Seizures Characteristics of Individuals with Succinic Semialdehyde Dehydrogenase Deficiency: Results from a Multinational Longitudinal Study
Abstract number :
2.443
Submission category :
4. Clinical Epilepsy / 4D. Prognosis
Year :
2022
Submission ID :
2232905
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:28 AM
Authors :
Itay Tokatly Latzer, MD – Boston Children's Hospital; Melissa DiBacco, MD – Boston Children's Hospital; Thomas Opladen, MD – University Children’s Hospital Heidelberg; Kathrin Jeltsch, MD – University Children's Hospital Heidelberg; Natalia Juliá-Palacios, MD – Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain; Àngels García-Cazorla, MD – Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain; Deniz Aygun, BA – Boston Children's Hospital; Alexander Rotenberg, MD – Boston Children's Hospital; Jean-Baptiste Roullet, MD – Washington State University; Michael Gibson, MD – Washington State University; Phillip Pearl, MD – Boston Children's Hospital
This is a Late Breaking abstract
Rationale: Seizures represent a common yet under-described manifestation of succinic semialdehyde dehydrogenase deficiency (SSADHD). This study aimed to characterize their specific features and complex mechanisms that may contribute to their occurrence in this population.
Methods: This prospective multicenter and multinational case-control study involved cross-sectional and longitudinal evaluations of individuals with SSADHD over 5 years. These evaluations included a medical intake, neurological and developmental examinations, neuropsychological assessments, electroencephalogram (EEG), magnetic resonance imaging (MRI) and spectroscopy (MRS), transcranial magnetic stimulation (TMS), and serum measurements of γ-aminobutyrate (GABA), γ-hydroxybutyrate (GHB), glutamate, guanidinobutyrate (GBA) and other oxidative stress markers. The three institutions at which the clinical evaluations were conducted were Boston Children’s Hospital (BCH), University Children's Hospital Heidelberg (UCHH), and Universitat de Barcelona (UDB). Additional institutions that participated were Washington State University (WSU) which performed the bioanalytical analyses, and the University of South Florida (USF), which provided the biostatistical core.
Results: A total of 103 participants were included in the study: 61 individuals with SSADHD (54% females) and 42 controls, who were the parents or siblings of 19 of the SSADHD participants. Seizures were present in 49% of the study group, were predominately generalized tonic-clonic, and were significantly more common in individuals who were older (p=.001), diagnosed with autism (p=.04), and had lower plasma levels of GABA (p=.002), GBA (p=.003), and GHB (p=.02). Seizure-control was achieved in 63% of the study group and was significantly associated with having only one seizure type, a normal EEG, higher plasma GABA levels, and a higher posterior cingulate gyrus peak of NAA/GABA as measured by MRS. Lamotrigine and levetiracetam, given as monotherapies or in combination with other ASDs, most commonly led to seizure control. No specific genetic variants were associated with seizures, nor with GABA or GHB levels.
Conclusions: This National History Study of the largest SSADHD cohort studied thus far has enabled us to deepen our perspectives of specific seizure-related features that may have meaningful therapeutic implications for individuals with SSADHD. By correlations of neurophysiological, genetic, and biochemical data with the clinical outcomes, we have found the protective factors which are associated with epilepsy being better controlled. Additionally, by elucidating the details related to the timing of the decline of GABA and GHB levels in correlation with seizure onset, we have added information that further advances the efforts of developing novel therapeutic approaches for individuals with SSADHD.
Funding: The succinic semialdehyde dehydrogenase deficiency (SSADHD) Natural History Study is an NIH-sponsored study.
Clinical Epilepsy