Five Stages of Lafora Disease Epilepsy: Early Biomarkers Are Occipital Seizures and Suppression of EEG Polyspike Waves and REM During Sleep
Abstract number :
3.348
Submission category :
12. Genetics / 12A. Human Studies
Year :
2021
Submission ID :
1826519
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:55 AM
Authors :
Andrew Kim, MD - University of Southern California, CHLA; Antonio V. Delgado-Escueta, MD – Professor, Neurology, UCLA and VA GLAHS; Viet-Huong Nguyen, PharmD, MPH – Chapman University School of Pharmacy, Irvine, CA; Maher Riad Arabi, MD – Ibn Sina Hospital, Kuwait; Nancy McNamara, MD – University of Michigan Medicine, Ann Arbor, MI; Deborah Holder, MD – Children’s Hospital Los Angeles, Los Angeles, CA; Arthur Partikian, MD – LA County+USC Medical Center, Los Angeles, CA; Julia Henry, MD – University of Chicago Medicine and Biological Sciences, Chicago, IL; Esther Tantsis, MD – Children’s Hospital, Westmead, Australia; René Silva Somoza, MD – Hospital de Especialidades Nuestra Senora Reina de la Paz and Hospital Nacional San Juan de Dios, San Miguel, El Salvador; Cesia Garrido, MD – VA GLAHS; Reyna Durón, MD – Universidad Tecnológica Centroamericana (UNITEC), Tegucigalpa, Honduras; Alenoush Aramian, PharmD – VA GLAHS; Iris Martinez-Juárez, MD, MSc – National Institute of Neurology & Neurosurgery and ABC Medical Center, Mexico City, Mexico; Veronica Rivas-Alonso, MD – National Institute of Neurology & Neurosurgery, Mexico City, Mexico; Edmar Benitez-Alonso, MD – National Institute of Neurology & Neurosurgery, Mexico City, Mexico; Paul Shkurovich Bialik – ABC Medical Center, Mexico City, Mexico; Adriana Ochoa – National Institute of Neurology & Neurosurgery, Mexico City, Mexico; Aurelio Jara-Prado, PhD – National Institute of Neurology & Neurosurgery, Mexico City, Mexico; Julia Bailey, PhD – UCLA Fielding School of Public Health, Los Angeles, CA; Dawn Eliashiv, MD – Neurology – UCLA David Geffen School of Medicine, Los Angeles, CA; Antonio Delgado-Escueta, MD, PhD (Honoris Causa) – Professor in Residence, Neurology, UCLA David Geffen School of Medicine and VA GLAHS, Los Angeles, CA
Rationale: Correlate early EEG biomarkers with Clinical Disability Progression Scale (CDPS) in prospectively enrolled Lafora Disease (LD) Epilepsy patients (16 EPM2A, 6 EPM2B) from Stage I: Visual Seizures Only to Stage IV: Myoclonic Encephalopathy.
Methods: To identify the earliest seizures, we separated 8 younger siblings from 14 older probands. CDPS was measured in all 22 LD patients from 2016 to 2021. Spike wave indexes and sleep cycles/stages were analyzed in overnight Video-EEG (V-EEG) in 14 patients.
Results: We describe five clinical stages (Figs 1-2). Stage I: Visual Seizures Only (6-9 years): Six children (younger siblings, #2, 3, 6, 12, 18, 21) presented with colored circles, rectangles or rainbows at 6-9 years. In sibs #8 and #15 visual seizures, at 10-13 years, led to convulsions. Five of the 8 sibs, who had overnight V-EEG, showed loss of Rapid Eye Movement (REM) and loss of diffuse 3.5-6Hz polyspikes-slow waves (zero spike wave index) during N3 delta sleep. Stage II: Beginning Cognitive Decline (11.5-14 years): Six probands (#1, 4, 5, 10, 16, 17) had their first myoclonic-tonic-clonic convulsions as EEG PDR slowed to 7Hz, and Montreal Cognitive Assessment (MOCA) scores declined (22 to 26/30). Loss of REM and loss of diffuse polyspikes during N3 delta sleep continued in the same 5 younger sibs and in 5 of 6 probands. Stage III: Established Dementia and Status (15-18 years): At about 15 years of age, 15 patients (Fig 2) advanced to their first status epilepticus, as EEG PDR further slowed < 6Hz, and MOCA dropped < 21/30. V-EEGs continued to show loss of REM and diffuse polyspikes during sleep in 10 patients with progressing status, dementia and ataxia and deteriorating daily living functions. When
Genetics