Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder: Experience of > 100 patients

Zhan Lim, Kingsley Wong, Heather E. Olson, Ann M. Bergin, Jenny Downs, Helen Leonard

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1415-1422
Number of pages8
JournalEpilepsia
Volume58
Issue number8
DOIs
Publication statusPublished - Aug 2017

Cite this

Lim, Zhan ; Wong, Kingsley ; Olson, Heather E. ; Bergin, Ann M. ; Downs, Jenny ; Leonard, Helen. / Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder : Experience of > 100 patients. In: Epilepsia. 2017 ; Vol. 58, No. 8. pp. 1415-1422.
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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.",
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Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder : Experience of > 100 patients. / Lim, Zhan; Wong, Kingsley; Olson, Heather E.; Bergin, Ann M.; Downs, Jenny; Leonard, Helen.

In: Epilepsia, Vol. 58, No. 8, 08.2017, p. 1415-1422.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder

T2 - Experience of > 100 patients

AU - Lim, Zhan

AU - Wong, Kingsley

AU - Olson, Heather E.

AU - Bergin, Ann M.

AU - Downs, Jenny

AU - Leonard, Helen

PY - 2017/8

Y1 - 2017/8

N2 - 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.

AB - 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.

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KW - CDKL5 disorder

KW - Refractory epilepsy

KW - Cyclin-dependent kinase-like 5 gene

KW - RANDOMIZED CONTROLLED-TRIAL

KW - CHILDHOOD EPILEPSY

KW - INFANTILE SPASMS

KW - CHILDREN

KW - MUTATIONS

KW - EFFICACY

KW - RETARDATION

KW - MECHANISMS

KW - BEHAVIOR

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DO - 10.1111/epi.13813

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JO - Epilepsia

JF - Epilepsia

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