Alejandra Darling1, Cristina Tello2, María Josep Martí3, Cristina Garrido4, Sergio Aguilera-Albesa5, Miguel Tomás Vila6, Itziar Gastón7, Marcos Madruga8, Luis González Gutiérrez9, Julio Ramos Lizana10, Montserrat Pujol11, Tania Gavilán Iglesias12, Kylee Tustin13, Jean Pierre Lin13, Giovanna Zorzi14, Nardo Nardocci14, Loreto Martorell15, Gustavo Lorenzo Sanz16, Fuencisla Gutiérrez17, Pedro J García18, Lidia Vela19, Carlos Hernández Lahoz20, Juan Darío Ortigoza Escobar1, Laura Martí Sánchez1, Fradique Moreira21, Miguel Coelho22, Leonor Correia Guedes23, Ana Castro Caldas24, Joaquim Ferreira22,23, Paula Pires24, Cristina Costa25, Paulo Rego26, Marina Magalhães27, María Stamelou28,29, Daniel Cuadras Pallejà30, Carmen Rodríguez-Blazquez31, Pablo Martínez-Martín31, Vincenzo Lupo2, Leonidas Stefanis28, Roser Pons32, Carmen Espinós2, Teresa Temudo4, Belén Pérez Dueñas1,33. 1. Unit of Pediatric Movement Disorders, Hospital Sant Joan de Déu, Barcelona, Spain. 2. Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, Centro de Investigación Príncipe Felipe, Valencia, Spain. 3. Neurology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomediques IDIBAPS. Barcelona, Catalonia, Centro de Investigación Biomédica en Red-Neurodegenerativas (CIBERNED), Madrid, Spain. 4. Pediatric Neurology Department, Centro Materno-Infantil Centro Hospitalario do Porto, Porto, Portugal. 5. Pediatric Neurology Department, Complejo Hospitalario de Navarra, Navarrabiomed, Pamplona, Spain. 6. Pediatric Neurology Department, Hospital Universitario Politécnico La Fe, Valencia, Spain. 7. Neurology Department, Complejo Hospitalario de Navarra, Pamplona, Spain. 8. Pediatric Neurology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain. 9. Pediatric Neurology Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. 10. Pediatric Neurology Department, Hospital Torrecárdenas, Almería, Spain. 11. Neurology Department, Hospital Santa María, Lérida, Spain. 12. Neurology Department, Hospital de Mérida, Extremadura, Spain. 13. Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 14. Department of Pediatric Neuroscience, Fondazione IRCCS "C. Besta", Milano, Italy. 15. Molecular Genetics Department, Hospital Sant Joan de Déu, Barcelona. CIBERER, Instituto de Salud Carlos III, Madrid, Spain. 16. Pediatric Neurology Department, Hospital Ramón y Cajal, Madrid, Spain. 17. Neurology Department, Complejo Asistencial Universitario de Palencia, Palencia, Spain. 18. Neurology Department, Fundación Jiménez Díaz, Madrid, Spain. 19. Neurology Department, Hospital de Alcorcón, Madrid, Spain. 20. Neurology Department, Hospital Central de Asturias, Oviedo, Spain. 21. Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. 22. Clinical Pharmacology Unit, Instituto de Medicina Molecular and Department of Neurosciences, Service of Neurology, Hospital Santa Maria, Lisboa, Portugal. 23. Laboratory of Clinical Pharmacology and Therapeutics, Lisbon Faculty of Medicine, Lisbon, Portual. 24. Neurology Department, Hospital de Santo Espirito, Ilha Terceira, Portugal. 25. Neurology Department, Hospital Fernando Fonseca, Lisboa, Portugal. 26. Pediatric Department, Hospital Central de Funchal, Funchal, Portugal. 27. Neurology Department, Centro Hospitalar Porto, Porto, Portugal. 28. Second Department of Neurology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 29. Parkinson's Disease and other Movement Disorders Department, HYGEIA Hospital, Athens, Greece. 30. Statistical Department, Sant Joan de Déu Fundation, Barcelona, Spain. 31. National Center of Epidemiology and CIBERNED, Institute of Health Carlos III, Madrid, Spain. 32. Pediatric Neurology Unit, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Hospital Agia Sofía, Athens, Greece. 33. CIBERER, Instituto de Salud Carlos III, Madrid, Spain.
Abstract
BACKGROUND: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration. METHODS: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs. RESULTS: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale. CONCLUSIONS: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing.
BACKGROUND: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration. METHODS: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs. RESULTS: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale. CONCLUSIONS: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing.
Authors: Randall D Marshall; Abigail Collins; Maria L Escolar; H A Jinnah; Thomas Klopstock; Michael C Kruer; Aleksandar Videnovic; Amy Robichaux-Viehoever; Colleen Burns; Laura L Swett; Dennis A Revicki; Randall H Bender; William R Lenderking Journal: Orphanet J Rare Dis Date: 2019-07-12 Impact factor: 4.123
Authors: Randall D Marshall; Abigail Collins; Maria L Escolar; H A Jinnah; Thomas Klopstock; Michael C Kruer; Aleksandar Videnovic; Amy Robichaux-Viehoever; Laura Swett; Dennis A Revicki; Randall H Bender; William R Lenderking Journal: Mov Disord Clin Pract Date: 2019-01-22
Authors: Thomas Klopstock; Maria L Escolar; Randall D Marshall; Belen Perez-Dueñas; Sarah Tuller; Aleksandar Videnovic; Feriandas Greblikas Journal: Clin Trials Date: 2019-05-06 Impact factor: 2.486