Jetan H Badhiwala1, Brij Karmur2, Lior M Elkaim3, Naif M Alotaibi1, Benjamin R Morgan2, Nir Lipsman1,4, Philippe De Vloo1,5, Suneil K Kalia1,5, Andres M Lozano1,5, George M Ibrahim1,6. 1. 1Division of Neurosurgery, Department of Surgery, and. 2. 2Faculty of Medicine, University of Toronto, Toronto, Ontario. 3. 3Faculty of Medicine, Université de Montréal, Montréal, Québec. 4. 4Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto, Ontario. 5. 5Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario; and. 6. 6Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: Although deep brain stimulation (DBS) is an accepted treatment for childhood dystonia, there is significant heterogeneity in treatment response and few data are available to identify ideal surgical candidates. METHODS: Data were derived from a systematic review and individual patient data meta-analysis of DBS for dystonia in children that was previously published. Outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale for movement (BFMDRS-M) and for disability (BFMDRS-D). The authors used partial least squares, bootstrapping, and permutation statistics to extract patterns of contributions of specific preoperative characteristics to relationship with distinct outcomes, in all patients and in patients with primary and secondary dystonia separately. RESULTS: Of 301 children undergoing DBS for dystonia, 167 had primary dystonia, 125 secondary dystonia, and 9 myoclonus dystonia. Three dissociable preoperative phenotypes (latent variables) were identified and associated with the following: 1) BFMDRS-M at last follow-up; 2) relative change in BFMDRS-M score; and 3) relative change in BFMDRS-D score. The phenotype of patients with secondary dystonia, with a high BFMDRS-M score and truncal involvement, undergoing DBS at a younger age, was associated with a worse postoperative BFMDRS-M score. Children with primary dystonia involving the trunk had greater improvement in BFMDRS-M and -D scores. Those with primary dystonia of shorter duration and proportion of life with disease, undergoing globus pallidus DBS, had greater improvements in BFMDRS-D scores at long-term follow-up. CONCLUSIONS: In a comprehensive, data-driven, multivariate analysis of DBS for childhood dystonia, the authors identified novel and dissociable patient phenotypes associated with distinct outcomes. The findings of this report may inform surgical candidacy for DBS.
OBJECTIVE: Although deep brain stimulation (DBS) is an accepted treatment for childhood dystonia, there is significant heterogeneity in treatment response and few data are available to identify ideal surgical candidates. METHODS: Data were derived from a systematic review and individual patient data meta-analysis of DBS for dystonia in children that was previously published. Outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale for movement (BFMDRS-M) and for disability (BFMDRS-D). The authors used partial least squares, bootstrapping, and permutation statistics to extract patterns of contributions of specific preoperative characteristics to relationship with distinct outcomes, in all patients and in patients with primary and secondary dystonia separately. RESULTS: Of 301 children undergoing DBS for dystonia, 167 had primary dystonia, 125 secondary dystonia, and 9 myoclonus dystonia. Three dissociable preoperative phenotypes (latent variables) were identified and associated with the following: 1) BFMDRS-M at last follow-up; 2) relative change in BFMDRS-M score; and 3) relative change in BFMDRS-D score. The phenotype of patients with secondary dystonia, with a high BFMDRS-M score and truncal involvement, undergoing DBS at a younger age, was associated with a worse postoperative BFMDRS-M score. Children with primary dystonia involving the trunk had greater improvement in BFMDRS-M and -D scores. Those with primary dystonia of shorter duration and proportion of life with disease, undergoing globus pallidus DBS, had greater improvements in BFMDRS-D scores at long-term follow-up. CONCLUSIONS: In a comprehensive, data-driven, multivariate analysis of DBS for childhood dystonia, the authors identified novel and dissociable patient phenotypes associated with distinct outcomes. The findings of this report may inform surgical candidacy for DBS.
Entities:
Keywords:
BFMDRS-D = Burke-Fahn-Marsden Dystonia Rating Scale for disability; BFMDRS-M = BFMDRS for movement; DBS = deep brain stimulation; GPi = globus pallidus internus; IPD = individual patient data; LV = latent variable; PKAN = pantothenate kinase–associated neurodegeneration; PLS = partial least squares; SVD = singular-value decomposition; clinical outcomes; deep brain stimulation; dystonia; functional neurosurgery; movement disorders; neuromodulation
Authors: Ethan G Brown; Ian O Bledsoe; Nijee S Luthra; Svjetlana Miocinovic; Philip A Starr; Jill L Ostrem Journal: Mov Disord Clin Pract Date: 2020-01-08