Bianca M L Stelten1, Maria Teresa Dotti2, Aad Verrips3, Bülent Elibol4, Tzipora C Falik-Zaccai5,6, Kate Hanman7, Andrea Mignarri8, Belina Sithole9, Robert D Steiner10,11, Surabhi Verma12, Gilad Yahalom13,14, Tanyel Zubarioglu15, Fanny Mochel16, Antonio Federico17. 1. Department of Neurology, Catharina Hospital, Eindhoven, The Netherlands. bianca.stelten@catharinaziekenhuis.nl. 2. Department of Medicine, Surgery and Neurosciences, Medical School, University of Siena and UO Clinical Neurology and Neurometabolic Diseases, AOU Senese, Siena, Italy. 3. Department of Neurology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands. 4. Hacettepe University Medical Faculty Hospital, Ankara, Turkey. 5. Institute of Human Genetics, Galilee Medical Center, Naharia, Israel. 6. The Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel. 7. Costello Medical, London, UK. 8. UO Clinical Neurology and Neurometabolic Diseases, AOU Senese, Siena, Italy. 9. Costello Medical, Manchester, UK. 10. University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 11. Marshfield Clinic Health System, Marshfield, WI, USA. 12. Leadiant Biosciences Ltd., London, UK. 13. Shaare Zedek Medical Center, Jerusalem, Israel. 14. Sheba Medical Center, Ramat Gan, Israel. 15. Division of Pediatric Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey. 16. Reference Center for Adult Neurometabolic Diseases, Department of Genetics, La Pitié-Salpêtrière University Hospital, Paris, France. 17. Department of Medicine, Surgery and Neurosciences, Medical School, University of Siena, Siena, Italy.
Abstract
BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established. AIM: To assess expert opinion on best care practices for patients with CTX using a modified Delphi method. METHODS: A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of ≥ 70% Delphi panellists selecting 1-2 (disagreement) or 5-6 (agreement) for 6-point Likert scale questions, or ≥ 70% Delphi panellists choosing the same option for ranking and proportion questions. RESULTS: Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients' care. CONCLUSIONS: The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.
BACKGROUND:Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established. AIM: To assess expert opinion on best care practices for patients with CTX using a modified Delphi method. METHODS: A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of ≥ 70% Delphi panellists selecting 1-2 (disagreement) or 5-6 (agreement) for 6-point Likert scale questions, or ≥ 70% Delphi panellists choosing the same option for ranking and proportion questions. RESULTS: Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients' care. CONCLUSIONS: The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.