Seizures in the Leukodystrophies Analyzed by Diagnosis and Pathogenetic Mechanism
Abstract number :
3.35
Submission category :
4. Clinical Epilepsy / 4D. Prognosis
Year :
2024
Submission ID :
457
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Ashley Hackett, MD – Emory University, University of Texas Southwestern
Helena Yan, MD – Weill Cornell Medicine
Katie Liu, MSPH – Emory University
Camille Corre, MD – University of Rochester Medical Center
Kerry Gao, BA – Weill Cornell/New York Presbyterian
Chloe Grzyb, BS – University of Pittsburgh
Jordan Goodman, MS – Johns Hopkins University School of Medicine
Daniel Kelly, BS – Harvard Medical School, Massachusetts General Hospital
Cassandra Ingemansson, MSN, FNP-C – University of California, Davis
Gabrielle Ghabash, MD – University of Utah School of Medicine
Kerry DiBenardo, BA – Emory University
Gerald Raymond, MD – Johns Hopkins University School of Medicine
William Benko, MD – University of California, Davis
Robert Thompson-Stone, MD – University of Rochester Medical Center
Ali Fatemi, MD, MBA – Johns Hopkins University School of Medicine
Florian Eichler, MD – Harvard Medical School, Massachusetts General Hospital
Stephanie Keller, MD – Emory University
Joshua Bonkowsky, MD PhD – University of Utah School of Medicine, Primary Children’s Hospital,
Maria Escolar, MD, MS – University of Pittsburgh
Eric Mallack, MD – Weill Cornell Medicine, Johns Hopkins University School of Medicine,
Rationale:
The pathogenesis of seizures and epilepsy in the leukodystrophies are poorly understood. This multisite study aimed to understand the difference in seizure prevalence and anti-seizure medication effectiveness characterized by leukodystrophy diagnosis and pathogenetic mechanism; specifically the myelinopathies versus the astrocytopathies.
Methods: Retrospective data was extracted from patients 18 years or younger across eight pediatric health centers from January 1st 2013 to March 31st 2020. Patients were grouped by diagnosis and by cellular pathology as proposed by van der Knaap et al. 2017. Age, diagnosis, imaging features, EEG findings, and clinical variables related to seizures/epilepsy were obtained. Continuous variables were reported by median and interquartile ranges, analyzed by Wilcoxon rank sum test. Continuous variables reported by frequency and percentage, analyzed by the Pearson’s Chi-squared test and Fisher’s exact test. A level of significance of 0.05 was considered statistically significant.
Results: 706 patients were analyzed. Seizures occurred in 70% in patients with Canavan disease, 50% in Alexander disease, 36% in Vanishing White Matter Disease, 33% in Metachromatic leukodystrophy, 29% in Aicardi-Goutières, 27% in Krabbe, 27% in Pelizaeus-Merzbacher, 18% in X-linked Adrenoleukodystrophy. Two or more antiseizure medications were required in 50% of patients with Canavan disease, 25.3% of patients with Alexander disease, 11.6% of patients with Krabbe, 9.1% of patients with Pelizaeus-Merzbacher, 8% of patients with Metachromatic leukodystrophy, 6.2% of patients with X-linked Adrenoleukodystrophy, 5.9% of patients with Aicardi-Goutières. Seizures are more common in astrocytopathies (43%) compared to myelinopathies (27%, p=0.019). Focal epilepsy is more common than generalized in the astrocytopathies (67%) vs myelinopathies (28%, p=0.038). Antiseizure medication response was highest for lacosamide (80%), followed by levetiracetam (72%), zonisamide (67%), valproic acid (58%), clonazepam (58%), topiramate (56%), then clobazam (53%).
Conclusions:
Seizure burden and use of multiple antiseizure medications varied based on underlying leukodystrophy. Patients with an astrocytopathy were more affected by seizures overall, and more often went on to develop focal epilepsy than patients with a myelinopathy. Lacosamide, levetiracetam, and zonisamide demonstrated the highest overall response rates.
Funding: Funding was received from the Hunter’s Hope Foundation/Leukodystrophy Care Network to support this work
Clinical Epilepsy