RESUMO
BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Assuntos
Cromossomos Humanos X , Doença de Parkinson , Feminino , Humanos , Masculino , Estudo de Associação Genômica Ampla , Hispânico ou Latino , América Latina , Doença de Parkinson/genética , Fatores Sexuais , Cromossomos Humanos X/genética , Desequilíbrio de Ligação/genéticaRESUMO
Sydenham's chorea (SC) is characterized by a combination of motor and behavioral findings. Cognitive function has been scarcely studied in this condition. The aim of this study is to investigate executive functions in adult patients with SC. We performed neuropsychological tests to evaluate executive functions in controls and adult patients with persistent and in remission SC. Patients with SC have impairment in Tower of London task, reduced verbal fluency, and lower scores in the Stroop test. A subset of adult patients with SC present with executive dysfunction, even when chorea is in remission.
Assuntos
Coreia/epidemiologia , Transtornos Cognitivos/epidemiologia , Função Executiva , Adolescente , Adulto , Idade de Início , Antibacterianos/uso terapêutico , Antidiscinéticos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Coreia/tratamento farmacológico , Coreia/fisiopatologia , Transtornos Cognitivos/diagnóstico , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Penicilina G Benzatina/uso terapêutico , Pimozida/uso terapêutico , Índice de Gravidade de Doença , Ácido Valproico/uso terapêutico , Adulto JovemRESUMO
Sydenham's chorea (SC) is a complication of Streptococcus infection characterized by a combination of motor and non-motor features. We have investigated the presence of vocalizations in 89 consecutive patients with SC evaluated during a one-year period in the UFMG Movement Disorders Clinic. Seven (4/3 M/F) of the 89 patients (29/60 M/F) presented with simple vocalizations not preceded by premonitory sensations but in association with facial chorea in five patients. These findings suggest that vocalizations are not a common feature in SC and their phenomenology is quite distinct from the characteristics of vocal tics in tic disorders.
Assuntos
Coreia/complicações , Distúrbios da Voz/etiologia , Adolescente , Criança , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
Diseases with a choreic phenotype can be due to a variety of genetic etiologies. As testing for Huntington's disease (HD) becomes more available in previously resource-limited regions, it is becoming apparent that there are patients in these areas with other rare genetic conditions which cause an HD-like phenotype. Documentation of the presence of these conditions is important in order to provide appropriate diagnostic and clinical care for these populations. Information for this article was gathered in two ways; the literature was surveyed for publications reporting a variety of genetic choreic disorders, and movement disorders specialists from countries in Latin America and the Caribbean were contacted regarding their experiences with chorea of genetic etiology. Here we discuss the availability of molecular diagnostics for HD and for other choreic disorders, along with a summary of the published reports of affected subjects, and authors' personal experiences from the regions. While rare, patients affected by non-HD genetic choreas are evidently present in Latin America and the Caribbean. HD-like 2 is particularly prevalent in countries where the population has African ancestry. The incidence of other conditions is likely determined by other variations in ethnic background and settlement patterns. As genetic resources and awareness of these disorders improve, more patients are likely to be identified, and have the potential to benefit from education, support, and ultimately molecular therapies.
Assuntos
Coreia/epidemiologia , Transtornos Cognitivos/epidemiologia , Demência/epidemiologia , Transtornos Heredodegenerativos do Sistema Nervoso/epidemiologia , Doença de Huntington/epidemiologia , Neuroacantocitose/epidemiologia , Ataxias Espinocerebelares/epidemiologia , Região do Caribe/epidemiologia , Coreia/genética , Transtornos Cognitivos/genética , Demência/genética , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Humanos , Doença de Huntington/genética , América Latina/epidemiologia , Neuroacantocitose/genética , Ataxias Espinocerebelares/genéticaRESUMO
Serious adverse effects with antichoreic drugs can occur in patients with acute Sydenham's chorea (SC). The response to conventional treatment in severe SC may also be poor. Thus alternative therapeutic strategies have been developed. We report on four patients with severe acute SC (two with chorea paralytica and two with neuroleptic-induced parkinsonism) treated with i.v. methyl-prednisolone pulse-therapy followed by oral prednisone. The mean+/-SEM clinical rating score dropped from 63.7+/-10.2 to 33.5+/-10.6 in the first month post-treatment but in a lesser degree thereafter. Only one patient developed weight gain and 'moon facies'. This case series suggests that immune suppression with corticosteroids may be an effective and safe treatment in complicated and severe acute SC.
Assuntos
Coreia/tratamento farmacológico , Metilprednisolona/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Doença Aguda , Criança , Pré-Escolar , Feminino , Humanos , Injeções Intravenosas , Masculino , Pulsoterapia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Sydenham's chorea is associated with dysfunction of fronto-striatal circuits induced by cross-reactive antibodies to group A ß-hemolytic streptococcus. High susceptibility of extrapyramidal effects of neuroleptics in patients with Sydenham's chorea suggests underlying nigro-striatal dysfunction. OBJECTIVE: To study the presence of parkinsonism in patients with a history of Sydenham's Chorea. METHODS: We used the UFMG Sydenham's Chorea Rating Scale (USCRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, respectively, to determine the presence of chorea and parkinsonian symptoms and signs in 25 adults with a history of previous Sydenham's Chorea currently without chorea or use of anti-choreic drugs. RESULTS: Bradykinesia was found in 64% of subjects. There was a statistically significant correlation between bradykinesia and hemichorea (-0.412; p = 0.036) and bradykinesia and generalized chorea (0.412; p = 0.036). There was no correlation between bradykinesia and use of anti-choreic drugs. CONCLUSIONS: Bradykinesia is common in patients with Sydenham's Chorea in remission. This finding suggests an immune-mediated dysfunction of the nigro-striatal system.
Assuntos
Coreia/complicações , Hipocinesia/fisiopatologia , Transtornos Parkinsonianos/etiologia , Adolescente , Adulto , Coreia/diagnóstico , Coreia/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Adulto JovemRESUMO
BACKGROUND: Sydenham's Chorea is a frequent cause of chorea during pregnancy, chorea gravidarum. The aim of this article is to describe the effect of pregnancy in a consecutive series of patients with diagnosis of Sydenham's Chorea. METHODS: A chart review was performed of all patients with the diagnosis of Sydenham's Chorea followed up at our institution from 07/1993 through 08/2010 and who became pregnant. RESULTS: From 66 patients, 20 became pregnant. Of these 20 patients, 15 (75%) developed chorea gravidarum. Generalized chorea was found in 67% of these 15 patients, focal or multifocal chorea was identified in 20% and 13.4% developed hemichorea. In 80% of cases chorea began in the first 6 months of gestation. Three women with previous persistent chorea experienced worsening of the movement disorder during pregnancy. Remission occurred after delivery in 11 patients whereas the other four remained with non-disabling chorea during the first 12 months after delivery. Abortion occurred in two patients (13%). All patients with chorea gravidarum subsequently treated with oral contraceptives developed recurrence of chorea. CONCLUSIONS: Chorea gravidarum is a frequent complication of pregnancy in patients with previous history of Sydenham's Chorea and an increased risk of miscarriage should be considered. Our findings confirm the notion that chorea gravidarum results from hormonal changes acting on previously dysfunctional basal ganglia.
Assuntos
Coreia/diagnóstico , Coreia/etiologia , Complicações na Gravidez/fisiopatologia , Adolescente , Adulto , Idade de Início , Coreia Gravídica/diagnóstico , Coreia Gravídica/etiologia , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
There are few studies of language and speech in patients with Sydenham's chorea (SC). We have done an acoustic analysis of fundamental frequency (F0), duration and intensity of declarative and interrogative sentences made by 20 SC patients, 20 patients with rheumatic fever (RF) without chorea, and compared them with 20 healthy age-matched controls (CO). Each group included 12 females. We found that there is no difference between the RF and CO groups in all studied parameters. Patients with SC, however, presented with a speech characterized by decreased F0 range (difference between minimum and maximum F0), shorter duration of sentences, and higher intensity of the first syllable of sentences. The findings were not influenced by the nature of the sentences (i.e. , declarative or interrogative), but for all variables they were significantly more severe in males than females. In conclusion, we have demonstrated that patients with acute SC have an impairment of modulation of F0 and longer duration of emission of sentences, resulting in a monotone and slow speech. This pattern is similar to what has been described in other basal ganglia illnesses, such as Parkinson's disease, Huntington's disease and Wilson's disease.
Assuntos
Coreia/fisiopatologia , Febre Reumática/fisiopatologia , Acústica da Fala , Percepção da Fala/fisiologia , Comportamento Verbal/fisiologia , Doença Aguda , Estudos de Casos e Controles , Criança , Feminino , Humanos , MasculinoRESUMO
Despite the renewed interest in Sydenham's chorea (SC) in recent years, there were no valid and reliable scales to rate the several signs and symptoms of patients with SC and related disorders. The Universidade Federal de Minas Gerais (UFMG) Sydenham's Chorea Rating Scale (USCRS) was designed to provide a detailed quantitative description of the performance of activities of daily living, behavioral abnormalities, and motor function of subjects with SC. The scale comprises 27 items and each one is scored from 0 (no symptom or sign) to 4 (severe disability or finding). Data from 84 subjects, aged 4.9 to 33.6 years, support the interrater reliability and internal consistency of the scale. The USCRS is a promising instrument for rating the clinical features of SC as well as their functional impact in children and adults.
Assuntos
Coreia/diagnóstico , Inquéritos e Questionários , Atividades Cotidianas , Adolescente , Adulto , Gânglios da Base/patologia , Criança , Pré-Escolar , Coreia/patologia , Avaliação da Deficiência , Análise Fatorial , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
There are few studies of language and speech in patients with Sydenham's chorea (SC). We have done an acoustic analysis of fundamental frequency (F0), duration and intensity of declarative and interrogative sentences made by 20 SC patients, 20 patients with rheumatic fever (RF) without chorea, and compared them with 20 healthy age-matched controls (CO). Each group included 12 females. We found that there is no difference between the RF and CO groups in all studied parameters. Patients with SC, however, presented with a speech characterized by decreased F0 range (difference between minimum and maximum F0), shorter duration of sentences, and higher intensity of the first syllable of sentences. The findings were not influenced by the nature of the sentences (i.e. , declarative or interrogative), but for all variables they were significantly more severe in males than females. In conclusion, we have demonstrated that patients with acute SC have an impairment of modulation of F0 and longer duration of emission of sentences, resulting in a monotone and slow speech. This pattern is similar to what has been described in other basal ganglia illnesses, such as Parkinson's disease, Huntington's disease and Wilson's disease.
Há poucos estudos sobre linguagem e fala em pacientes com coréia de Sydenham (CS). Fizemos uma análise acústica da freqüência fundamental (F0), duração e intensidade de sentenças declarativas e interrogativas feitas por 20 pacientes com CS, 20 pacientes com febre reumática (FR) sem coréia, comparando-os com 20 controles saudáveis e pareados por idade (CO). Cada grupo incluiu 12 mulheres. Foi encontrado que não há diferença entre os grupos FR e CO quanto a todos parâmetros estudados. Pacientes com CS, contudo, apresentaram-se com fala caracterizada pela redução da variação de F0 (diferença entre F0 mínima e máxima), duração mais curta das sentenças e maior intensidade da primeira sílaba das sentenças. Os achados não foram influenciados pela natureza das sentenças (i.e. , declarativas ou interrogativas), mas os achados foram mais evidentes em todas as variáveis em homens em contraste com mulheres. Em conclusão, demonstramos que pacientes com CS aguda têm prejuízo da modulação da F0 e duração mais longa da emissão de sentenças, resultando em fala mais lenta e monótona. Esse padrão é semelhante ao que tem sido descrito em outras fecções dos núcleos da base, tais como doença de Parkinson, doença de Huntington e doença de Wilson.