Daniel Natera-de Benito1, Jordi Muchart2, Debora Itzep1, Carlos Ortez1, Lidia González-Quereda3, Pía Gallano3, Alia Ramirez4, Javier Aparicio4, Jana Domínguez-Carral4, Laura Carrera-García1, Jessica Expósito-Escudero1, Nathalia Pardo Cardozo1, Daniel Cuadras5, Anna Codina6, Cristina Jou6, Cecilia Jimenez-Mallebrera1, Francesc Palau7,8,9,10, Jaume Colomer1, Alexis Arzimanoglou4,11, Andrés Nascimento1, Victoria San Antonio-Arce4. 1. Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Hospital Sant Joan de Déu and CIBERER U703, Barcelona, Spain. 2. Department of Radiology, Hospital Sant Joan de Déu, Barcelona, Spain. 3. Department of Genetics, Hospital de la Santa Creu i Sant Pau and CIBERER U705, Barcelona, Spain. 4. Unit of Epilepsy, Sleep and Neurophysiology, Neuropaediatrics Department, Hospital Sant Joan de Déu, Barcelona, Spain. 5. Statistics Department, Fundació Sant Joan de Déu, Barcelona, Spain. 6. Department of Pathology, Hospital Sant Joan de Déu, Barcelona, Spain. 7. Department of Genetic and Molecular Medicine, Hospital Sant Joan de Déu, Barcelona, Spain. 8. Laboratory of Neurogenetics and Molecular Medicine, Institut de Recerca Sant Joan de Déu, Barcelona, Spain. 9. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. 10. Institute of Medicine and Dermatology, Hospital Clínic and Division of Pediatrics, University of Barcelona School of Medicine and Health Sciences, Barcelona, Spain. 11. Epileptology, Sleep Disorders and Functional Pediatric Neurology, Member of ERN-EpiCARE; HFME, Hospices Civils de Lyon, Bron, France.
Abstract
OBJECTIVE: To delineate the epileptic phenotype of LAMA2-related muscular dystrophy (MD) and correlate it with the neuroradiological and muscle biopsy findings, as well as the functional motor phenotype. METHODS: Clinical, electrophysiological, neuroradiological, and histopathological data of 25 patients with diagnosis of LAMA2-related MD were analyzed. RESULTS: Epilepsy occurred in 36% of patients with LAMA2-related MD. Mean age at first seizure was 8 years. The most common presenting seizure type was focal-onset seizures with or without impaired awareness. Visual aura and autonomic signs, including vomiting, were frequently reported. Despite a certain degree of variability, bilateral occipital or temporo-occipital epileptiform abnormalities were by far the most commonly observed. Refractory epilepsy was found in 75% of these patients. Epilepsy in LAMA2-related MD was significantly more prevalent in those patients in whom the cortical malformations were more extensive. In contrast, the occurrence of epilepsy was not found to be associated with the patients' motor ability, the size of their white matter abnormalities, or the amount of residual merosin expressed on muscle. SIGNIFICANCE: The epileptic phenotype of LAMA2-related MD is characterized by focal seizures with prominent visual and autonomic features associated with EEG abnormalities that predominate in the posterior quadrants. A consistent correlation between epileptic phenotype and neuroimaging was identified, suggesting that the extension of the polymicrogyria may serve as a predictor of epilepsy occurrence.
OBJECTIVE: To delineate the epileptic phenotype of LAMA2-related muscular dystrophy (MD) and correlate it with the neuroradiological and muscle biopsy findings, as well as the functional motor phenotype. METHODS: Clinical, electrophysiological, neuroradiological, and histopathological data of 25 patients with diagnosis of LAMA2-related MD were analyzed. RESULTS:Epilepsy occurred in 36% of patients with LAMA2-related MD. Mean age at first seizure was 8 years. The most common presenting seizure type was focal-onset seizures with or without impaired awareness. Visual aura and autonomic signs, including vomiting, were frequently reported. Despite a certain degree of variability, bilateral occipital or temporo-occipital epileptiform abnormalities were by far the most commonly observed. Refractory epilepsy was found in 75% of these patients. Epilepsy in LAMA2-related MD was significantly more prevalent in those patients in whom the cortical malformations were more extensive. In contrast, the occurrence of epilepsy was not found to be associated with the patients' motor ability, the size of their white matter abnormalities, or the amount of residual merosin expressed on muscle. SIGNIFICANCE: The epileptic phenotype of LAMA2-related MD is characterized by focal seizures with prominent visual and autonomic features associated with EEG abnormalities that predominate in the posterior quadrants. A consistent correlation between epileptic phenotype and neuroimaging was identified, suggesting that the extension of the polymicrogyria may serve as a predictor of epilepsy occurrence.
Authors: Alberto A Zambon; Deborah Ridout; Marion Main; Rachael Mein; Rahul Phadke; Francesco Muntoni; Anna Sarkozy Journal: Ann Clin Transl Neurol Date: 2020-09-10 Impact factor: 4.511