Infantile Spasms in CDKL5 Deficiency Disorder: Delayed Treatment and Poor Response
Abstract number :
1.218
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2022
Submission ID :
2204846
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Heather Olson, MD, MS – Boston Children's Hospital; Caitlin Greene, BA – Boston Children's Hospital; Elia Pestana-Knight, MD – Epilepsy Center, Neurological Institute – Cleveland Clinic; Scott Demarest, MD – Pediatrics – Children's Hospital Colorado; Judith Weisenberg, MD – Pediatric Neurology – Washington University School of Medicine; Eric Marsh, MD, PhD – Child Neurology – Children’s Hospital of Philadelphia; Rajsekar Rajaraman, MD, MS – UCLA Mattel Children’s Hospital; Bernhard Suter, MD – Pediatrics and Neurology – Baylor College of Medicine; Akshat Katyayan, MD – Baylor College of Medicine; Ahsan Moosa, MD – Epilepsy Center, Neurological Institute – Cleveland Clinic; Carolyn Daniels, BA – Boston Children's Hospital; Michelle DeLeo, BA – Boston Children's Hospital; Isabel Haviland, MD – Boston Children's Hospital; Xiaoming Zhang, PhD – Cleveland Clinic; Lindsay Swanson, MS, CGC – Neurology – Boston Children's Hospital; Jamie Love-Nichols, MS, CGC – Boston Children's Hospital and Seattle Children's Hospital; Bo Zhang, PhD – Neurology – Boston Children's Hospital; Timothy Benke, MD, PhD – Children's Hospital Colorado; Chellamani Harini, MD – Neurology – Boston Children's Hospital; Annapurna Poduri, MD, MPH – Neurology – Boston Children's Hospital
Rationale: Epilepsy is refractory in CDKL5 deficiency disorder (CDD). We aimed to assess treatment response of IS in CDD compared to other etiologies.
Methods::We evaluated patients with IS onset from 2 months to 2 years from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC) who were treated with adrenocorticotropic hormone (ACTH), prednisolone, vigabatrin, and/or ketogenic diet. Due to known differential response to first-line medications for IS, we excluded children with Tuberous Sclerosis Complex, Trisomy 21, or unknown etiology with normal development. We compared time to treatment and clinical response (spasm freedom) at 14 days and 3 months.
Results: We evaluated 59 individuals with CDD (79% female, median spasms onset 6 months, interquartile range or IQR 3, 10 months) and 232 individuals from the NISC database (46% female, median spasms onset 7 months, IQR 5, 9 months) (Table 1). Seizures prior to IS were common in the CDD cohort (88%). Full hypsarrhythmia was reported as spasms onset in 14 (23%) of the CDD cohort and 118 (51%) of the NISC cohort. Initial treatment with ACTH, prednisolone, or vigabatrin was used within one month of IS onset in 27/59 (46%) of the CDD group and 182/232 (78%) of the NISC cohort (p< 0.0001). Short-term response to treatment was lower for the CDD group (26% by 14 days, 7/27, and 0 after 14 days) than for the NISC cohort (58% by 14 days, 106/182 and 10% after 14 days, 18/182) (p=0.0002, Figure 1). Day 14 clinical responses were higher with vigabatrin (3/ 7 with response) than hormonal treatments (4/ 20) in the CDD cohort, but failed to reach significance (p = 0.33). Sustained response at 3 months occurred in 1/27 (4%) of CDD patients vs. 96/182 (53%) of the NISC cohort (p< 0.0001). Comparable results were observed in patients treated with the same modalities after one month from IS onset or after any other treatment, with 13/58 (22%) in the CDD group and 46/82 (56%) in the NISC group with IS cessation (p< 0.001). Sustained response at 3 months occurred in 9% (5/58) of CDD patients vs. 51% (40/82 by 14 days, 2/82 after 14 days) (p < 0.0001). Ketogenic diet was used as initial treatment within 3 months of age of spasms onset in 5 individuals with CDD. Two of the 3 with known response had remission by 1 month, of whom 1 had sustained response at 3 months and for the other data was not available. Clinical remission of IS was reported with a non-standard therapy for IS at 2 to 4 weeks from initial goal dose in 7 individuals in the CDD cohort, including valproic acid (3), clobazam (2), topiramate (1), and purified cannabidiol (Epidiolex) in combination with ketogenic diet.
Clinical Epilepsy