Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder

Journal of Neurodevelopmental Disorders

Scott T. Demarest¹  Andrea Fidell¹  Timothy A. Benke¹  Judith L. Weisenberg²  Alan K. Percy³  Cary Fu⁴  Jeffrey L. Neul⁴  Eric D. Marsh⁵  Bernhard Suter⁶  Isabel Haviland⁷  Annapurna Poduri⁷  Heather E. Olson⁷  Anne Marie M. Denny⁷  Lindsay C. Swanson⁷  Carolyn I. Daniels⁷  Caitlin A. Greene⁷  Ahsan N. Moosa⁸  Xiaoming Zhang⁸  Elia Pestana-Knight⁸ 

[1] Children’s Hospital Colorado, University of Colorado, School of Medicine;Department of Pediatric Neurology, Washington University School of Medicine;Department of Pediatrics, University of Alabama at Birmingham;Department of Pediatrics, Vanderbilt University Medical Center;Division of Child Neurology, Children’s Hospital of Philadelphia, Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania;Division of Child Neurology, Texas Children’s Hospital, Departments of Neurology and Pediatrics, Baylor College of Medicine;Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital;Epilepsy Center, Neurological Institute, Cleveland Clinic;

关键词: CDKL5 deficiency disorder;    Developmental encephalopathy;    Epileptic encephalopathy;    Ketogenic diet;    Vagus nerve stimulator;    Movement disorders;   

DOI  :  10.1186/s11689-021-09384-z

来源: DOAJ

【 摘 要 】

Abstract Background CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population. Methods We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders. Results The four most frequently prescribed anti-seizure medications were broad spectrum, prescribed in over 50% of individuals. While the goal was not to ascertain efficacy, we obtained data from 86 individuals regarding response to treatment, with 2-week response achieved in 14–48% and sustained 3-month response in 5–36%, of those with known response. Additional treatments for seizures included cannabis derivatives, tried in over one-third of individuals, and clinical trial medications. In combination with pharmacological treatment, 50% of individuals were treated with ketogenic diet for attempted seizure control. Surgical approaches included vagus nerve stimulators, functional hemispherectomy, and corpus callosotomy, but numbers were too limited to assess response. Nearly one-third of individuals received pharmacologic treatment for sleep disturbances, 13% for behavioral dysregulation and movement disorders, and 43% had gastrostomy tubes. Conclusions Treatment for neurologic features of CDD is currently symptom-based and empiric rather than CDD-specific, though clinical trials for CDD are emerging. Epilepsy in this population is highly refractory, and no specific anti-seizure medication was associated with improved seizure control. Ketogenic diet is commonly used in patients with CDD. While behavioral interventions are commonly instituted, information on the use of medications for sleep, behavioral management, and movement disorders is sparse and would benefit from further characterization and optimization of treatment approaches. The heterogeneity in treatment approaches highlights the need for systematic review and guidelines for CDD. Additional disease-specific and disease-modifying treatments are in development.

【 授权许可】

Unknown