Clinical and neurophysiologic profile of Duchenne and Becker muscular dystrophy patients with seizures.



Poster Number: T338


Sreenath Thati Ganganna, MBBS, MD, University Of Iowa Stead Family Children's Hospital, Victoria Vivtcharenko, MD, University of Iowa Hospitals and Clinics, Erin Neil Knierbein, DO, University of Michigan, CS Mott Children's Hospital, Giulia Benedetti, MD, University of Michigan, CS Mott Children's Hospital, Katherine Mathews, MD, FAAN, University of Iowa

Objective: Duchenne (DMD) and Becker (BMD) muscular dystrophies are caused by mutations in the DMD gene encoding dystrophin. Dystrophin isoforms are present in muscle, retina, and brain. Previous reports describe the coexistence of DMD/BMD and seizures. We systematically evaluated seizure, electroencephalogram (EEG) characteristics, and DMD mutations in individuals with DMD/BMD and seizures.

Methods: After IRB approval, subjects were identified through electronic medical records (EMR) searches at University of Iowa and University of Michigan. Inclusion criteria included DMD mutation, > 1 seizure (provoked or unprovoked) between 2008 and 2021 (Iowa) and 1998 – 2022 (Michigan). Clinical data extracted from the EMR included age, epilepsy and medical history, anti-seizure medications (ASM), and EEG results.

Results: Nine DMD/BMD individuals were identified, 6 (66%) with DMD. DMD mutations of these patients: deletions (exons 52, 45 [2 patients], 45-53, 5 and 3-4), duplications (exons 46-37 and 50-55) and one frameshift variant in exon 59. Two individuals had risk factors for epilepsy: one with neonatal hypoxic ischemic encephalopathy, and another had a prior febrile seizure. Age at first unprovoked seizure was 3- 26 years. Three (34%) had pharmaco-resistant epilepsy. Seizure semiology was generalized tonic-clonic (5; 55%), focal impaired awareness (2; 22%), focal to bilateral tonic-clonic (3; 34%), and unclassifiable (1;11). Levetiracetam was the most common ASM prescribed (7; 77%). Four individuals (44%) had generalized epileptiform discharges on EEG, and 2 (40%) had focal epileptiform discharges. Intracranial EEG monitoring in 1 subject showed right temporal lobe seizures treated with lobectomy and ketogenic diet.

Conclusion: Individuals with DMD/BMD can have comorbid intractable epilepsy. We did not identify consistent seizure semiology or EEG features in this series. The distribution of mutations was broad and not weighted toward those that disrupt all brain DMD isoforms. Similar analysis of larger series might clarify any genotype phenotype relationships.