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.

Doxycycline to treat levodopa-induced dyskinesias in Parkinson's disease: a preliminary study.

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, week 4, 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.

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.

Doxycycline to treat levodopa-induced dyskinesias in Parkinson's disease: a preliminary study / Doxiciclina no tratamento das discinesias induzidas pela doença de Parkinson: um estudo preliminar

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.

The Effect of Cannabidiol for Restless Legs Syndrome/Willis-Ekbom Disease in Parkinson's Disease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2/3 Clinical Trial.

Background: Cannabidiol (CBD) is one of the main nonpsychoactive components of Cannabis sativa and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behavior disorder (RBD). Objective: Our purpose was a post hoc exploratory analysis to evaluate the CBD's efficacy to improve the severity of RLS/WED symptoms in patients with PD and RBD. Methods: A post hoc exploratory analysis of a phase II/III, a parallel, double-blind, placebo-controlled clinical trial was conducted in 18 patients with RLS/WED and PD plus RBD associated. Six patients were randomized to the CBD group in doses of 75-300 mg, and twelve received placebo capsules. They were followed up for 14 weeks. The primary outcome was the severity of RLS/WED by Restless Legs Syndrome Rating Scale of the International Restless Legs Syndrome Study Group (IRLSSG). Results: CBD showed no difference in relationship to placebo for primary and secondary outcomes. Conclusion: CBD showed no reduction in the severity of RLS/WED manifestation in patients with PD and RBD.

Reference Values for Dopamine Transporter Imaging With 99m Tc-TRODAT-1 in Healthy Subjects and Parkinson's Disease Patients.

PURPOSE: The aim of this study was to evaluate different quantitative indexes of striatum dopamine transporter density in healthy subjects and patients with PD. PATIENTS AND METHODS: Sixty-seven patients, 23 healthy (8 male; 59 ± 11 years old) and 44 age-matched patients (29 male; 59 ± 7 years old), with various degrees of severity of idiopathic PD (duration of symptoms, 10 ± 6 years; Hoehn and Yahr Scale, 2.16 ± 0.65; UPDRS-3, 29.74 ± 17.79). All patients performed 99m Tc-TRODAT-1 SPECT. Binding potential indexes (BPIs) of striatum and subregions, asymmetry index (AI), and putamen/caudate ratio (P/C) were calculated. RESULTS: Binding potential index was lower in the PD than in healthy subjects. A BPI cutoff for striatum and putamen ranging from 0.73 to 0.78 showed 95% to 100% sensitivity and 84% to 88% specificity. For the caudate nucleus, a BPI threshold of 0.8 to 0.88 revealed 100% sensitivity and 77% to 84% specificity. The BPI's respective areas under the curve ranged from 0.92 to 0.98. For AI and P/C, the area under the curve was less than 0.70. Binding potential index intraclass correlation coefficient was close to 1.0 in the intraobserver evaluation and 0.76 to 0.87 in the interobserver assessment. Intraclass correlation coefficient for AI and P/C was inferior to 0.75 in the intraobserver and interobserver evaluations. CONCLUSIONS: Different semiquantitative indices differentiated PD and healthy subjects and may help the differential diagnosis of other entities involving the dopaminergic system. Asymmetry index and P/C performances were lower than BPI, including their intraobserver and interobserver reliability, and therefore should be used with caution.

Direct and indirect assessment of functional abilities in patients with Parkinson's disease transitioning to dementia.

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.

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.

Direct and indirect assessment of functional abilities in patients with Parkinsons disease transitioning to dementia / Avaliação direta e indireta das habilidades funcionais em pacientes com doença de parkinson em transição para demência

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. 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

Pediatric multiple sclerosis-a challenging demyelinating disease: case report and brief review of the literature.

Multiple sclerosis (MS) is an inflammatory, demyelinating, neurodegenerative disorder of the central nervous system (CNS) of unknown etiology. The peak onset is between age 20 and 40 years and usually affects more women than men. Although much knowledge has been achieved on the diagnosis and treatment of adult patients with MS, it remains a matter of debate and controversy in childhood. We present a case of MS in 9-year-old girl, review the current state of the knowledge on pediatric MS, and discuss the available tools for the diagnosis and treatment.