONCLUSIONS: Mobility, balance, and gait performance as well as anxiety and depression in PSP and MSA, and apathy in MSA, were determinants of FoF. These findings underline the importance of a multidisciplinary approach to FoF in neurodegenerative atypical parkinsonism.
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Atrofia de Múltiples Sistemas , Trastornos Parkinsonianos , Parálisis Supranuclear Progresiva , Humanos , Estudios Transversales , Equilibrio Postural , Miedo , Estudios de Tiempo y MovimientoRESUMEN
Spinocerebellar ataxia type 17 or ATX-TBP is a CAG/CAA repeat expansion disorder characterized by marked clinical heterogeneity. Reports of affected carriers with subthreshold repeat expansions and of patients with Parkinson's disease (PD) with expanded repeats have cast doubt on the established cutoff values of the expansions and the phenotypic spectrum of this disorder. The objective of this systematic review was to explore the genotype-phenotype relationships for repeat expansions in TBP to delineate the ATX-TBP phenotype and reevaluate the pathological range of repeat expansions. The International Parkinson and Movement Disorder Society Genetic Mutation Database (MDSGene) standardized data extraction protocol was followed. Clinically affected carriers of reported ATX-TBP expansions were included. Publications that contained repeat sizes in screened cohorts of patients with PD and/or healthy individuals were included for a separate evaluation of cutoff values. Phenotypic and genotypic data for 346 ATX-TBP patients were curated. Overall, 97.7% of the patients had ≥41 repeats, while 99.6% of patients with PD and 99.9% of healthy individuals had ≤42 repeats, with a gray zone of reduced penetrance between 41 and 45 repeats. Pure parkinsonism was more common in ATX-TBP patients with 41 to 45 repeats than in the group with ≥46 repeats, which conversely more often presented with a complex phenotype with mixed movement disorders. An updated genotype-phenotype assessment for ATX-TBP is provided, and new repeat expansion cutoff values of reduced penetrance (41-45 expanded repeats) and full penetrance (46-66 expanded repeats) are proposed. These adjusted cutoff values will have diagnostic and counseling implications and may guide future clinical trial protocol. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Enfermedad de Parkinson , Ataxias Espinocerebelosas , Humanos , Estudios de Asociación Genética , Enfermedad de Parkinson/genética , Ataxias Espinocerebelosas/genética , Proteína de Unión a TATA-Box/genética , Expansión de Repetición de TrinucleótidoRESUMEN
BACKGROUND: Mutations in the glucocerebrosidase (GBA) gene represent the most common genetic risk factor for Parkinson's Disease (PD) and are associated with a more aggressive motor phenotype at late stages. However, the motor response at early stages of disease remains understudied. METHODS: Retrospective study of PD patients that underwent next-generation sequencing panel tests for PD-related genes. We extracted demographic data and the MDS-UPDRS III response to an acute levodopa challenge (LDC), the best ON score, and the levodopa equivalent daily dose (LEDD) during the first six months after the LDC and initiation of DRT. We compared the response of GBA-PD patients to that of patients without pathogenic variants or rearrangements in other PD related genes (sporadic PD). RESULTS: 13 GBA-PD and 48 sporadic PD patients were identified. Baseline MDS-UPDRS III score (24.6 ± 9.6 vs. 21.8 ± 9.3. p = 0.4), response to LDC (39.2% ± 7.9% vs. 32.7% ± 13.4%; p = 0.1), best ON score (36.9% ± 39.5% vs. 41.6% ± 20.8%; p = 0.6) and LEDD (188 mg ± 100 mg vs. 261.8 mg ± 164.8 mg; p = 0.2) during the first six months after initiation of DRT were not different between GBA-PD and sporadic PD patients. CONCLUSIONS: At early disease stages of GBA-PD, the motor response to acute levodopa challenge test and the initial response to DRT are similar to that of patients with sporadic PD. Although limited by small sample size, these preliminary findings should be confirmed by future prospective larger studies.
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Glucosilceramidasa , Enfermedad de Parkinson , Dopamina , Glucosilceramidasa/genética , Humanos , Levodopa/uso terapéutico , Mutación/genética , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Estudios RetrospectivosRESUMEN
In 2016, the Movement Disorder Society Task Force for the Nomenclature of Genetic Movement Disorders presented a new system for naming genetically determined movement disorders and provided a criterion-based list of confirmed monogenic movement disorders. Since then, a substantial number of novel disease-causing genes have been described, which warrant classification using this system. In addition, with this update, we further refined the system and propose dissolving the imaging-based categories of Primary Familial Brain Calcification and Neurodegeneration with Brain Iron Accumulation and reclassifying these genetic conditions according to their predominant phenotype. We also introduce the novel category of Mixed Movement Disorders (MxMD), which includes conditions linked to multiple equally prominent movement disorder phenotypes. In this article, we present updated lists of newly confirmed monogenic causes of movement disorders. We found a total of 89 different newly identified genes that warrant a prefix based on our criteria; 6 genes for parkinsonism, 21 for dystonia, 38 for dominant and recessive ataxia, 5 for chorea, 7 for myoclonus, 13 for spastic paraplegia, 3 for paroxysmal movement disorders, and 6 for mixed movement disorder phenotypes; 10 genes were linked to combined phenotypes and have been assigned two new prefixes. The updated lists represent a resource for clinicians and researchers alike and they have also been published on the website of the Task Force for the Nomenclature of Genetic Movement Disorders on the homepage of the International Parkinson and Movement Disorder Society (https://www.movementdisorders.org/MDS/About/Committees--Other-Groups/MDS-Task-Forces/Task-Force-on-Nomenclature-in-Movement-Disorders.htm). © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
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Distonía , Trastornos Distónicos , Trastornos del Movimiento , Enfermedad de Parkinson , Trastornos Parkinsonianos , Distonía/genética , Trastornos Distónicos/genética , Humanos , Trastornos del Movimiento/genética , Trastornos Parkinsonianos/genética , FenotipoRESUMEN
INTRODUCTION: The implementation of accepted clinical diagnostic criteria has improved the accuracy of a clinical diagnosis of Parkinson's disease (PD). Time frames of 3-10 years have been empirically proposed to reach a diagnosis of clinically established PD. METHODS: We explored the time to a Final Clinical Diagnosis (FCD) and the factors that predict faster diagnoses in patients presenting with parkinsonism and/or tremor between 2009 and 2015 at our tertiary center. All patients underwent a standardized workout process to reach a FCD, which included an acute levodopa challenge (LDC) after the first visit. RESULTS: Among the 326 patients included, 215 (66%) received a FCD within the first six months after the LDC. A FCD was reached in 95% and 100% of patients in 33 and 108 months, respectively. PD was the FCD in 196 patients (60.1%). The FCD was reached faster in patients with a positive response to levodopa and when the FCD was PD. CONCLUSION: The time needed to reach a final diagnosis in the clinical setting was 2.75 years in 95% of patients presenting initially with parkinsonism and/or tremor. Patients with positive responses to levodopa at the LDC, benefited from shorter delays until the FCD.
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Enfermedad de Parkinson/diagnóstico , Trastornos Parkinsonianos/diagnóstico , Evaluación de Síntomas/estadística & datos numéricos , Factores de Tiempo , Temblor/diagnóstico , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Levodopa , Masculino , Persona de Mediana Edad , Evaluación de Síntomas/métodosRESUMEN
OBJECTIVE: To determine whether technetium-99m-labeled tropane derivative single-photon emission computed tomography (99mTc-TRODAT-1 SPECT) provides results comparable to those of the less widely available, less accessible tool fluorine-18-labeled fluorodopa positron-emission tomography (18F-FDOPA PET) in the setting of a movement disorders clinic. MATERIALS AND METHODS: In this prospective pilot study, eight subjects with a clinical diagnosis of Parkinson's disease were randomly selected from among patients under treatment at a movement disorders clinic and submitted to 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET. The results were read by two experienced observers, and a semiquantitative analysis was performed. RESULTS: The visual and semiquantitative analyses were concordant for all studies, showing that radiotracer uptake in the contralateral striatum on the most affected side was lower when 99mTc-TRODAT-1 SPECT was employed. The semiquantitative analysis demonstrated a significant correlation between 18F-FDOPA PET and 99mTc-TRODAT-1 SPECT (r = 0.73; p < 0.01). CONCLUSION: It appears that 99mTc-TRODAT-1 SPECT is a valid option for the study of dopaminergic function in a clinical setting.
OBJETIVO: Determinar se a 99mTc-TRODAT-1 SPECT fornece resultados comparáveis aos da 18F-FDOPA PET, ferramenta menos acessível e menos amplamente disponível, no contexto de uma clínica de distúrbios do movimento. MATERIAIS E MÉTODOS: Neste estudo prospectivo, oito indivíduos com diagnóstico clínico de doença de Parkinson foram selecionados aleatoriamente entre pacientes em tratamento em uma clínica de distúrbios do movimento e submetidos a 99mTc-TRODAT-1 SPECT e 18F-FDOPA PET. Os resultados foram lidos por dois observadores experientes e uma análise semiquantitativa foi realizada. RESULTADOS: As análises visual e semiquantitativa foram concordantes para todos os estudos, mostrando que a captação do radiotraçador no estriado contralateral do lado mais afetado foi menor quando a 99mTc-TRODAT-1 SPECT foi empregada. A análise semiquantitativa demonstrou uma correlação significativa entre 18F-FDOPA PET e 99mTc-TRODAT-1 SPECT (r = 0,73; p < 0,01). CONCLUSÃO: A 99mTc-TRODAT-1 SPECT parece ser uma opção válida para o estudo da função dopaminérgica em um ambiente clínico.
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Abstract Objective: To determine whether technetium-99m-labeled tropane derivative single-photon emission computed tomography (99mTc-TRODAT-1 SPECT) provides results comparable to those of the less widely available, less accessible tool fluorine-18-labeled fluorodopa positron-emission tomography (18F-FDOPA PET) in the setting of a movement disorders clinic. Materials and Methods: In this prospective pilot study, eight subjects with a clinical diagnosis of Parkinson's disease were randomly selected from among patients under treatment at a movement disorders clinic and submitted to 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET. The results were read by two experienced observers, and a semiquantitative analysis was performed. Results: The visual and semiquantitative analyses were concordant for all studies, showing that radiotracer uptake in the contralateral striatum on the most affected side was lower when 99mTc-TRODAT-1 SPECT was employed. The semiquantitative analysis demonstrated a significant correlation between 18F-FDOPA PET and 99mTc-TRODAT-1 SPECT (r = 0.73; p < 0.01). Conclusion: It appears that 99mTc-TRODAT-1 SPECT is a valid option for the study of dopaminergic function in a clinical setting.
Resumo Objetivo: Determinar se a 99mTc-TRODAT-1 SPECT fornece resultados comparáveis aos da 18F-FDOPA PET, ferramenta menos acessível e menos amplamente disponível, no contexto de uma clínica de distúrbios do movimento. Materiais e Métodos: Neste estudo prospectivo, oito indivíduos com diagnóstico clínico de doença de Parkinson foram selecionados aleatoriamente entre pacientes em tratamento em uma clínica de distúrbios do movimento e submetidos a 99mTc-TRODAT-1 SPECT e 18F-FDOPA PET. Os resultados foram lidos por dois observadores experientes e uma análise semiquantitativa foi realizada. Resultados: As análises visual e semiquantitativa foram concordantes para todos os estudos, mostrando que a captação do radiotraçador no estriado contralateral do lado mais afetado foi menor quando a 99mTc-TRODAT-1 SPECT foi empregada. A análise semiquantitativa demonstrou uma correlação significativa entre 18F-FDOPA PET e 99mTc-TRODAT-1 SPECT (r = 0,73; p < 0,01). Conclusão: A 99mTc-TRODAT-1 SPECT parece ser uma opção válida para o estudo da função dopaminérgica em um ambiente clínico.
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BACKGROUND: Several conditions represented mainly by movement disorders are associated with cardiac disease, which can be overlooked in clinical practice in the context of a prominent primary neurological disorder. OBJECTIVES: To review neurological conditions that combine movement disorders and primary cardiac involvement. METHODS: A comprehensive and structured literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was conducted to identify disorders combining movement disorders and cardiac disease. RESULTS: Some movement disorders are commonly or prominently associated with cardiac disease. Neurological and cardiac symptoms may share underlying physiopathological mechanisms in diseases, such as Friedreich's ataxia and Wilson's disease, and in certain metabolic disorders, including Refsum disease, Gaucher disease, a congenital disorder of glycosylation, or cerebrotendinous xanthomatosis. In certain conditions, such as Sydenham's chorea or dilated cardiomyopathy with ataxia syndrome (ATX-DNAJC19), heart involvement can present early in the course of disease, whereas in others such as Friedreich's ataxia or Refsum disease, cardiac symptoms tend to present in later stages. In another 68 acquired or inherited conditions, cardiac involvement or movement disorders are seldom reported. CONCLUSIONS: As cardiac disease is part of the phenotypic spectrum of several movement disorders, heart involvement should be carefully investigated and increased awareness of this association encouraged as it may represent a leading cause of morbidity and mortality.
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Involuntary moaning has been reported in sporadic cases of neurodegenerative diseases. A five-generation Hispanic family with eight members exhibiting involuntary moaning, most of whom with isolated moaning in the absence of any additional neurological disorder carried a missense variant in the NEFH gene segregating in the family.
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Trastornos Heredodegenerativos del Sistema Nervioso/genética , Proteínas de Neurofilamentos/genética , Adulto , Niño , Femenino , Trastornos Heredodegenerativos del Sistema Nervioso/fisiopatología , Heterocigoto , Hispánicos o Latinos , Humanos , Masculino , Mutación Missense , Linaje , Fonética , Tics/genéticaRESUMEN
BACKGROUND: A myriad of disorders combine myoclonus and ataxia. Most causes are genetic and an increasing number of genes are being associated with myoclonus-ataxia syndromes (MAS), due to recent advances in genetic techniques. A proper etiologic diagnosis of MAS is clinically relevant, given the consequences for genetic counseling, treatment, and prognosis. OBJECTIVES: To review the causes of MAS and to propose a diagnostic algorithm. METHODS: A comprehensive and structured literature search following PRISMA criteria was conducted to identify those disorders that may combine myoclonus with ataxia. RESULTS: A total of 135 causes of combined myoclonus and ataxia were identified, of which 30 were charted as the main causes of MAS. These include four acquired entities: opsoclonus-myoclonus-ataxia syndrome, celiac disease, multiple system atrophy, and sporadic prion diseases. The distinction between progressive myoclonus epilepsy and progressive myoclonus ataxia poses one of the main diagnostic dilemmas. CONCLUSIONS: Diagnostic algorithms for pediatric and adult patients, based on clinical manifestations including epilepsy, are proposed to guide the differential diagnosis and corresponding work-up of the most important and frequent causes of MAS. A list of genes associated with MAS to guide genetic testing strategies is provided. Priority should be given to diagnose or exclude acquired or treatable disorders.
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BACKGROUND: We assessed the clinimetric properties of ataxia rating scales and functional tests, and made recommendations regarding their use. METHODS: A systematic literature search was conducted to identify the instruments used to rate ataxia symptoms. The identified rating scales and functional ability tests were reviewed and ranked by the panel as "recommended," "suggested," or "listed" for the assessment of patients with discrete cerebellar disorders, using previously established criteria. RESULTS: We reviewed 14 instruments (9 rating scales and 5 functional tests). "Recommended" rating scales for the assessment of symptoms severity were: for Friedreich's ataxia, the Friedreich's Ataxia Rating Scale, the International Cooperative Ataxia Rating Scale (ICARS), and the Scale for the Assessment and Rating of Ataxia (SARA); for spinocerebellar ataxias, ICARS and SARA; for ataxia telangiectasia: ICARS and SARA; for brain tumors, SARA; for congenital disorder of glycosylation-phosphomannomutase-2 deficiency, ICARS; for cerebellar symptoms in multiple sclerosis, ICARS; for cerebellar symptoms in multiple system atrophy: Unified Multiple System Atrophy Rating Scale and ICARS; and for fragile X-associated tremor ataxia syndrome, ICARS. "Recommended" functional tests were: for Friedreich's ataxia, Ataxia Functional Composite Score and Composite Cerebellar Functional Severity Score; and for spinocerebellar ataxias, Ataxia Functional Composite Score, Composite Cerebellar Functional Severity Score, and SCA Functional Index. CONCLUSIONS: We identified some "recommended" scales and functional tests for the assessment of patients with major hereditary ataxias and other cerebellar disorders. The main limitations of these instruments include the limited assessment of patients in the more severe end of the spectrum and children. Further research in these populations is warranted. © 2020 International Parkinson and Movement Disorder Society.