Authors :
Presenting Author: Viet-Huong Nguyen, PharmD, MPH, MS – Chapman University School of Pharmacy, Irvine, CA, USA
Reyna Duron, MD – Universidad Tecnologica Centroamericana, Tegucigalpa, Honduras
Iris E. Martinez-Juarez, MD – Epilepsy Clinic, ABC Medical Center, National Institute of Neurology and Neurosurgery, Mexico City, Mexico
Alison Dolce, MD – University of Texas at Southwestern Medical Center, Dallas, TX, USA
Maher Riad Arabi, MD – 8. Comprehensive Epilepsy Program, Ibn Sina Hospital, Kuwait
Deborah Holder, MD – Children’s Hospital Los Angeles, Los Angeles, CA, USA
Andrew Kim, MD – Children’s Hospital Los Angeles, Los Angeles, CA, USA
Arthur Partikian, MD – Los Angeles General Medical Center, USC Keck School of Medicine, Los Angeles, CA, USA
Nancy McNamara, MD – Corewell Health William Beaumont University Hospital, Royal Oak, MI
Julia Henry, MD – University of Chicago, Chicago, IL, USA
Esther Tantsis, MD – Children’s Hospital Westmead Australia
Rene Silva, MD – Hospital de Especialidades Nuestra Señora Reina de la Paz and Hospital Nacional San Juan de Dios, San Miguel, El Salvador
Mitchell Williams, MD – University of Chicago, Chicago, IL
Douglas Nordi III, MD – University of Chicago, Chicago, IL
Cesia Garrido, MD – Loma Linda University Health, Loma Linda, CA, USA
Alenoush Aramian, PharmD – Cedars-Sinai Medical Group
Berge Minassian, MD – University of Texas at Southwestern Medical Center
Jose-Maria Serratosa, MD, PhD – Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid
Antonio Delgado-Escueta, MD – David Geffen School of Medicine, UCLA
Rationale:
Lafora Disease (LD) is an ultra-rare, progressive, and fatal neurodegenerative disorder. LD is is frequently misdiagnosed as Juvenile Myoclonic Epilepsy (JME) during its early stages and typically not recognized until the disease is more advanced. Consequently, the initial manifestations of LD remain poorly characterized. As LD disease-modifying therapies may soon be available, earlier identification of patients who may be at risk for LD is needed. To facilitate earlier identification, this study aimed to ascertain and evaluate the earliest seizure phenotypes observed in patients with LD.
Methods:
Twenty-five genetically confirmed EPM2A and EPM2B LD patients were followed prospectively in an observational cohort study to describe LD natural history. Outcomes of interest were seizure phenotypes during first year of seizure onset and age of seizure onset. Outcomes were stratified by sibling-proband status to account for ascertainment and recall bias. Risk ratios with 95% confidence issues were calculated for seizure phenotypes. Fisher’s Exact Test was used to evaluate the association between sibling/proband status and seizure occurrence.Results:
The mean age of seizure onset was 9 years (sd 3.26, median 8.63 years) in the sibling group, 10.8 (sd 2.26, median 11.8 years) in the proband group, 10.1 (sd 2.78, median 11) in combined groups; 70% of the sibling group reported first seizures occurring prior to age 10 compared to 30% in the proband group (RR 3.5, p=0.03). The most common seizure phenotype reported in the first year of seizure onset was focal occipital visual seizures (FOVs); 80% of the sibling group and 67% of the proband group reported FOVs occurring in the first year of seizure onset (RR 1.2 [95% CI: 0.18-7.9], p=0.66). FOVs appeared earlier than other seizure types with mean age of onset at 8.3 years (sd 2.73) and 10.8 years (sd 2.78) in siblings and probands respectively. Tonic clonic seizures (TC) were reported in 50% of siblings 60% of probands (RR 0.83 [95% CI: 0.17-4.18, p=0.7]) with mean age of onset at 9.25 years (sd 2.64 ) and 11.9 years (sd1.17) respectively). Myoclonic seizures were reported in 40% and 53% of siblings and probands (mean age 11.75 (sd 3.01) and 12.3 years (sd 1.13)). Absence seizures (AS) were least likely to be reported in the first year of seizure onset (10% of reported siblings, 33 % of probands).
Conclusions:
Seizure onset in LD likely begins in childhood (< 10 years) contrary to what is currently reported in the literature. Seizure onset is likely to begin with FOVs in the first year as this seizure phenotype was observed to be the first or one of the first seizure phenotypes to manifest in the majority of patients. FOVs were less reported in probands where there is likely underascertainment at time of seizure onset due to underreporting, underdetection, or misclassification (e.g. migraine with visual aura). TCs can occur early or later in LD while MS and AS tended to appear later. As LD disease-modifying therapies may soon be available, assessing for presence of FOVs may be helpful in earlier identification of patients who may be at risk for LD.
Funding: none