Treatment of refractory amblyopia with levodopa associated with full-time occlusion in the dominant eye / Tratamento da ambliopia refratária com o uso de levodopa associada à oclusão total do olho dominante

Abstract Purpose: To evaluate visual outcomes of levodopa treatment associated with full occlusion of the dominant eye in patients with refractory amblyopia. Methods: A prospective study of 19 attended patients who were subject to treatment with Levodopa and Carbidopa on doses of 0.7mg/kg/day, a ratio of 4:1 divided into three daily doses for 5 weeks, combined with full occlusion (24 hours/day) of the dominant eye. The ophthalmologic exam from previous consultations up to treatment and after 8 weeks of therapy were collected from medical record data. Patients who had completed treatment for more than 12 months were included for complete eye examination. Results: The mean age before treatment with levodopa was 11.0 ± 4.2 years old (varying from 7 to 23 years). The best-corrected visual acuity (Snellen chart) of the amblyopic eye before treatment was 0.24 (0.6 in logMAR) ± 0.16, after 8 weeks of treatment it was 0.47(0.3 in logMAR) ± 0.33, while during the final evaluation it was 0.46 (0.3 in logMAR) ± 0.34. There was a statistically significant improvement in vision after 8 weeks of therapy which was maintained until the final evaluation (p = 0.007). Conclusion: Levodopa/Carbidopa therapyat doses of 0.7 mg/kg/day at a ratio of 4:1 divided in three daily doses, associated with full occlusion of the dominant eye during 5 weeks had a significant improvement on the visual acuity of the amblyopic eye, and persisted up to 1 year after the treatment.

Resumo Objetivo: Avaliar os resultados visuais do tratamento com levodopa associada à oclusão total do olho dominante em pacientes amblíopes. Métodos: Estudo prospectivo de 19 pacientes atendidos e submetidos ao tratamento com levodopa e carbidopa na dose de 0,7 mg/kg/dia e proporção de 4:1, divididos em três doses diárias, durante cinco semanas, combinada a oclusão total (24 horas/dia) do olho dominante. Foram coletados dados do prontuário referentes ao exame oftalmológico da consulta anterior ao tratamento e após 8 semanas de terapia. Os pacientes com término do tratamento com mais de 12 meses foram reconvocados para exame oftalmológico completo. Resultados: A média de idade dos pacientes previamente ao tratamento com levodopa foi de 11,0 ± 4,2 anos (variando de 7 a 23 anos). A acuidade visual melhor corrigida (Snellen) do olho amblíope antes do tratamento foi de 0,24 (0,6 em logMAR) ± 0,16, após 8 semanas de tratamento foi de 0,47 (0,3 em logMAR) ± 0,33 e na avaliação final foi de 0,46 (0,3 em logMAR) ± 0,34. Houve melhora estatisticamente significante da visão após 8 semanas de tratamento que se manteve até a avaliação final (p = 0,007) Conclusão: A terapia com levodopa/carbidopa em doses de 0,7mg/kg/dia na proporção de 4:1 dividida em três doses diárias, associada à oclusão total do olho dominante durante 5 semanas, apresentou uma melhora significativa na acuidade visual do olho ambliópico e persistiu até 1 ano após o tratamento.

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.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

A multidisciplinaridade na redução da levodopa na pessoa com doença de Parkinson avançada / Multidisciplinary care and the reduction of levodopa intake of patients with advanced Parkinson's disease

Objetivo: Identificar e comparar as pessoas com Doença de Parkinson (DP) que fazem atividades multidisciplinares com aqueles que não fazem. Método: Os participantes foram avaliados quanto ao estadiamento Hoehn e Yahr (HY) (1-4), idade, dose diária de levodopa, que atividades que participa, qualidade de vida (PDQ-39), atividade de vida diária e motor (UPDRS). Eles compararam os participantes e não participantes de atividades multidisciplinares quanto a estratificação dos níveis de HY entre aqueles com déficit de equilíbrio (níveis 3 e 4 HY), e aqueles que não têm problemas de equilíbrio (níveis 1 e 2 HY). Resultados: Avaliados 49 participantes de ambos os sexos (21 mulheres, 28 homens), destes 17 não participam de terapias multidisciplinares e 32 realizam pelo menos uma atividade interdisciplinar. Não houve diferenças entre os grupos. No entanto, ao estratificar os níveis de HY, percebemos que houve uma diferença estatística no nível de HY mais elevado quanto a dose diária de levodopa prescrita, entre participantes e não participantes de atividades multidisciplinares (P = 0,017). Conclusões: O achado aponta que para esse grupo de pessoas com maior gravidade da DP, que praticam atividades multidisciplinares precisam de dose de levodopa estatisticamente menor

Objective: To identify and compare people with Parkinson Disease (PD) doing multidisciplinary activities with those who do not realize. Method: Participants were evaluated for the Hoehn and Yahr (HY) (1-4), age, daily dose of levodopa, what activities they participate in and quality of life (PDQ-39), UPDRS activities of daily living and motor (UPDRS). They compared participants and non-practicing multidisciplinary activities stratifying the levels of HY between those with balance deficit (levels 3 and 4 HY), and those who do not have balance problems (levels 1 and 2 HY). Results: Attended by 49 participants of both genders (21 women, 28 men), these 17 do not participate in other therapies and 32 perform at least one multidisciplinary activity. There were no differences between groups participants and non-participating multidisciplinary activities. However, when stratifying the levels of HY, we realized that there was a statistical difference at the highest level of HY, the daily dose prescribed levodopa, between participants and non-participating multidisciplinary activities (P=0.017). Conclusions: The finding points that for this group of people with PD, with greater severity of PD, those who practice multidisciplinary activities need a statistically lower dose of levodopa

Efectividad de la terapia farmacológica oral utilizada para el tratamiento del control postural en niños con parálisis cerebral disquinética: una revisión sistemática / Effectiveness of oral pharmacologic therapy usedfor treatment of postural control in children withdyskinetic cerebral palsy (DCP): a systematic review

Objective: To evaluate the effectiveness of oral pharmacologic therapy in improving postural control and functionality in patients with DCP, with less than 20 years old, compared with any therapy or placebo. Methods: Randomized clinical trials and quasi-experimental with no restriction in publication date or language were included. The search was conducted in PubMed, EMBASE, The Cochrane Library (CENTRAL), Virtual Health Library (LILACS, SCIELO), ClinicalTrials.gov and Opengrey. The risk of bias was assessed according to the Cochrane Handbook for Interventions Systematic Reviews. Results: 3 cross over studies were included, according to the established criteria. The three drugs that were analyzed were: levodopa, and trihexyphenidyl and tetrabenazine, compared to placebo. No study had significant favorable results for the use of the drug over placebo. Conclusion: At the moment there is no evidence to support the use of oral medication in patients with DCP, based on the small number of high quality studies found, it is necessary to increase research on oral pharmacologic therapy in this group of patients.

Objetivo: Evaluar la efectividad del tratamiento farmacológico oral destinado a mejorar el control postural y la funcionalidad en pacientes con parálisis cerebral disquinética (PCD) menores de 20 años comparado con cualquier terapia o placebo. Métodos: Se incluyeron ensayos clínicos aleatorizados y cuasi experimentales sin restricción de fecha de publicación o lenguaje. La búsqueda se realizó en Pubmed, EMBASE, The Cochrane Library (CENTRAL), Biblioteca Virtual de la Salud (LILACS, SCIELO), ClinicalTrials.gov y Opengrey. El riesgo de sesgo fue evaluado de acuerdo al Manual Cochrane de Revisiones Sistemáticas de Intervenciones. Resultados: Se incluyeron 3 estudios cross-over de acuerdo a los criterios establecidos. Los tres fármacos analizados fueron: levodopa, tetrabenazina y trihexifenidilo, comparados con placebo. Ningún estudio tuvo resultados favorables de manera significativa para el uso del medicamento sobre placebo. Conclusión: Por el momento no existe evidencia que sustente el uso de la medicación oral en los pacientes con PCD en base al escaso número de estudios de alta calidad encontrados, siendo necesario que se aumente la investigación sobre el tratamiento farmacológico oral en este grupo de pacientes.

Análisis de costo-efectividad de pramipexol comparado con levodopa y cabergolina para pacientes con síndrome de piernas inquietas en Colombia / Análise de custo-eficácia do pramipexol e cabergolina comparação com levodopa para pacientes com síndrome das pernas inquietas na Colômbia

Problema de investigación: Describir los costos y la efectividad del pramipexol comparado con levodopa y cabergolina para el tratamiento de pacientes con síndrome de piernas inquietas.Tipo de evaluación económica\r\nAnálisis de costo-utilidad. Población objetivo: Población adulta con diagnóstico de síndrome de piernas inquietas. Intervención y comparadores: Intervención: Pramipexol, Comparadores: Levodopa y cabergolina. Horizonte temporal: 16 semanas. Perspectiva Sistema: General de Seguridad Social en Salud (SGSSS). Tasa de descuento: No aplica. Estructura del modelo: Modelo de Markov. Fuentes de datos de efectividad y \r\nseguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayos clínicos aleatorizados. Desenlaces y valoración: Años de vida ajustados por calidad (AVAC). Costos incluidos: Costos de medicamentos, Costos de procedimientos. Fuentes de datos de costos:SISMED, Manual tarifario ISS 2001. Resultados del caso base: En el escenario del caso base, pramipexol es una estrategia costo-efectiva con respecto a levodopa. El costo por AVAC ganado con pramipexol es de $7.480 comparado con levodopa. Análisis de sensibilidad: El análisis de sensibilidad determinístico y el diagrama de tornado mostraron que la variable con mayor impacto sobre las estimaciones de costo-efectividad es el precio de levodopa. No se realizó análisis de sensibilidad probabilístico. Conclusiones y discusión: Pramipexol ofrece una mejor relación entre costos y efectividad respecto a levodopa y cabergolina. De acuerdo con el criterio de los expertos clínicos la cabergolina no hace parte de la práctica clínica habitual para este trastorno y la \r\nlevodopa tiene un uso que requiere de supervisión por el efecto que agudiza las manifestaciones clínicas. La principal limitación de este estudio está relacionada con la poca información proveniente de estudios de investigación clínica y evaluaciones económicas.(AU)

Análisis de impacto presupuestal de pramipexol comparado con levodopa como terapia de primera línea para pacientes con síndrome de piernas inquietas en Colombia / Budget impact analysis of pramipexole compared to levodopa as first-line therapy for patients with restless legs syndrome in Colombia

Tecnologías evaluadas: Nuevas: pramipexol y cabergolina; Actuales: levodopa (en combinación con carbidopa). Población: Pacientes mayores de 18 años con síndrome de piernas inquietas. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costo por mg de los medicamentos. Fuente de costos: Sistema de información de Precios de Medicamentos y Dispositivos Médicos - SISMED. Escenarios: En la construcción de escenarios se consideró una participación de\r\nmercado más alta para pramipexol en comparación con levodopa. Lo anterior a partir de las recomendaciones resultado de la consulta con expertos y la participación de mercado de los medicamentos en el SISMED. \r\nResultados: Para la inclusión en el POS de pramipexol y cabergolina como terapia de primera línea para pacientes con síndrome de piernas inquietas en Colombia, se requeriría una inversión de $21.708.230.419 en el año 1 y de $53.499.840.477 en el año 3. En el caso que los medicamentos del escenario nuevo sean incluidos con un precio común basado en las metodologías de grupos terapéuticos del Ministerio de Salud y protección Social, el impacto presupuestal sería el mismo con una inversión de $21.708.230.419 en el año 1 y $53.499.840.477, en el año 3.(AU)

Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson's Disease

PURPOSE: To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peakdose dyskinesia in patients with Parkinson's disease (PD). MATERIALS AND METHODS: A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads. RESULTS: Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048). CONCLUSION: Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage.

Efectividad y seguridad de Pramipexol comparado con Levodopa, Pergolida, Cabergolina, Ropinirole para el tratamiento del Síndrome de Piernas Inquietas / Effectiveness and safety of Pramipexole compared to Levodopa, Pergolide, Cabergoline, Ropinirole for the treatment of Restless Legs Syndrome

IIntroducción: el Síndrome de Piernas Inquietas (SPI) se define como un trastorno neurológico que afecta de un 5 % a un 15% de la población general, de causa desconocida, incurable y de evolución crónica, con afectación del sueño y la calidad de vida en alerta. Se cuenta con tratamientos para aliviar los síntomas que afectan la calidad de vida, una primera línea de tratamiento son los agonistas dopaminérgicos entre ellos la Levodopa, el Pramipexol y la Pergolida (8), (9), (10). Objetivo: evaluar la efectividad y seguridad del pramipexol, comparado con otros agonistas dopaminergicos para el tratamiento del Síndrome de Piernas Inquietas (RSL). Metodología: la evaluación fue realizada de acuerdo al protocolo definido previamente por el grupo desarrollador el cual incluye una revisión sistemática de la literatura en MEDLINE, EMBASE, LILACS, COCHRANE y Google para dar respuesta a la pregunta de investigación desarrollada bajo la estrategia PICOT en compañía de expertos técnicos y metodológicos. En el estudio de Scholz con el uso del pramipexol se observó una diferencia de medias de -5.16 [IC95% -6.87 a -3.45] comparado con placebo en la escala de síntomas IRLS (I²= 76%). Los agonistas dopaminérgicos comparados con el placebo produjeron una diferencia de medias en la reducción del PLMSI de −22.38 (IC95% −27.82 a −16.94) por hora de sueño (I² = 73%). El Pramipexol produjo contra placebo una diferencia de medias de -30.47 [IC9% -51.58 a -9.35] (I² = 85%) en el Cambio en el PLMSI (calidad del sueño, a favor de pramipexol. Los agonistas dopaminérgicos comparados con placebo reportaron una diferencia de medias de 0.4 [IC95% 0.33 a 0.47] a favor de los agonistas dopaminergicos respecto a la calidad del sueño autoreportada. En un análisis de subgrupos por medicamentos, el pramipexol produjo contra placebo un cambio en la calidad del sueño autoreportada con una diferencia de medias de 0.44 [IC: 0.33, 0.54], a favor de pramipexol. Los agonistas dopaminérgicos produjeron mejoría en la calidad de vida comparado contra placebo con una diferencia de medias de 0.34 [IC95% 0.23 a 0.44] (I²= 61%). En un análisis de subgrupos por medicamento, el pramipexol produjo mejoría en la calidad de vida comparado contra placebo con una diferencia estandarizada de medias de 0.30 [IC95% 0.13 a 0.47]. Los agonistas dopaminérgicos (cabergolina o pramipexol) comparados con levodopa produjeron un cambio en la línea de base del IRLS con una diferencia de medias de -5.25 [IC95% -8.40 a -2.10] (I²= 55%). En comparaciones indirectas dentro del estudio Ying Sun el pramipexol versus el ropirinole mostró una diferencia de medias en la escala de síntomas IRLS de -1.48 (IC95% -4.47 a 0.45) sin embargo esta diferencia no fue estadísticamente significativa. Respecto a la seguridad, los eventos adversos fueron más frecuentes en el grupo de pacientes que recibió agonistas dopaminérgicos comparado con los pacientes que recibieron placebo con un OR de 1.82 [IC95% 1.59 a 2.08]. Los retiros por eventos adversos fue superior en el grupo de agonistas dopaminergicos versus placebo, con un OR 1.82, (IC95% 1.35 a 2.45), diferencia estadísticamente significativa y mostró una heterogeneidad moderada (I² = 41%). Los retiros por eventos adversos fue superior en el grupo de agonistas dopaminergicos versus placebo, con un OR 1.82, (IC95% 1.35 a 2.45), diferencia estadísticamente significativa y mostró una heterogeneidad moderada (I² = 41%). En un análisis de subgrupos por medicamentos, se reportaron más retiros con pramipexol que con placebo con un OR de 1.11 [IC95% 0.66 a 1.87], esta diferencia no fue estadísticamente significativa con una heterogeneidad moderada (I²= 44%). Conclusiones: Efectividad: Los agonistas dopaminergicos, dentro de los cuales está incluido el pramipexol, son más efectivos que el placebo en el tratamiento de las personas con RLS para los desenlaces de escala de síntomas IRLS, la reducción del PLMSI , la calidad de sueño autoreportada y calidad de vida. En un análisis por subgrupos dentro de la comparación entre agonistas dopaminergicos y el placebo, el pramipexol se mostró más efectivo que el placebo en los desenlaces del cambio del PLMSI, calidad del sueño y en la calidad de vida. Los agonistas dopaminergicos, dentro de los cuales está incluido el pramipexol, son más efectivos que la levodopa para los desenlaces de escala de síntomas IRLS. Al comparar el pramipexol de forma indirecta con el ropirinole (agonista dopaminergico) no se observaron diferencias estadísticamente significativas. Seguridad: Los eventos adversos son más frecuentes en el de grupo tratamiento con agonistas dopaminergicos (dentro de los cuales se encuentra el pramipexol) comparado con placebo. No se encontraron diferencias en seguridad entre el pramipexol y el placebo.(AU)

Anti-Allodynic Effects of Levodopa in Neuropathic Rats

PURPOSE: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats. MATERIALS AND METHODS: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not. RESULTS: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p0.05). CONCLUSION: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.

Overweight is more prevalent in patients with Parkinson's disease / Excesso de peso é mais frequente em pacientes com doença de Parkinson

Underweight and malnutrition are well documented in Parkinson's disease (PD), while overweight has been less reported. We carried out a cross-sectional study including 177 healthy controls and 177 PD patients attending a tertiary care center. We recorded weight and height for all participants. A statistically significant difference was found in body mass index (BMI) between controls and PD patients (29.1±5.4 versus 27.2±4.7, p<0.001). In the PD Group, two patients were underweight, 32.7% were within normal range, 46.9% had overweight, and 19.2% were obese. Overweight and normal weight were more prevalent in the PD Group (p=<0.01 and <0.001, respectively) when compared to controls. In conclusion, overweight/obesity are common among patients with PD, while underweight is almost negligible.

Baixo peso e desnutrição são muito documentadas na doença de Parkinson (DP), enquanto que o excesso de peso tem sido menos relatado. Foi realizado um estudo transversal com 177 controles saudáveis e 177 pacientes com DP que frequentavam um centro terciário. O peso e a altura de todos os participantes foram arquivados. Uma diferença estatisticamente significativa no índice de massa corporal (IMC) foi encontrada entre controles e pacientes com DP (29,1±5,4 versus 27,2±4,7, p<0,001). No Grupo DP, dois pacientes estavam abaixo do peso, 32,7% estavam dentro do intervalo normal, 46,9% apresentavam sobrepeso e 19,2% eram obesos. Peso normal e excesso de peso foram mais prevalentes no Grupo DP (p=<0,01 e <0,001, respectivamente) em relação aos controles. Em conclusão, o sobrepeso/obesidade são comuns entre os pacientes com DP, enquanto baixo peso nessa população é quase insignificante.

Respiratory changes in Parkinson's disease may be unrelated to dopaminergic dysfunction / Alterações respiratórias na doença de Parkinson podem não ter relação com a disfunção dopaminérgica

OBJECTIVE: To investigate the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in patients with Parkinson's disease (PD) during the on and off periods of levodopa and to compare with healthy controls. METHODS: Twenty-six patients were analyzed with Hoehn and Yahr scores (2-3) and 26 age and gender matched-controls. Statistical analysis was performed with Student's t-test for paired and independent samples. RESULTS: MIP and MEP values in patients were significantly lower than the values obtained in controls both for off and on stages -excepted for MIP in women (p=0.28). For patients with PD, the studied parameters did not differ between stages on and off, with the exception of MEP in women (p=0.00). CONCLUSIONS: Patients with PD have respiratory pressure lower than controls, even in early stages of the disease, and dopamine replacement has little impact over these respiratory pressures. These findings suggest that respiratory changes in PD may be unrelated to dopaminergic dysfunction.

OBJETIVO: Investigar as pressões inspiratórias máximas (PImáx) e as pressões expiratórias máximas (PEmáx) em pacientes com doença de Parkinson (DP) durante períodos on e off e comparar com controles MÉTODOS: Foram estudados 26 pacientes com scores de Hoehn e Yahr (2-3) e 26 indivíduos saudáveis pareados sexo e idade. A análise estatística foi realizada com o teste t de Student para amostras pareadas e para amostras independentes. RESULTADOS: Os valores de PImáx e PEmáx nos pacientes foram significativamente menores que os valores observados nos controles, tanto no período off como no período on -exceto PImáx nas mulheres (p=0,28). Nos pacientes com DP, os parâmetros estudados não diferiram entre os estágios off e on (exceto PEmáx nas mulheres-p=0,00). CONCLUSÕES: Pacientes com DP têm pressões respiratórias inferiores a controles mesmo em estágios iniciais da doença, e a reposição de dopamina tem pouco impacto sobre pressões respiratórias. Esses achados sugerem que as alterações respiratórias na DP podem não estar relacionadas às disfunções dopaminérgicas.

Treatment of Parkinson's disease in Thailand: review of the literature and practical recommendations.

The mainstay of treatment for Parkinson's Disease (PD) remains symptomatic despite the rapid expansion in knowledge of its neurodegenerative process. Therapeutic options, both medical and surgical, have been markedly improved over the past decades, resulting in better motor function, activities of daily living, and quality of life for PD patients. The principle of PD management should be individualized and the selection of treatments should aim to control symptoms as well as to prevent or delay motor complications. In Thailand, various pharmacologic and surgical options are available, including different formulations of levodopa, dopamine agonists, monoamine oxidase B inhibitor, cathechol-O-methyltransferase inhibitor pallidotomy, and lastly deep brain stimulation. The use of dopamine agonists in early PD has a levodopa-sparing effect and reduces the incidence of motor complications. Continuous dopaminergic stimulation (CDS), which mimics physiological activation of dopaminergic receptors, has been proposed as a strategy to prevent motor complications. Based on current evidence, practical guidelines in the medical management of different types of motor complications are outlined in the present article according to what are available in Thailand. Surgical interventions should be reserved for patients with intractable motor complications after careful patient selection.

Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele

Recently it was shown that single nucleotide polymorphisms (SNPs) can explain individual variation because of the small changes of the gene expression level and that the 50% decreased expression of an allele might even lead to predisposition to cancer. In this study, we found that a decreased expression of an allele might cause predisposition to genetic disease. Dopa responsive dystonia (DRD) is a dominant disease caused by mutations in GCH1 gene. The sequence analysis of the GCH1 in a patient with typical DRD symptoms revealed two novel missense mutations instead of a single dominant mutation. Family members with either of the mutations did not have any symptoms of DRD. The expression level of a R198W mutant allele decreased to about 50%, suggesting that modestly decreased expression caused by an SNP should lead to predisposition of a genetic disease in susceptible individuals.

Factitious disorder mimicking addiction to levodopa in a patient with advanced Parkinson's disease

Relatamos o caso de mulher de 43 anos de idade com doença de Parkinson de início precoce cujo controle neurológico foi significativamente afetado por co-morbidades psiquiátricas incluindo depressão maior e síndrome do pânico. A paciente também apresentou critérios para transtorno factício o qual mimetizava a síndrome de desregulação dopaminérgica, sendo responsável por significativa incapacidade clínica e social.

Efficacy and safety of piribedil in early combination with L-dopa in the treatment of Parkinson's disease: a 6-month open study.

BACKGROUND: Piribedil is a non-ergot D2/D3 dopamine agonist with antagonistic effect on alpha2-adrenoceptors and lack of agonist properties at 5-HT2A/2C receptors. Previous studies indicated its efficacy in monotherapy as well as in combinatio' s disease in L-dopa-treated parkinsonian patients. PATIENTS AND METHOD: A 6-month, open-labeled, multicenter study was conducted in Thai Parkinsonian patients who were insufficiently controlled by L-dopa (< or = 600 mg/day). Piribedil 50 mg in retard form was titrated upward to 150 mg/day (50 mg tid) by the 5th week and up to 6 months as an add-on treatment. L-dopa daily dose was kept stable until the 3rd month and could be adjusted afterwards. The main efficacy parameter was the change in UPDRS part III score versus baseline over Full Analysis Set, score variation, and percentage of responders defined by at least 30% decrease from baseline of total UPDRS part III score. The secondary efficacy criteria were changes in L-dopa dose between the third month and the end of the study, UPDRS part II score variation, Hoehn and Yahr stage variation and Schwab and England Activities of Daily Living Scale variation. The acceptability of piribedil was assessed by physical examination, weight, blood pressure and heart rate as well as the reported adverse events. RESULTS: Twenty-nine patients (55.2% male) with the mean age of 64.0 +/- 7.2 years and mean duration of disease of 18.3 +/- 8.2 months were recruited The mean UPDRS part III score at baseline was 19.8 +/- 11.4. After 6-month treatment with piribedil, mean UPDRS part III score significantly decreased to 6.6 +/- 4.7 (p < 0.0001) with mean score variation of 13.3 +/- 10.3. Twenty-seven patients (93.1%) were responders. Mean UPDRS part II score was significantly decreased from 7.2 +/- 5.4 at baseline to 2.7 +/- 2.1 at the end of 6 months (p < 0.0001). Hoehn and Yahr stage and Schwab and England Activities of Daily Living Scale were also significantly improved Reported adverse events were mainly gastrointestinal symptoms. Blood pressure and heart rate were not significantly changed during the study period. Peak dose dyskinesia was reported only in one patient. Two patients (6.9%) were withdrawn because of adverse events. CONCLUSION: Piribedil was effective on motor symptoms during a 6-month treatment in early parkinsonian patients insufficiently controlled by L-dopa and it was well tolerated.

Sporadic variety of pallido-pyramidal syndrome.

A rare case of a 40-year-old lady with a sporadic variety of the pallido-pyramidal syndrome (PPS) is reported. She had marked parkinsonian features on the left side. Her single photon emission computed tomography showed left frontoparietal and basal ganglia hypoperfusion. CT scan and central motor conduction time were normal. She responded partially to a combination of trihexyphenydil and L dopa/C dopa therapy. In view of the diversity in the genetic, clinical and laboratory features, it is possible that PPS may be a heterogeneous condition.

Comparación farmacocinética de Sinemet y Grifoparkin (levodopa/carbidopa 250/25 mg) en pacientes con enfermedad de Parkinson avanzada: un estudio con dosis única / Pharmacokinetic comparison of Sinemet and Grifoparkin (levodopa/carbidopa 250/25 mg) in Parkinson s disease: a single dose study

BACKGROUND: There are doubts wether generic medications have the same bioavailability and efficacy compared with the original drugs developed by pharmaceutical companies with research capabilities. AIM: To compare the pharmacokinetics and clinical (motor) responses of Sinemet and Grifoparkin (generic carbidopa/levodopa 250/25 mg) in patients with advanced Parkinson's disease. PATIENTS AND METHODS: Patients were randomly assigned to Sinemet (15 patients 62 +/- 12 years old; mean disease duration 11 +/- 7 years) or Grifoparkin (15 patients, 64 +/- 11 years old; mean disease duration 12 +/- 4 years) groups. Medication and food were withheld 12 h before the study. Fifteen blood samples were collected (starting 9 AM) immediately before (sample 1, t = 0 min) and after (samples 2-15, t = 20-360 min) oral administration of a single dose of Sinemet or Grifoparkin, and plasmatic L-DOPA was quantified using HPLC with electrochemical detection. Additionally, each patient was clinically evaluated every 20 minutes, using the tapping test and the unified Parkinson's disease scale Hoehn & Yarh. RESULTS: Tmax (time at which the maximal L-DOPA concentration was reached) were 69 +/- 12 min and 64 +/- 11 min for Sinemet and Grifoparkin respectively (NS). Cmax (maximal L-DOPA concentration reached) was 3161 +/- 345 ng/ml for Sinemet and 3274 +/- 520 ng/ml for Grifoparkin (NS). The t1/2 (half life time), CL (clearance) and volume of distribution (Vd) values calculated were 159 +/- 32 min, 51.7 +/- 5.1 1/h and 3.6 +/- 1.2 l/kg for Sinemet and 161 +/- 48 min, 58.7 +/- 8 l/h and 3.0 +/- 0.7 l/kg for Grifoparkin (NS). UPDRS-III value for the best on state and for the worst off state were 23 +/- 11 and 50 +/- 19 for Sinemet and 20 +/- 7 and 46 +/- 13 for Grifoparkin respectively (NS). CONCLUSION: The results obtained showed that both drugs are bioequivalent in patients with advanced Parkinson's disease.