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Introduction. In a degenerative disorder such as Parkinson’s disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr’s motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient’s quality of life (QoL) with regard to a defined clinical stage. Materials and Methods. Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0–20; B: NMSS = 21–40; C: NMSS = 41–70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results. A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p

Introduction The Positive and Negative Syndrome Scale for Schizophrenia Autism Severity Scale (PAUSS) scale can be derived from the Positive and Negative Schizophrenia Syndrome Scale, enabling an assessment of psychotic and autistic dimensions with a single tool. Objectives The aim of the study was to investigate the prevalence of autistic traits and the diagnostic, developmental, clinical, and functional correlates of this phenotype in a sample of early-onset psychosis (onset before age 18 years; EOP). Methods Prospective observational 2 year- follow-up study in a sample of young people with a first-episode of EOP. Demographic, perinatal, developmental, cognitive, clinical, and functional data were collected. PAUSS total scores and socio-communication and repetitive behaviors subscores were calculated. We used the proposed cut-off points for adult populations to define prevalence of autistic traits (PAUSS≥30). Subgroups of patients with and without autistic traits were identified based on the total PAUSS terciles. We used the Cronbach’s alpha test to assess the PAUSS internal consistency. Linear mixed models were performed to compare changes in PAUSS during follow-up between diagnostic subgroups [i.e., non-affective psychosis (including schizophrenia and schizophreniform disorder), affective psychosis (including bipolar disorder, schizoaffective disorder and major depressive disorder with psychotic features), and other psychosis (including brief psychotic disorder and psychosis not otherwise specified)]. Developmental, clinical, and functional variables were compared between subgroups with and without autistic traits with logistic regression analysis. Results 248 patients with PIT were included (age 15.69 ± 1.86 years, 38.65% female). The prevalence of autistic traits in EOP was 7.04%, with significantly higher prevalence in the group of patients with non-affective psychosis (15.20%) than in other diagnostic groups. PAUSS scores significantly decreased over time, with no significant differences in the trajectories of the total PAUSS and its subscores among the three diagnostic subgroups during the 2-year follow-up. The PAUSS showed good internal consistency at all visits (Cronbach’s alpha > 0,88). Patients with autistic traits presented longer duration of untreated psychosis, longer duration of the first inpatient admission, poorer social adjustment in childhood, poorer functionality, greater clinical severity, and poorer response to treatment during follow-up than patients without autistic traits. Conclusions The PAUSS is an easy-to-apply tool that can be useful to differentiate psychosis subgroups with worse prognosis. Disclosure of Interest J. Suárez Campayo: None Declared, L. Pina-Camacho: None Declared, J. Merchán-Naranjo: None Declared, C. Ordas: None Declared, V. Cavone: None Declared, R. Panadero: None Declared, G. Sugranyes: None Declared, I. Baeza: None Declared, J. Castro-Fornieles: None Declared, E. de la Serna: None Declared, C. Arango Consultant of: Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda, C. Diaz Caneja Grant / Research support from: Exeltis and Angelini

Background: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD)., Objective: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL)., Patients and Methods: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL., Results: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (β = 0.073; P = 0.027; R 2  = 0.62) and to develop disabling LID at V5 (β = 0.088; P = 0.009; R 2  = 0.73) were independently associated with a higher score on the PDQ-39SI., Conclusion: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL., (© 2024 International Parkinson and Movement Disorder Society.)

Background and Objective: Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non-motor, cognition, and dependency) and five stages, correlated with disease severity and patients' quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status., Patients and Methods: Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross-sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), PQ-10, and EUROHIS-QOL 8-item index (EUROHIS-QOL8)., Results: Two hundred and twenty-four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4-5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p < .0001) and CSI (p < .0001), and a lower score on the PQ-10 (p = .001), but no significant differences were observed in the BDI-II (p = .310) and EUROHIS-QOL8 (p = .133). Moderate correlations were observed between the MNCD total score and the ZCBI (r = .496; p < .0001), CSI (r = .433; p < .0001), and BDI-II (r = .306; p < .0001) in caregivers., Conclusion: Staging PD according to the MNCD classification is correlated with caregivers' strain and burden., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background and Objective: Patients with young-onset Parkinson's disease (YOPD) have a slower progression. Our aim was to analyze the change in cognitive function in YOPD compared to patients with a later onset and controls., Patients and Methods: Patients with Parkinson's disease (PD) and controls from the COPPADIS cohort were included. Cognitive function was assessed with the Parkinson's Disease Cognitive Rating Scale (PD-CRS) at baseline (V0), 2-year ± 1 month (V2y), and 4-year ± 3 months follow-up (V4y). Regarding age from symptoms onset, patients were classified as YOPD (< 50 years) or non-YOPD (≥ 50). A score in the PD-CRS < 81 was defined as cognitive impairment (CI): ≤ 64 dementia; 65-80 mild cognitive impairment (MCI)., Results: One-hundred and twenty-four YOPD (50.7 ± 7.9 years; 66.1% males), 234 non-YOPD (67.8 ± 7.8 years; 59.3% males) patients, and 205 controls (61 ± 8.3 years; 49.5% males) were included. The score on the PD-CRS and its subscore domains was higher at all visits in YOPD compared to non-YOPD patients and to controls (p < 0.0001 in all analysis), but no differences were detected between YOPD patients and controls. Only non-YOPD patients had significant impairment in their cognitive function from V0 to V4y (p < 0.0001). At V4y, the frequency of dementia and MCI was 5% and 10% in YOPD compared to 25.2% and 22.3% in non-YOPD patients (p < 0.0001). A lower score on the Parkinson's Disease Sleep Scale at baseline was a predictor of CI at V4y in YOPD patients (Adjusted R 2  = 0.61; OR = 0.965; p = 0.029)., Conclusion: Cognitive dysfunction progressed more slowly in YOPD than in non-YOPD patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Purpose: Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson's disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson's disease and normal cognition (PD-NC)., Methods: Patients with PD-NC (total score of >80 on the Parkinson's Disease Cognitive Rating Scale [PD-CRS]) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as "with SCC" and "with VH," respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81., Results: At V0 ( n =376, 58.2% males, age 61.14±8.73 years [mean±SD]), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142), p <0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio [OR]=2.68, 95% confidence interval=1.05-6.83, p =0.0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36-10.17, p =0.011)., Conclusions: VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC., Competing Interests: Santos-García D. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, and Teva., (Copyright © 2023 Korean Neurological Association.)

Background: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group., Methods: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI., Results: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041)., Conclusion: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI., (© 2023 John Wiley & Sons Ltd.)

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  < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p  < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p  = 0.012), being male (OR = 2.333; p  < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p  < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012; p  < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121; 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., Competing Interests: Santos García D. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, Teva, Archímedes, Esteve, Stada, and grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017–2020 por el proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”). De Deus Fonticoba T.: None. Cores Bartolomé C. has received honoraria for educational presentations and advice service by Lundbeck and UCB Pharma. Feal Painceiras M. J.: None. Íñiguez Alvarado MC: None. Jesús S. has received honoraria from AbbVie, Bial, Merz, UCB, and Zambon and 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). Buongiorno M. T.: Planellas LL.: None. Cosgaya M.: None. 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 from Bial, Italfarmaco, Qualigen, Zambon, UCB, Teva, and KRKA and sponsorship from Zambon, TEVA, and Abbvie for attending medical conferences. 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. Cabo I. has received honoraria for educational presentations and advice service by Abbvie, Zambon, and Bial. López Manzanares L.: Compensated advisory services, consulting, research grant support, or speaker honoraria: AbbVie, Acorda, Bial, Intec Pharma, Italfarmaco, Pfizer, Roche, Teva, UCB, and Zambon. 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. Gómez Mayordomo V.: None. Nogueira V.: None. Puente V. has served as consultant for Abbvie and Zambon; has received grant/research from Abbvie. Dotor García-Soto J.: Compensated advisory services, consulting, research grant support, or speaker honoraria: Merck, Sanofi-Genzyme, Allergan, Biogen, Roche, UCB, and Novartis. Borrué C.: None. Solano Vila B. has received honoraria for educational presentations and advice service by UCB, Zambon, Teva, Abbvie, and Bial. 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. Carrillo Padilla F. has received honoraria from Zambon (SEN Congress assistance). Martínez Castrillo JC. has received research support from Lundbeck, Italfarmaco, Allergan, Zambon, Merz, and Abbvie. He has received speaking honoraria from AbbVie, Bial, Italfarmaco, Lundbeck, Krka, TEVA, UCB, Zambon, Allergan, Ipsen, and Merz. Sánchez Alonso P. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Alonso Losada M. G. 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. Gastón I. has received research support from Abbvie and Zambon and has served as a consultant for Abbvie, Exelts, and Zambon. Kulisevsky J.: (1) Consulting fees: Roche, Zambon; (2) Stock/allotment: No; (3) Patent royalties/licensing fees: No; (4) Honoraria (e.g. lecture fees): Zambon, Teva, Bial, UCB; (5) Fees for promotional materials: No; (6) Research funding: Roche, Zambon, Ciberned; Instituto de SaludCarlos III; FundacióLa Maratóde TV3; (7) Scholarship from corporation: No; (8) Corporate laboratory funding: No; (9) Others (e.g. trips, travel, or gifts): No. Blázquez Estrada M. has received honoraria for educational presentations and advice service by Abbvie, Abbott, UCB Pharma, Allergan, Zambon, Bial, and Qualigen. Seijo M. has received honoraria for educational services from KRKA, UCB, Zambon, Bial; travel grants from Daiichi and Roche. Ruiz Martínez J. has received honoraria for educational presentations, attending medical conferences, and advice service by Abbvie, UCB Pharma, Zambon, Italfarmaco, Bial, and Teva. Valero C. has received honoraria for educational services from Zambon, Abbvie, and UCB. Kurtis M. has received honoraria from Bial, the Spanish Neurology Society, and the International and Movement Disorders Society. de Fábregues O. has received honoraria for educational presentations and advice service by Bial, Zambon, Abbvie, KRKA, and Teva. González Ardura J. has recieved honoraria for speking from italofarma, Krka, Genzyme, UCB, Esteve, Psyma iberica marketing research SL and Ferrer, course grant from Teva and travel grant from Merck. Alonso Redondo R.: None. Ordás C.: None. López Díaz L. M. has received honoraria from UCB, Lundbeck, and KRKA. McAfee D.: None. Martínez-Martin P. has received honoraria from National School of Public Health (ISCIII), Editori-al Viguera and Takeda Pharmaceuticals for lecturing in courses, and from the International Parkinson and Movement Disorder Society (MDS) for management of the Program on Rating Scales. Mir P. has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon and have 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) and by 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, the Fundación Mutua Madrileña., (Copyright © 2023 Diego Santos-García et al.)

Tension type headache (TTH) is a prevalent but poorly understood pain disease. Current understanding supports the presence of multiple associations underlying its pathogenesis. Our aim was to compare competing multivariate pathway models that explains the complexity of TTH. Headache features (intensity, frequency, or duration - headache diary), headache-related disability (Headache Disability Inventory-HDI), anxiety/depression (Hospital Anxiety and Depression Scale), sleep quality (Pittsburgh Sleep Quality Index), widespread pressure pain thresholds (PPTs) and trigger points (TrPs) were collected in 208 individuals with TTH. Four latent variables were formed from the observed variables - Distress (anxiety, depression), Disability (HDI subscales), Severity (headache features), and Sensitivity (all PPTs). Structural equation modelling (SEM) and Bayesian network (BN) analyses were used to build and compare a theoretical (model theory ) and a data-driven (model BN ) latent variable model. The model BN (root mean square error of approximation [RMSEA] = 0.035) provided a better statistical fit than model theory (RMSEA = 0.094). The only path common between model bn and model theory was the influence of years with pain on TrPs. The model BN revealed that the largest coefficient magnitudes were between the latent variables of Distress and Disability (β=1.524, P = .006). Our theoretical model proposes a relationship whereby psycho-physical and psychological factors result in clinical features of headache and ultimately affect disability. Our data-driven model proposes a more complex relationship where poor sleep, psychological factors, and the number of years with pain takes more relevance at influencing disability. Our data-driven model could be leveraged in clinical trials investigating treatment approaches in TTH. PERSPECTIVE: A theoretical model proposes a relationship where psycho-physical and psychological factors result in clinical manifestations of headache and ultimately affect disability. A data-driven model proposes a more complex relationship where poor sleep, psychological factors, and number of years with pain takes more relevance at influencing disability., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD., Patients and Methods: PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used., Results: At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression ( p < 0.0001), fatigue ( p < 0.0001), and pain ( p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia ( p < 0.0001), speech problems ( p < 0.0001), rigidity ( p < 0.0001), and hypersexuality ( p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose ( p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males ( p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females ( p = 0.001)., Conclusion: The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.

Background: Chronic migraine (CM) causes great disability and affects an individual's quality of life. OnabotulinumtoxinA (OBT-A, Botox®) was the first prophylactic treatment specifically indicated for CM. The aim of this study was to describe the experiences of women with CM treated with OBT-A., Materials and Methods: The study design is a qualitative descriptive study. A purposeful sampling of 30 women (mean age, 42.7; standard deviation, 10.6) who had received at least two administrations of OBT-A for CM (PREEMPT protocol) was performed. Data collection included in-depth interviews and researchers' field notes. A thematic analysis was carried out according to qualitative research guidelines., Results: Five themes were identified: (a) A long way to go before Botox®, (b) First time hearing about the treatment and its expectations, (c) The administration of Botox®, (d) Treatment effects, and (e) Follow-up. Patients described a long history of treatment failures prior to the start of OBT-A treatment. Information about this migraine treatment came from the neurologist; following the information, patients had high expectations, including unrealistic expectations regarding the onset and duration of effect. They acknowledged fear of the injections and some discomfort due to the procedure. With treatment, participants reported better migraine control and an improvement in their quality of life. Follow-up had some barriers, such as delayed appointments for subsequent doses, but also strengths, such as effectiveness and few side effects., Conclusions: Qualitative research offers insight into how patients with CM experience treatment with OBT-A. Our results highlight some relevant aspects that should be considered when providing OBT-A treatment.

Background: Recent research has shown that background music may improve memory consolidation and retrieval. Nevertheless, in the clinical conditions preceding dementia such as mild cognitive impairment (MCI), there is no current evidence speaking to what effect background music during memory tasks has on impaired cognition., Objective: Across three experiments, we investigated if background music is able to improve memory performance, the most impacted cognitive domain in amnestic MCI., Methods: We tested the effect of background music by using a face recognition memory task in patients with amnestic MCI. In Experiment 1, we tested the effect of background music on memory when it was played solely during an encoding phase. In Experiment 2, we explored effects of background music when played during both encoding and recognition phases. In Experiment 3, we explored the role of musically induced arousal on memory., Results: The main finding from these three experiments was that background music played during a memory task did not improve or worsen participant performance. However, when exposed to high-arousal music, memory performance was predicted by individual mood regulation. For low-arousal music conditions, there was a negative relationship between rating scores for music pleasantness and performance on the memory task., Conclusion: Our results suggest that the benefits of background music on memory in individuals with MCI are modulated by interindividual preferences towards music.

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: 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.

Evidence supports that migraine is a complex pain condition with different underlying mechanisms. We aimed to quantify potential associations between demographic, migraine-related, and psychophysical and psychophysical variables in women with migraine. Demographic (age, height, and weight), migraine-related (intensity, frequency, and duration), related-disability (Migraine Disability Assessment Scale, Headache Disability Inventory), psychological (Hospital Anxiety and Depression Scale), and psycho-physical (pressure pain thresholds -PPTs-) variables were collected from a sample of 74 women suffering from migraine. We calculated adjusted correlations between the variables by using a network analysis. Additionally, we also calculated centrality indices to identify the connectivity among the variables within the network and the relevance of each variable in the network. Multiple positive correlations (ρ) between PPTs were observed ranging from 0.1654 (C5-C6 and tibialis anterior) to 0.40 (hand and temporalis muscle). The strongest associations within the network were those between migraine attack frequency and diagnosis of chronic migraine (ρ = 0.634) and between the HDI-E and HDI-P (ρ = 0.545). The node with the highest strength and betweenness centrality was PPT at the second metacarpal, whereas the node with the highest harmonic centrality was PPT at the tibialis anterior muscle. This is the first study applying a network analysis to understand the underlying mechanisms in migraine. The identified network revealed that a model where each subgroup of migraine-related, psychological, and psycho-physical variables showed no interaction between each variable. Current findings could have clinical implications for developing multimodal treatments targeting the identified mechanisms.

Background and Objective: Caregiver burden in Parkinson's disease (PD) has been studied in many cross-sectional studies but poorly in longitudinal ones. The aim of the present study was to analyze the change in burden, strain, mood, and quality of life (QoL) after a 2-year follow-up in a cohort of caregivers of patients with PD and also to identify predictors of these changes., Patients and Methods: PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers of Spain from the COPPADIS cohort were included in the study. They were evaluated again at 2-year follow-up. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at baseline (V0) and at 2-year follow-up (V2). General linear model repeated measure and lineal regression models were applied., Results: Significant changes, indicating an impairment, were detected on the total score of the ZCBI (p < 0.0001), CSI (p < 0.0001), BDI-II (p = 0.024), and EUROHIS-QOL8 (p = 0.002) in 192 PD caregivers (58.82 ± 11.71 years old; 69.3% were females). Mood impairment (BDI-II; β = 0.652; p < 0.0001) in patients from V0 to V2 was the strongest factor associated with caregiver's mood impairment after the 2-year follow-up. Caregiver's mood impairment was the strongest factor associated with an increase from V0 to V2 on the total score of the ZCBI (β = 0.416; p < 0.0001), CSI (β = 0.277; p = 0.001), and EUROHIS-QOL (β = 0.397; p = 0.002)., Conclusion: Burden, strain, mood, and QoL were impaired in caregivers of PD patients after a 2-year follow-up. Mood changes in both the patient and the caregiver are key aspects related to caregiver burden increase., (© 2022 John Wiley & Sons Ltd.)

Objective: The aim of the present study was to analyze the progression of non-motor symptoms (NMS) burden in Parkinson's disease (PD) patients regarding the development of motor fluctuations (MF). Methods: PD patients without MF at baseline, who were recruited from January 2016 to November 2017 (V0) and evaluated again at a 2-year follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this analysis. MF development at V2 was defined as a score ≥ 1 in the item-39 of the UPDRS-Part IV, whereas NMS burden was defined according to the Non-motor Symptoms Scale (NMSS) total score. Results: Three hundred and thirty PD patients (62.67 ± 8.7 years old; 58.8% males) were included. From V0 to V2, 27.6% of the patients developed MF. The mean NMSS total score at baseline was higher in those patients who developed MF after the 2-year follow-up (46.34 ± 36.48 vs. 34.3 ± 29.07; p = 0.001). A greater increase in the NMSS total score from V0 to V2 was observed in patients who developed MF (+16.07 ± 37.37) compared to those who did not develop MF (+6.2 ± 25.8) ( p = 0.021). Development of MF after a 2-year follow-up was associated with an increase in the NMSS total score (β = 0.128; p = 0.046) after adjustment to age, gender, years from symptoms onset, levodopa equivalent daily dose (LEDD) and the NMSS total score at baseline, and the change in LEDD from V0 to V2. Conclusions: In PD patients, the development of MF is associated with a greater increase in the NMS burden after a 2-year follow-up.

Background: Motor phenotype (MP) can be associated with a different prognosis in Parkinson's disease (PD), but it is not fixed and can change over time., Objective: Our aim was to analyze how the MP changed over time and to identify factors associated with the changes in PD patients from a multicenter Spanish PD cohort., Methods: PD patients who were recruited from January-2016 to November-2017 (baseline visit; V0) and evaluated again at a 2-year±30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this study.MP was calculated at both visits based on Jankovic classification in TD (tremor dominant), IND (indeterminate), or PIGD (postural instability and gait difficulty). Sociodemographic and clinical data were collected, including serum biomarkers., Results: Five hundred eleven patients (62.57±8.59 years old; 59.2%males) were included in the study. At V0, MP was: 47.4%(242/511) TD; 36.6%(187/511) PIGD; 16%(82/511) IND. Up to 38%(194/511) of the patients changed their phenotype from V0 to V2, being the most frequent from TD to IND (8.4%) and from TD to PIGD (6.7%). A worse cognitive status (OR = 0.966) and less autonomy for activities of daily living (OR  =  0.937) at V0 and a greater increase in the globalNMS burden (OR  =  1.011) from V0 to V2 were associated with changing from TD to another phenotype after 2-year follow-up., Conclusion: The MP in PD can change over time. With disease progression, the percentage of cases with non-tremoric MP increases. PD patients who changed from TD to postural instability and gait difficulty increased NMS burden significantly.

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 < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p < 0.0001; Coehn's effect = -0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p = 0.250) (p = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= -0.1; 95% CI, -4.36 - -0.27; p = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 - 3.17; p = 0.045)., Conclusion: Constipation is associated with cognitive decline in PD patients but not in controls.

Background and Objective: Diplopia is relatively common in Parkinson's disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it., 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 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as "with diplopia" or "without diplopia" according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls., Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269-4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012-1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson's Disease Rating Scale-III (OR = 1.039; 95%CI, 1.023-1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001-1.057; p = 0.049) scores were independent factors associated with diplopia (R 2 = 0.25; Hosmer and Lemeshow test, p = 0.716)., Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.

Quality of life (QOL) plays an important role in independent living in Parkinson's disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ≥ 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 ± 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 ± 13 to 20.3 ± 16.4; p < 0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (OR = 0.896; 95% CI 0.829-0.968; p = 0.006), to be a female (OR = 4.181; 95% CI 1.422-12.290; p = 0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (OR = 1.139; 95% CI 1.053-1.231; p = 0.001) and NMSS (Non-Motor Symptoms Scale) (OR = 1.052; 95% CI 1.027-1.113; p < 0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (Hosmer-Lemeshow test, p = 0.665; R 2  = 0.655). An increase in ≥5 and ≥10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663-17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975-22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patients., (© 2021. The Author(s).)

Background and Objective: The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson's disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD)., Patients and Methods: PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%., Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen's effect size = -0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2., Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) ( p < 0.0001). NMSS total score at baseline (β = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (β = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.

Introduction: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage., Materials and Methods: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale., Results: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB ( p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively ( p < 0.005; e.g., PDQ-39SI in 1D [ n  = 15] vs 2A [ n  = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001)., Conclusion: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden., Competing Interests: Santos García D has received honoraria for educational presentations and advice service by AbbVie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, and Teva. Paz González JM has received honoraria for educational presentations and/or advice service by UCB Pharma, Lundbeck, KRKA, and Zambon. Jesús S has received honoraria from AbbVie, Bial, Merz, UCB, and Zambon and 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). Aguilar M obtained from UCB and Schwabe with assistance to a Congress and Nutricia with assistance to a Congress and payment of lecture. 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 from Bial, Italfarmaco, Qualigen, Zambon, UCB, Teva, and KRKA and sponsorship from Zambon, TEVA, and AbbVie for attending medical conferences. 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. Cabo I has received honoraria for educational presentations and advice service by AbbVie, Zambon, and Bial. López Manzanares L compensated advisory services, consulting, research grant support, or speaker honoraria from AbbVie, Acorda, Bial, Intec Pharma, Italfarmaco, Pfizer, Roche, Teva, UCB, and Zambon. Ávila Rivera MA has received honoraria from Zambon, UCB Pharma, Qualigen, Bial, and Teva and ana sponsorship from Zambon and Teva for attending conferences. Puente V has served as consultant for AbbVie and Zambon and has received grant/research from AbbVie. García Moreno JM has received honoraria for educational presentations and advice service by AbbVie, Ital-Pharma, Lundbeck, Merz, KRKA, UCB, Pharma, Zambon, Bial, and Teva. Solano Vila B has received honoraria for educational presentations and advice service by UCB, Zambon, Teva, AbbVie, Bial. 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 has travel grants from AbbVie, Allergan, and Boston; lecturing honoraria from AbbVie and International Parkinson's Disease Movement Disorder Society. Carrillo Padilla F has received honoraria from Zambon (SEN Congress assistance). Martínez Castrillo JC has received research support from Lundbeck, Italfarmaco, Allergan, Zambon, Merz, and AbbVie and speaking honoraria from AbbVie, Bial, Italfarmaco, Lundbeck, Krka, TEVA, UCB, Zambon, Allergan, Ipsen, and Merz. 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. Gastón I has received research support from AbbVie and Zambon and has served as a consultant for AbbVie, Exelts, and Zambon. Kulisevsky J has obtained the following: (1) consulting fees: Roche and Zambon; (2) honoraria (e.g., lecture fees): Zambon, Teva, Bial, and UCB; (3) research funding: Roche, Zambon, Ciberned, Instituto de SaludCarlos III, and Fundació La Marató De TV3. Blázquez Estrada M has received honoraria for educational presentations and advice service by AbbVie, Abbott, UCB Pharma, Allergan, Zambon, Bial, and Qualigen. Seijo M has received honoraria for educational services from KRKA, UCB, Zambon, and Bial and travel grants from Daiichi and Roche. Ruiz Martínez J has received honoraria for educational presentations, attending medical conferences, and advice service by AbbVie, UCB Pharma, Zambon, Italfarmaco, Bial, and Teva. Valero C has received honoraria for educational services from Zambon AbbVie and UCB. Kurtis M has received honoraria from Bial, the Spanish Neurology Society, and the International and Movement Disorders Society. de Fábregues O has received honoraria for educational presentations and advice service by Bial, Zambon, AbbVie, KRKA, and Teva. González Ardura J has received honoraria for speaking from Italfarmaco, Krka, Genzyme, UCB, Esteve, Psyma iberica marketing research SL and Ferrer, course grant from Teva, and travel grant from Merck. López Díaz L has received honoraria from UCB, Lundbeck, and KRKA. Mir P has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon and has received grants from the Spanish Ministry of Economy and Competitiveness (PI16/01575) cofounded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by 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. Martínez-Martin P has received honoraria from Editorial Viguera for lecturing in courses, International Parkinson and Movement Disorder Society (IPMDS) for management of the Program on Rating Scales, Air Liquide, AbbVie, and HM Hospitales de Madrid for advice in clinic-epidemiological studies; license fee payments for the King's Parkinson's Disease Pain scale; financial support by the IPMDS for attending the IPMDS International Congress 2018; and grant for research from IPMDS for development and validation of the MDS-NMS. Borrué C, Ordás C, Catalán MJ, Nogueira V, González Aramburu I, Cosgaya M, Pastor P, De Deus T, Cores Bartolomé C, Valdés Aymerich L, Muñoz Enríquez JG, and Suárez declare that they have no conflicts of interest., (Copyright © 2021 D. Santos García et al.)

MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson's disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2-3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.

Objectives: To describe the therapeutic management of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) in patients initiating treatment with biological agents., Materials and Methods: Observational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analyzed., Results: Four hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS., Conclusions: Our results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

(1) Background: Spatial changes in pressure sensitivity have been described in migraine and tension-type headaches. Our aim was to determine differences in the spatial distribution of pressure pain sensitivity of the temporalis muscle between cluster headache (CH) patients and headache-free controls; (2) Methods: Pressure pain thresholds (PPTs) were determined over nine points covering the temporalis muscle in 40 men with episodic CH and 40 matched headache-free controls in a blinded fashion. Topographical pressure pain sensitivity maps were constructed based on interpolation of the PPTs. Patients were evaluated in a pain-free period (remission phase), at least 3 months from the last attack and without medication; (3) Results: The analysis of covariance (ANCOVA) found significant difference between points (F = 21.887; P < 0.001) and groups (F = 24.416; P = 0.602), but not between sides (F = 0.440; P = 0.508). No effect of depression (F = 0.014; P = 0.907) or anxiety (F = 0.696; F = 0.407) was observed. A post-hoc analysis revealed: 1) lower PPTs at all points in patients than in controls, 2) an anterior-to-posterior gradient in patients but not in controls, with lower PPTs located in the anterior column. Large between-groups effects were shown in all points (standardized mean difference, SMD > 0.8); (4) Conclusions: Bilateral pressure pain hypersensitivity to pressure pain in the temporalis muscle and an anterior-to-posterior gradient to pressure pain was observed in men with episodic CH.

Aims: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2years of symptom evolution., Methods: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups., Conclusions: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objectives: To analyze the association between the rs4680 catechol-O-methyltransferase Val158Met polymorphism and to determine the association of this polymorphism with clinical, psychological, and pain sensitivity variables in women with episodic or chronic migraine., Methods: Fifty women with episodic migraine, 50 with chronic migraine, and 50 matched healthy women participated. After amplifying the Val158Met polymorphism by polymerase chain reaction, we assessed genotype frequencies and allele distributions. Participants were classified according to the Val158Met polymorphism genotype into Val/Val, Val/Met, or Met/Met. A headache diary was used for collecting migraine pain features. Disability was assessed with the Migraine Disability Assessment Scale, trait/state anxiety levels with the State-Trait Anxiety Inventory, and depression/anxiety with the Hospital Anxiety and Depression Scale. Pressure pain thresholds (PPTs) were bilaterally assessed over the temporalis, the upper trapezius, the second metacarpal, and the tibialis anterior., Results: The distribution of the rs4680 Val158Met genotype was not significantly different between women with and without migraine (P = 0.157). No differences in migraine features were found to be dependent on the Val158Met genotype. Women with the Met/Met genotype showed higher migraine-related disability than those with the Val/Val or Val/Met genotype in both migraine groups (P < 0.01). Women with chronic, but not episodic, migraine with the Met/Met genotype exhibited higher depressive and anxiety levels and lower PPTs than those with the Val/Val or Val/Met genotype., Conclusions: The Val158Met rs4680 polymorphism does not appear to be involved in predisposition to suffer from migraine; however, this genetic factor may be involved in the phenotypic expression of chronic migraine, as anxiety, depression, and widespread pressure pain sensitivity were greater in those women with chronic, but not episodic, migraine with the Met/Met genotype., (© 2018 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objective of this study was to investigate differences in clinical, psychological, and psychophysical outcomes according to use of prophylactic medication (amitriptyline) in tension-type headache (TTH)., Methods: In total, 173 individuals with TTH participated. Headache features and symptomatic medication intake were collected with a 4-weeks headache diary at baseline and at 6-months. Burden of headache (Headache Disability Inventory-HDI), sleep quality (Pittsburgh Sleep Quality Index-PSQI), anxiety/depression (Hospital Anxiety and Depression Scale-HADS), and trait/state anxiety levels (State-Trait Anxiety Inventory-STAI) were also assessed at baseline. Pressure pain thresholds (PPT) were assessed over the temporalis, C5-C6 joint, second metacarpal, and tibialis anterior at baseline. Differences between participants taking or not taking prophylactic medication based on self-perceived effectiveness of the medication on headache characteristics were assessed., Results: In total, 49 (28%) reported taking prophylactic medication for the headaches (amitriptyline: 100%). From these, 11 (23%) reported no effect, 25 (51%) reported moderate effect, and 13 (26%) reported positive effect with medication. Patients taking prophylactic medication had longer headache history, higher frequency of headaches (61% CTTH), higher headache burden, worse quality of sleep, and higher depression than those not taking medication. Prophylactic medication was less effective in patients with generalized pressure pain hyperalgesia. No other significant differences were found., Conclusions: Prophylactic medication is used by TTH patients with higher headache frequency, higher headache burden, worse sleep quality, and higher depression. Lower effectiveness of prophylactic amitriptyline was associated with widespread pain hyperalgesia.

Objective: The purpose of this study was to investigate the correlation between head and neck posture and superficial neck flexor and extensor activity during performance of the craniocervical flexion test (CCFT) in women with migraine and healthy controls., Methods: Fifty-two women with episodic migraine, 16 with chronic migraine, and 23 healthy controls participated. Head and neck posture were determined by assessing the craniovertebral (CV) angle and cervical lordosis angle. Surface electromyography signals were recorded bilaterally from sternocleidomastoid, anterior scalene, splenius capitis, and upper trapezius muscles as participants performed the CCFT. Differences in electromyogram activity and posture among groups were compared with analyses of variance. Correlations between posture and electromyogram activity were analyzed with the Pearson correlation coefficient., Results: Both migraine groups had a significant increase in splenius capitis muscle activity, when acting as an antagonist, at the last stage of CCFT (F = 4.687; P = .012) compared with controls. No differences among groups were observed for head and neck posture. No significant correlation was found in the episodic migraine group. Moderate correlations between the CV angle and upper trapezius activity at the majority stages of the CCFT (-0.61 < r < -0.65, all P < .05) were observed within the chronic migraine group: the more extended the head posture, the higher the activity of the upper trapezius muscle. The CV angle also was correlated with upper trapezius muscle activity at the first stage of the CCFT and with splenius capitis muscle activity at the last stages (-0.42 < r < -0.52; P < .05)., Conclusion: An extended (forward) head posture was moderately correlated with an increased in electrical activity of superficial neck extensor muscles, particularly the upper trapezius, when acting as an antagonist, during the performance of the CCFT in women with chronic but not episodic migraine., (Copyright © 2018. Published by Elsevier Inc.)

Objective To investigate the association between trigger points (TrPs) and widespread pressure pain sensitivity in people with tension-type headache (TTH) and to determine if this association is different between frequent episodic (FETTH) or chronic (CTTH) headache. Design A cross-sectional study. Methods One hundred and fifty-seven individuals (29% male) with TTH participated. Clinical features of headache, i.e., intensity, duration, and frequency, were recorded in a headache diary. Active and latent TrPs were bilaterally explored in the temporalis, masseter, suboccipital, upper trapezius, sternocleidomastoid, and splenius capitis muscles. Pressure pain thresholds (PPT) were assessed over the trigeminal area (i.e., temporalis muscle), extra-trigeminal (i.e., C5/C6 zygapophyseal joint), and two distant pain-free points (i.e., second metacarpal and tibialis anterior muscle). Results Eighty (51%) patients were classified as FETTH, whereas 77 (49%) were classified as CTTH. No differences in the number of either active or latent TrPs (all p > 0.171) or widespread pressure pain sensitivity (all p > 0.351) were observed between FETTH and CTTH groups. The number of active and latent TrPs was significantly and negatively associated with PPTs: The higher the number of active or latent TrPs, the lower the widespread PPT, and the more generalized sensitization. This association was stronger within the FETTH group than the CTTH group. Conclusions This study found that the number of TrPs in head and neck/shoulder muscles was associated with widespread pressure hypersensitivity independently of the frequency of headache.

The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer's disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease.

Background: The role of musculoskeletal disorders of the cervical spine in migraine is under debate., Aim: To investigate differences in musculoskeletal impairments of the neck including active global and upper cervical spine mobility, the presence of symptomatic upper cervical spine joints, cervicocephalic kinesthesia and head/neck posture between women with episodic migraine, chronic migraine, and controls., Design: A cross-sectional study., Setting: Tertiary university-based hospital., Population: Fifty-five women with episodic migraine, 16 with chronic migraine, and 22 matched healthy women., Methods: Active cervical range of motion, upper cervical spine mobility (i.e., flexion-rotation test), referred pain from upper cervical joints, cervicocephalic kinesthesia (joint position sense error test, JPSE), and head/neck posture (i.e. the cranio-vertebral and cervical lordosis angles) were assessed by an assessor blinded to the subject's condition., Results: Women with migraine showed reduced cervical rotation than healthy women (P=0.012). No differences between episodic and chronic migraine were found in cervical mobility. Significant differences for flexion-rotation test were also reported, suggesting that upper cervical spine mobility was restricted in both migraine groups (P<0.001). Referred pain elicited on manual examination of the upper cervical spine mimicking pain symptoms was present in 50% of migraineurs. No differences were observed on the frequency of symptomatic upper cervical joints between episodic and chronic migraine. No differences on JPSE or posture were found among groups (P>0.121)., Conclusions: Women with migraine exhibit musculoskeletal impairments of the upper cervical spine expressed as restricted cervical rotation, decreased upper cervical rotation, and the presence of symptomatic upper cervical joints. No differences were found between episodic or chronic migraine., Clinical Rehabilitation Impact: Identification treatment of the musculoskeletal impairments of the cervical spine may help to clinician for better management of patients with migraine.