Delineating the motor phenotype of SGCE-myoclonus dystonia syndrome

Objective To perform phenotype and genotype characterization in myoclonus-dystonia patients and to validate clinical rating tools. Method Two movement disorders experts rated patients with the Burke-Fahn-Marsden and Unified-Myoclonus rating scales using a video-recording protocol. Clinimetric analysis was performed. SGCE mutations were screened by Sanger sequencing and multiplex ligation-dependent probe amplification. Results 48 patients were included and 43/48 rated. Mean age at assessment was 12.9±10.5 years (range 3–51) and 88% were ≤18 years of age. Myoclonus was a universal sign with a rostro-caudal severity-gradient. Myoclonus increased in severity and spread to lower limbs during action tests. Stimulus-evoked myoclonus was observed in 86.8% cases. Dystonia was common but mild. It had a focal distribution and was action-induced, causing writer's cramp (69%) and gait dystonia (34%). The severity of both myoclonus and dystonia had a strong impact on hand writing and walking difficulties. The Unified Myoclonus Rating scale showed the best clinimetric properties for the questionnaire, action myoclonus and functional subscales, and exceeded the Burke-Fahn-Marsden scale in its utility in assessing functional impairment in MDS patients. Twenty-one different SGCE mutations were identified in 45/48 patients, eleven being novel (most prevalent p. Val187*, founder mutation in Canary Islands). Conclusion This study quantifies the severity of the motor phenotype in SGCE-myoclonus dystonia syndrome, with a special focus on children, and identifies disabilities in gross and fine motor tasks that are essential for childhood development. Our results contribute to the knowledge of SGCE-related MDS in the early stage of evolution, where disease-modifying therapies could be initiated in order to prevent long-term social and physical burdens.This work was supported by a Grant from Myoclonus Dystonia Syndrome Spanish association (ALUDME) (grant PIC/124/16), grant FPU16/07203 from Ministerio de Educación y formación profesional, and grant PI15/00287 and PI18/01319 from the Plan Nacional de I + D + I

High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson’s disease patients

COPPADIS Study Group.C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. 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). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105–17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113–7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005–1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.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. Aneiros Díaz A: None. Paz González JM. has received honoraria for educational presentations and/or advice service by UCB Pharma, Lundbeck, KRKA, and Zambon. Feal Panceiras MJ: None. García Sancho C: None. Jesús S. has received honoraria from Abbvie, Bial, Merz, UCB, and Zambon. She holds the competitive contract “Juan Rodés” supported by the Instituto de Salud Carlos III. Also, she has received grants from the Spanish Ministry of Economy and Competitiveness (PI18/01898) as well as 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. 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). He also received grants from 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. Aguilar M: UCB and Schwabe with assistance to a Congress; Nutricia with assistance to a Congress and payment of lecture. Pastor P: None. 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. de Fábregues-Boixar O. has received honoraria for educational presentations and advice service by Bial, Zambon, Abbvie, KRKA, and Teva. Puente V. has served as consultant for Abbvie and Zambon; has received grant/research from Abbvie. Crespo Cuevas A: None. González-Aramburu I: None. Infante J. has received travel bursaries and honoraria for educational presentations from Abbvie and Zambon. Carrillo Padilla F. has received honoraria from Zambon (SEN Congress assistance). Pueyo M. has received honoraria from Zambon for educational presentations and SEN Congress assistance and of Medtronic for course assistance. Escalante S. has received honoraria for educational presentations and advice service by Abbvie, Zambon, and Bial. Bernardo N: None. Solano B. has received honoraria for educational presentations and advice service by UCB, Zambon, Teva, Abbvie, and Bial. Cots Foraster A has received honoraria for educational presentations by UCB and Zambon, Has received financial help to Master courses (Master en Trastornos del Movimiento, Ed Viguera, 2017–2018) from UCB an Zambon. Martinez-Martin P: Honoraria: from Editorial Viguera for lecturing in courses; International Parkinson and Movement Disorder Society 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

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation

[Background and purpose]: In Parkinson's disease (PD ), the course of the disorder is highly variable between patients. Well‐designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS ‐2015 (Co hort of Patients with PA rkinson's DI sease in Spain, 2015).[Methods]: This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants.[Results]: In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 ± 8.9 years old, 60.3% males), 273 caregivers (58.5 ± 11.9 years old, 31.8% males) and 207 controls (61 ± 8.3 years old, 49.5% males). The mean disease duration was 5.5 ± 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non‐Motor Symptoms Scale total score was 45.4 ± 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non‐motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging).[Conclusions]: Parkinson's disease is a complex disorder and different non‐motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them

Non-motor symptoms burden, mood, and gait problems are the most significant factors contributing to a poor quality of life in non-demented Parkinson's disease patients: Results from the COPPADIS Study Cohort

[Objective] To identify factors related to a poor health-related and global quality of life (QoL) in a cohort of non-demented Parkinson's disease (PD) patients and compare to a control group.[Methods] The data correspond to the baseline evaluation of the COPPADIS-2015 Study, an observational, 5-year follow-up, multicenter, evaluation study. Three instruments were used to assess QoL: (1) the 39-item Parkinson's disease Questionnaire (PDQ-39), (2) a subjective rating of global QoL (PQ-10), and (3) the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Multiple linear regression methods were used to evaluate the direct impact of different variables on these QoL measures.[Results] QoL was worse in PD patients (n = 692; 62.6 ± 8.9 years old, 60.3% males) than controls (n = 206; 61 ± 8.3 years old, 49.5% males): PDQ-39, 17.1 ± 13.5 vs 4.4 ± 6.3 (p < 0.0001); PQ-10, 7.3 ± 1.6 vs 8.1 ± 1.2 (p < 0.0001); EUROHIS-QOL8, 3.8 ± 0.6 vs 4.2 ± 0.5 (p < 0.0001). A high correlation was observed between PDQ-39 and Non-Motor Symptoms Scale (NMSS) (r = 0.72; p < 0.0001), and PDQ-39 and Beck Depression Inventory-II (BDI-II) (r = 0.65; p < 0.0001). For health-related QoL (PDQ-39), non-motor symptoms burden (NMSS), mood (BDI-II), and gait problems (Freezing Of Gait Questionnaire [FOGQ]) provided the highest contribution to the model (β = 0.32, 0.28, and 0.27, respectively; p < 0.0001); whereas mood and gait problems contributed the most to global QoL (PQ-10, β = -0.46 and −0.21, respectively; EUROHIS-QOL8, β = -0.44 and −0.23, respectively).[Conclusions] QoL is worse in PD patients than in controls. Mood, non-motor symptoms burden, and gait problems seem to be the most relevant factors affecting health-related and global perceived QoL in non-demented PD patients.Peer reviewe