Motor Fluctuations Development Is Associated with Non-Motor Symptoms Burden Progression in Parkinson's Disease Patients: A 2-Year Follow-Up Study

Diego Santos-García; Teresa de Deus Fonticoba; Carlos Cores Bartolomé; Maria J Feal Painceiras; Ester Suárez Castro; Héctor Canfield; Cristina Martínez Miró; Silvia Jesús; Miquel Aguilar; Pau Pastor; Lluís Planellas; Marina Cosgaya; Juan García Caldentey; Nuria Caballol; Ines Legarda; Jorge Hernández-Vara; Iria Cabo; Lydia López Manzanares; Isabel González Aramburu; Maria A Ávila Rivera; Víctor Gómez Mayordomo; Víctor Nogueira; Víctor Puente; Julio Dotor García-Soto; Carmen Borrué; Berta Solano Vila; María Álvarez Sauco; Lydia Vela; Sonia Escalante; Esther Cubo; Francisco Carrillo Padilla; Juan C Martínez Castrillo; Pilar Sánchez Alonso; Maria G Alonso Losada; Nuria López Ariztegui; Itziar Gastón; Jaime Kulisevsky; Marta Blázquez Estrada; Manuel Seijo; Javier Rúiz Martínez; Caridad Valero; Mónica Kurtis; Oriol de Fábregues; Jessica González Ardura; Ruben Alonso Redondo; Carlos Ordás; Luis M López Díaz; Darrian McAfee; Pablo Martinez-Martin; Pablo Mir; Coppadis Study Group

doi:10.3390/diagnostics12051147

Motor Fluctuations Development Is Associated with Non-Motor Symptoms Burden Progression in Parkinson's Disease Patients: A 2-Year Follow-Up Study

Diagnostics (Basel). 2022 May 5;12(5):1147. doi: 10.3390/diagnostics12051147.

Authors

Diego Santos-García¹, Teresa de Deus Fonticoba², Carlos Cores Bartolomé¹, Maria J Feal Painceiras¹, Ester Suárez Castro², Héctor Canfield², Cristina Martínez Miró¹, Silvia Jesús^{3

4}, Miquel Aguilar⁵, Pau Pastor⁵, Lluís Planellas⁶, Marina Cosgaya⁷, Juan García Caldentey⁸, Nuria Caballol⁹, Ines Legarda¹⁰, Jorge Hernández-Vara^{4

11}, Iria Cabo¹², Lydia López Manzanares¹³, Isabel González Aramburu^{4

14}, Maria A Ávila Rivera¹⁵, Víctor Gómez Mayordomo¹⁶, Víctor Nogueira¹⁷, Víctor Puente¹⁸, Julio Dotor García-Soto¹⁹, Carmen Borrué²⁰, Berta Solano Vila²¹, María Álvarez Sauco²², Lydia Vela²³, Sonia Escalante²⁴, Esther Cubo²⁵, Francisco Carrillo Padilla²⁶, Juan C Martínez Castrillo²⁷, Pilar Sánchez Alonso²⁸, Maria G Alonso Losada²⁹, Nuria López Ariztegui³⁰, Itziar Gastón³¹, Jaime Kulisevsky^{4

32}, Marta Blázquez Estrada³³, Manuel Seijo¹², Javier Rúiz Martínez³⁴, Caridad Valero³⁵, Mónica Kurtis³⁶, Oriol de Fábregues¹¹, Jessica González Ardura³⁷, Ruben Alonso Redondo³⁸, Carlos Ordás³⁹, Luis M López Díaz⁴⁰, Darrian McAfee⁴¹, Pablo Martinez-Martin⁴, Pablo Mir^{3

4}, Coppadis Study Group

Affiliations

¹ Department of Neurology, Hospital Universitario de A Coruña (HUAC), Complejo Hospitalario Universitario de A Coruña (CHUAC), C/As Xubias 84, 15006 A Coruña, Spain.
² CHUF, Complejo Hospitalario Universitario de Ferrol, 15006 A Coruña, Spain.
³ Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain.
⁴ CIBERNED (Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas), 28031 Madrid, Spain.
⁵ Hospital Universitari Mutua de Terrassa, 08221 Terrassa, Barcelona, Spain.
⁶ Clínica del Pilar, 08006 Barcelona, Spain.
⁷ Hospital Clínic de Barcelona, 08036 Barcelona, Spain.
⁸ Centro Neurológico Oms 42, 07003 Palma de Mallorca, Spain.
⁹ Consorci Sanitari Integral, Hospital Moisés Broggi, 08970 Sant Joan Despí, Barcelona, Spain.
¹⁰ Hospital Universitario Son Espases, 07120 Palma de Mallorca, Spain.
¹¹ Hospital Universitario Vall d'Hebron, 08035 Barcelona, Spain.
¹² Complejo Hospitalario Universitario de Pontevedra (CHOP), 36071 Pontevedra, Spain.
¹³ Hospital Universitario La Princesa, 28006 Madrid, Spain.
¹⁴ Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain.
¹⁵ Consorci Sanitari Integral, Hospital General de L'Hospitalet, L'Hospitalet de Llobregat, 08906 Barcelona, Spain.
¹⁶ Hospital Universitario Clínico San Carlos, 28040 Madrid, Spain.
¹⁷ Hospital Da Costa, 27880 Burela, Lugo, Spain.
¹⁸ Hospital del Mar, 08003 Barcelona, Spain.
¹⁹ Hospital Universitario Virgen Macarena, 41009 Sevilla, Spain.
²⁰ Hospital Infanta Sofía, 28703 Madrid, Spain.
²¹ Institut d'Assistència Sanitària (IAS)-Institut Català de la Salut, 17190 Girona, Spain.
²² Hospital General Universitario de Elche, 03203 Elche, Spain.
²³ Fundación Hospital de Alcorcón, 28922 Madrid, Spain.
²⁴ Hospital de Tortosa Verge de la Cinta (HTVC), Tortosa, 43500 Tarragona, Spain.
²⁵ Complejo Asistencial Universitario de Burgos, 09006 Burgos, Spain.
²⁶ Hospital Universitario de Canarias, 38320 San Cristóbal de la Laguna, Santa Cruz de Tenerife, Spain.
²⁷ Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain.
²⁸ Hospital Universitario Puerta de Hierro, 28222 Madrid, Spain.
²⁹ Hospital Álvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo (CHUVI), 36213 Vigo, Spain.
³⁰ Complejo Hospitalario de Toledo, 45004 Toledo, Spain.
³¹ Complejo Hospitalario de Navarra, 31008 Pamplona, Spain.
³² Hospital de Sant Pau, 08041 Barcelona, Spain.
³³ Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
³⁴ Hospital Universitario Donostia, 20014 San Sebastián, Spain.
³⁵ Hospital Arnau de Vilanova, 46015 Valencia, Spain.
³⁶ Hospital Ruber Internacional, 28034 Madrid, Spain.
³⁷ Hospital de Cabueñes, 33394 Gijón, Spain.
³⁸ Hospital Universitario Lucus Augusti (HULA), 27003 Lugo, Spain.
³⁹ Hospital Rey Juan Carlos, 28933 Madrid, Spain.
⁴⁰ Complejo Hospitalario Universitario de Orense (CHUO), 32005 Orense, Spain.
⁴¹ University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract

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.

Keywords: Parkinson’s disease; burden; follow-up; motor fluctuations; non-motor symptoms.

Grants and funding

Santos García D. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, and Teva. 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. Martínez Miró C.: None. Suárez Castro E.: None. Canfield H.: 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). Aguilar M.: UCB and Schwabe with assistance to a Congress; Nutricia with assistance to a Congress and payment of lecture. Pastor P.: None. 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, Italfármaco, 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, 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 from Abbvie, Allergan, and Boston; and lecturing honoraria from 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 also 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, 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 italofarma, Krka, Genzyme, UCB, Esteve, Psyma iberica marketing research SL, and Ferrer; a 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 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.