X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

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.

Clinical and functional correlates of parkinsonism in a population-based sample of individuals aged 75 + : the Pietà study.

BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG]. METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG individuals (64.8% women, median age of 80 years). RESULTS: PG individuals had significantly more functional impairment, clinical comorbidities (including number of falls, loss of bladder control and dysphagia) and major depression. Multivariate analysis revealed that older age, higher UPDRSm scores, lower category fluency test (animals/minute) and delayed recall memory scores were associated with PG. This group was also more cognitively impaired, with lower performance than NPG individuals in the Mini-Mental State Examination, category fluency test (animals/minute), clock drawing and in delayed recall (p < 0.001 for all tests). UPDRSm scores were the most contributing factor to cognition that independently explained variability in functionality of the entire sample. CONCLUSION: Individuals aged 75 + years with parkinsonism were significantly more clinically and functionally impaired in this population-based sample. Cognitive dysfunction explained most of the loss of functionality in these patients. UPDRS-m scores contributed independently to explain variability in functionality in the whole sample.

Parkinsonism in a population-based study of individuals aged 75+ years: The Pietà study.

INTRODUCTION: Parkinsonism is one of the most prevalent neurological syndromes in the elderly. There are only a few epidemiological studies focusing on parkinsonism in oldest-old individuals, particularly in Latin America. This study aims to investigate the prevalence and characteristics of parkinsonism in subjects aged 75 + years living in the community. METHODS: The Pietà study is a population-based investigation on brain aging conducted in Caeté, southeast Brazil. A sample composed of 610 community-dwelling individuals aged 75 + years (48.7% of the total population within this age range) underwent clinical, neurological, cognitive and functional assessments. RESULTS: The sample comprised mostly women (61.5%), with mean age of 83.3 years and mean schooling of 2.5 years. Parkinsonism was identified in 65 subjects (crude prevalence = 10.7%). Parkinson's disease, Parkinsonism + dementia syndrome, drug-induced parkinsonism, vascular parkinsonism and Lewy-body dementia were identified in, respectively, 19 (29.2%), 19 (29.2%), 8 (12.3%), 4 (6.1%) and 1 (1.5%) subjects. In 14 individuals (21.5%), the etiology of parkinsonism could not be determined. The most important vascular risk factor was hypertension (64.6%). Cognitive evaluation disclosed dementia in 37 (56.9%) subjects. Mean Pfeffer's functional activities questionnaire score was 12.2 points and 22 (33.8%) subjects were impaired in basic activities of daily living. CONCLUSION: Parkinsonism was common in this oldest-old population, being associated with dementia and vascular risk factors, particularly hypertension. Different confounders, such as concomitant dementia and exposure to anti-dopaminergic drugs, were present in this population, challenging the definition of causes of parkinsonism.

Síndrome de opsoclonia-mioclonia-ataxia em paciente com AIDS / Opsoclonus-myoclonus-ataxia syndrome in an AIDS patient

É relatado aqui o caso de uma mulher de 38 anos com AIDS que desenvolveu a síndrome de opsoclonia-mioclonia-ataxia em um período diferente dos outros casos já relatados na literatura. A síndrome de opsoclonia-mioclonia-ataxia já tinha sido relatada como manifestação inicial de AIDS, assim como no momento da soroconversão de HIV e na síndrome de reconstituição imune. Este caso é único, uma vez que a paciente tinha contagem elevada de CD4 e carga viral negativa no momento em que a síndrome de opsoclonia-mioclonia-ataxia ocorreu.

We report the case of a 38-year-old woman with AIDS who developed opsoclonus-myoclonus-ataxia syndrome during a period different from other cases reported in literature. Opsoclonus-myoclonus-ataxia syndrome had already been reported as the initial neurological presentation of AIDS, as well as at the time of HIV-seroconversion and immune reconstitution syndrome. Our case is unique since the patient had an elevated CD4 count and negative viral load in the period when the opsoclonus-myoclonus-ataxia syndrome occurred.

Prevalence and clinical classification of tremor in elderly--a community-based survey in Brazil.

Prevalence data on different types of tremor among the elderly population are very scarce. The objective of this study was to study the prevalence of tremor in a community-dwelling elderly population in the town of Bambuí, Brazil. The authors studied 1186 inhabitants aged≥64 years. This was a 2-phase study in which all participants who screened positive in a questionnaire for tremor and parkinsonism or who used drugs capable of causing/suppressing tremor were examined. In this population, the prevalence rate was 17.4% for tremor, 7.4% for essential tremor, 5.6% for parkinsonian tremor, 2.8% for enhanced physiological tremor, and 1.6% for other causes. There were no gender differences in prevalence rates for all types. Patients who had Parkinson's disease with tremor were older than those who had essential tremor, whereas patients who had enhanced physiological tremor were significantly younger. The age-specific prevalence of tremor increased with advancing age for both men and women. The prevalence of tremor in the studied population was high and increased with advancing age. Essential tremor, parkinsonian tremor, and enhanced physiological tremor were the most commonly identified causes. © 2013 Movement Disorder Society.

Opsoclonus-myoclonus-ataxia syndrome in an AIDS patient.

We report the case of a 38-year-old woman with AIDS who developed opsoclonus-myoclonus-ataxia syndrome during a period different from other cases reported in literature. Opsoclonus-myoclonus-ataxia syndrome had already been reported as the initial neurological presentation of AIDS, as well as at the time of HIV-seroconversion and immune reconstitution syndrome. Our case is unique since the patient had an elevated CD4 count and negative viral load in the period when the opsoclonus-myoclonus-ataxia syndrome occurred.

Pregnancy in patients with Sydenham's Chorea.

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.

Acoustic analysis of prosody in Sydenham's chorea.

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.

Acoustic analysis of prosody in Sydenham's chorea / Análise acústica da prosódia em coréia de Sydenham

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.

Parkinsonism and Parkinson's disease in the elderly: a community-based survey in Brazil (the Bambuí study).

Several community-based surveys on the prevalence of Parkinsonism and Parkinson's disease have been conducted worldwide, with variations on their methodology and results. The objective of this study is to assess the prevalence of Parkinsonism and its causes in a cohort of individuals age 64 years or older in Bambuí, a Brazilian town. In phase I, 1,186 people older than 64 years responded to a 9-question screening questionnaire for Parkinsonism. In phase II, all subjects who scored > or = 2 points on the test were examined independently by at least 2 movement disorder-trained physicians. A movement disorder senior specialist excluded or confirmed the diagnosis in all suspected cases. The response rate was high for both phases (96% for phase I and 94% for phase II). The prevalence rate per 100 population over 64 years of age in this group was 7.2% for Parkinsonism of all types (n = 86). The most frequent causes were idiopathic Parkinson's disease and drug-induced Parkinsonism, with prevalence rates of 3.3% (n = 39) and 2.7% (n = 32), respectively. The prevalence of vascular Parkinsonism was 1.1% (n = 13). We found 1 case of posttraumatic Parkinsonism and another with multiple system atrophy. In this first population-based study of Parkinsonism conducted in Brazil, the prevalence in a cohort of elderly subjects was higher than the observed in other populations worldwide, especially because of the high rates of drug-induced and vascular Parkinsonism. The prevalence of Parkinson's disease was similar to that observed in elderly people in door-to-door surveys in other American, European, and Eastern countries.

Sydenham's chorea is associated with decreased verbal fluency.

BACKGROUND: Sydenham's chorea (SC) is a disorder associated with rheumatic fever and related to Streptococcus-induced immune reaction cross-reactive with basal ganglia antigens. Obsessive-compulsive disorder and other behavioral abnormalities have been described in SC. There are scarce data of cognitive function in this condition. OBJECTIVE: To assess verbal fluency in patients with SC. PATIENTS AND METHODS: We have compared the semantic (SVF) and phonemic verbal fluency (PVF) of 20 subjects with SC and 40 controls matched by age, gender and years of school. RESULTS: The scores of the control group on the SVF and PVF tests were 26.3 +/- 5.7 and 18.0 +/- 6.4 whereas the SC patients scored 25.1 +/- 6.9 and 12.5 +/- 8.2. PVF was significantly decreased in the SC group (p < 0.01). CONCLUSION: SC is associated with reduction of PVF. This finding may reflect disruption of the dorsolateral prefrontal-striatal circuit caused by the auto-immune process characteristic of SC.

Obsessive compulsive behavior, hyperactivity, and attention deficit disorder in Sydenham chorea.

The authors investigated obsessive-compulsive behavior, obsessive-compulsive disorder (OCD), and attention deficit and hyperactivity disorder (ADHD) in 50 healthy subjects, 50 patients with rheumatic fever without chorea, and 56 patients with Sydenham chorea. Obsessive-compulsive behavior, OCD, and ADHD were more frequent in the Sydenham chorea group (19%, 23.2%, 30.4%) than in the healthy subjects (11%, 4%, 8%) and in the rheumatic fever without chorea group (14%, 6%, 8%). ADHD was more common in persistent Sydenham chorea.

Nerve conduction study in Sydenham's chorea.

Sydenham's chorea (SC) is a late complication of group A beta-hemolytic streptococci infection presumably caused by an abnormal autoimmune reaction. Despite rare case reports of peripheral neuropathy associated with streptococcal infection, there is no investigation of peripheral nerve in SC. We performed nerve conduction studies in a cohort of patients with SC. The neurophysiology investigation comprised measurement of amplitude and sensory conduction velocity of median, ulnar, and sural nerves; amplitude and motor conduction velocity; and F-wave latency of median, ulnar, fibular, and tibial nerves. Twenty-six patients entered the study (12 females, 14 males; mean age 12.8 +/- 3.6 years). Thirteen subjects had absent or decreased deep reflexes. All investigated neurophysiological parameters fell within the normal range for our population. We failed to find neurophysiological evidence of peripheral nerve involvement in patients with a history of SC. Our findings suggest that the possible autoimmune dysfunction in SC patients is not targeted against epitopes present in peripheral nerves.

Treatment of Sydenham chorea with corticosteroids.

Despite treatment with valproic acid and neuroleptics, a significant proportion of patients with Sydenham chorea (SC) remain with chorea. We evaluated the effect of intravenous methyl-prednisolone followed by oral prednisone in patients with SC refractory to conventional treatment. Patients were enrolled in the study if they failed to improve with conventional treatment, despite the development of side effects. Chorea was rated on a 0 to 4 score. Five patients, 3 of them women, were included in the study. The median pretreatment rating score of the chorea was 3 (range, 3-4) and dropped to 1 (range, 0-2) after a median follow-up of 7 months (range, 3-7 months). Two patients developed Cushing syndrome. Our data suggest that intravenous methyl-prednisolone followed by oral prednisone is an effective and well-tolerated treatment of refractory SC.