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Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Results: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.

Nonmotor symptoms negatively affect health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD). However, it is unknown which nonmotor symptoms are most commonly associated with HRQoL. Considering the complex interacting network of various nonmotor symptoms and HRQoL, this study aimed to reveal the network structure, explained HRQoL variance, and identify the nonmotor symptoms that primarily affect HRQoL. We included 689 patients with PD from the Cohort of Patients with Parkinson’s Disease in Spain (COPPADIS) study who were rated on the Nonmotor Symptoms Scale in Parkinson’s disease (NMSS) and the Parkinson´s Disease Questionnaire 39 (PDQ-39) at baseline. Network analyses were performed for the 30 items of the NMSS and both the PDQ-39 summary index and eight subscales. The nodewise predictability, edge weights, strength centrality, and bridge strength were determined. In PD, nonmotor symptoms are closely associated with the mobility, emotional well-being, cognition, and bodily discomfort subscales of the PDQ-39. The most influential nonmotor symptoms were found to be fatigue, feeling sad, hyperhidrosis, impaired concentration, and daytime sleepiness. Further research is needed to confirm whether influencing these non-motor symptoms can improve HRQoL.

IntroductionParkinson's disease (PD) is a multisystem neurodegenerative disorder characterized by motor and non-motor symptoms. In particular, non-motor symptoms have become increasingly relevant to disease progression. This study aimed to reveal which non-motor symptoms have the highest impact on the complex interacting system of various non-motor symptoms and to determine the progression of these interactions over time.MethodsWe performed exploratory network analyses of 499 patients with PD from the Cohort of Patients with Parkinson's Disease in Spain study, who had Non-Motor Symptoms Scale in Parkinson's Disease ratings obtained at baseline and a 2-year follow-up. Patients were aged between 30 and 75 years and had no dementia. The strength centrality measures were determined using the extended Bayesian information criterion and the least absolute shrinkage and selection operator. A network comparison test was conducted for the longitudinal analyses.ResultsOur study revealed that the depressive symptoms anhedonia and feeling sad had the strongest impact on the overall pattern of non-motor symptoms in PD. Although several non-motor symptoms increase in intensity over time, their complex interacting networks remain stable.ConclusionOur results suggest that anhedonia and feeling sad are influential non-motor symptoms in the network and, thus, are promising targets for interventions as they are closely linked to other non-motor symptoms.

Introduction. Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results. The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p p p = 0.012), being male (OR = 2.333; p p p p = 0.007) as a predictor of drooling at V2. Conclusion. Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden.

Background: Despite the frequent use of the Timed Up and Go (TUG) test in clinical trials, evaluation of longitudinal test-retest reliability is generally lacking and still inconclusive for patients with Parkinson’s disease (PD). Objective: We aimed to further investigate long-term reliability and sensitivity of the TUG test among this population. Furthermore, we explored alternative assessment strategies of the test aimed at elucidating whether the inclusion or combination of timed trials may have potential implications on outcome measure. Methods: Relative and absolute reliability of the TUG performance were obtained in forty-three subjects with PD over three timed trials in two different testing sessions separated by a two-months period. Results: Our results reported excellent intra-session and moderate inter-session reliability coefficients. The use of different assessment strategies of the TUG was found to have an important impact on outcome measure, highlighting the averaging of several timed trials in each testing session as a recommended alternative to minimize measurement error and increase reliability in longitudinal assessments. Nevertheless, beyond acceptable reliability, poor trial-to-trial stability of the measure appears to exist, since the ranges of expected variability upon retesting were wide and the incidence of spurious statistical effects was not negligible, especially in longitudinal repeated testing. Conclusion: Limitations may exist in the interpretation of the TUG outputs as part of longitudinal assessments aimed at evaluating treatment effectiveness in PD population. Researchers and practitioners should be aware of these concerns to prevent possible misrepresentations of functional ability in patients for a particular intervention.

Introduction Mood disorders are frequent in Parkinson’s disease (PD) and a favorable effect of safinamide on mood has been observed. We aimed to analyze the effectiveness of safinamide on mood as a secondary objective from the SAFINONMOTOR (an open-label study of the effectiveness of SAFInamide on NON-MOTOR symptoms in patients with Parkinson’s disease) study. Methods SAFINONMOTOR is a prospective open-label single-arm study conducted in five centers from Spain. Patients with PD were required to have at baseline a Non-Motor Symptoms Scale (NMSS) total score of at least 40. In this analysis, the changes from V1 (baseline) to V4 (6 months ± 1 month) in the BDI-II (Beck Depression Inventory-II), NMSS mood/apathy domain, and PDQ-39 (Parkinson’s Disease Questionnaire-39) emotional well‐being domain were analyzed. Depression was identified and classified (DSM-IV and Judd criteria) at baseline and at the end of follow-up as major depression (MD), minor depression (mD), subthreshold depression (subD), and non-depression (nonD). Results Fifty patients with PD were included (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis) and 44 patients (88%) completed the follow-up at 6 months. The BDI-II total score was reduced by 35.9% (from 15.88 ± 10.46 at V1 to 10.18 ± 6.76 at V4; p

Background and objective Some studies observed a benefit of PD patients after treatment with safinamide in some non-motor symptoms. Our aim was to analyze the effectiveness of safinamide on sleep and daytime sleepiness in Parkinson’s disease (PD) patients. Material and methods SAFINONMOTOR is a prospective open-label single-arm study conducted in 5 centers from Spain. In this analysis, a secondary objective of the study, the score in the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) at V1 (baseline) and V4 (6 months ± 1 month) were compared. Results Fifty patients were included between May/2019 and February/2020 (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The PSQI total score was reduced by 19.8% (from 10.43 ± 4.02 at V1 to 8.36 ± 4.41 at V4; p = 0.001). By domains, improvement was observed in subjective sleep quality (PSQI-C1; − 23.9%; p = 0.009), sleep latency (PSQI-C2; − 25%; p = 0.025), sleep duration (PSQI-C3; − 40%; p = 0.001), and habitual sleep efficiency (PSQI-C4; − 25.9%; p = 0.023). A significant reduction (− 24.7%) in the ESS total score from V1 to V4 was observed as well (from 9.20 ± 5.64 to 6.93 ± 5.11; p = 0.012). Specifically, the improvement in daytime sleepiness was observed in sitting and reading (p = 0.024) and sitting inactive in a public space (p = 0.027). A total of 21 adverse events in 11 patients (22%) were reported, 5 of which were severe (not related to safinamide). Conclusion Safinamide was well-tolerated and improved sleep and daytime sleepiness in PD patients at 6 months. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05607-2.

Objectives: To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa–carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain. Methods: A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients’ clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation. Results: Significant differences were observed between CAs for several baseline variables: duration of disease progression prior to CIILC onset, off time (34.9%–59.7%) and on time (2.6%–48.0%; with or without disabling dyskinesia), Hoehn and Yahr score during on time, Unified Parkinson's Disease Rating Scale-III score during both on and off time, presence of =4 motor symptoms, and CIILC dose. Significant differences were observed during follow-up (>24 months in 9 of the 11 CAs studied) for the percentage of off time and on time without disabling dyskinesia, adverse events frequency, and Clinical Global Impression scores. The rate of CIILC discontinuation was between 20% and 40% in 9 CAs (78% and 80% in remaining 2 CAs). Conclusions: This study reveals a marked variability between CAs in terms of patient selection and CIILC safety and effectiveness. These results may have been influenced by patients’ baseline characteristics, the availability of multidisciplinary teams, and clinical experience. Resumen: Objetivos: Comparar las características de los pacientes con enfermedad de Parkinson avanzada en tratamiento con infusión intestinal continua de levodopa-carbidopa (IICLC) y los datos de efectividad y seguridad de IICLC entre diferentes comunidades autónomas (CC. AA.). Métodos: Estudio longitudinal observacional y retrospectivo. Se incluyeron 177 pacientes de 11 CC. AA. que iniciaron tratamiento con IICLC entre enero de 2006 y diciembre de 2011. Se compararon las características clínicas y demográficas, las variables de efectividad (cambios en el tiempo OFF, ON con y sin discinesias discapacitantes, cambios en la escala de Hoehn y Yahr y puntuación de la Unified Parkinson's Disease Rating Scale, síntomas no motores e Impresión Clínica Global) y seguridad (acontecimientos adversos), y la tasa de suspensión de IICLC. Resultados: Se hallaron diferencias significativas entre las CC. AA. en diversas variables basales: duración de la enfermedad hasta el inicio de IICLC, tiempo OFF (34,9-59,7%) y ON (con o sin discinesias; 2,6-48,0%), Hoehn y Yahr en ON, Unified Parkinson's Disease Rating Scale-III en ON y OFF, presencia de = 4 síntomas motores y dosis de IICLC. En el seguimiento (> 24 meses en 9 de 11 CC. AA.) hubo diferencias significativas en el porcentaje de tiempo OFF, tiempo ON sin discinesias discapacitantes, frecuencia de acontecimientos adversos e Impresión Clínica Global. La tasa de suspensión fue de entre 20-40% en todas las CC. AA., excepto en 2 (78 y 80%). Conclusiones: Este estudio muestra una amplia variabilidad en la selección de los pacientes y en la efectividad y seguridad de IICLC entre las diferentes CC. AA. Podrían influir las características basales de los pacientes, la disponibilidad de un equipo multidisciplinar y la experiencia clínica.

Introduction: The main challenge of Parkinson’s disease in women of childbearing age is managing symptoms and drugs during pregnancy and breastfeeding. The increase in the age at which women are having children makes it likely that these pregnancies will become more common in future. Objectives: This study aims to define the clinical characteristics of women of childbearing age with Parkinson’s disease and the factors affecting their lives, and to establish a series of guidelines for managing pregnancy in these patients. Results: This consensus document was developed through an exhaustive literature search and a discussion of the available evidence by a group of movement disorder experts from the Spanish Society of Neurology. Conclusions: Parkinson’s disease affects all aspects of sexual and reproductive health in women of childbearing age. Pregnancy should be well planned to minimise teratogenic risk. A multidisciplinary approach should be adopted in the management of these patients in order to take all relevant considerations into account. Resumen: Introducción: El manejo de la enfermedad de Parkinson en la mujer en edad fértil nos plantea como principal reto el manejo de la enfermedad y los fármacos durante el embarazo y lactancia. El aumento de la edad gestacional de la mujer hace más probable que la incidencia de embarazos pueda incrementarse. Objetivo: Definir las características clínicas y los factores que condicionan la vida de la mujer en edad fértil con enfermedad de Parkinson y definir una guía de actuación y manejo del embarazo en estas pacientes. Desarrollo: Este documento de consenso se ha realizado mediante una búsqueda bibliográfica exhaustiva y discusión de los contenidos llevadas a cabo por un grupo de expertos en trastornos del movimiento de la Sociedad Española de Neurología. Conclusiones: La enfermedad de Parkinson afecta a todos los aspectos relacionados con la salud sexual y reproductiva de la mujer en edad fértil. Se debe planificar el embarazo en las mujeres con enfermedad de Parkinson para minimizar los riesgos teratogénicos sobre el feto. Se recomienda un abordaje multidisciplinar de estas pacientes para tener en cuenta todos los aspectos implicados.

[ES] Introducción: El manejo de la enfermedad de Parkinson en la mujer en edad fértil nos plantea como principal reto el manejo de la enfermedad y los fármacos durante el embarazo y lactancia. El aumento de la edad gestacional de la mujer hace más probable que la incidencia de embarazos pueda incrementarse. Objetivo: Definir las características clínicas y los factores que condicionan la vida de la mujer en edad fértil con enfermedad de Parkinson y definir una guía de actuación y manejo del embarazo en estas pacientes. Resultados: Este documento de consenso se ha realizado mediante una búsqueda bibliográfica exhaustiva y discusión de los contenidos realizados por un grupo de expertos en trastornos del movimiento de la Sociedad Española de Neurología. Conclusiones: La enfermedad de Parkinson afecta a todos los aspectos relacionados con la salud sexual y reproductiva de la mujer en edad fértil. Se debe planificar el embarazo en las mujeres con enfermedad de Parkinson para minimizar los riesgos teratogénicos sobre el feto. Se recomienda un abordaje multidisciplinar de estas pacientes para tener en cuenta todos los aspectos implicados., [EN] Introduction: The main challenge of Parkinson's disease in women of childbearing age is managing symptoms and drugs during pregnancy and breastfeeding. The increase in the age at which women are having children makes it likely that these pregnancies will become more common in future. Objectives: This study aims to define the clinical characteristics of women of childbearing age with Parkinson's disease and the factors affecting their lives, and to establish a series of guidelines for managing pregnancy in these patients. Results: This consensus document was developed through an exhaustive literature search and a discussion of the available evidence by a group of movement disorder experts from the Spanish Society of Neurology. Conclusions: Parkinson's disease affects all aspects of sexual and reproductive health in women of childbearing age. Pregnancy should be well planned to minimise teratogenic risk. A multidisciplinary approach should be adopted in the management of these patients in order to take all relevant considerations into account.

Background: The asymmetry of motor manifestations present in Parkinson’s disease (PD) suggests the existence of differences between both hemispheres. As a consequence, this asymmetry might contribute to different PD clinical phenotypes. Objective: To study the relationship between motor symptom laterality with motor, non-motor symptoms (NMS), freezing of gait (FOG), and quality of life (QoL) impairment in PD. Methods: In this cross-sectional study, we measured motor symptoms severity and complications with the Unified Parkinsons’ disease Rating Scale (UPDRS), FOG with the FOG questionnaire, QoL with the 39-item PD Quality of Life Questionnaire Summary Index, and NMS with the NMS, Visual Analogue Scales for Pain and Fatigue, Beck Depression Inventory-II, Impulsive-Compulsive Disorders, and PD Sleep and Cognitive Rating scales. We defined left and right motor laterality using the UPDRS part III. We used comparative, regression, and effect size analyses to evaluate the impact of asymmetry on motor and NMS, FOG, and QoL. Results: 342 left (LPD) and 310 right (RPD) patients, with a mean age of 62.0±8.8 years, were included. In multivariate regression analysis, LPD was associated with a greater motor (OR = 1,50, 95% CI 1.02–2.21), FOG (OR = 1.56, 95% CI 1.01–2.41), and overall NMS impairment (OR = 1.43, 95% CI 1.001–2.06), and better QoL (OR = 0.52 95% CI 0.32–0.85). Overall, only a mild effect size was found for all comparisons in which significant differences were present. Conclusion: In this large multicenter study, motor symptom laterality seems to carry a mild but significant impact on PD clinical manifestations, and QoL.

BACKGROUND: The aim of this study was to know the impact of the coronavirus disease 2019 (COVID-19) pandemic on Spanish patients with Parkinson's disease (PD). METHODS: This is a descriptive, observational, cross-sectional study. An anonymous online survey with 95 questions was distributed among patients. Responses were collected from 11 May 2020 to 20 July 2020. RESULTS: Of a total of 570 questionnaires received, 568 (99.6%) were considered valid for the analysis (mean age, 63.5 ± 12.5 years; 53% females). A total of 553 patients (97.4%) were aware of the COVID-19 pandemic and 68.8% were concerned about it; 95.6% took preventive measures. A total of 484 patients (85.2%) had no contact with cases of COVID-19, and only 15 (2.6%) had confirmed COVID-19. Although up to 72.7% remained active during confinement, 65.7% perceived a worsening of their symptoms. CONCLUSIONS: Spanish patients with PD perceived the COVID-19 pandemic with concern and responsibility. More than half experienced worsening of their symptoms during confinement. © 2020 International Parkinson and Movement Disorder Society.

[Background] Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective:Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods:PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes., [Results] At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p, [Conclusion] Constipation is associated with cognitive decline in PD patients but not in controls.

Introduction The evaluation of patients with Parkinson's disease (PD) is complex and the detection of non-motor symptoms by the neurologist a very important aspect. However, it takes time and is not easy in daily clinical practice. As an alternative, a trained nurse can perform this evaluation. Objective To describe the non-motor evaluation of the patients from the Cohort of Patients with Parkinson's Disease in Spain, 2015 study (COPPADIS-2015) conducted by movement disorder specialist nurse from our centre. Methods Patients and caregivers from the COPPADIS-2015 study were included. The assessment included: (1) cognition (PD-CRS and puzzle test); (2) non motor symptoms as a whole (NMSS); (3) mood (BDI-II); (4) sleep (PDSS); (5) neuropsychiatric symptoms (NPI, QUIP-RS); (6) pain and fatigue (VAS); 7) gait problems (FOGQ); 8) disability (ADLS); 9) quality of life (PDQ-39SI, PQ-10, WHOQL-8); (10) caregiver status (ZCBI, CSI, BDI-II, PQ-10, WHOQL-8). Results 102 patients (65.3 ± 8.2 y; 52% males) and 62 caregivers were evaluated between January 2016, and October, 2017. Mean time of non-motor evaluation was 73.7 ± 20.5 min. Twenty-three point five percent of the patients had cognitive impairment, 17.6% major depression, 14.7% impulse control disorder, and 66.7% pain. Conclusions The non-motor assessment of patients with PD takes a long time but is very valuable given that it provides a great deal of information about the patient's condition and can be done by trained nurses.

Resumen Introduccion La evaluacion de los pacientes con enfermedad de Parkinson (EP) es compleja siendo fundamental para el neurologo detectar diferentes sintomas no motores. Sin embargo, lleva tiempo y no es facil en la practica diaria. Como alternativa, una enfermera entrenada puede realizar dicha evaluacion. Objetivos Describir la evaluacion no motora llevada a cabo por la enfermera especialista en trastornos del movimiento dentro del proyecto de investigacion Cohort of Patients with Parkinson's DIsease in Spain, 2015 (COPPADIS-2015) en nuestro centro (CHUF). Metodos Se incluyeron pacientes con EP asi como cuidadores principales que cumplieran con los criterios de participacion del estudio COPPADIS-2015. La evaluacion llevada a cabo por la enfermera incluia: 1) cognicion (PD-CRS y test del puzle); 2) SNM en general (NMSS); 3) estado de animo (BDI-II); 4) sueno (PDSS); 5) sintomas neuropsiquiatricos (NPI, QUIP-RS); 6) dolor y fatiga (VAS-Pain y VAS-Fatigue); 7) alteraciones de la marcha (FOGQ); 8) autonomia (ADLS); 9) calidad de vida (PDQ-39SI, PQ-10, WHOQL-8); 10) estado del cuidador (ZCBI, CSI, BDI-II, PQ-10, WHOQL-8). Resultados Un total de 102 pacientes (65,3 ± 8,2 anos; 52% varones) con EP y 62 cuidadores fueron evaluados entre enero de 2016 y octubre de 2017. El tiempo medio de evaluacion fue de 73,7 ± 20,5 min. El 23,5% de los pacientes presentaba deterioro cognitivo, 17,6% depresion mayor, 14,7% trastorno de control de impulsos y 66,7% dolor. Conclusiones La evaluacion no motora de los pacientes con EP consume tiempo pero es muy valiosa dado que proporciona gran informacion del estado del paciente y puede ser llevada a cabo por personal de enfermeria entrenado.

Some studies observed a benefit of Parkinson´s disease (PD) patients after treatment with safinamide in some non-motor symptoms (NMSs). The aim of this study was to analyze the effectiveness of safinamide on NMS burden in PD. SAFINONMOTOR (an open-label study of the effectiveness of safinamide on non-motor symptoms in Parkinson´s disease patients) is a prospective open-label single-arm study conducted in five centers from Spain. The primary efficacy outcome was the change from baseline (V1) to the end of the observational period (6 months) (V4) in the non-motor symptoms scale (NMSS) total score. Between May/2019 and February/2020 50 patients were included (age 68.5 ± 9.12 years, 58% females, 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The NMSS total score was reduced by 38.5% (from 97.5 ± 43.7 in V1 to 59.9 ± 35.5 in V4, p &lt, 0.0001). By domains, improvement was observed in sleep/fatigue (−35.8%, p = 0.002), mood/apathy (−57.9%, 0.0001), attention/memory (−23.9%, p = 0.026), gastrointestinal symptoms (−33%, p = 0.010), urinary symptoms (-28.3%, p = 0.003), and pain/miscellaneous (−43%, 0.0001). Quality of life (QoL) also improved with a 29.4% reduction in the PDQ-39SI (from 30.1 ± 17.6 in V1 to 21.2 ± 13.5 in V4, 0.0001). A total of 21 adverse events in 16 patients (32%) were reported, 5 of which were severe (not related to safinamide). Dyskinesias and nausea were the most frequent (6%). Safinamide is well tolerated and improves NMS burden and QoL in PD patients with severe or very severe NMS burden at 6 months.

[ES] Introducción: Muchas enfermedades que cursan con trastornos del movimiento hipercinético comienzan o afectan a mujeres en edad fértil. Es importante conocer los riesgos que tienen las mujeres con estas enfermedades durante el embarazo, así como los posibles efectos de los tratamientos sobre el feto. Objetivos: Definir las características clínicas y los factores que condicionan la vida de la mujer en edad fértil con distonía, corea, síndrome de Tourette, temblor y síndrome de piernas inquietas. Definir una guía de actuación y manejo del embarazo y lactancia en las pacientes con esta enfermedad. Desarrollo: Este documento de consenso se ha realizado mediante una búsqueda bibliográfica exhaustiva y discusión de los contenidos llevadas a cabo por un Grupo de Expertos en Trastornos del Movimiento de la Sociedad Española de Neurología (SEN). Conclusiones: En todas las mujeres que padecen o comienzan con trastornos del movimiento hipercinéticos se debe valorar el riesgo-beneficio de los tratamientos, reducir al máximo la dosis eficaz o administrarlo de forma puntual en los casos en que sea posible. En aquellas enfermedades de causa hereditaria es importante un consejo genético para las familias. Es importante reconocer los trastornos del movimiento desencadenados durante el embarazo como determinadas coreas y síndrome de piernas inquietas., [EN] Introduction: Many diseases associated with hyperkinetic movement disorders manifest in women of childbearing age. It is important to understand the risks of these diseases during pregnancy, and the potential risks of treatment for the fetus. Objectives: This study aims to define the clinical characteristics and the factors affecting the lives of women of childbearing age with dystonia, chorea, Tourette syndrome, tremor, and restless legs syndrome, and to establish guidelines for management of pregnancy and breastfeeding in these patients. Results: This consensus document was developed through an exhaustive literature search and a discussion of the content by a group of movement disorder experts from the Spanish Society of Neurology. Conclusions: We must evaluate the risks and benefits of treatment in all women with hyperkinetic movement disorders, whether pre-existing or with onset during pregnancy, and aim to reduce effective doses as much as possible or to administer drugs only when necessary. In hereditary diseases, families should be offered genetic counselling. It is important to recognise movement disorders triggered during pregnancy, such as certain types of chorea and restless legs syndrome.

COPPADIS Study Group., [Introduction] The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients., [Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson’s disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems., [Results] The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015–1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009–1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments., [Conclusion] Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.

Malaltia de Parkinson; Levodopa; Factors de risc Enfermedad de Parkinson; Levodopa; Factores de riesgo Parkinson Disease; Levodopa; Risk Factors Background:There is a need for identifying risk factors for hospitalization in Parkinson’s disease (PD) and also interventions to reduce acute hospital admission. Objective:To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort.Methods:PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit.Results:Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065–5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319–6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757–8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124–4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080–8.322; p = 0.035) was an independent predictor of AH. Conclusion:Falls is an independent predictor of AH in PD patients

Background Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. Methods PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: = 10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). Results Six hundred and sixty-three PD patients (62.6 +/- 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). Conclusions Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

COPPADIS Study Group., The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson’s disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p, Funding sources: www.curemoselparkinson.org.

The health crisis caused by COVID-19 required the prompt launch of research in order to generate scientific evidence pertaining to the new disease oriented to control its devastating effects and continuous spread. Therefore, it was essential to adapt the work flow of Research Ethics Committees, to prioritize and to accelerate the evaluation of projects related to this disease.This work analyses the evaluation conducted by our Regional Ethics Committees during the initial period of the health emergency (between 13th March and 28th May 2020).81 research projects were evaluated, 73 of them of regional scope (62 single-centre), 4 national and 4 international. 57 projects obtained a favourable opinion, 4 were withdrawn by the sponsors, 6 did not require ethics approval and 14 did not respond to the clarifications requested up to the date of the study's closure.The most important research procedures to be analysed in this context are those related to the methodology and informed consent process. It is also essential to address aspects related to the privacy of personal data, and to take into account the workload of the researchers. As an improvement proposal, we think that greater collaboration between the different research teams should be encourage to obtain more robust results.La crisis sanitaria motivada por la COVID-19 hace necesaria la puesta en marcha, con celeridad, de investigaciones encaminadas a generar evidencias científicas que incidan en el control de sus devastadores efectos. Por ello, fue necesario realizar ajustes en la dinámica de trabajo de los Comités de Ética de la Investigación, así como priorizar y agilizar la evaluación de los proyectos relacionados con dicha enfermedad. Este trabajo pretendió analizar la actividad la actividad evaluadora del Comité de Ética de la Investigación con Medicamentos de Galicia (CEIm-G) durante dicho período de emergencia sanitaria.Se evaluaron 81 proyectos de investigación, 73 de ellos de ámbito autonómico (62 unicéntricos), 4 nacionales y 4 internacionales.En 57 proyectos el dictamen fue favorable, 4 fueron retirados por los promotores, en 6 no procedía dictamen y 14 no respondieron a las aclaraciones solicitadas hasta la fecha del cierre del estudio.Las causas más frecuentes de solicitud de aclaraciones están relacionadas con la metodología y, a continuación, con la hoja de información al paciente y el consentimiento informado. También es imprescindible abordar los aspectos relacionados con la intimidad de los datos personales y las muestras, e igualmente tener en cuenta la carga de trabajo de los investigadores. Como propuesta de mejora, consideramos que se debe incidir en una mayor coordinación entre los diferentes equipos de investigación para tratar de obtener resultados más robustos.

Background: Depression and impulse control disorders (ICDs) are both common in Parkinson's disease (PD) patients and their coexistence is frequent. Our aim was to determine the relationship between depression and impulsive-compulsive behaviors (ICBs) in a large cohort of PD patients. Methods: PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were included in the study. The QUIP-RS (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale) was used for screening ICDs (cutoff points: gambling >6, buying >8, sex >8, eating >7) and compulsive behaviors (CBs) (cutoff points: hobbyism-punding >7). Mood was assessed with the BDI-II (Beck Depression Inventory - II) and major, minor, and subthreshold depression were defined. Results: Depression was more frequent in PD patients with ICBs than in those without: 66.3% (69/104) vs 47.5% (242/509); p

Background: The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. Material and methods: PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. Results: The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 +/- 12.8 vs 11.6 +/- 10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 +/- 0.5 vs 4 +/- 0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 +/- 32 vs 29.1 +/- 25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. Conclusions: SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.

Objective. 5- (5 times oral levodopa tablet taken/day) 2- (2 hours of OFF time/day) 1- (1 hour/day of troublesome dyskinesia) criteria have been proposed by a Delphi expert consensus panel for diagnosing advanced Parkinson’s disease (PD). The aim of the present study is to compare quality of life (QoL) in PD patients with “5-2-1 positive criteria” vs QoL in PD patients without “5-2-1 positive criteria” (defined as meeting ≥1 of the criteria). Methods. This is a cross-sectional, observational, monocenter study. Three different instruments were used to assess QoL: the 39-Item Parkinson’s Disease Quality of Life Questionnaire Summary Index Score (PDQ-39SI); a subjective rating of perceived QoL (PQ-10); and the EUROHIS-QOL 8-Item Index (EUROHIS-QOL8). Results. From a cohort of 102 PD patients (65.4 ± 8.2 years old, 53.9% males; disease duration 4.7 ± 4.5 years), 20 (19.6%) presented positive 5-2-1 criteria: 6.9% for 5, 17.6% for 2, and 4.9% for 1. 37.5% (12/32) and 25% (5/20) of patients with motor complications and dyskinesia, respectively, presented 5-2-1 negative criteria. Both health-related (PDQ-39SI, 25.6 ± 14 vs 12.1 ± 9.2; p<0.0001) and global QoL (PQ-10, 6.1 ± 2 vs 7.1 ± 1.3; p=0.007; EUROHIS-QOL8, 3.5 ± 0.5 vs 3.7 ± 0.4; p=0.034) were worse in patients with 5-2-1 positive criteria. Moreover, nonmotor symptoms burden (Non-Motor Symptoms Scale total score, 64.8 ± 44.8 vs 39.4 ± 35.1; p<0.0001) and autonomy for activities of daily living (ADLS scale, 73.5 ± 13.1 vs 89.2 ± 9.3; p<0.0001) were worse in patients with 5-2-1 positive criteria. Patient’s principal caregiver’s strain (Caregiver Stain Index, 4.3 ± 3 vs 1.5 ± 1.6; p<0.0001), burden (Zarit Caregiver Burden Inventory, 28.4 ± 12.5 vs 10.9 ± 9.8; p<0.0001), and mood (Beck Depression Inventory II, 12.2 ± 7.2 vs 6.2 ± 6.1; p<0.0001) were worse in patients with 5-2-1 positive criteria as well. Conclusions. QoL is worse in patients meeting ≥1 of the 5-2-1 criteria. This group of patients and their caregivers are more affected as a whole. These criteria could be useful for identifying patients in which it is necessary to optimize Parkinson’s treatment.

[ES] Objetivos: Comparar las características de los pacientes con enfermedad de Parkinson avanzada en tratamiento con infusión intestinal continua de levodopa-carbidopa (IICLC) y los datos de efectividad y seguridad de IICLC entre diferentes comunidades autónomas (CC. AA.). Métodos: Estudio longitudinal observacional y retrospectivo. Se incluyeron 177 pacientes de 11 CC. AA. que iniciaron tratamiento con IICLC entre enero de 2006 y diciembre de 2011. Se compararon las características clínicas y demográficas, las variables de efectividad (cambios en el tiempo OFF, ON con y sin discinesias discapacitantes, cambios en la escala de Hoehn y Yahr y puntuación de la Unified Parkinson's Disease Rating Scale, síntomas no motores e Impresión Clínica Global) y seguridad (acontecimientos adversos), y la tasa de suspensión de IICLC. Resultados: Se hallaron diferencias significativas entre las CC. AA. en diversas variables basales: duración de la enfermedad hasta el inicio de IICLC, tiempo OFF (34,9-59,7%) y ON (con o sin discinesias; 2,6-48,0%), Hoehn y Yahr en ON, Unified Parkinson's Disease Rating Scale-III en ON y OFF, presencia de ≥ 4 síntomas motores y dosis de IICLC. En el seguimiento (> 24 meses en 9 de 11 CC. AA.) hubo diferencias significativas en el porcentaje de tiempo OFF, tiempo ON sin discinesias discapacitantes, frecuencia de acontecimientos adversos e Impresión Clínica Global. La tasa de suspensión fue de entre 20-40% en todas las CC. AA., excepto en 2 (78 y 80%). Conclusiones: Este estudio muestra una amplia variabilidad en la selección de los pacientes y en la efectividad y seguridad de IICLC entre las diferentes CC. AA. Podrían influir las características basales de los pacientes, la disponibilidad de un equipo multidisciplinar y la experiencia clínica., [EN] Objectives: To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain. Methods: A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients’ clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation. Results: Significant differences were observed between CAs for several baseline variables: duration of disease progression prior to CIILC onset, off time (34.9-59.7%) and on time (2.6-48.0%; with or without disabling dyskinesia), Hoehn and Yahr score during on time, Unified Parkinson's Disease Rating Scale-III score during both on and off time, presence of ≥ 4 motor symptoms, and CIILC dose. Significant differences were observed during follow-up (> 24 months in 9 of the 11 CAs studied) for the percentage of off time and on time without disabling dyskinesia, adverse events frequency, and Clinical Global Impression scores. The rate of CIILC discontinuation was between 20-40% in 9 CAs (78 and 80% in remaining 2 CAs). Conclusions: This study reveals a marked variability between CAs in terms of patient selection and CIILC safety and effectiveness. These results may have been influenced by patients’ baseline characteristics, the availability of multidisciplinary teams, and clinical experience., AbbVie Spain, S. L. U. financió este estudio, fue responsable del diseño y coordinó la recogida de datos.

Background and objective: Pain is a frequent and disabling symptom in Parkinson’s disease (PD) patients. Our aim was to analyze the effectiveness of safinamide on pain in PD patients from the SAFINONMOTOR (an open-label study of the effectiveness of SAFInamide on NON-MOTOR symptoms in Parkinson´s disease patients) study. Material and Methods: SAFINONMOTOR is a prospective open-label single-arm study conducted in five centers from Spain. In this analysis, a secondary objective of the study, the score in the KPPS (King´s Parkinson´s Disease Pain Scale) at V1 (baseline) and V4 (6 months ± 1 month) were compared. Wilcoxon´s rank sum test was performed to test the changes from V1 to V4. Results: Forty-four (88%) out of 50 PD patients (age 68.5 ± 9.12 years, 58% women, 6.4 ± 5.1 years from diagnosis) completed the study. The KPPS total score was reduced by 43.6% (from 40.04 ± 36.18 in V1 to 22.60 ± 21.42 in V4, p &lt, 0.0001). By domains, improvement was observed in musculoskeletal (−35.9%, p = 0.009), fluctuation-related (−51.7%, p = 0.020), nocturnal (−46.1%, p = 0.001), discoloration and/or edema/swelling (−50.4%, p = 0.009) and radicular pain (−40.1%, p = 0.048). A total of 21 adverse events in 11 patients (22%) were reported, five being severe, but not related to safinamide. Conclusion: Safinamide is well tolerated and improves pain in PD patients at 6 months. Future studies are necessary to analyze the possible beneficial effect of safinamide on pain in PD patients.

Background and objective: Freezing of gait (FOG) is a disabling symptom more frequent in Parkinson’s disease (PD) patients with postural instability gait difficulty (PIGD) phenotype. The aim of this study was to determine the prevalence of self-reported FOG in a large group of PD patients as well as assess its relationship with functional dependency with regard to motor phenotype. Methods: The data correspond to the baseline evaluation of the COPPADIS-2015 study. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the freezing of gait questionnaire (FOG-Q). Functional dependency was defined as a Schwab and England (S&E) ADL scale score less than 80%. PIGD and non-PIGD (tremor dominant + indeterminate) groups were considered regarding to motor phenotype. Results: Among the 689 PD patients (62.6 ± 8.9 years old, 59.8% males), 240 reported FOG (34.8%), whereas 63 presented functional dependency (9.1%). A total of 22.1% of patients with FOG presented functional dependency vs. only 2.2% of those without FOG (p < 0.0001). FOG was related to functional dependency (OR = 3.470; 95%CI 1.411–8.530; p = 0.007) after adjustment to age, gender, disease duration, daily equivalent levodopa dose, comorbidity (number of non-antiparkinsonian drugs/day), motor status (UPDRS-III), PIGD phenotype, motor complications (UPDRS-IV), NMS burden (NMSS total score), cognition (PD-CRS), and mood (BDI-II). However, according to motor phenotype, FOG was related to functional dependency only in PIGD patients (OR = 7.163; 95%CI 1.206–42.564; p = 0.030). Conclusions: Self-reported FOG is associated with functional dependency in PIGD but not in non-PIGD motor phenotype patients., Santos-García D. has received honoraria for educational presentations and/or advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. de Deus Fonticoba T. has received honoraria for educational presentations and advice service by Abbvie. Suárez Castro E: None. Ángel Aneiros Díaz: None. Feal Painceiras M: None. Paz González JM has received honoraria for educational presentations and/or advice service by UCB Pharma, Lundbeck, KRKA y Zambon. García Sancho C: None. Jesús S. has received honoraria from AbbVie, Bial, Merz, UCB, and Zambon. She also holds the competitive contract “Juan Rodés” supported by the Instituto de Salud Carlos III. She has received grants from the Spanish Ministry of Economy and Competitiveness (PI18/01898) and the Consejería de Salud de la Junta de Andalucía (PI-0459-2018). Mir P. has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon. Also, he has received grants from the Spanish Ministry of Economy and Competitiveness (PI16/01575) co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación), Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, and the Fundación Mutua Madrileña. Planellas LL. has received travel bursaries grant from Abbvie. García Caldentey J. has received honoraria for educational presentations and advice service by Qualigen, Nutricia, Abbvie, Italfarmaco, UCB Pharma, Lundbeck, Zambon, Bial, and Teva. Caballol N. has received honoraria for educational presentations and advice service by Qualigen, Nutricia, Abbvie, Italfarmaco, UCB Pharma, Lundbeck, Zambon, Bial, and Teva. Legarda I. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Zambon, Bial, and Teva. Hernández Vara J. has received travel bursaries and educational grants from Abbvie and has received honoraria for educational presentations from Abbvie, Teva, Bial, Zambon, Italfarmaco, and Sanofi-Genzyme. González Aramburu I: None. Ávila Rivera MA. has received honoraria from Zambon, UCB Pharma, Qualigen, Bial, and Teva, and sponsorship from Zambon and Teva for attending conferences. Catalán MJ: None. Nogueira V: None. Álvarez Sauco M. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Zambon, Bial, and Teva. Vela L. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Escalante S. has received honoraria for educational presentations and advice service by Abbvie, Zambon, and Bial. Cubo E: travel grants: Abbvie, Allergan, Boston; lecturing honoraria: Abbvie, International Parkinson’s disease Movement Disorder Society. Sánchez Alonso P. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Alonso Losada MG. has received honoraria for educational presentations and advice service by Zambon and Bial. López Ariztegui N. has received honoraria for educational presentations and advice service by Abbvie, Italfarmaco, Zambon, and Bial. Martinez-Martin P: Honoraria: from Editorial Viguera and National School of Health for lecturing in courses; International Parkinson and Movement Disorder Society for management of the Program on Rating Scales; Abbvie and Zambon for advice in clinic-epidemiological studies www.curemoselparkinson.org.

La certificación como anillador de aves consiste en validar el nivel de conocimiento y experiencia de personas frente a un estándar consolidado de trabajo en el ejercicio de la captura, anillado, manejo, y liberación de aves, con el fin de promover la seguridad del ave, la seguridad del anillador y la calidad de los datos colectados. El Consejo Norteamericano de Anillado (NABC) es una organización sin fines de lucro, engloba a diversas organizaciones de investigación, conservación y gestión de la avifauna en Norteamérica. Continuando con su principal misión de promover prácticas responsables de la técnica del anillado de aves bajo criterios estandarizados y éticos, en un trabajo conjunto con el Centro de Ornitología y Biodiversidad (CORBIDI) y otras instituciones afines, entre el 2017 y el 2018 se han desarrollado las tres primeras sesiones de certificación NABC en el Perú. El presente trabajo intenta responder algunas de las preguntas más frecuentes relacionados con estas sesiones de certificación, así como los esfuerzos del anillado de aves promovidos por el Programa de Anillamiento CORBIDI (PAC). Certification as bird bander implies to validate the level of knowledge and experience of people with regard to a consolidated standard of work in the exercise of capture, banding, handling, and release of birds, in order to promote the safety of the bird, the security of the bander and the quality of the data collected. The North American Banding Council (NABC) is a non-profit organization that includes diverse organizations of research, conservation and management of North American avifauna. Continuing with its mission to promote responsible bird-banding practices under standardized and ethical criteria, in a joint effort with the Centro de Ornitologia y Biodiversidad (CORBIDI) and other related institutions, the first three NABC certification sessions were recently held in Peru. This work tries to answer some of the most frequent questions related to these certification events and the bird banding efforts promoted by the Programa de Anillamiento CORBIDI (PAC).

[Background] Levodopa-carbidopa intestinal gel (LCIG) is effective in the treatment of advanced Parkinson’s disease (PD). However, the patients’ profile that might benefit from treatment with LCIG has not been characterized., [Objective]This retrospective study explored the influence of disease duration (DD) on the effectiveness of LCIG and identified factors associated with treatment discontinuation in a cohort of advanced PD patients., [Methods] Patients initiating LCIG therapy between Jan-2006 and Dec-2011 in 18 Spanish centers were included. Effectiveness in treating motor symptoms (MSs), non-motor symptoms (NMSs), and adverse events (AEs) occurrence was compared in DD≥10 or, [Results] Overall, 177 PD patients were included (52.5% male; mean age 70.6±8.4 years; mean LCIG duration 35.6±18.6 months). Patients with DD≥10 years (n = 125) experienced less reduction in “off” time (–29%) than those with DD, [Conclusions] Advanced PD patients with DD

Aim: To assess long-term effectiveness and tolerability of levodopa–carbidopa intestinal gel (LCIG) in Spanish patients with advanced Parkinson's disease. Patients & methods: This was an observational, multicenter, cross-sectional, retrospective study. Results: Data of 177 patients were analyzed. LCIG treatment led to a reduction in the percentage of daily ‘off’ time (16.2 vs 47.6% before LCIG), an increase in the percentage of daily ‘on’ time without disabling dyskinesia (55.6 vs 21.6%). Most patients experienced improvements in freezing of gait, tremor, dizziness, fatigue or flat mood. Adverse events related to levodopa, gastrostomy and technical issues were reported in 36.2, 42.4 and 43.5% of patients, respectively. Conclusion: This study confirms the long-term effectiveness and safety profile of LCIG in patients with advanced Parkinson's disease.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by rigidity, tremor, bradykinesia, and postural instability. Although dopaminergic therapies ameliorate many of the parkinsonian symptoms, especially in the early stages of the disease, as the disease progresses, efficacy of pharmacological therapy is diminished. Therefore, treatment of these symptoms continues to be a challenge. As a result, a significant number of rehabilitation strategies have been explored in order to improve the functional capability in this population. In the last two decades an interest in the role of physical exercise in the treatment of PD has emerged. In the current review we examine two modalities of exercise that have shown beneficial effects in improving motor action, balance, and gait in patients: aerobic training and resistance training. We conclude that although there are promising results suggesting the use of both modalities of exercises for the motor improvement in PD patients, the mechanism underlying these improvements are unknown and more studies with more defined designs and outcome measures are needed to further explore the impact of these two modalities of exercise on PD. La enfermedad de Parkinson (EP) es un trastorno neurodegenerativo progresivo caracterizado por rigidez, temblor, bradicinesia e inestabilidad postural. Aunque las terapias dopaminérgicas mejoran muchos de los síntomas parkinsonianos, especialmente en las primeras etapas de la enfermedad, a medida que la enfermedad progresa, la eficacia de la terapia farmacológica disminuye. Por lo tanto, el tratamiento de estos síntomas sigue siendo un desafío. Como resultado, se ha explorado un número significativo de estrategias de rehabilitación para mejorar la capacidad funcional en esta población. En las últimas dos décadas he emergido un interés en el papel del ejercicio físico en el tratamiento de la EP. En la presente revisión examinamos dos modalidades de ejercicio que han demostrado efectos beneficiosos en la mejora de la acción motora, el equilibrio y la marcha de los pacientes: el entrenamiento aeróbico y el entrenamiento de fuerza. Concluimos que aunque existen resultados prometedores que sugieren el uso de ambas modalidades de ejercicios para la mejora motora en pacientes con EP, el mecanismo subyacente a estas mejoras es desconocido y se necesitan más estudios con diseños y variables bien definidas para explorar el impacto de estas dos modalidades de ejercicio sobre la EP.

Background and Objective: The aim of this study is to identify risk factors for mortality in a community-based cohort of nondemented patients with Parkinson disease (PD) during prospective long-term follow-up, while also comparing the effect of motor complications to nonmotor symptoms (NMS) on risk of mortality. Methods: One hundred forty seven nondemented patients with PD (57.1% males; 70.9 ± 8.6 years old) were included in this 48 month follow-up, longitudinal, single, evaluation study. Motor and therapy-related complications were assessed using the Unified Parkinson’s Disease Rating Scale/part-IV (UPDRS-IV). Non-Motor Symptoms Scale (NMSS) total score was used to assess NMS burden. Cox proportional hazard models were applied to identify independent predictors of mortality during follow-up. Results: Twenty-two patients of 146 (15.1%) died (1 case without information). Both UPDRS-IV and NMSS total scores were higher at baseline in patients with PD who died (3.5 ± 3.1 vs 2.4 ± 2.4, P = .049 and 96.9 ± 58.6 vs 61.9 ± 51.0, P = .004, respectively). Unadjusted hazard ratios (HRs) associated with UPDRS-IV and NMSS total scores among those who died during follow-up were 1.171 (95% confidence interval [CI]: 1.012-1.357; P = .035) and 1.008 (95% CI: 1.002-1.013; P = .006), respectively. Independent predictors of mortality during follow-up after adjusting for other covariates were UPDRS-IV (HR: 1.224; 95% CI: 1.002-1.494; P = .047), age (HR: 1.231; 95% CI: 1104-1.374; P < .0001), and comorbidity (Charlson Index; HR: 1.429; 95% CI: 1.023-1.994; P = .036), but not NMSS total score (HR: 1.005; 95% CI: 0.996-1.014; P = .263). Conclusions: Both motor complications (UPDRS-IV) and NMS (NMSS) were associated with mortality at 4 years, being motor complications an independent predictor of it.

Background and objective To analyze the main determinants of burden and stress in caregivers of Spanish Parkinson's disease (PD) patients. Methods One-hundred and twenty-one non-demented patients with PD (57.9% males; 70.9 ± 8.2 years old) were included in this cross-sectional, monocenter, evaluation study. Caregivers (n = 121; 71.9% females; 60.2 ± 15 years old) were assessed using the Zarit Caregiver Burden Inventory (ZCBI) and Caregiver Strain Index (CSI). Multiple linear regression methods were used to evaluate factors contributing to caregivers' stress and burden: (i) PD motor dysfunction (ON-state Hoehn & Yahr/Unified Parkinson's Disease Rating Scale [UPDRS] part III and motor complications [UPDRS part IV]); (ii) Mood (Beck Depression Inventory [BDI]); (iii) Non-motor symptoms (Non-Motor Symptoms Scale [NMSS]); (iv) Disability (Schwab & England Activities of Daily Living Scale [ADLS]); and (v) Socio-demographic and other disease-related variables. Results Zarit Caregiver Burden Inventory and CSI mean scores were 16 ± 13.9 and 2.1 ± 2.3, respectively. High correlation was found between ZCBI and CSI (r = 0.819; P 40) was present in 9.1% of caregivers; 5.8% had high levels of stress (CSI ≥ 7). Moderate to strong correlations were observed between patient-related variables (Hoehn&Yahr, UPDRS-III, UPDRS-IV, BDI, NMSS, and ADLS) and ZCBI and CSI (P

To investigate the impact of non-motor symptoms on health-related and perceived quality of life in Parkinson's disease (PD).One hundred and fifty PD patients (57.3% males; 70.9±8.6years old) were included in this cross-sectional, monocenter, evaluation study. Multiple linear regression methods were used to evaluate the direct impact of non-motor symptoms (as assessed by the Non-Motor Symptoms Scale [NMSS]) on 1) the 39-item PD Quality of Life Questionnaire Summary Index score (PDQ-39SI), and 2) a subjective assessment of perceived quality of life (PQ-10), after adjusting for age, sex, mood (Beck Depression Inventory), disability (SchwabEngland Activities of Daily Living Scale), and PD-specific motor dysfunction (ON-state HoehnYahr/Unified Parkinson's Disease Rating Scale [UPDRS] part III, and motor complications [UPDRS part IV]).Higher NMSS total scores were systematically associated with worse quality of life (for PDQ-39SI, p=0.013; for PQ-10, p=0.017). PD-specific motor dysfunction had a larger negative impact on health-related quality of life (PDQ-39SI) than non-motor symptoms (2.8% vs 0.7%). In contrast, the negative impact of non-motor symptoms on perceived quality of life (PQ-10) was larger than that found for PD-specific motor dysfunction (2.8% vs 0.9%). While the model for PDQ-39SI provided an adequate fit (adjusted R-squared, 0.83), a substantial proportion of the PQ-10 variance remained unexplained (adjusted R-squared, 0.48).Non-motor symptoms have a direct negative impact on health-related and perceived quality of life in PD. Perceived quality of life is not adequately explained by motor and non-motor manifestations of the disease.

Santos-García, Diego et al.-- COPPADIS Study Group, [Background] Parkinson's disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression., [Methods/design] Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. Study population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson's Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson's Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson's disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Funding: Public/Private., [Discussion] COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers., Diego Santos-García has received honoraria for educational presentations by Abbvie, UCB Pharma and Lundbeck. Pablo Mir has received honoraria for lecturing or advisory boards from AbbVie, UCB, Zambon, Allergan and Merz, and research grants from the Ministerio de Economía y Competitividad de España [SAF2007-60700], the Instituto de Salud Carlos III [PI10/01674, CP08/00174, PI13/01461], the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0377/2007, PI-0741/2010, PI-0437-2012], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation and the Fundación Alicia Koplowitz. Esther Cubo has received travel funding from Abbvie, Allergan and UCB Pharmaceuticals, and received research support from the Movement Disorder Society, World Federation of Neurology and Junta de Castilla y León. Lydia Vela has received honoraria for educational presentations by Abbvie, UCB Pharma and Lundbeck. Maria C Rodriguez-Oroz has received payment for lectures, travel and accommodation to attend scientific meetings from UCB, Lundbeck, Abbvie and Boston Scientific. She has received grants from CIBERNED, Government of Basque Country and Guipuzcoa, Spanish Health Institute and Era-net. Maria J Marti has received speaking fees from Ipsen, Merz, Allergan and UCB Pharma and research grants from Ministery of Health and Social Services, Marató TV3, Centro Investigacion Biomedica en Red and Michael J Fox Foundation for Parkinson’s research. Jose M Arbelo has received honoraria for educational presentations or clinical studies participation by Abbvie, UCB Pharma and Italfarmaco. Jon Infante has received honoraria as a speaker from UCB Pharma and traveling grants from Abbvie. Jaime Kulisevsky has received honoraria for lecturing or advisoring from Abbvie, UCB and Zambon. Pablo Martínez-Martin has received honorarium from Abbvie for a symposium and participation in the Advisory Board for an epidemiological study, Editorial Viguera for a master course, UCB for lecturing in International University Menendez Pelayo summer course.Santos-García

[Abstract] Background. Auditory external cues enhance step initiation in Parkinson's disease (PD) patients. We wanted to explore whether a startle reaction has a comparable effect on step initiation in PD. Methods. Thirteen PD patients and 13 aged-matched controls participated in this study. Electromyography pattern and onset toe-off time during a step initiation task were recorded in response to three different stimuli: a visual imperative stimulus; visual stimulus simultaneous with a nonstartle auditory stimulus and with a startle auditory stimulus. Results. In all subjects, onset of tibialis anterior was faster in the startle auditory condition, compared with the nonstartle auditory condition. However, in the patient group, there was no difference in onset of soleus and toe-off between the startle and nonstartle conditions. Conclusions. Startle reaction in PD patients demonstrates a disordered coupling between the anticipatory postural adjustments that initiate the weight shift and the movement to initiate toe-off during step initiation. Ministerio de Ciencia e Innovación; PSI2008-03175

Background: Continuous duodenal levodopa infusion (DLI) is an effective therapy that improves quality of life (QoL) in advanced Parkinson’s disease (PD). However, the impact of DLI on caregivers’ stress and burden has not been reported. Methods: We evaluated prospectively open-label seven advanced PD patients (65.7 ± 9.6 years, 71.4% men) treated with DLI. Schwab & England Activities of Daily Living Scale (ADLS), 39-item Parkinson’s disease QoL Questionnaire Summary Index score (PDQ-39SI), Zarit Caregiver Burden Interview (ZCBI), and Caregiver Strain Index (CSI) were used. Comparisons were made between scores obtained at baseline and those at a mean follow-up of 31.4 ± 7.9 months (range, 23–42). Results: In patients, mean ± SD ADLS was increased from 50 ± 8.2 to 80 ± 11.6 (P = 0.014), and mean ± SD PDQ-39SI was decreased from 53.7 ± 11.9 to 33.6 ± 12.8 (P = 0.018). In caregivers, ZCBI decreased from 43 ± 13.3 to 20.7 ± 12.1 (P = 0.018) and CSI from 6.3 ± 2.5 to 1.6 ± 0.9 (P = 0.018). At baseline, 57.1% of caregivers reported moderate to severe burden (ZCBI 41–88) compared to 28.6% at the end of the follow-up (P = 0.015); at that time, no caregiver reported high level of stress (CSI ≥ 7) compared to 57.1% at baseline (P = 0.046). There were significant correlations between ZCBI and CSI improvement (r = 0.813, P = 0.026), ZCBI and PDQ-39SI (r = 0.875, P = 0.01), and ZCBI and ADLS (r = 0.813, P = 0.026). Conclusions: Duodenal levodopa infusion-related clinical improvement in patients with advanced PD leads to substantial reductions in caregivers’ stress and burden.

Santos-Garcia D, Sanjurjo LF, Macias M, Llaneza M, Carpintero P, de la Fuente-Fernandez R. Long-term exposure to duodenal levodopa/carbidopa infusion therapy improves quality of life in relation especially to mobility, activities of daily living, and emotional well-being. Acta Neurol Scand: 2012: 125: 187–191. © 2011 John Wiley & Sons A/S. Background – Continuous duodenal levodopa infusion (DLI) is an effective therapy that improves quality of life (QoL) in advanced Parkinson′s disease (PD). However, in which aspects improve the patients their QoL has been poorly documented. Methods – We evaluated 39-item Parkinson′s disease Quality of Life Questionnaire Summary Index score (PDQ-39SI) changes analyzing its different domains in nine patients with advanced PD treated with DLI. Results – All the patients (64.7 ± 11.1 years, 55.5% men) improved PDQ-39SI 6 months after beginning with DLI (29.7 ± 8.6, P = 0.008) and after median duration infusion of 25.3 ± 8.8 months (34.8 ± 11.2, P = 0.008) compared with baseline (55.6 ± 11.5). All domains except social support improved significantly at 6 months. Mobility (P = 0.012), activities of daily living (P = 0.015), and emotional well-being (P = 0.008) improved significantly at the end of the follow-up. Conclusions– DLI improves QoL in patients with advanced PD after short- and long-term exposure. Whereas all domains except social support improve after 6 months under DLI, only mobility, activities of daily living and emotional well-being improve significantly after long-term exposure to DLI.

Background and Objective: Brachial arterial flow-mediated dilation (FMD) is associated with an increased risk of vascular events. Our aim was to investigate the relationship between FMD measured in the acute phase of ischemic stroke and a new major adverse vascular event in a consecutive cohort of patients followed up for 48 months after an acute first-ever stroke. Methods: We measured FMD in 120 consecutive patients with acute ischemic stroke using high-resolution ultrasonography. FMD was calculated as the relationship between the basal diameter of the brachial artery before and after transient vascular occlusion. Intima-media thickness, extracranial carotid atherosclerosis, stroke severity National Institute of Health Stroke Scale, and modified Rankin Scale at 3 months were also evaluated. A vascular event was defined as any of the following: vascular disease (VD) death, nonfatal myocardial infarction (MI), nonfatal recurrent stroke (RS), claudication or peripheral arterial thrombosis (PVD), angioplasty or cardiac bypass graft surgery. Results: There were 34 new major adverse vascular events in 32 of 120 patients (26.7%): 21 (61.8%) RS, 5 (14.7%) VD death, 5 (14.7%) MI, and 3 (8.8%) PVD. The presence of carotid artery plaque (81.3 vs. 46%; p < 0.0001), atrial fibrillation (37.5 vs. 14.8%; p = 0.007) and FMD (5.30 ± 7.48 vs. 10.54 ± 7.02; p = 0.001) were associated with new-onset vascular events. FMD ≤4.5% was an independent predictor of new-onset vascular events (hazards ratio 3.48; 95% confidence interval 1.26–9.63; p = 0.01). Conclusions: FMD is an independent predictor for a new-onset vascular event after first-ever ischemic stroke.