Zhan Lim1, Kingsley Wong1, Heather E Olson2, Ann M Bergin2, Jenny Downs1,3, Helen Leonard1. 1. Telethon Kids Institute, University of Western Australia, West Perth, Western Australia, Australia. 2. Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, U.S.A. 3. School of Physiotherapy and Exercise Science, Curtin University, Perth, Western Australia, Australia.
Abstract
OBJECTIVE: Pathogenic variants involving the CDKL5 gene result in a severe epileptic encephalopathy, often later presenting with features similar to Rett syndrome. Cardinal features of epilepsy in the CDKL5 disorder include early onset at a median age of 6 weeks and poor response to antiepileptic drugs. The ketogenic diet (KD) was first introduced in the 1920s as a treatment option for refractory epilepsy in children. This study investigated use of the KD in the CDKL5 disorder and its influences on seizures. METHODS: The International CDKL5 Disorder Database, established in 2012, collects information on individuals with the CDKL5 disorder. Families have provided information regarding seizure characteristics, use, and side effects of the KD treatment. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided on patients attending Boston Children's Hospital. RESULTS: Data regarding KD use were available for 204 individuals with a pathogenic CDKL5 variant. Median age of inclusion in the database was 4.8 years (range = 0.3-33.9 years), with median age of 6 weeks (range = 1 day-65 weeks) at seizure onset. History of KD use was reported for 51% (104 of 204) of individuals, with a median duration of use of 17 months (95% confidence interval = 9-24). Changes in seizure activity after commencing KD were reported for two-thirds (69 of 104), with improvements in 88% (61 of 69). Nearly one-third (31.7%) experienced side effects during the diet. At ascertainment, only one-third (32%) remained on the diet, with lack of long-term efficacy as the main reason for diet cessation (51%, 36 of 70). SIGNIFICANCE: Benefits of KD in the CDKL5 disorder are in keeping with previous trials on refractory epilepsies. However, poor long-term efficacy remains as a significant barrier. In view of its side effect profile, KD administration should be supervised by a pediatric neurologist and specialist dietician. Wiley Periodicals, Inc.
OBJECTIVE: Pathogenic variants involving the CDKL5 gene result in a severe epilepticencephalopathy, often later presenting with features similar to Rett syndrome. Cardinal features of epilepsy in the CDKL5 disorder include early onset at a median age of 6 weeks and poor response to antiepileptic drugs. The ketogenic diet (KD) was first introduced in the 1920s as a treatment option for refractory epilepsy in children. This study investigated use of the KD in the CDKL5 disorder and its influences on seizures. METHODS: The International CDKL5 Disorder Database, established in 2012, collects information on individuals with the CDKL5 disorder. Families have provided information regarding seizure characteristics, use, and side effects of the KD treatment. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided on patients attending Boston Children's Hospital. RESULTS: Data regarding KD use were available for 204 individuals with a pathogenic CDKL5 variant. Median age of inclusion in the database was 4.8 years (range = 0.3-33.9 years), with median age of 6 weeks (range = 1 day-65 weeks) at seizure onset. History of KD use was reported for 51% (104 of 204) of individuals, with a median duration of use of 17 months (95% confidence interval = 9-24). Changes in seizure activity after commencing KD were reported for two-thirds (69 of 104), with improvements in 88% (61 of 69). Nearly one-third (31.7%) experienced side effects during the diet. At ascertainment, only one-third (32%) remained on the diet, with lack of long-term efficacy as the main reason for diet cessation (51%, 36 of 70). SIGNIFICANCE: Benefits of KD in the CDKL5 disorder are in keeping with previous trials on refractory epilepsies. However, poor long-term efficacy remains as a significant barrier. In view of its side effect profile, KD administration should be supervised by a pediatric neurologist and specialist dietician. Wiley Periodicals, Inc.
Authors: Heather E Olson; Scott T Demarest; Elia M Pestana-Knight; Lindsay C Swanson; Sumaiya Iqbal; Dennis Lal; Helen Leonard; J Helen Cross; Orrin Devinsky; Tim A Benke Journal: Pediatr Neurol Date: 2019-02-23 Impact factor: 3.372
Authors: William Hong; Isabel Haviland; Elia Pestana-Knight; Judith L Weisenberg; Scott Demarest; Eric D Marsh; Heather E Olson Journal: CNS Drugs Date: 2022-05-28 Impact factor: 6.497
Authors: Sam Amin; Marie Monaghan; Angel Aledo-Serrano; Nadia Bahi-Buisson; Richard F Chin; Angus J Clarke; J Helen Cross; Scott Demarest; Orrin Devinsky; Jenny Downs; Elia M Pestana Knight; Heather Olson; Carol-Anne Partridge; Graham Stuart; Marina Trivisano; Sameer Zuberi; Tim A Benke Journal: Front Neurol Date: 2022-06-20 Impact factor: 4.086
Authors: Eric H Kossoff; Beth A Zupec-Kania; Stéphane Auvin; Karen R Ballaban-Gil; A G Christina Bergqvist; Robyn Blackford; Jeffrey R Buchhalter; Roberto H Caraballo; J Helen Cross; Maria G Dahlin; Elizabeth J Donner; Orkide Guzel; Rana S Jehle; Joerg Klepper; Hoon-Chul Kang; Danielle A Lambrechts; Y M Christiana Liu; Janak K Nathan; Douglas R Nordli; Heidi H Pfeifer; Jong M Rho; Ingrid E Scheffer; Suvasini Sharma; Carl E Stafstrom; Elizabeth A Thiele; Zahava Turner; Maria M Vaccarezza; Elles J T M van der Louw; Pierangelo Veggiotti; James W Wheless; Elaine C Wirrell Journal: Epilepsia Open Date: 2018-05-21
Authors: Ara Ko; Da E Jung; Se H Kim; Hoon-Chul Kang; Joon S Lee; Seung T Lee; Jong R Choi; Heung D Kim Journal: Front Neurol Date: 2018-07-16 Impact factor: 4.003
Authors: Joseph D Symonds; Sameer M Zuberi; Kirsty Stewart; Ailsa McLellan; Mary O'Regan; Stewart MacLeod; Alice Jollands; Shelagh Joss; Martin Kirkpatrick; Andreas Brunklaus; Daniela T Pilz; Jay Shetty; Liam Dorris; Ishaq Abu-Arafeh; Jamie Andrew; Philip Brink; Mary Callaghan; Jamie Cruden; Louise A Diver; Christine Findlay; Sarah Gardiner; Rosemary Grattan; Bethan Lang; Jane MacDonnell; Jean McKnight; Calum A Morrison; Lesley Nairn; Meghan M Slean; Elma Stephen; Alan Webb; Angela Vincent; Margaret Wilson Journal: Brain Date: 2019-08-01 Impact factor: 13.501