Parkinson's Disease Gene Screening in Familial Cases from Central and South America.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Characterizing the Genetic Architecture of Parkinson's Disease in Latinos.

OBJECTIVE: This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. METHODS: We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value <1 × 10-5 were tested in a replication cohort of 1,234 self-reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. RESULTS: One locus, SNCA, achieved genome-wide significance (p-value <5 × 10-8 ); rs356182 achieved genome-wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35-1.86, p-value 2.48 × 10-8 ; 23andMe, G allele: 1.26 OR, 95% CI 1.16-1.37, p-value 4.55 × 10-8 ). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6, achieved significance in a joint test of ancestries and in the Native American single-ancestry test (p-value <5 × 10-5 ). A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in the African single-ancestry test (p-value <5 × 10-5 ). INTERPRETATION: This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study. ANN NEUROL 2021;90:353-365.

High prevalence of self-reported non-motor symptoms and lack of correlation with motor severity in adult patients with idiopathic isolated dystonia.

BACKGROUND: Although abnormal movements and postures are the hallmark of dystonia, non-motor symptoms (NMS) are common and negatively affect quality of life. OBJECTIVES: The aim of this study was to screen dystonia patients for NMS and analyze their association with clinical parameters, including motor disability. METHODS: Adult patients with idiopathic isolated dystonia were interviewed and examined. Dystonia severity was evaluated with the Fahn-Marsden Dystonia Rating Scale and the presence of NMS was assessed using a list of 29 complaints. RESULTS: A hundred and two patients (63.7% female) were enrolled. Dystonia began after 20 years of age in 61.8% and was focal or segmental in 82.8% of patients. Only eight patients (7.8%) had no NMS and 59.8% reported more than five. The most prevalent NMS were pain (72.5%) and anxiety (63.7%), followed by difficulty recalling information (44.1%), sadness/anhedonia (41.2%), and difficulty falling asleep (38.2%). No correlation was found between the total number of NMS and dystonia severity (p = 0.18) or regular botulinum toxin use (p = 0.66). The majority of NMS domains correlated with each other. CONCLUSIONS: Our results confirm a high prevalence of NMS among dystonia patients, even in those with mild motor disability. The pathophysiology of NMS in dystonia remains to be completely understood.

Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients.

BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. METHODS: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. RESULTS: Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69-10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10-7 ). CONCLUSIONS: We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population. © 2020 International Parkinson and Movement Disorder Society.

Association of a neuronal nitric oxide synthase gene polymorphism with levodopa-induced dyskinesia in Parkinson's disease.

BACKGROUND: Levodopa-induced dyskinesia (LID) is a common complication of advanced Parkinson's disease (PD). PD physiopathology is associated with dopaminergic and non-dopaminergic pathways, including the nitric oxide system. The present study aims to examine the association of a neuronal nitric oxide synthase gene (NOS1) single nucleotide polymorphism (rs2682826) with LID in PD patients. METHODS AND RESULTS: We studied 186 PD patients using levodopa. The presence of LID was defined as a MDS-UPDRS Part IV score ≥1 on item 4.1. We tested for association between NOS1 rs2682826 and the presence, daily frequency, and functional impact of LID using regression models, adjusting for important covariates. There was no significant association between genotype and any of the LID-related variables examined. CONCLUSIONS: Our results suggest that this NOS1 polymorphism does not contribute to LID susceptibility or severity. However, additional studies that include a comprehensive set of NOS1 variants will be needed to fully define the role of this gene in LID.

Validation of the National Institute of Neurological Disorders and Stroke Criteria for Psychosis in Parkinson Disease.

OBJECTIVES: Parkinson disease (PD) psychosis is a condition associated with several negative outcomes. Despite its impact, there is a lack of validated diagnostic tools for this condition. In this study, we aim to verify the validity of the proposed NINDS criteria for PD psychosis and explore its possible applications in clinical practice. DESIGN, SETTINGS, PARTICIPANTS: We prospectively selected 104 subjects with idiopathic PD referred to a movement disorder clinic for a cross-sectional evaluation. MEASUREMENTS: A neurological evaluation confirmed idiopathic PD and classified PD psychosis according to the NINDS criteria. A psychiatrist then classified the subject according to DSM-IV-TR criteria for psychosis, considered the reference standard. We used Cohen's kappa (κ) to quantify reliability between methods. Finally, we designed models assigning a weighted score to each characteristic psychotic symptom from the NINDS criteria (criterion A), and plotted receiver operating curves for each model. RESULTS: Of the total sample, 52 (50%) met proposed criteria for NINDS PD psychosis and 16 (15.6%) met reference standard criteria. Inter-rater reliability showed only a fair agreement (κ = 0.30). By using a scoring approach for each NINDS criteria item and a cutoff total score for the diagnosis of PD psychosis, we significantly increased the agreement for diagnosis reliability (κ = 0.72), with sensitivity of 94% and specificity of 91%. CONCLUSIONS: Although the NINDS criteria had limited reliability for diagnosing PD psychosis, a scoring approach for symptoms showed good reliability, with sensitivity and specificity above 90%. This scoring approach may be an accurate tool for identifying patients with PD psychosis.

Economic Burden of Huntington's Disease: Analysis from a Brazilian Tertiary Care Perspective.

Background: Huntington's disease (HD) exerts significant impacts on individuals and families worldwide. Nevertheless, data on its economic burden in Brazil are scarce, revealing a critical gap in understanding the associated healthcare costs. Objective: This study was conducted at a tertiary neurology outpatient clinic in Brazil with the aim of assessing annual healthcare service utilization and associated costs for HD patients. Methods: We conducted a cross-sectional observational study involving 34 HD patients. A structured questionnaire was applied to collect data on direct medical costs (outpatient services, medications), non-medical direct costs (complementary therapies, mobility aids, home adaptations), and indirect costs (lost productivity, caregiver costs, government benefits) over one year. Results: Significant economic impacts were observed, with average annual direct medical costs of $4686.82 per HD patient. Non-medical direct and indirect costs increased the financial burden, highlighting extensive resource utilization beyond healthcare services. Thirty-three out of 34 HD patients were unemployed or retired, and 16 relied on government benefits, reflecting broader socioeconomic implications. Despite the dataset's limitations, it provides crucial insights into the economic impact of HD on patients and the Brazilian public health system. Conclusions: The findings underscore the urgent need for a more comprehensive evaluation of the costs to inform governmental policies related to HD. Future research is needed to expand the data pool and develop a nuanced understanding of the economic burdens of HD to help formulate effective healthcare strategies for patients.

Clinical, neuroimaging and genetic findings in Brazilian patients with neurodegeneration with brain iron accumulation.

Neurodegeneration with brain iron accumulation (NBIA) encompasses a clinically and genetically heterogeneous group of rare disorders. Here, we report clinical, neuroimaging and genetic studies in twenty three Brazilian NBIA patients. In thirteen subjects, deleterious variants were detected in known NBIA-causing genes (PANK2, PLA2G6, C9ORF12, WDR45 and FA2H), including previously unreported variants in PANK2 and PLA2G6. Two patients carried rare, likely pathogenic variants in genes not previously associated with NBIA: KMT2A c.11785A > C (p.Ile3929Leu), and TIMM8A c.127T > C (p.Cys43Arg), suggesting an expansion of their associated phenotypes to include NBIA. In eight patients the etiology remains unsolved, suggesting variants undetectable by the adopted methods, or the existence of additional NBIA-causing genes.

Task-related brain activity in upper limb dystonia revealed by simultaneous fNIRS and EEG.

OBJECTIVE: The aim of this study was to explore differences in brain activity and connectivity using simultaneous electroencephalography and near-infrared spectroscopy in patients with focal dystonia during handwriting and finger-tapping tasks. METHODS: Patients with idiopathic right upper limb focal dystonia and controls were assessed by simultaneous near-infrared spectroscopy and electroencephalography during the writing and finger-tapping tasks in terms of the mu-alpha, mu-beta, beta and low gamma power and effective connectivity, as well as relative changes in oxyhemoglobin (oxy-Hb) and deoxyhemoglobin using a channel-wise approach with a mixed-effect model. RESULTS: Patients exhibited higher oxy-Hb levels in the right and left motor cortex and supplementary motor area during writing, but lower oxy-Hb levels in the left sensorimotor and bilateral somatosensory area during finger-tapping compared to controls. During writing, patients showed increased low gamma power in the bilateral sensorimotor cortex and less mu-beta and beta attenuation compared to controls. Additionally, patients had reduced connectivity between the supplementary motor area and the left sensorimotor cortex during writing. No differences were observed in terms of effective connectivity in either task. Finally, patients failed to attenuate the mu-alpha, mu-beta, and beta rhythms during the finger-tapping task. CONCLUSIONS: Cortical blood flow and EEG spectral power differ between controls and dystonia patients, depending on the task. Writing increased blood flow and altered connectivity in dystonia patients, and it also decreased slow-band attenuation. Finger-tapping decreased blood flow and slow-band attenuation. SIGNIFICANCE: Simultaneous fNIRS and EEG may show relevant information regarding brain dynamics in movement disorders patients in unconstrained environments.

Blepharospasm Patients after Botulinum Toxin - Sleep Approach.

Background Blepharospasm is a focal dystonia that affects the orbicularis oculi muscles. The interest in nonmotor symptoms is due to their impact on quality of life. Objective We evaluated the frequency of sleep disorders and circadian rhythm in a sample of Brazilian blepharospasm patients. Methods A total of 51 patients, who met the clinical criteria for blepharospasm, evaluated by 2 specialists in movement disorders, were recruited from the outpatient clinic for movement disorders of two reference centers in the city of São Paulo: Universidade Federal de São Paulo and Hospital do Servidor Público do Estado de São Paulo. The selected 13 patients were evaluated from 13 days before to 13 days after using botulinum toxin. They were interviewed, underwent physical examination and actigraphy, and completed sleep diaries. Results After using botulinum toxin, the group that reported sleep improvement exhibited a 50% decrease in sleep latency. There was no change in restless leg syndrome or circadian rhythm. Patients who reported no sleep improvement after using botulinum toxin presented poorer synchronization of the light-dark cycle. Conclusion Blepharospasm patients have poor sleep quality. About 50% of the patients had sleep improvement after using botulinum toxin. The synchronization of the light-dark cycle should be influenced by this finding.

Neurological symptoms and comorbidity profile of hospitalized patients with COVID-19.

BACKGROUND: The neurological manifestations in COVID-19 adversely impact acute illness and post-disease quality of life. Limited data exist regarding the association of neurological symptoms and comorbid individuals. OBJECTIVE: To assess neurological symptoms in hospitalized patients with acute COVID-19 and multicomorbidities. METHODS: Between June 2020 and July 2020, inpatients aged 18 or older, with laboratory-confirmed COVID-19, admitted to the Hospital São Paulo (Federal University of São Paulo), a tertiary referral center for high complexity cases, were questioned about neurological symptoms. The Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire was used. The data were analyzed as a whole and whether subjective olfactory dysfunction was present or not. RESULTS: The mean age of the sample was 55 ± 15.12 years, and 58 patients were male. The neurological symptoms were mostly xerostomia (71%), ageusia/hypogeusia (50%), orthostatic intolerance (49%), anosmia/hyposmia (44%), myalgia (31%), dizziness (24%), xerophthalmia (20%), impaired consciousness (18%), and headache (16%). Furthermore, 91% of the patients had a premorbidity. The 44 patients with subjective olfactory dysfunction were more likely to have hypertension, diabetes, weakness, shortness of breath, ageusia/hypogeusia, dizziness, orthostatic intolerance, and xerophthalmia. The COMPASS-31 score was higher than that of previously published controls (14.85 ± 12.06 vs. 8.9 ± 8.7). The frequency of orthostatic intolerance was 49% in sample and 63.6% in those with subjective olfactory dysfunction (2.9-fold higher risk compared to those without). CONCLUSION: A total of 80% of inpatients with multimorbidity and acute COVID-19 had neurological symptoms. Chemical sense and autonomic symptoms stood out. Orthostatic intolerance occurred in around two-thirds of the patients with anosmia/hyposmia. Hypertension and diabetes were common, mainly in those with anosmia/hyposmia.

ANTECEDENTES: As manifestações neurológicas na COVID-19 impactam adversamente na enfermidade aguda e na qualidade de vida após a doença. Dados limitados existem em relação a associação de sintomas neurológicos e indivíduos com comorbidades. OBJETIVO: Avaliar os sintomas neurológicos em pacientes de hospitalizados com COVID-19 aguda e múltiplas comorbidades. MéTODOS: Entre junho e julho de 2020, pacientes de hospitais com idade 18 anos ou acima e COVID-19 laboratorialmente confirmada, admitidos no Hospital São Paulo (Universidade Federal de São Paulo), um centro de referência terciário para casos de alta complexidade, foram perguntados sobre sintomas neurológicos. O questionário Pontuação composta de sintoma autonômico (COMPASS-31) foi usado. Os dados foram analisados no geral e se a disfunção olfatória subjetiva estava presente ou não. RESULTADOS: A média de idade da amostra foi 55 ± 15.12 anos. 58 pacientes eram homens. Os sintomas neurológicos foram principalmente xerostomia (71%), ageusia/hipogeusia (50%), intolerância ortostática (49%), anosmia/hiposmia (44%), mialgia (31%), tontura (24%), xeroftalmia (20%), comprometimento na consciência (18%) e cefaleia (16%). Além disso, 91% dos pacientes tinham uma pré-morbidade. Os 44 pacientes com disfunção olfatória tinham maior chance de ter hipertensão, diabetes, fraqueza, falta de ar, ageusia/hipogeusia, tontura, intolerância ortostática e xeroftalmia. A pontuação do COMPASS-31 foi maior do que a de controles previamente publicados (14,85 ± 12,06 vs. 8,9 ± 8,7). A frequência de intolerância ortostática foi 49% na amostra e 63,6% naqueles com disfunção olfatória subjetiva (risco 2.9 vezes maior comparado com os sem). CONCLUSãO: Um total de 80% dos pacientes hospitalizados com múltiplas morbidades e COVID-19 aguda tinham sintomas neurológicos. Os sintomas do sentido químico e autonômicos se destacaram. A intolerância ortostática ocorreu em cerca de dois terços dos pacientes com anosmia/hiposmia. A hipertensão e o diabetes foram comuns, principalmente naqueles com anosmia/hiposmia.

Floor and ceiling effects on the Montreal Cognitive Assessment in patients with Parkinson's disease in Brazil.

Parkinson's disease (PD) is a common neurodegenerative disease associated with cognitive impairment. The Montreal Cognitive Assessment (MoCA) has been used as a recommended global cognition scale for patients with PD, but there are some concerns about its application, partially due to the floor and ceiling effects. Objective: To explore the floor and ceiling effects on the MoCA in patients with PD in Brazil. Methods: Cross-sectional study with data from patients with PD from five Brazilian Movement Disorders Clinics, excluding individuals with a possible diagnosis of dementia. We analyzed the total score of the MoCA, as well as its seven cognitive domains. The floor and ceiling effects were evaluated for the total MoCA score and domains. Multivariate analyses were performed to detect factors associated with floor and ceiling effects. Results: We evaluated data from 366 patients with PD and approximately 19% of individuals had less than five years of education. For the total MoCA score, there was no floor or ceiling effect. There was a floor effect in the abstraction and delayed memory recall domains in 20% of our sample. The ceiling effect was demonstrated in all domains (80.8% more common in naming and 89% orientation), except delayed recall. Education was the main factor associated with the floor and ceiling effects, independent of region, sex, age at evaluation, and disease duration. Conclusion: The floor and ceiling effects are present in specific domains of the MoCA in Brazil, with a strong impact on education. Further adaptations of the MoCA structure for underrepresented populations may reduce these negative effects.

A doença de Parkinson (DP) é uma doença neurodegenerativa comum associada ao declínio cognitivo. A Avaliação Cognitiva de Montreal (Montreal Cognitive Assessment ­ MoCA) tem sido usada como uma escala de cognição global recomendada para pacientes com DP, mas existem algumas preocupações sobre sua aplicação, em parte pelos efeitos solo e teto. Objetivo: Explorar os efeitos solo e teto na MoCA em pacientes com DP no Brasil. Métodos: Estudo transversal com dados de pacientes com DP oriundos de cinco Clínicas de Distúrbios de Movimento no Brasil, excluindo-se pessoas com possível diagnóstico de demência. Nós analisamos a pontuação total da MoCA, assim como a de seus sete domínios cognitivos. Os efeitos solo e teto foram avaliados para a pontuação total da MoCA e seus domínios. Foram feitas análises multivariadas para a detecção de fatores associados os efeitos solo e teto. Resultados: Nós avaliamos dados de 366 pacientes com DP, e aproximadamente 19% das pessoas tinham menos que cinco anos de escolaridade. Para a pontuação total do MoCA, não houve efeito solo ou teto. Houve efeito solo nos domínios abstração e memória de evocação tardia em 20% de nossa amostra. O efeito teto foi demonstrado em todos os domínios (80,8% mais comum em nomeação e 89% orientação), com exceção de memória de evocação tardia. A educação foi o principal fator associado aos efeitos solo e teto, independentemente de região, sexo, idade na avaliação e duração da doença. Conclusão: Os efeitos solo e teto estão presentes em domínios específicos da MoCA no Brasil, com forte impacto da educação. Adaptações adicionais à estrutura da MoCA para populações vulneráveis podem reduzir esses efeitos negativos.

History of high household pesticide use and Parkinson's disease in Brazil.

The prevalence of Parkinson's disease (PD) is growing worldwide and household pesticides exposure may be related to this phenomenon. We showed that individuals with high exposure to household pesticides have two times more risk of developing PD. Household pesticide exposure did not impact age at PD onset.

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

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson's Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 × 10 -5 ; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4 . We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

Combined assessment by transcranial sonography and Sniffin' Sticks test has a similar diagnostic accuracy compared to brain SPECT for Parkinson's disease diagnosis.

OBJECTIVES: This study aimed to investigate the accuracy of TCS combined with the Sniffin' sticks olfactory test (SST-16) for differentiation between idiopathic PD patients and healthy controls compared to that of 99 mTc-TRODAT-1 SPECT (TRODAT). METHODS: A cross-sectional study included PD patients diagnosed in accordance with United Kingdom PD Society Brain Bank criteria and a control group of age and sex- matched healthy subjects. All patients were examined by a movement disorder specialist and underwent brain SPECT using TRODAT, TCS examination and SST-16 test. Receiver Operating Characteristic (ROC) curves were used to calculate cut-off points for TCS, striatal TRODAT binding potentials and SST-16. The area under the ROC curve determined the diagnostic accuracy of the method. RESULTS: Twenty patients with PD (13 males and 7 females) and nine healthy subjects were included. Median age of PD onset was 56.5 years with median disease duration of 5 years. A larger substantia nigra (SN) echogenic area was observed in the PD group (p = 0.013). SN echogenic area cut-off point of 0.22 cm2 was obtained from a ROC curve for PD diagnosis. Considering this cut-off point, TCS diagnostic accuracy was estimated at 79.2% for PD diagnosis. The cut-off value of 0.90 for striatal TRODAT binding was associated with 99% diagnostic accuracy for the diagnosis of PD. SST-16 values equal or less than 9 points showed an 85.8% diagnostic accuracy for PD diagnosis. Combination of both SST-16 and TCS improved the diagnostic accuracy to 95% for PD diagnosis. CONCLUSION: Combined SST-16 and TCS assessment was indicated as accurate for distinguishing PD patients from healthy controls. The diagnostic accuracy of TCS combined with SST-16 for differentiation between idiopathic PD patients and healthy controls is similar to that of SPECT TRODAT.

Guidelines for Parkinson's disease treatment: consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology - motor symptoms.

The treatment of Parkinson's disease (PD) is challenging, especially since it is considered highly individualized. The Brazilian Academy of Neurology has recognized the need to disseminate knowledge about the management of PD treatment, adapting the best evidence to the Brazilian reality. Thus, the main published treatment guidelines were reviewed based on the recommendations of group from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology.

Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort.

BACKGROUND: Large-scale Parkinson's disease (PD) genome-wide association studies (GWAS) have, until recently, only been conducted on subjects with European-ancestry. Consequently, polygenic risk scores (PRS) constructed using PD GWAS data are likely to be less predictive when applied to non-European cohorts. METHODS: Using GWAS data from the largest study to date, we constructed a PD PRS for a Latino PD cohort (1497 subjects from LARGE-PD) and tested it for association with PD status and age at onset. We validated the PRS performance by testing it in an independent Latino cohort (448 subjects) and by repeating the analysis in LARGE-PD with the addition of 440 external Peruvian controls. We also tested SNCA haplotypes for association with PD risk in LARGE-PD and a European-ancestry PD cohort. RESULTS: The GWAS-significant PD PRS had an area under the receiver-operator curve (AUC) of 0.668 (95% CI: 0.640-0.695) in LARGE-PD. The inclusion of external Peruvian controls mitigated this result, dropping the AUC 0.632 (95% CI: 0.607-0.657). At the SNCA locus, haplotypes differ by ancestry. Ancestry-specific SNCA haplotypes were associated with PD status in both LARGE-PD and the European-ancestry cohort (p-value < 0.05). These haplotypes both include the rs356182 G-allele, but only share 14% of their variants overall. CONCLUSION: The PD PRS has potential for PD risk prediction in Latinos, but variability caused by admixture patterns and bias in a European-ancestry PD PRS data limits its utility. The inclusion of diverse subjects can help elucidate PD risk loci and improve risk prediction in non-European cohorts.

Neuroimaging Assessment of Nigrosome 1 with a Multiecho Gre Magnetic Resonance Sequence in the Differentiation Between Parkinsons Disease from Essential Tremor and Healthy Individuals.

Background and purpose: Parkinsonism is commonly seen in many clinical conditions, and the establishment of its etiology may take many years. The possible development of neuroprotective treatments for Parkinsons disease (PD) in the near future will require correct and early diagnosis. This study aims to analyze the accuracy of a low-cost MRI sequence to differentiate PD from patients with essential tremor (ET) and healthy control (HC) individuals. Material and methods: We recruited 70 individuals with clinical diagnoses of PD (38 patients), ET (11 patients) and healthy volunteers (21 individuals), all of whom underwent 3T MRI multiecho GRE sequence. Two blinded neuroradiologists independently evaluated the presence or absence of nigrosome-1(N1). We considered the unilateral or bilateral absence of nigrosome 1 signal as indicative of PD. Results: The absence of at least one N1 could differentiate with 98% accuracy patients with clinical established PD from healthy controls. The presence of both nigrosomes was 96% accurate as a sign to differentiate PD from ET patients. Conclusion: The 3T MRI with multiecho GRE is a simple and universally available technique and it can be used as a good auxiliary tool to differentiate PD from ET patients and controls.

What can be expected to be seen in a Neurology ward? Eleven-year experience in a Brazilian university hospital.

BACKGROUND: Neurological disorders are significant causes of morbidity and mortality worldwide. However, data about general neurological inpatient admissions in Brazil is limited. Objective: To investigate the prevalence of neurological disorders according to disease group and lesion site among patients admitted to a general Neurology ward. METHODS: This was an observational and descriptive study. The hospital discharge database for the Neurology ward was surveyed in accordance with the International Classification of Diseases, 10th edition (ICD-10), from September 2008 to October 2019. The final diagnosis was classified into neurological disorder groups and site. RESULTS: Overall, 2,606 clinical neurological patient files were included, with mean length of hospitalization of 16.7 days and a total of 325 readmissions (12.5%). The overall mortality rate in the ward was 3.8% (100 patients). Among all the diagnoses, cerebrovascular disease was the most prevalent (45.8%), followed by inflammatory disorders (22.2%). The brain was the most common lesion site (66.0%), followed by peripheral nerves (10.0%) and meninges and cerebrospinal fluid (7.7%). CONCLUSIONS: The disease pattern upon admission showed that a majority of the cases consisted of cerebrovascular disorders and that the brain was the most frequently affected structure, although we observed that a wide variety of cases were admitted, encompassing all neurological disorders.