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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.

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] 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.

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.

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.

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.

[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.

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 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.

Antiganglioside antibodies can appear after several acute infections and are often associated with various clinical patterns of Guillain-Barré syndrome. Thus, for example, cytomegalovirus infection has been associated with anti-GM2 antibodies and Guillain-Barré syndrome variants with severe sensory loss and cranial nerve involvement. We report on a patient who developed multiple cranial neuropathy associated with herpes simplex virus infection and anti-GM2 immunoglobulin M antibodies.

Bifurcacion carotidea (T) hiperdensa en el ictus: el 'signo del arbol'

Functional connectivity was evaluated in patients with schizophrenia (SC) and in patients with Parkinson's disease (PD) during the performance of a local contextual processing paradigm, to investigate the proposition that functional disconnection is involved with contextual processing deficits in these populations. To this end, we utilized event-related EEG signals, synchronization likelihood and graph theoretical analysis. Local context was defined as the occurrence of a predictive sequence of stimuli before the presentation of a target event. In the SC patients, we observed a decrease in path length (L) in the beta band, for the predictive sequence and for predicted and random targets, compared with controls. These abnormalities were associated with weaker frontal-temporal-parietal connections. In the PD patients we found longer L (theta band) for predicted targets, and higher cluster coefficients for both the predictive sequence (theta band) and predicted targets (alpha and theta bands), compared with controls. Detection of predicted targets was associated with weaker frontal-parietal connections in PD. No group differences were found for randomized standard stimuli in both SC and PD patients. These findings provide evidence of task-specific functional connectivity abnormalities within frontal networks during local contextual processing.

[Abstract] Background. Gait impairment in Parkinson's disease (PD) patients is characterized by the inability to generate appropriate stride length. Treadmill training has been proposed as a therapeutic tool for PD patients. However, it remains unknown whether treadmill training effects are different from overground walking training. Thus, our goal was to explore the effects of two training programs, walking on a treadmill and walking overground, in PD patients. Methods. 22 PD patients were randomly assigned to a treadmill or overground training group. The training program consisted of 5 weeks (3 sessions/week). Before and after the program we evaluated gait kinematics during walking at preferred and maximal speed; Timed Up and Go (TUG); static posturography and knee extensors strength. Gait parameters were reevaluated in the treadmill training group one month after the cessation of the training. Results. Preferred speed walking improved in both groups after the training program. The treadmill training program, but not the overground, led to an improvement in the stride length at the preferred and maximal walking speed in the PD patients. In addition, the treadmill training group showed improvement of the TUG and static posturography tests. The improvement in gait parameters was maintained one month after the cessation of the treadmill training. Conclusions. This study provides evidence of a specific therapeutic effect of treadmill training on Parkinsonian gait and balance. Walking on a treadmill may be used as an easy, effective and accessible way to improve the stride length and balance in PD patients. Background. Gait impairment in Parkinson's disease (PD) patients is characterized by the inability to generate appropriate stride length. Treadmill training has been proposed as a therapeutic tool for PD patients. However, it remains unknown whether treadmill training effects are different from overground walking training. Thus, our goal was to explore the effects of two training programs, walking on a treadmill and walking overground, in PD patients. Methods. 22 PD patients were randomly assigned to a treadmill or overground training group. The training program consisted of 5 weeks (3 sessions/week). Before and after the program we evaluated gait kinematics during walking at preferred and maximal speed; Timed Up and Go (TUG); static posturography and knee extensors strength. Gait parameters were reevaluated in the treadmill training group one month after the cessation of the training. Results. Preferred speed walking improved in both groups after the training program. The treadmill training program, but not the overground, led to an improvement in the stride length at the preferred and maximal walking speed in the PD patients. In addition, the treadmill training group showed improvement of the TUG and static posturography tests. The improvement in gait parameters was maintained one month after the cessation of the treadmill training. Conclusions. This study provides evidence of a specific therapeutic effect of treadmill training on Parkinsonian gait and balance. Walking on a treadmill may be used as an easy, effective and accessible way to improve the stride length and balance in PD patients. Ministerio de Ciencia e Innovación;DEP-2011-22466

Background Although dopamine agonists (DAs) are useful in Parkinson′s disease (PD), they are not frequently used in elderly patients due to adverse effects. However, there is a lack of evidence because few elderly PD patients are enrolled in clinical trials. Aims of the study The aims of this study were to analyze the reasons of DA withdrawal (DAW) in a group of PD patients in clinical practice and to identify the related factors. Specifically, we studied the effect of age, comorbidity, and polypharmacy as potential risk factors for DAW. Methods A retrospective chart review of the follow‐up (from May, 2012 to March, 2015) of a subgroup of PD patients receiving a DA (n = 68; 60.3% males, 69.3 ± 9.2 years old) from a cohort (n = 150) previously studied in detail in 2012 was used to identify predictive factors of DAW. Results The DAW percentage was 18.2% (12/66; follow‐up of 690.2 ± 232.6 days). DAW causes were cognitive impairment (3), reduction therapy (3), hallucinations (2), dyskinesia (2), and excessive diurnal somnolence (2). Only a higher levodopa daily dose (HR 1.003; 95% CI 1.001–1.006; P = 0.044) was an independent predictor of DAW after adjustment for other explanatory variables. Conclusions The frequency of DAW was low. Advanced age alone is not a contraindication to the administration of DAs.

Some reports have emerged describing the occurrence of Guillain- Barré syndrome and polyneuropathy related to vitamin B 12 deficiency in some patients with Parkinson's disease (PD) treated with continuous duodenal levodopa infusion. We describe five PD patients who developed axonal polyneuropathy and vitamin B 12 deficiency while on treatment with duodenal levodopa infusion, review other cases reported in the literature, discuss potential etiologic factors, and suggest a possible algorithm for the management and prevention of this complication. One case of Guillain-Barré syndrome and at least 12 cases of polyneuropathy related to vitamin B 12 deficiency have been reported in PD patients treated with duodenal levodopa infusion. Levodopa gel infusion may induce a decrease in vitamin B 12 levels, leading to peripheral neuropathy. Additional pathogenetic mechanisms include alterations related to the metabolism of L-dopa, abnormal L-dopa absorption, and direct neurotoxicity of L-dopa at high doses. Vitamin B 12 supplementation may need to be considered in PD patients on duodenal levodopa infusion therapy. Vitamin B 12 deficiency in patients on duodenal levodopa infusion therapy may be more frequent than the published data suggest. We must be alert. © Springer-Verlag 2012., F. Carrillo and P. Mir were supported by grants from the Ministerio de Ciencia e Innovación de España (SAF2007-60700); the Instituto de Salud Carlos III (PI10/01674); the Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526); the Consejería de Salud de la Junta de Andalucía (PI-0377/2007, PI-0741/2010), the Sociedad Andaluza de Neurología and the Jaques and Gloria Gossweiler Foundation. The remaining authors received no relevant financial support and funding for the preceding 12 months.

Objective To test whether adherence to non-ergot, once-daily dopamine agonist (ODDA) therapy depends upon concomitant levodopa daily dose in Parkinson's disease (PD). Methods Consecutive levodopa-treated PD patients on ODDA therapy were invited to participate in the study. ODDA adherence was measured using subjective (Morisky–Green test, MGT) and objective (electronic monitoring of refill compliance, IANUS) methods. A combination of MGT and IANUS was used to define full (100%) adherence to ODDA therapy. Logistic regression methods were used to investigate the impact of levodopa daily dose on ODDA adherence after adjusting for relevant covariates. Results Thirty-nine patients (19 men, 20 women; age, 70.2 ± 8.9 years) were enrolled in the study. Twelve (31%) participants admitted to suboptimal ODDA compliance. Only 18 (46%) were estimated to be fully compliant. As expected, adherence was inversely related to levodopa daily dose. For every 100 mg increase in levodopa dose, the risk to failure to adhere increased 1.86 times (95% CI, 1.21–3.74; p = 0.0020). The covariate “total daily number of drugs” (not total daily number of pills) was also associated with worse adherence (p = 0.0061). In contrast, patients who were initially treated with a dopamine agonist showed better ODDA adherence than those who were initially treated with levodopa (p = 0.012). Levodopa doses greater than 600 mg/day were associated with suboptimal compliance. Conclusions In levodopa-treated PD patients, adherence to ODDA therapy is suboptimal and strongly associated with the levodopa daily dose and the total number of drugs used to treat patients' medical conditions.

Brachial artery flow mediated dilation (FMD) is a validated, noninvasive physiological measure widely used as a research tool to quantify endothelial function. FMD is diminished in patients with several coronary risk factors, coronary artery disease, peripheral arterial disease, stroke, and is an independent predictor of cardiovascular events. FMD represents a useful method for identify asymptomatic atherosclerotic subjects with raised risk of developing atherothrombotic complications and improves with risk-reduction therapy such as antihypertensive or antidiabetic drugs, antiplatelet agents and statins. FMD could be a great usefulness in ischemic stroke such as stroke subtypes classification, prognostic significance in acute phase, and independent predictor for new-onset vascular event after first-ever stroke, but also in other disease such as cerebral haemorrhage, migraine or syncope. In this review article, brachial artery FMD and its role in experimental and clinical practice is extensively discussed.

Pain is one of the most common non motor symptoms in patients with Parkinson's disease (PD). However, it is underrecognized. We examine the prevalence of pain, characteristics, associated factors, and relation with quality of life and autonomy in a consecutive series of PD patients.Pain was identified according to International Association for the Study of Pain. Brief Pain Inventory and Medical Outcomes Study 36-Item Short Form were used.Of the 159 patients (72.31 ± 8.83 years; 51.3% female), 115 (72.3%) presented pain. Of these, 51.3% reported pain onset before PD-diagnosis, 27.8% two or more pain types, and 53% PD-related pain. Musculoskeletal (74.8%) and radicular-neuropathic (24.3%) were the types of pain most frequent. The 37.4% of the patients with pain did not received analgesic treatment. Depression was an independent predictor of pain (OR = 7.82; 95% CI = 1.151-53.183; p = 0.035). Pain was an independent predictor of worst quality of life (PDQ-39; regression coefficient: 25.53; standard error: 11.852; 95% CI = 1.48-49.57; p = 0.03) and lower autonomy (Schwab and England; regression coefficient: -13.85; standard error: 6.327; 95% CI = -26.58 to -1.2; p = 0.034).Pain is very frequent in PD patients. It is associated with depression, and predicts a worst quality of life and lower autonomy for the patient.

Objective We investigated the role of the frontostriatal system in contextual processing, by examining neural correlates of local contextual processing in Parkinson’s disease (PD). Local context was defined as the occurrence of a short predictive series of visual stimuli occurring before delivery of a target event. Methods EEG was recorded in eight PD patients and eight controls. Recording blocks consisted of targets preceded by randomized sequences of standards and by sequences including a predictive sequence signaling the occurrence of a subsequent target event. Subjects pressed a button in response to targets. Peak P3b amplitude and latency were evaluated for targets after predictive and non-predictive sequences. Results Behavioral and electrophysiological measures showed that controls processed predicted and random targets differentially, while PD patients processed these similarly. Reaction times were shorter for predictable than for random targets in controls but not in patients. PD patients failed to generate the expected P3b latency shift between predicted and random targets, which is observed in controls. Conclusions These findings show that predictive local context effects on target detection are altered in PD patients. Significance The findings suggest a key role for the frontostriatal system in contextual processing.

Chronic migraine refractory to preventive treatment is a common clinical situation in general neurology clinics. The aim is to analyse our experience with zonisamide in the preventive treatment of patients with frequent refractory migraine.Those patients with no response or intolerance to topiramate and at least one more preventative received zonisamide. This drug was increased 25 mg per week up to 200 mg/day. The efficacy of zonisamide was evaluated in terms of 'response' (reduction in attack frequency below 50%) at the third month of treatment.Our series comprises a total of 172 patients, with ages ranging from 22 to 69 years. 85% were women. The final dosage of zonisamide was 50-200 mg/day, with the 100 mg/day being the most frequently administered dose. Zonisamide was efficacious (response) in 76 (44%) patients; response being excellent in 22 (13%). MIDAS score was reduced by 43.2%. Zonisamide was not tolerated by 27% of the patients, mainly due to subjective mental slowness or digestive symptoms.These results, obtained in a big sample of patients refractory or intolerant to topiramate and other preventatives, indicate that, at least in conditions of daily clinical practice, zonisamide, at relatively low dosages, is an option to be considered for the preventive treatment of patients with frequent migraine.

The degree of verbal production necessary to be considered logorrhoea has still not been defined, and no clear correlation has been established between the topography of the dysfunction and this symptom.To provide quantitative data about normal verbal production and to identify the location within the brain of the alterations observed in neuroimage of patients with logorrhoea.The oral verbal production of 60 control subjects between 20 and 80 years of age was quantified by analysing five speeches. Ten patients who exceeded the 75th percentile in at least two of the five speeches underwent structural and functional neuroimaging tests. RESULTS. The data on verbal production of normal subjects are reported. Age, sex and habits (smoking, coffee, alcoholic drinks) did not exert an influence, but the degree of schooling was seen to have an effect. All the patients were diagnosed with frontotemporal degeneration, although in one case there were also coexisting vascular risk factors and subcortical vascular lesions, which reduce the degree of certainty of the diagnosis. Cortical atrophy is located in the right anterior temporal lobes (100% anteromedial, 100% anteroinferior, 70% anterolateral), left anterior temporal (90% anteromedial, 90% anteroinferior, 60% anterolateral), right prefrontal (30% basal, 50% dorsolateral, 20% medial) and left prefrontal (20% basal, 30% dorsolateral, 20% medial).Oral verbal production is influenced by level of education and, in a sample of patients with probable frontotemporal degeneration and logorrhoea, all the patients showed alterations in the anteroinferior and anteromedial regions of the right temporal lobe.

Epidermal nevus syndrome is a rare congenital sporadic neurocutaneous disorder characterized by an epidermal nevus and various developmental abnormalities of the skin, eyes, nervous, cardiovascular and urogenital systems. We describe a patient with an extensive epidermal nevus associated with various organ abnormalities, particularly polyostotic fibrous dysplasia, central nervous system lipoma, and aplasia cutis. Our patient demonstrates the polymorphic spectrum of involvement in epidermal nevus syndrome.

Background and purpose: Brachial arterial flow-mediated dilation (FMD) reflects endothelium-dependent vasodilation function. FMD is diminished in patients with endothelial dysfunction (ED). Our aim was to investigate the relationship between FMD and outcome for patients with acute ischemic stroke. Methods: We measured FMD in 120 consecutive patients (58.3% male, median age 73 years) with acute ischemic stroke within the first 48 h of onset of the stroke, using high-resolution ultrasonography. FMD was calculated as the relationship between basal diameter of the brachial artery before (d1) and after (d2) transient vascular occlusion (300 mmHg for 4 min) was measured using a sphygmomanometer (FMD = d2 − d1/d1 × 100). Poor outcome was defined as modified Rankin Scale at 3 months >2. FMD was categorized according to ROC analysis and we defined ED as FMD ≤ 4.5%. Results: Thirty-three patients (27.5%) had ED. Median % FMD was 9.12 (7.48). FMD negatively correlated to stroke severity (P = 0.045). Median FMD was significantly lower [4.5 (2.3, 10.3) vs. 9.4 (5.6, 15.1), P = 0.003] for patients with poor outcome (n = 38). The adjusted odds ratio of poor outcome for FMD ≤ 4.5% was 3.03 (95% CI, 1.09–27.3). Conclusions: Impaired FMD in patients with acute ischemic stroke is associated with poor outcome.

The relationship between hepatitis B virus and hepatitis B vaccine with central nervous system demyelinating diseases is controversial.We describe two male patients, who in their 70's developed recurrent pictures of acute demyelinating diseases. The first one had recurrent acute disseminated encephalomyelitis (diplopia, paraparesis and urinary retention) and the second one recurrent transverse myelitis (paraparesis and urinary retention).The cerebrospinal fluid test showed mononuclear pleocytosis with negative oligoclonal bands in both patients. Visual evocated potentials were normal. Magnetic resonance imaging (T2-WI and FLAIR) showed hyperintense lesions located in the brain and spinal cord in the first case and only in the spinal cord in the second. With negative antigenemia, antibodies against hepatitis B core and hepatitis B surface antigens were positive in both patients. No patient had been vaccinated for nor had suffered symptomatic hepatic disease. In the second patient, there was an almost total remission of the symptoms with periodic treatment with immunoglobulins.We recommend hepatitis B virus infection investigation in all patients with central nervous system demyelinating disease.

The risk of side effects secondary to global and non-specific immune suppression has limited the systematic application of immunosuppressive therapy in multiple sclerosis (MS). However, when a patient with MS develops a cancer, cytostatic drugs as treatment for the neoplastic process may induce improvement not only of the cancer but also of MS.We present a series of four women with clinically defined MS and subjected to cytostatic therapy (cisplatin, 5-fluorouracil, leukovorin, adriamycin, tamoxifen and anastrozole) after the development of cancer: two presented breast cancer, one colon cancer, and the fourth parotid gland malignancy. Their clinical and neuroimaging course is described, following chemotherapy for the malignant disease. None of the patients have suffered further MS outbreaks. The four women have improved and remain clinically stable after neoplastic treatment. Magnetic resonance imaging showed persistence of the same lesion burden in three patients, and reduction in the other. At the present one patient receives weekly intramuscular interferon-beta 1a, whereas the other did not received any treatment.Probably there are no specific cytostatics for MS. Immunosuppressive therapy could be a therapeutic option among patients with an aggressive clinical course.

In addition to the motor disturbances experienced by the patients suffering from Parkinson's disease (PD), several non-motor symptoms also affect the PD patients: neurobehavior symptoms (dementia, depression, anxiety, psychosis), autonomic (postural hypotension, urinary symptoms, gastro intestinal symptoms, diaphoresis), sleep disorders (insomnia, somnolence, REM sleep behavior disorder, apnea), sensitive-motor (fatigue, diplopia, restless legs syndrome), and sensory symptoms.We review the most relevant about sensory symptoms in PD: visual dysfunction, olfactory dysfunction, taste, hearing loss, and pain and other sensitive associate symptoms.Pain is frequently observed in patients with PD, being its prevalence high and probably infra diagnosed. Its identification and classification is very important for a correct treatment. Hyposmia is a common symptom in PD and could be a predictor of future PD. Visual dysfunction and hearing dysfunction among others must be considered in patients with PD.

Different gastrointestinal symptoms, such as excessive salivation, deterioration and other disorders affecting the teeth, dysphagia, gastroparesis, gastroesophageal reflux, constipation, difficult defecation or loss of weight are frequent events in all the stages of the development of Parkinson's disease and affect at least a third of the patients. These symptoms reflect the dysfunction of the enteric nervous system, and the stomach is one of the organs where alpha-synuclein is first deposited. Other factors, such as the dysfunction of structures in the central nervous system like the dorsal motor nucleus of the vagal nerve, hormonal factors or secondary effects deriving from the consumption of antiparkinsonian drugs, are involved in its origin. The present article offers a detailed review of the epidemiological, pathophysiological, clinical and therapeutic management aspects of the different gastrointestinal symptoms in Parkinson's disease.Gastroparesia y otros sintomas gastrointestinales en la enfermedad de Parkinson.Diferentes sintomas gastrointestinales, como salivacion excesiva, deterioro y otros trastornos de las piezas dentarias, disfagia, gastroparesia, reflujo gastroesofagico, estreñimiento, dificultades en la defecacion o perdida de peso, son frecuentes en todos los estadios evolutivos de la enfermedad de Parkinson y afectan al menos a un tercio de los pacientes. Estos sintomas reflejan la disfuncion del sistema nervioso enterico, siendo el estomago uno de los organos donde mas precozmente se deposita la alfa-sinucleina. Otros factores, como la disfuncion de estructuras del sistema nervioso central como el nucleo motor dorsal del nervio vago, factores hormonales o efectos secundarios derivados del consumo de farmacos antiparkinsonianos estan implicados en su origen. El presente articulo revisa en detalle aspectos epidemiologicos, fisiopatologicos, clinicos y de manejo terapeutico de los diferentes sintomas gastrointestinales en la enfermedad de Parkinson.