Authors :
Presenting Author: Mohamad Mikati, MD – Duke University
Eleni Panagiotakaki, MD – University of Lyon
Lyndsey Prange, ARNP – Duke University
Maria Papadopoulou, MD – University of Lyon
Carmen Fons, MD – Sant Joan de Déu Children’s Hospital
Elisa De Grandis, MD – Istituto Giannina Gaslini, Genoa
Aikaterini Vezyroglou, MD – UCL NIHR BRC Great Ormond Street Institute of Child Health
Simona balestrini, MD – University College of London (UCL) Queen Square Institute of Neurology
Francesca Ragona, MD – IRCCS Foundation Carlo Besta Neurological Institute
Claudio Zucca, MD – Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini
Giacomo Garone, MD – Neurology, Epilepsy and Movement Disorders, Bambino Gesù Children's Hospital, IRCCS
Matthildi papathanasiou, MD – University of Lyon
Jennifer Anticona, MD – Sant Joan de Déu Children’s Hospital
Hwanhee Hong, PhD – Duke University
Beiyu Liu, PhD – Duke University
Sanjay Sisodiya, MD – University College of London (UCL) Queen Square Institute of Neurology
J. Helen Cross, MBChB, PhD – UCL-Great Ormond Street Institute of Child Health; Great Ormond Street Hospital
Alexis Arzimanoglou, MD – Barcelona Children’s Hospital San Juan de Dios, Universitat the Barcelona, Coordinator of the European Reference Network (ERN) EpiCARE
Shital Patel, MD – Duke University
Rosaria vavassori, PhD – Euro Mediterranean Institute of Science and Technology
Rationale: Approximately half of the patients with Alternating Hemiplegia of Childhood (AHC), a condition usually caused by
ATP1A3 mutations, have epilepsy. However, there are no prospective studies of the natural history of epilepsy, potentially related morbidities, mortality or of SUDEP in AHC. We investigated the following hypotheses: 1) Severity of epilepsy worsens with age. 2) Presence of epilepsy is associated with worse developmental status. 3) Mortality is high.
Methods: Prospective enrollment and follow-up of 115 consecutive AHC patients (0.4-24.4 yrs old) from 9 European/USA centers/5 countries, for
>1yr (range 1-3) using a rigorous, across-centers-standardized, protocol with multiple validated scales: Vineland-Adaptive-Behavior-Scales, Paroxysmal (hemiplegia/dystonia/associated spells) Index, Non-Paroxysmal Disability Index, Intellectual-Disability-Scale, Manual-Ability-Classification-System and Gross-Motor-Function-Scale (VAB, PDI, NPDI, IDS MACS, GMFCS,). For epilepsy severity an Epilepsy Severity Index (ESI), range 1-8 incorporating seizure and status epilepticus (SE) frequencies, was used. Statistics: Univariable and multivariable linear-mixed-effects models with random intercepts and random slopes for age, fitted to study the associations after adjusting for covariates including sex, epilepsy, historical PDI and NPDI at age 1-1.5 years, country and
ATP1A3 mutations. This is a powerful methodology which allows, with a follow-up of 1-3 yrs, determination of the effect of age throughout the total age range of patients studied- 0.4-24.4 yrs- while correcting for potential confounding variables.
Results: 67/115 (59%) had epilepsy, most commonly with focal and focal-to-bilateral tonic-clonic seizures. 26/67 (39%) had at least one episode of SE by the time of last follow-up. In the 67 patients ESI at baseline was 2.8 (SD: 2.2). Patients with E815K
ATP1A3 mutations had 1.57-units higher ESI than those with D801N (p=0.005) and 1.86-units higher than those with other mutations (p< 0.001). Multivariable analysis showed no change of epilepsy index within the above age range (p=0.83): ESI was 2.6 (SD: 2.0), 2.1 (SD: 1.4), and 2.2 (1.7) at 1-year, 2-year and 3-year follow-ups, respectively. 3/115 died and all had epilepsy: two died after SE and one from SUDEP. This constituted a mortality rate of