Abstract Background Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinson’s disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties. Objective To evaluate the efficacy and safety of doxycycline in patients with PD and LID. Methods This was an open-label, uncontrolled, single-arm, single-center, phase 2 proof-of-concept study in patients with PD with functional impact of dyskinesia, which used levodopa three times daily, in a movement disorders clinic in Brazil. Participants were treated with doxycycline 200 mg/day for 12 weeks, with evaluations at baseline, week4, and week 12 of treatment. The primary outcome measure was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) total score at week 12, evaluated by two blinded raters. Key secondary outcomes measures were OFF time and ON time with troublesome dyskinesia in the PD home diary. Results Eight patients with PD were treated and evaluated. Doxycycline 200 mg/day reduced the UDysRS total score at week 12, compared with baseline (Friedman χ2 = 9.6; p = 0.008). Further, doxycycline reduced the ON time with troublesome dyskinesia (Friedman χ2 = 10.8; p = 0.004) without worsening parkinsonism. There were no severe adverse events, and dyspepsia was the commonest event. Conclusion In this preliminary, open-label and uncontrolled trial, doxycycline was effective in reducing LID and safe after a 12-week treatment. Further well-designed placebo-controlled clinical trials with a longer duration and a larger number of participants are needed. Clinical trial registration https://ensaiosclinicos.gov.br, identifier: RBR-1047fwbf

Resumo Antecedentes A discinesia induzida por levodopa (DIL) é uma complicação motora comum da terapia com levodopa em pacientes com doença de Parkinson (DP). A doxiciclina é uma tetraciclina amplamente usada e barata, com propriedade anti-inflamatória. Objetivo Avaliar a eficácia e segurança da doxiciclina em pacientes com DP e DIL. Métodos Este foi um estudo aberto, não-controlado, de braço único, monocêntrico, fase 2 e de prova de conceito, em pacientes com DP e impacto funcional das discinesias, que usavam levodopa três vezes ao dia, em um ambulatório de distúrbios de movimento no Brasil. Os participantes foram tratados com doxiciclina 200 mg/dia por 12 semanas, com avaliações na base, na semana 4 e na semana 12 do tratamento. A medida de desfecho primário foi a mudança no escore total da Unified Dyskinesia Rating Scale (UDysRS) da base à semana 12, avaliada por dois avaliadores cegos. As medidas-chave de desfecho secundário fora o tempo em OFF e tempo em ON com discinesia problemática. Resultados Oito pacientes com DP foram tratados e avaliados. A doxiciclina 200 mg/dia reduziu o escore total da UDysRS na semana 12, comparado com a avaliação inicial (χ2 de Friedman = 9.6; p = 0.008). Além disso, a doxiciclina reduziu o tempo em ON com discinesia problemática (χ2 de Friedman = 10.8; p = 0.004) sem piorar o parkinsonismo. Não houve eventos adversos graves, e dispepsia foi o evento mais comum. Conclusão No presente estudo preliminar, aberto e não-controlado, a doxiciclina foi eficaz em reduzir as DIL e segura após tratamento por 12 semanas. Estudos clínicos bem-desenhados e placebo-controlados adicionais, com duração mais longa e maior número de participantes, são necessários.

ABSTRACT 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.

RESUMO 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.

Abstract Background Juvenile Dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children. Imaging exams are useful for muscle assessment, with ultrasonography (US) being a promising tool in detecting disease activity and tissue damage. There are few studies about muscle elastography. Objectives Our aim was to associate clinical, laboratory, and nailfold capillaroscopy (NC) assessments with US in JDM patients; and to compare the findings of US and Strain Elastography (SE) from patients and healthy controls. Methods An analytic cross-sectional study was performed with JDM patients and healthy controls. Patients underwent clinical exam to access muscle strength and completed questionnaires about global assessment of the disease and functional capacity. Patients were submitted to NC and measurement of muscle enzymes. All subjects underwent US assessment, using gray scale, Power Doppler (PD), and SE. Results Twenty-two JDM patients and fourteen controls, aged between 5 and 21 years, matched for age and sex were assessed. In qualitative and semi-quantitative gray scale, we observed a higher frequency of alterations in patients (p < 0.001), while in PD, there was a higher frequency of positivity in patients’ deltoids and anterior tibialis (p < 0.001). Active disease was associated with an important change in the semi-quantitative gray scale in deltoids (p = 0.007), biceps brachii (p = 0.001) and quadriceps femoris (p = 0.005). The SE demonstrated a high negative predictive value of 87.2. Conclusion US was able, through gray scale, to differentiate JDM patients from controls, while PD achieved such differentiation only for deltoids and anterior tibialis. The semi-quantitative gray scale showed disease activity in proximal muscles. SE was not able to differentiate patients from controls.

Abstract Background Telemedicine allows Parkinson disease (PD) patients to overcome physical barriers to access health care services and increases accessibility for people with mobility impairments. Objective To investigate the feasibility indicators of a telehealth intervention for PD patients, including patient recruitment, attendance, technical issues, satisfaction, and benefits on levels of physical activity and sleep. Methods We conducted a single-center, single-arm study of telehealth video consultations using WhatsApp (Meta Platforms, Inc., Menlo Park, CA, USA). Also, we collected the feasibility indicators as the primary endpoints. All the patients in the study were previously evaluated in person by the same team. Results Patient recruitment, attendance, and technical issues rates were 61.3%, 90.5%, and 13.3%, respectively, with good scores of patient acceptance and satisfaction with the study intervention. The telehealth intervention improved physical activity, including the number of walks for at least 10 continuous minutes (p = 0.009) and the number of moderate-intensity activities lasting at least 10 continuous minutes (p = 0.001). The Pittsburgh sleep quality index (PSQI) scores also improved for one of its components: perceived sleep duration (p < 0.001) and for total Pittsburgh score (p < 0,001). The average travel time saving was 289.6 minutes, and money-saving was R$106.67 (around USD 18; almost 10% of the current minimum wage in Brazil). Conclusions Direct-to-patient telehealth video consultations proved to be feasible and effective and had a positive impact on physical activity levels and sleep in PD patients.

Resumo Antecedentes A telemedicina permite que pacientes com doença de Parkinson (DP) superem barreiras físicas para acessar serviços de saúde e aumenta a acessibilidade para pessoas com mobilidade reduzida. Objetivo Investigar indicadores de viabilidade de uma intervenção em telessaúde para pacientes com DP, incluindo recrutamento, atendimento, aderência, problemas técnicos, satisfação e benefícios nos níveis de atividade física e sono. Métodos Foi conduzido um estudo de centro e braço únicos baseado em consultas por telessaúde com utilização do WhatsApp (Meta Platforms, Inc., Menlo Park, CA, EUA). Foram calculados indicadores de viabilidade como desfechos primários. Resultados As taxas de recrutamento, atendimento e problemas técnicos foram 61,3%, 90,5% e 13,3%, respectivamente, com bons escores de aceitação e satisfação com a intervenção. A intervenção melhorou os níveis de atividade física, incluindo o número de passos por pelo menos 10 minutos contínuos (p = 0,009) e o número de atividades intensas e moderadas com duração de pelo menos 10 minutos contínuos (p = 0,001). O Índice de Qualidade do Sono de Pittsburgh melhorou nos seguintes componentes: duração percebida do sono (p < 0,001) e escore total (p < 0,001). A média do tempo de viagem médio poupado foi de 289,6 minutos, e a economia financeira foi de R$ 106,67 reais (por volta de USD 18; quase 10% do salário mínimo atual do Brasil). Conclusões As consultas por vídeo provaram ser viáveis e efetivas, com impacto positivo nos níveis de atividade física e sono de pacientes com DP.

RESUMO: O objetivo foi avaliar os efeitos das doses anuais de 100 e 200 kg ha-1 de nitrogênio (N) sobre as características morfogênicas e estruturais do capim-ipyporã, em lotação intermitente durante as estações do ano. O delineamento experimental foi em blocos ao acaso, com dois tratamentos e três repetições de área. Os pastos de capim-ipyporã foram submetidos ao pastejo por bovinos de corte. Foram avaliadas as características morfogênicas e estruturais do dossel forrageiro por meio da técnica de perfilhos marcados. Também foi avaliado o acúmulo de forragem e a densidade populacional de perfilhos (DPP). Foi observada interação significativa (P < 0,05) das doses de N e estações do ano para o período de descanso (PD), duração de vida das folhas (DVF), filocrono, taxa de alongamento de colmos (TAlC) e comprimento final das folhas (CFF). Durante o inverno, o PD foi menor (40 vs 50 dias) nos pastos adubados com 200 kg ha-1 de N. Em contra partida, no inverno, os pastos adubados com 100 kg ha-1 de N apresentaram maiores valores para DVF, filocrono e TAlC, e menores para o CFF. Não foi observado efeito isolado de doses de N (P > 0,05) para as taxas de acúmulo de forragem; de aparecimento, alongamento e de senescência de folhas, relação folha:colmo e para a DPP. No entanto, o efeito das estações foi significativo para estas variáveis, com os maiores valores observados durante a primavera e verão. O uso de 200 kg ha-1 de N para pastos de capim-ipyporã promove redução da estacionalidade de produção da forrageira.

ABSTRACT: This study examined the effects of annual nitrogen (N) rates of 100 and 200 kg ha-1 on the morphogenetic and structural traits of Ipyporã grass (Brachiaria brizantha × Brachiaria ruziziensis) under intermittent grazing during the seasons of the year. The experiment was laid out in a randomized-block design with two treatments and three area replicates. Ipyporã grass pastures were grazed by beef cattle. Morphogenetic and structural traits of the forage canopy were evaluated using the marked-tiller technique. Forage accumulation and tiller density (TD) were also evaluated. Significant interaction effects (P < 0.05) between N rates and seasons were observed for the rest period, leaf lifespan (LLS), phyllochron, stem elongation rate (SER) and final leaf length (FLL). During winter, the rest period was shorter (40 vs. 50 days) in the pastures fertilized with 200 kg ha-1 N. Conversely, in winter, the pastures fertilized with 100 kg ha-1 N showed higher LLS, SER and phyllochron values, but lower FLL values. There was no isolated effect of N rates (P > 0.05) on forage accumulation rate; leaf appearance, elongation or senescence rates; leaf:stem ratio; or TD. However, the effect of seasons was significant for these variables, with the highest values occurring during spring and summer. The use of 200 kg ha-1 N in Ipyporã grass pastures reduces the seasonality of forage production.

Objective: Decades of research have highlighted the involvement of the prefrontal cortex, anterior cingulated cortex, and limbic areas (amygdala) in panic disorder (PD). However, little attention has been given specifically to the inferior frontal gyrus. The current study aimed to investigate the neural substrates, including the inferior frontal gyrus, of both panic-related and negative conditions among individuals with PD and healthy controls. Methods: We examined 13 medication-free PD patients and 14 healthy controls with functional magnetic resonance imaging (fMRI) during exposure to negative and neutral pictures and a set of specific panic-related pictures. Results: Subtraction between the conditions indicated activation of the left amygdala region and the right inferior frontal gyrus in PD patients during the specific panic-related condition, whereas the left amygdalar region and left inferior frontal gyrus were activated during the negative condition in controls. Conclusion: These results suggest that in patients with PD, a prominent bottom-up process is involved in specific panic-related conditions, which might be associated with weak modulation of the left frontal area. These data add to our current understanding of the neural correlates of PD and can contribute to future clinical interventions targeting the functional reestablishment of these regions.

SUMMARY OBJECTIVES: To assess the effect of withdrawal of the antiparkinsonian drug regimen administration on patients with PD and its relation to pain. METHODS: The sample included 22 men and 12 women who were candidates for neurosurgery to control motor signs and symptoms treated with L-dopa as a drug, alone or in combination with others (Cholinergic Antagonists; Dopamine Agents). All of them were examined at two different moments, with and without medication, and analyzed for painful symptoms. The Hoehn and Yahr scale was used for functional staging of the disease. Pain intensity was assessed by using the numerical verbal scale. RESULTS: The mean pain intensity among those on medication {2.17±0.39 (SE)} was significantly lower than in the abstinence group {4.2±0.59 (SE), p=0.006, Wilcoxon}, which corresponded to the increase in the total functional staging score from 93 to 111, respectively. CONCLUSION: The interruption of the administration of specific medications in patients with Parkinson’s disease caused, or increased the intensity of, painful discomfort correlated with the intensity of functional impairment. This effect was also observed in women, but it was statistically relevant only for men. The results suggest that pain may be a “red flag” that points to the need for a therapeutic drug review when its presence or worsening is detected.

Evidence shows that metabolic syndrome (MS) is associated with a greater risk of developing Parkinson's disease (PD) because of the increase in oxidative stress levels along with other factors such as neuroinflammation and mitochondrial dysfunction. However, because some studies have reported that MS is associated with a lower risk of PD, the relationship between MS and PD should be investigated. This study aimed to investigate the effect of MS on PD. Two authors searched five electronic databases, namely, MEDLINE, PubMed, Scopus, PsycINFO, Web of Science, and Science Direct, for relevant articles between September and October 2020. After screening the title and abstract of all articles, 34 articles were selected for full-text review. Finally, 11 articles meeting the eligibility criteria were included in the study. The quality of articles was critically evaluated using the Joanna Briggs Institute. Overall, we evaluated data from 23,586,349 individuals (including healthy individuals, with MS and PD) aged 30 years or more. In cohort studies, the follow-up period varied between 2 and 30 years. MS contributed considerably to the increase in the incidence of PD. In addition, obesity, a component of MS, alone can increase the probability of developing neurodegenerative diseases. However, despite few studies on MS and PD, changes in cognitive function and more rapid progression of PD disease has been documented in patients with MS using methods commonly used in research.

Resumo Introdução A associação entre tabagismo e doença periodontal tem sido descrito em estudos clínicos e epidemiológicos. Objetivo O objetivo deste estudo foi comparar os níveis de LL-37 e beta defensina-2 (hBD-2) no fluido crevicular de pacientes com periodontite generalizada fumantes (F) e não fumantes (NF). Material e método Um total de 35 pacientes com periodontite generalizada estágios III e IV, 15 NF (11 mulheres, 4 homens) e 20 F (7 mulheres e 13 homens), foram incluídos no estudo. Os parâmetros clínicos avaliados foram sangramento à sondagem (SS), profundidade de sondagem (PS) e nível de inserção clínica (NIC). Ensaios imuno enzimáticos foram realizados para quantificar os níveis de LL-37 e hBD-2 no fluido crevicular das gengivas dos pacientes. Resultado Os resultados foram analisados estatisticamente, com nível de significância de 5%. Em relação aos parâmetros clínicos periodontais, não foi observada diferença estatisticamente significativa para SS e PS comparando os grupos F e NF. Houve maior NIC nos pacientes do grupo F, quando comparados ao grupo NF (p = 0,0095). Não houve diferença estatisticamente significativa entre os níveis de LL-37 e hBD-2 quando comparados os grupos F e NF (p> 0,05). Conclusão Concluiu-se que os fumantes apresentam maior perda de inserção clínica do que os não fumantes, mas o tabagismo não influenciou nos níveis de LL-37 e hBD-2 do fluido gengival em indivíduos com periodontite.

Abstract Introduction The association between smoking and periodontal diseases has been described in clinical and epidemiological studies. Objective The aim of this study was to compare the LL-37 and human β-defensin-2 (hBD-2) levels in crevicular fluid of patients with generalized periodontitis in smokers (S) and nonsmokers (NS). Material and method A total of 35 patients with generalized periodontitis stages III and IV, 15 NS (11 female, 4 male) and 20 S (7 female and 13 male), were included in the study. The evaluated clinical parameters were bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL). Enzyme-linked immunosorbent assays were performed to quantify the LL-37 and hBD-2 levels in the gingival crevicular fluid of these patients. The results were analyzed statistically with the level of significance set at 5%. Result In relation to periodontal clinical parameters, no statistically significant difference was observed for BOP and PD between groups S and NS. There was a higher CAL in the S group than in the NS group (p = 0.0095). There was no statistically significant difference between the levels of LL-37 and hBD-2 when comparing groups S and NS (p>0.05). Conclusion It was concluded that smokers have a higher clinical attachment loss than nonsmokers, but that smoking did not influence the levels of LL-37 and hBD-2 in the gingival crevicular fluid in periodontitis.

RESUMO Introdução: Os instrumentos que mensuram o impacto da fadiga nos aspectos físicos, cognitivos e psicossociais ainda não foram validados na população brasileira com doença de Parkinson (DP). O objetivo deste estudo foi adaptar culturalmente e avaliar as propriedades psicométricas da versão brasileira da escala modificada de impacto da fadiga (MFIS-PD/BR). Métodos: Setenta indivíduos com DP foram recrutados. A adaptação do MFIS-PD foi realizada pela metodologia de tradução e retrotradução. Na análise psicométrica foi realizada a administração de questionário socioclínico, Miniexame do estado mental (Mini-Mental State Examination - MMSE), Escala Unificada de Avaliação da DP (Unified Parkinson’s Disease Rating Scale - UPDRS Parte I-IV), escala de incapacidade Hoehn-Yahr (HY), escala hospitalar de ansiedade e depressão (Hospital Anxiety and Depression Scale - HADS), escala de depressão geriátrica (Geriatric Depression Scale - GDS), escala de gravidade da fadiga (Fatigue Severity Scale - FSS), escala de fadiga de Parkinson (Parkinson Fatigue Scale - PFS-16) e a MFIS-PD/BR com reteste após 7 dias. Resultados: A fase de adaptação manteve os mesmos itens do MFIS-PD original. O coeficiente alfa de Cronbach para o MFIS-PD/BR foi de 0,878 quando todos os itens das respostas foram pontuados. Os coeficientes de correlação intraclasse teste-reteste foram superiores a 0,80 (p<0,01) para o escore MFIS-PD/BR, que foi moderadamente correlacionado com o escore HADS, GDS, MDS-UPDRS, total e aspectos não-motores da vida diária, FSS e PFS-16. Foi revelado o ponto de corte do MFIS-PD/BR>29 pontos para indicar indivíduos fatigados com acurácia de 0,835 (p<0,001). Conclusões: O MFIS-PD/BR é válido e reprodutível para a avaliação do sintoma de fadiga em indivíduos brasileiros com DP.

ABSTRACT Background: The instruments that measure the impact of fatigue on physical, cognitive and psychosocial aspects has yet to be validated in Brazilian population with Parkinson’s disease (PD). The aim of this study was to cross-culturally adapt and assess the psychometric properties of the Brazilian version of the Modified Fatigue Impact Scale (MFIS-PD/BR). Methods: Ninety PD individuals were recruited. The adaptation of the MFIS-PD was performed by translation and back translation methodology. Psychometric analysis was applied in order to perform the administration of the socio-clinical questionnaire, Mini-Mental State Examination (MMSE), Unified Parkinson’s Disease Rating Scale (UPDRS Part I-IV), Hoehn-Yahr disability scale (HY), hospital anxiety and depression scale (HADS), Geriatric Depression Scale (GDS), fatigue severity scale (FSS), Parkinson Fatigue Scale (PFS-16), and MFIS-PD/BR with retest of the MFIS-PD/BR after 7 days. Results: The adaptation phase kept the same items of original MFIS-PD. The Cronbach’s alpha for the MFIS-PD/BR was 0.878 when all responses items were scored. The test-retest intraclass correlation coefficients was above 0.80 (p<0.01) for the MFIS-PD/BR score, which was moderately correlated with the HADS, GDS, MDS-UPDRS score total and non-motor experiences of daily living, FSS and PFS-16. It was revealed the MFIS-PD/BR>29 points as cut-off point to indicate fatigued subjects with accuracy of 0.835 (p<0.001). Conclusions: The MFIS-PD/BR is valid and reproducible to use in assessing the fatigue symptom in Brazilian PD subjects.

RESUMO. O comprometimento cognitivo é comum em pacientes com doença de Parkinson (DP), e a avaliação das habilidades funcionais é crucial para o diagnóstico de demência. Objetivo: Avaliamos diferenças entre os métodos de avaliação funcional direta e indireta para avaliar habilidades funcionais em pacientes com DP. Métodos: Foram avaliados 32 pacientes com DP e suspeita de demência inicial usando métodos de avaliação direta e indireta. Resultados: Houve uma diferença significativa entre os escores dos métodos diretos e indiretos de avaliação. Pacientes e informantes geralmente superestimaram suas habilidades em muitas atividades da vida diária (AVD). No entanto, todas as ferramentas de avaliação funcional utilizadas neste estudo tiveram uma precisão relativamente boa para prever desempenho anormal em uma escala cognitiva global. Pacientes com cognição normal, de acordo com os escores em uma escala cognitiva global, podem apresentar algum comprometimento funcional nas AVD. As pontuações do Direct Assessment of Functional Ability (DAFA) correlacionaram-se linearmente com as pontuações nas escalas cognitivas globais e, especialmente, com as pontuações nos domínios da memória e concentração. Conclusão: Pacientes e informantes próximos geralmente superestimam suas habilidades instrumentais nas AVD. A avaliação direta do funcionamento diário foi mais confiável do que ferramentas indiretas para avaliar perdas funcionais em pacientes com DP. Finalmente, alguns pacientes com DP, mas sem demência, podem apresentar perdas funcionais nas AVD

ABSTRACT. Cognitive impairment is common in patients with Parkinson’s disease (PD), and evaluation of functional abilities is crucial for diagnosis of dementia. Objective: We evaluated differences between direct and indirect functional assessment methods to evaluate functional abilities in PD patients. Methods: We evaluated 32 patients with PD and suspected mild dementia using direct and indirect assessment methods. Results: There was a significant difference between the scores of direct and indirect methods of assessment. Patients and close informants usually overestimated their abilities in many ADL. However, all functional assessment tools used in this study had a relatively good accuracy to predict abnormal performance in a global cognitive scale. Patients with normal cognition according to scores in a global cognitive scale may have some functional impairment in ADL. Direct Assessment of Functional Ability (DAFA) scores correlated linearly with scores in global cognitive scales, and especially with scores in the domains of memory and concentration. Conclusion: Patients and close informants usually overestimate their instrumental abilities in ADL. The direct assessment of daily functioning was more reliable than indirect tools to assess functional losses in patients with PD. Finally, some patients with PD but no dementia may present functional losses in ADL.

Resumo Introdução: No momento, não há métodos para se predizer o desenvolvimento de discinesias induzidas por levodopa (DIL), uma frequente complicação do tratamento da doença de Parkinson (DP). Preditores clínicos e polimorfismos de nucleotídeo único (SNP) têm sido associados às DIL na DP. Objetivo: Investigar a associação entre variáveis clínicas e genéticas com as DIL e desenvolver um modelo de predição diagnóstica de DIL na DP. Métodos: Foram avaliados 430 pacientes com DP em uso de levodopa. A presença de DIL foi definida como escore ≥1 no item 4.1 da MDS-UPDRS Parte IV. Nós testamos a associação entre variáveis clínicas específicas e sete SNPs com o desenvolvimento de DIL, usando modelos de regressão logística. Resultados: Em relação às variáveis clínicas, idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos estiveram associados às DIL. Apenas o genótipo CC do SNP rs2298383 no gene ADORA2A esteve associado com DIL após o ajuste. Nós desenvolvemos dois modelos preditivos diagnósticos com acurácia razoável, mas sugerimos o uso do modelo preditivo clínico. Esse modelo de predição tem uma área sob a curva de 0,817 (intervalo de confiança de 95% [IC95%] 0,77‒0,85) e sem perda significativa de ajuste (teste de qualidade de ajuste de Hosmer-Lemeshow p=0,61). Conclusão: A probabilidade prevista de DIL pode ser estimada, com acurácia razoável, por meio do uso de um modelo preditivo diagnóstico clínico, que combina a idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos.

Abstract Background: There are currently no methods to predict the development of levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD) treatment. Clinical predictors and single nucleotide polymorphisms (SNP) have been associated to LID in PD. Objective: To investigate the association of clinical and genetic variables with LID and to develop a diagnostic prediction model for LID in PD. Methods: We studied 430 PD patients using levodopa. The presence of LID was defined as an MDS-UPDRS Part IV score ≥1 on item 4.1. We tested the association between specific clinical variables and seven SNPs and the development of LID, using logistic regression models. Results: Regarding clinical variables, age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists were associated to LID. Only CC genotype of ADORA2A rs2298383 SNP was associated to LID after adjustment. We developed two diagnostic prediction models with reasonable accuracy, but we suggest that the clinical prediction model be used. This prediction model has an area under the curve of 0.817 (95% confidence interval [95%CI] 0.77‒0.85) and no significant lack of fit (Hosmer-Lemeshow goodness-of-fit test p=0.61). Conclusion: Predicted probability of LID can be estimated with reasonable accuracy using a diagnostic clinical prediction model which combines age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists.

Resumo Introdução: O inventário multidimensional da fadiga (MFI) não tem sido administrado em indivíduos brasileiros com doença de Parkinson (DP) devido à falta de validação. Objetivo: Adaptar transculturalmente, validar e investigar as propriedades psicométricas da versão brasileira do MFI na DP. Método: Foram recrutados indivíduos com DP (N=90). O MFI foi traduzido para o português falado no Brasil usando procedimentos de tradução e retrotradução e as propriedades psicométricas foram avaliadas. Todos os indivíduos foram avaliados por meio de um questionário sócio-clínico, mini-exame do estado mental (MEEM), escala modificada de avaliação na DP (MDS-UPDRS Parte I-IV), escala de incapacidade de Hoehn-Yahr (HY), escala de ansiedade e depressão (HADS), escala de gravidade de fadiga (FSS), escala de fadiga da DP (PFS-16) e MFI-DP/ BR com reteste do MFI-PD/BR em sete dias. Resultados: A adaptação manteve os mesmos itens do instrumento original do MFI-PD. Nenhum dado perdido, efeito chão ou teto foram encontrados. O coeficiente alpha de Cronbach de todos os 20 itens foram 0.81, variando entre 0.73 a 0.81 entre as cinco subescalas. A análise de Bland-Altman não demonstrou nenhuma diferença sistemática entre as avaliações. O coeficiente de correlação intraclasse teste-reteste foi maior ou igual a 0.70 (p < 0.01) para os escores do MFI-DP/BR com correlações moderadas com HADS, MDS-UPDRS escore (exame físico, experiências motoras e não motoras de atividades de vida diária e complicações motoras), FSS e PFS-16. Foi revelado MFI-DP/ BR > 55 pontos como ponto de corte para indicar indivíduos com fadiga com acurácia de 0.84 (p < 0.001). Conclusão: O MFI-DP/BR pode ser considerado um instrumento válido e reprodutível para avaliar fadiga na DP.

Abstract Introduction: The multidimensional fatigue inventory (MFI) has not been applied in Brazilian Parkinson`s disease (PD) population due to the lack of validation. Objective: The aim of this study was to cross-culturally adapt, to validate, and investigate the psychometric properties of Brazilian version of the MFI in PD. Method: Idiopathic PD individuals (N = 90) were recruited. The MFI was translated into Brazilian Portuguese using established forward-backward translation procedures, and the psychometric properties were evaluated. All individuals were assessed by socio-clinical questionnaire, Mini-Mental State Examination (MMSE), Unified Parkinson’s Disease Rating Scale (MDS-UPDRS Part I-IV), Hoehn-Yahr disability scale (HY), hospital anxiety and depression scale (HADS), fatigue severity scale (FSS), Parkinson Fatigue Scale (PFS-16) and MFI-PD/ BR with retest of the MFI-PD/BR after seven days. Results: The adaptation phase kept the same items of original MFI-PD. No data missing, floor nor ceiling effects were found. The overall Cronbach's alpha coefficient for the 20 items was 0.81, ranging from 0.73 to 0.81 for each of the five subscales. Bland and Altman analysis showed no systematic differences between assessments. The intraclass correlation coefficient test-retest was higher or equal 0.70 (p < 0.01) for the MFI-PD/BR score, which was moderately correlated with the HADS, MDS-UPDRS score (motor examination, motor and non-motor experiences of daily living and motor complications), FSS and PFS-16. It was revealed the MFI-PD/ BR > 55 points as cut-off point to indicate fatigued subjects with accuracy of 0.84 (p < 0.001). Conclusion: The MFI-PD/BR can be considered a valid and reproducible instrument for assessing PD-related fatigue.

RESUMO Mutações no gene GBA têm sido reportadas em pacientes com doença de Parkinson (DP) em diferentes países, incluindo o Brasil. Com o objetivo de confirmar esse padrão em uma amostra de pacientes com DP provenientes do Norte brasileiro, foi conduzindo esse estudo caso-controle investigando a frequência das duas mutações mais comuns do gene GBA (c.1226A>G; p.N370S e c.1448T>C; p.L444P) em um grupo de 81 pacientes com DP e 81 controles, usando PCR-RFLP e confirmado pelo sequenciamento direto de produtos de PCR. No grupo experimental, três pacientes (3,7%) foram heterozigotos para a mutação c.1226A>G; p.N370S e três (3,7%), para a mutação c.1448T>C; p.L444P Nenhuma das duas mutações foi detectada no grupo controle (p =0,0284). Pacientes com a mutação c.1448T>C; p.L444P demonstraram uma tendência a apresentar os sintomas mais precocemente, porém um número amostrai maior é necessário para confirmar essa observação. Nossos resultados sugerem uma associação entre essas duas mutações no gene GBA e o desenvolvimento de DP na população de pacientes do norte Brasileiro.

ABSTRACT Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.

RESUMO Objetivo Analisar o efeito da levodopa na dinâmica coclear, bem como na via eferente olivococlear medial de indivíduos com doença de Parkinson idiopática (DP). Método Indivíduos com e sem DP, acompanhados em um hospital universitário, realizaram a pesquisa das emissões otoacústicas por produto de distorção (EOAPD) e do efeito inibitório das EOAPD (EIEOA) na presença de ruído contralateral. Foram estabelecidas as medidas de correlação entre os resultados das EOAPD e do EIEOA com estágio Hoehn&Yahr (H&Y), dose diária de levodopa e tempo de diagnóstico da DP. Além disso, as medidas eletroacústicas foram comparadas entre os indivíduos sem DP e com DP, estratificados de acordo com a dose de levodopa administrada diariamente. Resultados Foi identificada correlação fraca e negativa entre a amplitude das EOAPD com a dose diária de levodopa e correlações positivas, de força moderada e fraca, entre o EIEOA com a dose diária de levodopa e o tempo de diagnóstico da DP, respectivamente. A amplitude das EOAPD foi maior nos indivíduos com DP em uso de levodopa ≤ 600 miligramas quando comparada à de indivíduos sem DP e com DP, em uso de dose superior. Já o EIEOA foi menor nos indivíduos em uso de doses ≤ 600 miligramas, quando comparado aos demais grupos. Conclusão Doses diárias de levodopa iguais ou inferiores a 600 mg/dia aumentam as respostas mecanotransdutoras cocleares nas frequências de 2 e 3 kHz, enquanto que a ação dos sistemas eferentes olivococleares é reduzida nesta região.

ABSTRACT Purpose To evaluate the effect of levodopa on cochlear dynamics and on the medial olivocochlear efferent pathway of idiopathic Parkinson's disease (PD) individuals. Methods Individuals with and without PD, followed at a University Hospital, were submitted to Distortion Product Otoacoustic Emissions (DPOAE) and DPOAE Inhibitory Effect (OAEIE) in the presence of contralateral noise. Correlation measures between DPOAE and OAEIE results with Hoehn&Yahr (H&Y) stage, daily dose of levodopa and PD diagnosis period were established. Furthermore, electroacoustic measures were compared between individuals without and those with PD, stratified by dose of levodopa daily administered. Results Weak negative correlation between DPOAE amplitude and daily dose of levodopa was found, as well positive correlations between EIEOA with daily dose of levodopa and time of PD diagnosis, respectively. Higher DPOAE amplitude was found in individuals with PD using daily doses of levodopa ≤ 600 milligrams when compared to individuals without PD and those with PD using higher doses. EIEOA was lower in individuals using doses ≤ 600 milligrams, when compared to the other groups. Conclusion Daily doses of levodopa up to 600 mg / day increase the cochlear mechanical-transducer responses in 2 and 3 kHz frequencies, while the action of olivocochlear efferent systems is reduced in this region.