Efficacy and Safety of Ketogenic Diet Initiation Before Age 6 Months in CDKL5 Deficiency Disorder
Abstract number :
3.228
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2022
Submission ID :
2204962
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
Elia Pestana, MD – Cleveland Clinic; Better Kline, RD – dietician, Epilepsy Center, Cleveland Clinic; Xiaoming Zhang, RC – researcher coordinator, Epilepsy Center, Cleveland Clinic; Honglian Huang, RC – research coordinator, Epilepsy Center, Cleveland Clinic; Abby Opher, RD – dietician, Epilepsy Center, Cleveland Clinic; Ahsan Moosa Naduvil, MD – staff physician, Epilepsy Center, Cleveland Clinic
Rationale: The ketogenic diet (KD) is a well-known treatment for medically refractory seizures in children with CDKL5 Deficiency Disorder (CDD). Although the effects of the KD in seizure control and development are variable from patient to patient, there is a consensus that KD should be included in the treatment paradigm of these patients. The KD is typically initiated for refractory infantile spasms or when other seizure types are refractory to antiseizure medications (ASMs). The initiation of the KD before age 6 months in infants with CDD has not been reported. We report the experience of the Cleveland Clinic CDD Center of Excellence in early KD initiation, tolerability and treatment, and developmental response during the initial 3 months on the KD.
Methods: We included infants with CDD who had KD initiated before age 6 months at our institution. All infants had confirmed pathogenic mutation in the CDKL5 gene. KD initiation was done in the hospital during a video-EEG admission. All patients were started at the ratio 1:1 with daily advancement of the diet based on tolerability and lack of side effects to a 3:1 ratio or until ketosis was achieved based on serum Beta Hydroxybutyrate (BHB) >2mmol/L . Seizure outcome and development was assessed in the KD and epilepsy clinic thereafter. Side effects during KD initiation and at follow-up were reported. We report outcome at 3 months, and the last follow up after the KD initiation.
Results:Six infants from our cohort had KD initiation before age 6 months. Three infants were excluded as the KD was initiated in another hospital and details of the KD induction are unknown. Genotype, electroclinical, and treatment with ASMs are included in Table 1. Table 2 shows the age and seizure type at KD initiation, diet formulation, time to ketosis, BHB, side effects and KD ratio at discharge from the hospital. KD was initiated via the oral route in all patients. Nutritional status was normal in all patients prior to KD initiation. One child experienced asymptomatic hypoglycemia and one had metabolic acidosis with anion gap that did not lead to diet discontinuation.
At 3 months follow up, the KD ratio was 2:1 in 2 infants and 2.5:1 in another. BHB raged from 2.75 to 7.62mmol/L. No side effects to KD were reported in any infant. Seizures were reduced from daily to weekly or monthly. One patient entered honeymoon. ASM were reduced in all the infants. All infants gained milestones in the initial 3 months of the diet. Currently 2/3 children are still on the KD. One patient (case 2) discontinued the KD due to worsening epileptic encephalopathy with regression at age 2 years.
Conclusions: Early introduction of KD was well tolerated in infants with CDD. Side effects were minor and did not lead to discontinuation of the KD. KD diet led to a reduction of seizures, developmental gains and reduction of ASMs. Long term, KD was well tolerated, and 2/3 patients are still benefiting from it. KD should be considered earlier in the treatment algorithm of infants with CDD.
Funding: None
Clinical Epilepsy