Effect of medication withdrawal on pain in Parkinson's disease patients - an observational study based on a sample of patients without antiparkinsonian medications

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.

Risco para quedas em pessoas idosas residentes na comunidade / Riesgo de caídas en personas mayores que viven en la comunidad / Risk for falls in community-dwelling elderly

RESUMO Objetivo: avaliar os fatores de risco para quedas em pessoas idosas residentes na comunidade. Métodos: estudo descritivo, transversal e quantitativo, desenvolvido na região Nordeste do Brasil com 221 pessoas idosas residentes na comunidade. A coleta de dados ocorreu de junho a setembro de 2016 com a utilização de instrumentos estruturados. Realizou-se uma análise exploratória dos dados com medidas de tendência central, dispersão e associação entre as variáveis. Resultados: em relação ao perfil, observaram-se faixa etária entre 60 e 79 anos (75,6%); sexo feminino (70,6%); casados (43,9%); até quatro anos de escolaridade (33,9%); renda pessoal mensal de até um salário mínimo (45,7%) proveniente da aposentadoria (60,2%); três a cinco comorbidades (51,6%). Quanto ao risco para quedas, destacou-se como preditores a Fall Risk Score classificada como "alto risco", seguida por medicamentos antiparkinsonianos, antidepressivos e diuréticos, hipoglicemia, deficiência auditiva, dor, incontinência urinária e sintomas neurológicos. Conclusão: faz-se necessário estabelecer ações individuais e coletivas para a prevenção e promoção da saúde diante dos riscos para quedas. A rede de saúde deve trabalhar para possibilitar a conscientização de que as quedas constituem um problema de saúde pública e, por isso, ressalta-se a necessidade de cuidados direcionados, evitando consequências na qualidade de vida da pessoa idosa.

RESUMEN Objetivo: evaluar los factores de riesgo para caídas en personas mayores residentes en la comunidad. Métodos: estudio descriptivo, transversal y cuantitativo, desarrollado en la región Nordeste de Brasil con 221 personas mayores residentes en la comunidad. La recolección de datos tuvo lugar de junio a septiembre de 2016 con la utilización de instrumentos estructurados. Se realizó un análisis exploratorio de los datos con medidas de tendencia central, dispersión y asociación entre las variables. Resultados: en relación al perfil, se observaron franja etaria entre 60 y 79 años (75,6%); sexo femenino (70,6%); casados (43,9%); hasta cuatro años de escolaridad (33,9%); renta personal mensual de hasta un salario mínimo (45,7%) proveniente de la jubilación (60,2%); tres a cinco comorbilidades (51,6%). En cuanto al riesgo de caídas, se destacó como predictores la FallRisk Score clasificada como "alto riesgo", seguida por fármacosAntiparkinsonianos, antidepresivos y diuréticos, hipoglucemia, deficiencia auditiva, dolor, incontinencia urinaria y síntomas neurológicos. Conclusión: se hace necesario establecer acciones individuales y colectivas para la prevención y promoción de la salud frente a los riesgos para caídas. La red de salud debe trabajar para posibilitar la concienciación de que las caídas constituyen un problema de salud pública y, por eso, se resalta la necesidad de cuidados dirigidos, evitando consecuencias en la calidad de vida de la persona anciana.

ABSTRACT Objective: to assess risk factors for falls in elderly people living in the community. Methods: descriptive, cross-sectional, and quantitative study, developed in the Northeast region of Brazil with 221 elderly people living in the community. Data collection took place from June to September 2016 using structured instruments. An exploratory data analysis was performed with measures of central tendency, dispersion, and association between variables. Results: regarding the profile, there was an age group between 60 and 79 years old (75.6%); females (70.6%); married (43.9%); up to four years of education (33.9%); monthly personal income of up to one minimum wage (45.7%) from retirement (60.2%); three to five comorbidities (51.6%). As for the risk of falls, the Fall Risk Score classified as "high risk" stood out as predictors, followed by antiparkinsonian drugs, antidepressants and diuretics, hypoglycemia, hearing loss, pain, urinary incontinence, and neurological symptoms. Conclusion: it is necessary to establish individual and collective actions for the prevention and promotion of health because of the risks of falls. The health network must work to raise awareness that falls are a public health problem and, therefore, the need for targeted care is emphasized, avoiding consequences on the quality of life of elderly people.

Diagnostic prediction model for levodopa-induced dyskinesia in Parkinson's disease / Modelo de predição diagnóstica para discinesias induzidas por levodopa na doença de Parkinson

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: 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.

Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Deep brain stimulation in parkinson disease

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Efeito da levodopa na mecânica coclear e no sistema auditivo eferente de indivíduos com doença de Parkinson / Effect of levodopa on cochlear mechanics and efferent auditory system of Parkinson's disease individuals

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.

Apomorphine in the treatment of Parkinson's disease: a review / O uso da apomorfina no tratamento da doença de Parkinson: revisão da literatura

ABSTRACT Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.

RESUMO A optimização do tratamento da doença de Parkinson idiopática se faz um desafio, pois tem impacto direto na qualidade de vida do paciente. O melhor esquema terapêutico é o que permite o melhor controle motor com os menores efeitos adversos, através de terapêutica individualizada. A apomorfina é o único medicamento antiparkinsoniano que pode ser comparável à potência da levodopa no controle dos sintomas motores. Trata-se de um agonista dopaminérgico empregado na terapia de resgate em pacientes com flutuações motoras e também contribui para a melhora de muitos sintomas não motores. A via subcutânea, com injeções intermitentes, ou com infusão contínua, parece ser a melhor opção pela eficácia e tolerabilidade. Essa revisão resume aspectos históricos, estrutura da molécula, mecanismo de ação, indicação, contra-indicação e efeitos colaterais, compara a terapia de infusão com apomorfina com outros tratamentos, como a terapia oral, estimulação cerebral profunda e infusão enteral contínua de levodopa/carbidopa gel, e fornece instruções práticas de como iniciar o tratamento.

Prescribing patterns of antiparkinson drugs in a group of Colombian patients, 2015 / Patrones de prescripción de fármacos antiparkinsonianos en un grupo de pacientes de Colombia, 2015

Introduction: Parkinson's disease, whose prevalence in Colombia is 4.7 per 1,000 inhabitants, is a public health problem and a therapeutic challenge for health professionals. Objective: To determine the prescribing patterns of antiparkinson drugs and the variables associated with its use in a population from Colombia. Materials and methods: We conducted a descriptive cross-sectional study. We selected patients who had been given antiparkinson drugs uninterruptedly between January 1st and March 31st, 2015 from a systematized database of approximately 3.5 million people affiliated to the Colombian health system. We included sociodemographic, pharmacologic and comedication variables. For the multivariate analysis, we used the IBM SPSS™-22 software. Results: A total of 2,898 patients was included; the mean age was 65.1years, and 50.7% were men; 69.4% (n=2010) of people received monotherapy and 30.6% combination therapy with two to five antiparkinson drugs. The most frequently prescribed drugs were: levodopa 45.5% (n=1,318 patients), biperiden 23.1% (670), amantadine 18.3% (531) and pramipexole 16.3% (471). The most commonly used association was levodopa/carbidopa + entacapone (n=311; 10.7%). Multivariate analysis showed that being male (OR=1.56; 95%CI: 1.321-1.837), over 60 years (OR=1.41; 95%CI 1.112-1.782) and receiving treatment in the city of Barranquilla (OR=2.23; 95%CI 1.675-2.975) were statistically associated with a greater risk of using combination therapy; 68.2% (n=1,977) patients were given concomitant treatment with other drugs. Conclusions: Prescribing habits of drugs with high therapeutic value predominated, mainly in antiparkinson drugs monotherapy. Most were employed in the usual recommended doses. It is necessary to explore the clinical effectiveness of the medications studied and differentiate between disease and parkinsonian syndromes subtypes.

Introducción. La enfermedad de Parkinson, cuya prevalencia en Colombia es de 4,7 por 1.000 habitantes, constituye un problema de salud pública y un reto terapéutico para los profesionales de la salud. Objetivo. Determinar los patrones de prescripción de fármacos antiparkinsonianos y las variables asociadas con su utilización en una población colombiana. Materiales y métodos. Se hizo un estudio descriptivo de corte transversal. A partir de una base de datos de 3,5 millones de afiliados al sistema de salud, se seleccionaron pacientes con prescripción de medicamentos antiparkinsonianos de manera ininterrumpida entre el 1º de enero y el 31 de marzo de 2015. Se incluyeron variables sociodemográficas, farmacológicas y de medicación concomitante. El análisis multivariado se hizo con el programa IBM SPSS™-22. Resultados. Se hallaron 2.898 pacientes, con una edad media de 65,1 años, de los cuales el 50,7 % correspondía a hombres. El 69,4 % (n=2.010) de las personas recibía monoterapia y el 30,6 %, tratamiento combinado con dos a cinco medicamentos antiparkinsonianos. Los más prescritos eran la levodopa (45,5 %; n=1.318 pacientes), el biperideno (23,1 %; n=670), la amantadina (18,3 %; n=531) y el pramipexol (16,3 %; n=471). La asociación más utilizada fue la de levodopa-carbidopa y entacapone (n=311; 10,7 %). En el análisis multivariado se encontró que ser hombre (odds ratio, OR=1,56; IC95% 1,321-1,837), ser mayor de 60 años (OR=1,41; IC95% 1,112-1,782) y recibir tratamiento en Barranquilla (OR=2,23; IC95% 1,675-2,975), se asociaban con una mayor probabilidad de emplear el tratamiento combinado. Al 68,2 % (n=1.977) de los pacientes se les había prescrito tratamiento concomitante con otros medicamentos. Conclusión. Predominaron los hábitos de prescripción de medicamentos con gran valor terapéutico, principalmente en la monoterapia, la mayoría en las dosis usuales recomendadas. Es necesario explorar la efectividad clínica de las prescripciones estudiadas, y diferenciar entre la enfermedad y los subtipos de síndromes parkinsonianos.

Motor and non-motor wearing-off and its impact in the quality of life of patients with Parkinson's disease / Flutuações motoras e não-motoras e seu impacto na qualidade de vida de pacientes com doença de Parkinson

ABSTRACT The wearing-off phenomenon is common in patients with Parkinson's disease. Motor and non-motor symptoms can fluctuate in relation to the "on/off" periods. Objective: To assess the impact of motor and non-motor wearing-off on activities of daily living and quality of life of patients with PD. Methods: A cross-sectional study was carried out. All patients were evaluated using the Movement Disorders Society Unified Parkinson's Disease Rating Scale. Wearing-off was assessed using the Wearing-Off Questionnaire-19, and quality of life was assessed using the Parkinson's Disease Questionnaire-8. Results: A total of 271 patients were included; 73.4% had wearing-off; 46.8% had both motor and non-motor fluctuations. Patients with both motor and non-motor wearing-off had a worst quality of life compared with those with only motor fluctuations (p = 0.047). Conclusions: Motor and non-motor fluctuations have an impact on activities of daily living and quality of life. Non-motor wearing-off may have a higher impact.

RESUMO O fenômeno de encurtamento do fim de dose é comum em pacientes com doença de Parkinson. Tanto os sintomas motores quanto os não motores podem flutuar em relação aos períodos de "on/off". Objetivo: Avaliar o impacto das flutuações motoras e não-motoras nas atividades da vida diária e qualidade de vida em pacientes com doença de Parkinson. Métodos: Um estudo transversal foi realizado. Todos os sujeitos foram avaliados utilizando a escala unificada para a doença de Parkinson da Sociedade de Distúrbios do Movimento. O encurtamento do fim de dose foi avaliado através do questionário WOQ-19 e a qualidade de vida foi avaliada através do PDQ-8. Resultados: Um total de 271 pacientes foram incluídos, 73,4% tiveram deterioração de fim de dose. A maioria dos pacientes tiveram tanto flutuações motoras quanto não-motoras (46,8%). Os pacientes com ambos os tipos de flutuações motoras e não-motoras tiveram pior qualidade de vida do que pacientes apenas com flutuações motoras (p = 0.047). Conclusões: Pacientes com flutuações motoras e não-motoras tiveram impacto significativo nas atividades da vida diária e na qualidade de vida. As flutuações não-motoras parecem ter um impacto maior que as flutuações motoras sobre a qualidade de vida.

Conducta terapéutica en ancianos con enfermedad de Parkinson / Therapeutic behavior in elderly with Parkinson disease

La enfermedad de Parkinson es un proceso degenerativo del sistema nervioso central de inicio insidioso progresivo y desarrollo lento, que es consecuencia de una lesión idiopática en el sistema extrapiramidal y cuyas manifestaciones clínicas son rigidez, temblor y bradicinesia. Se presenta en personas de edad avanzada, sin diferencias en cuanto a sexo, raza o clase socioeconómica, y su diagnóstico definitivo se determina por el método clínico. Al respecto, en este artículo se describe la conducta terapéutica que se debe seguir en los ancianos que padezcan la enfermedad, donde el tratamiento no farmacológico se debe enfocar a mejorar la situación física y psíquica del paciente y la familia, según el estadio evolutivo, y el farmacológico se basa en la levodopa como medicamento de elección, con la cual se logra elevar la calidad de vida de los ancianos afectados

Parkinson disease is a degenerative process of the central nervous system of progressive insidious beginning and slow development which is the consequence of an idiopathic lesion in the extrapiramidal system and which clinical manifestations are rigidity, tremor and bradykinesia. It is presented in people of advanced age, without differences as for sex, race or social-economic class, and its definitive diagnosis is determined through the clinical method. In this respect, the therapeutic approach that should be followed in the elderly that suffers the disease is described in this work, in which the non pharmacological treatment should be focused to improve the patient and family physical and psychical situation, according to the evolutive course, and the pharmacological treatment is based on levodopa as election drug, with which it is possible to elevate the life quality of the affected patients

Chronic treatment with carvacrol improves passive avoidance memory in a rat model of Parkinson's disease / O tratamento com carvacrol melhora a memória de esquiva passiva em um modelo da doença de Parkinson em ratos

ABSTRACT The present study investigated the effects of carvacrol on motor and memory deficits as well as hyperalgesia in the 6-OHDA-lesioned rat model of Parkinson's disease. The animals were subjected to unilateral microinjection of 6-OHDA into the medial forebrain bundle and treated with carvacrol (25, 50 and 100 mg/kg, ip) for six weeks after surgery. The 6-OHDA-lesioned rats showed contralateral rotations towards the lesion side, which was accompanied by learning and memory deficits in a passive avoidance test and a decrease in tail withdrawal latency in a tail flick test at the end of week 6. The results also showed that treatment with carvacrol at a dose of 25 mg/kg ameliorated memory deficits, with no effect on rotations and hyperalgesia in lesioned rats. In conclusion, carvacrol improves memory impairments in rats with Parkinson's disease; therefore, it may serve as an adjunct therapy for the alleviation of memory deficits in Parkinson's disease patients.

RESUMO O presente estudo investigou os efeitos do carvacrol nos déficits motores e de memória, bem como na hiperalgesia, em um modelo da doença de Parkinson (DP) em ratos com lesões 6-OHDA. Os animais foram submetidos a microinjeção unilateral de 6-OHDA no feixe mediano do prosencéfalo e tratados com carvacrol (25, 50 e 100 mg / kg, ip) durante 6 semanas após a cirurgia. Os ratos com lesões 6-OHDA mostraram rotações contralaterais para o lado da lesão, que foram acompanhadas de déficits de aprendizagem e de memória em um teste de evitação passiva, e de uma diminuição da latência de retirada da cauda em um teste de cauda no final da semana 6. Os resultados também mostraram que o tratamento crônico com carvacrol a uma dose de 25 mg / kg aliviou os déficits de memória, sem efeito sobre rotações e hiperalgesia em ratos lesados. Em conclusão, o carvacrol melhora a deficiência de memória em ratos com DP e, portanto, pode servir como uma terapia complementar para aliviar os déficits de memória em pacientes com DP.

Moutan Cortex Radicis inhibits the nigrostriatal damage in a 6-OHDA-induced Parkinson's disease model / 中国天然药物

The traditionally used oriental herbal medicine Moutan Cortex Radicis [MCR; Paeonia Suffruticosa Andrews (Paeoniaceae)] exerts anti-inflammatory, anti-spasmodic, and analgesic effects. In the present study, we investigated the therapeutic effects of differently fractioned MCR extracts in a 6-hydroxydopamine (OHDA)-induced Parkinson's disease model and neuro-blastoma B65 cells. Ethanol-extracted MCR was fractionated by n-hexane, butanol, and distilled water. Adult Sprague-Dawley rats were treated first with 20 μg of 6-OHDA, followed by three MCR extract fractions (100 or 200 mg·kg) for 14 consecutive days. In the behavioral rotation experiment, the MCR extract-treated groups showed significantly decreased number of net turns compared with the 6-OHDA control group. The three fractions also significantly inhibited the reduction in tyrosine hydroxylase-positive cells in the substantia nigra pars compacta following 6-OHDA neurotoxicity. Western blotting analysis revealed significantly reduced tyrosine hydroxylase expression in the substantia nigra pars compacta in the 6-OHDA-treated group, which was significantly inhibited by the n-hexane or distilled water fractions of MCR. B65 cells were exposed to the extract fractions for 24 h prior to addition of 6-OHDA for 30 min; treatment with n-hexane or distilled water fractions of MCR reduced apoptotic cell death induced by 6-OHDA neurotoxicity and inhibited nitric oxide production and neuronal nitric oxide synthase expression. These results showed that n-hexane- and distilled water-fractioned MCR extracts inhibited 6-OHDA-induced neurotoxicity by suppressing nitric oxide production and neuronal nitric oxide synthase activity, suggesting that MCR extracts could serve as a novel candidate treatment for the patients with Parkinson's disease.

Moutan Cortex Radicis inhibits the nigrostriatal damage in a 6-OHDA-induced Parkinson's disease model / 中国天然药物

The traditionally used oriental herbal medicine Moutan Cortex Radicis [MCR; Paeonia Suffruticosa Andrews (Paeoniaceae)] exerts anti-inflammatory, anti-spasmodic, and analgesic effects. In the present study, we investigated the therapeutic effects of differently fractioned MCR extracts in a 6-hydroxydopamine (OHDA)-induced Parkinson's disease model and neuro-blastoma B65 cells. Ethanol-extracted MCR was fractionated by n-hexane, butanol, and distilled water. Adult Sprague-Dawley rats were treated first with 20 μg of 6-OHDA, followed by three MCR extract fractions (100 or 200 mg·kg) for 14 consecutive days. In the behavioral rotation experiment, the MCR extract-treated groups showed significantly decreased number of net turns compared with the 6-OHDA control group. The three fractions also significantly inhibited the reduction in tyrosine hydroxylase-positive cells in the substantia nigra pars compacta following 6-OHDA neurotoxicity. Western blotting analysis revealed significantly reduced tyrosine hydroxylase expression in the substantia nigra pars compacta in the 6-OHDA-treated group, which was significantly inhibited by the n-hexane or distilled water fractions of MCR. B65 cells were exposed to the extract fractions for 24 h prior to addition of 6-OHDA for 30 min; treatment with n-hexane or distilled water fractions of MCR reduced apoptotic cell death induced by 6-OHDA neurotoxicity and inhibited nitric oxide production and neuronal nitric oxide synthase expression. These results showed that n-hexane- and distilled water-fractioned MCR extracts inhibited 6-OHDA-induced neurotoxicity by suppressing nitric oxide production and neuronal nitric oxide synthase activity, suggesting that MCR extracts could serve as a novel candidate treatment for the patients with Parkinson's disease.

Impact of levodopa treatment in the voice pattern of Parkinson's disease patients: a systematic review and meta-analysis / O impacto do tratamento com levodopa na voz de pacientes com doença de Parkinson: revisão sistemática e meta-análise

Abstract Purpose Investigate the association between levodopa therapy and vocal characteristics in Parkinson's disease patients. Search strategy Studies published at MEDLINE, LILACS, and SciELO, from 1960 to December 2016. A systematic review and meta-analysis was performed using the following keywords: Parkinson's disease; levodopa; L-dopa; voice; speech disorders; dysphonia; dysarthria. After analyzing titles and abstracts, two independent reviewers selected all clinical trials that met the eligibility criteria and selected the articles and the data recorded in a previously standardized table. Selection criteria Trials published in English between 1960 and December 2016 individuals with clinical diagnosis of Parkinson's disease; use of levodopa therapy in stable doses; acoustic analysis combined or not with auditory-perceptual analysis to evaluate the vocal parameters under investigation. Data analysis The following vocal parameters were analyzed: fundamental frequency (F 0), jitter, and vocal intensity. Standardized mean differences (SMD) were calculated using the Comprehensive Meta-analysis V2 software. Results Nine articles met the eligibility criteria and were selected, with a total of 119 individuals. From these, six articles with 83 individuals were included in the meta-analysis. During the levodopa therapy "on" state, modifications in F 0 (SMD=0.39; 95% CI - 0.21-0.57) and jitter (SMD=0.23; 95% CI - 0.02-0.45) were observed. Vocal intensity was not affected (SMD=0.09; 95% CI - 0.22-0.39) by levodopa ingestion. Data of the included studies were controversial in the auditory-perceptual analysis of voice. Conclusion Levodopa therapy modifies F0 and jitter. No changes in vocal intensity were observed in either the "on" or "off" states of levodopa therapy.

RESUMO Objetivo investigar a associação entre o uso da levodopa e as características vocais em pacientes com doença de Parkinson. Estratégia de pesquisa estudos publicados nas bases MEDLINE, LILACS e SciELO, de 1960 a dezembro de 2016. Uso dos descritores: doença de Parkinson; levodopa; L-dopa; voz; distúrbios do discurso; disfonia e disartria. Depois de analisar os títulos e os resumos, dois revisores independentes selecionaram todos os ensaios clínicos que atendiam aos critérios de seleção, selecionaram os artigos e registraram os dados em uma tabela padronizada anteriormente. Critérios de seleção ensaios publicados em inglês entre 1960 e dezembro de 2016 assuntos com diagnóstico clínico de doença de Parkinson; uso de terapia com levodopa em doses estáveis; análise acústica combinada ou não com a análise auditiva-perceptiva para avaliar os parâmetros vocais sob investigação. Análise dos dados os parâmetros vocais analisados ​​foram: frequência fundamental (F0), Jitter e intensidade vocal. As diferenças de médias padronizadas (SMD) foram calculadas com o software Metanálise Abrangente V2. Resultados 9 artigos preencheram os critérios de elegibilidade e foram selecionados, com um total de 119 indivíduos. Desses 9 artigos, 6, com 83 indivíduos, foram incluídos na metanálise. Durante a fase "on", houve uma modificação no F0 (SMD = 0,39; IC 95% 0,21-0,57) e Jitter (SMD = 0,23; IC 95% 0,02-0,45). A intensidade vocal não foi afetada (SMD = 0,09; IC 95% -0,22-0,39) pela ingestão da levodopa. Ao considerar a análise auditiva-perceptiva, os dados foram controversos entre os estudos incluídos. Conclusão a terapia com levodopa modifica F0 e Jitter. Não houve alteração na intensidade vocal nas fases "on" e "off" da terapia com levodopa.

Severo edema inducido por la terapia dopaminérgica en la enfermedad de Parkinson. Caso clínico / Severe leg edema associated with the use of dopaminergic drugs in Parkinson's disease. Report of one case

The main adverse effects of dopaminergic drugs used in Parkinson's disease are hypotension, somnolence, hallucinations and impulse control disorder. Less common is leg edema. We report on a 68-year-old male receiving levodopa and pramipexole consulting for severe leg edema lasting two years, whose etiology was not ascertained with multiple lab tests. This edema subsided substantially when pramipexole was discontinued and the dose of levodopa was increased to treat motor symptoms.

Polineuropatia periférica na doença de Parkinson: prevalência e fatores de risco em uma amostra na cidade de Campina Grande - PB / Peripheral neuropathy in Parkinson's disease: prevalence and risk factors in a sample of Campina Grande city - Paraíba

Polineuropatia periférica (PNP) tem sido descrita na doença de Parkinson idiopática (DP), porém a prevalência e os fatores de risco não estão bem definidos. Objetivo: Investigar a prevalência e os fatores de risco para PNP na DP, em comparação com a população geral. Método: Participaram 36 pacientes com DP recrutados no ambulatório de Neurologia do Hospital Universitário Alcides Carneiro (HUAC) da Universidade Federal de Campina Grande (UFCG), Paraíba, e 30 sujeitos controles. Todos os participantes foram submetidos a caracterização clínica da PNP, ao estudo de neurocondução (ENC) dos nervos peroneal e sural bilateral e as dosagens de vitamina B12, homocisteina, ácido metilmalônico e ácido fólico. A Escala Unificada de Avaliação da Doença de Parkinson - III e a de Hoehn-Yahr foram utilizadas na avaliação motora do grupo Parkinson (GP). Resultados: Sinais e sintomas neuropáticos foram mais frequentes no GP (61%). Alterações nos parâmetros do ENC foram observadas em 44,4% do GP e 26,7% do grupo controle, sendo a PNP confirmada em três pacientes e um controle. Análise de regressão revelou associação significativa entre os sintomas neuropáticos e a DP, sem associação com aspectos clínicos e bioquímicos. Conclusão: Pacientes com DP possuem maiores escores neuropáticos e maior prevalência de PNP que controles. Os dados sugerem a própria DP como fator de risco para o desenvolvimento da PNP, minimizando o papel da vitamina B12 e de seus metabólitos neste processo.(AU)

Peripheral neuropathy (PN) has been described in idiopathic Parkinson disease (PD) however the prevalence and the risk factors are not well established. Objective: To assess the prevalence of PN and the risk factors for neuropathy in PD against the general population. Method: Participated in the study 36 PD patients recruited from Neurology Outpatient Unit of Hospital Universitário Alcides Carneiro of the Federal University of Campina Grande, Paraíba, and 30 controls. All the participants were submitted to clinical characterization of PN, nerve conduction study (NCS) and biochemical dosages (B12 vitamin, homocysteine, methylmalonic acid and folic acid). Results: Neuropathic signs and symptoms were more frequent in PD (61%). Alterations in parameters of NCS were observed in 44.4% of Parkinson group and 26.7% of control group, and PN was confirmed in 3 PD patients and 1 control. Regression analyses showed a significant association between symptoms of PN and PD, without association with clinical and biochemical features. Conclusion: PD patients have higher neuropathic scores and frequency of PN than controls. Data suggests the PD by itself as a risk factor for development of PN, reducing the role of B12 vitamin and its metabolites in this process.(AU)

Análise dos sintomas motores na Doença de Parkinson em pacientes de hospital terciário do Rio de Janeiro / Analysis of motor symptoms in patients with Parkinson's disease from a tertiary hospital in Rio de Janeiro

A doença de Parkinson (DP) é a segunda doença neu-rodegenerativa mais comum. Caracteriza-se clinicamente por tremor de repouso, rigidez, bradicinesia e instabilidade postural. O presente estudo busca caracterizar clinicamente uma população com DP em nosso meio. Objetivos: Descrever o perfil clínico de pacientes com DP de um hospital terciário do Rio de Janeiro, com foco nos sinais e sintomas motores da doença, para caracterização local da mesma. Métodos: Análise retrospectiva de 115 prontuários de pacientes com DP acompanhados no ambulatório de Distúrbios do Movimento do Hospital Universitário Pedro Ernesto da Universidade do Estado do Rio de Janeiro. Os parâmetros avaliados incluíram: idade, sexo, tem-po de doença, sinais motores predominantes, dimídio mais afetado, complicações motoras e tratamento utilizado. Resultados: Foram selecionados 95 participantes com DP, sendo a média de idade da amostra de 64,7 anos, com tempo médio de doença de 9,9 anos, pre-dominando no sexo masculino, em uma proporção de 2.5 homens para 1 mulher. Em relação ao tratamento utilizado, predominou o uso da levodopa /inibidor da dopa-descarboxilase, seguindo-se o pramipexole em monoterapia ou a associação de ambos. Conclusão: Apesar da grande variação na faixa etária, observou-se maior acome-timento da doença entre 60 e 80 anos, chamando atenção o tremor como sinal predominante. Entre as complicações motoras destaca-mos o "wearing off", seguido pelas discinesias. (AU)

Parkinson's disease (PD) is the second most common neurodegenerative disease. The main clinical features are rest tremor, rigidity, bradykinesia and postural instability. The present study aims to characterize clinically a population with PD in our commu-nity. Objective: To describe the clinical profile of PD patients from a tertiary hospital in Rio de Janeiro, with emphasis on motor signs and symptoms, for its local characterization. Methods: Retrospective analysis of 115 files from PD patients followed at the Movement Disorders Outpatient Clinic at Pedro Ernesto University Hospital from the State University of Rio de Janeiro. Parameters evaluated included: age, sex, disease duration, predominant motor signs, most affected side, motor complications and treatment prescribed. Results: Ninety five PD patients were selected, with an average age of the sample of 64.7 years, average disease duration of 9.9 years, male predominance, in a proportion of 2.5 men:1 woman. Regarding treatment, levodopa/dopa decarboxylase inhibitor was the most common drug prescribed, followed by pramipexol monotherapy or both in association. Conclusion: In spite of the wide age range, the disease affected mainly individuals between 60 and 80 years old. Tremor was the pre-dominant sign. Among motor complications, wearing off and dyskinesias should be highlighted. (AU)

Bereitschaftspotential preceding eyelid blinks in Parkinson's disease / Potencial de Bereitschafts precedendo o piscamento ocular na doença de Parkinson

ABSTRACT The Bereitschaftspotential (BP) is a negative wave observed in EEG retrograde averaging, preceding a motor act. The objective was to study the BP preceding voluntary eyelid blinks in Parkinson's disease (PD) patients during off and on phases of levodopa. Methods Ten PD patients in stages 1 and 2 of the Hoehn & Yahr classification were compared to 18 healthy controls. Artifact-free EEG segments of two seconds preceding the onset of the blink potential were averaged and analyzed, and the statistical significance of the measured amplitudes were evaluated by analysis of variance models. Results The presence of a BP in the PD patients was demonstrated. The mean amplitudes at 0 ms were respectively 0.6 µV and 3.3 µV for the BP patients and the normal controls, respectively. Conclusions The BP amplitudes were significantly smaller in PD patients than normal participants. The amplitudes of the BP were not modified by levodopa.

RESUMO O Potencial de Bereitschafts (PB) é uma onda negativa observada retrogradamente no EEG precedendo um ato motor. Objetivo Estudar o PB precedendo o piscamento palpebral voluntário em pacientes com doença de Parkinson (DP) durante as fases off e on da levodopa. Foram comparados dez pacientes com DP nos estágios 1 e 2 de Hoehn & Yahr com 18 controles saudáveis. Os segmentos de EEG livres de artefatos 2 segundos antes do início do potencial foram calculados e analisados e a significância estatística das amplitudes foi medida por modelos de análise de variância. Resultados A presença de PB nos pacientes com DP foi demonstrada. As amplitudes médias a 0 ms foram respectivamente 0,6 μV e 3,3 μV para os pacientes com DP e controles respectivamente. Conclusões As amplitudes do PB foram significativamente menores nos pacientes com DP do que controles. As amplitudes do PB não foram modificadas pela levodopa.