Authors :
Presenting Author: Gia Melikishvili, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Shari Welch, Project Manager – Angelman Syndrome Foundation, Aurora, IL, United States.
Giorgi Mamardashvili, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Gvantsa Labadze, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Tekla Koberidze, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Otar Koniashvili, MD – Stony Brook Children’s Hospital, Stony Brook, New York, USA
Nazhi Tabatadze, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Mariam Melikishvili, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Tamar Gachechiladze, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Olivier Dulac, MD – AdPueriVitam, Antony, France.
Rationale:
Nonconvulsive status epilepticus (NCSE) affects up to 50% of individuals with Angelman syndrome (AS), often without overt seizures [1]. Undetected NCSE may underlie regression in communication, behavior, and motor function [2]. In 2022, we reported two siblings with AS and EEG-confirmed NCSE who improved dramatically with ketogenic therapy [3]. This prompted us to explore whether proactive EEG screening, guided by clinical changes, could enable timely treatment and prevent further deterioration.
Methods:
We prospectively studied six children with genetically confirmed AS. EEG recordings, neurological examination, and caregiver interviews focusing on attention, mood changes, sleep disturbances, and gait were performed every six months, as well as during episodes of clinical worsening or when seizure frequency exceeded the individual’s baseline. EEGs were recorded during both wakefulness and sleep using a standard bipolar montage. Patients identified with NCSE were treated with either a ketogenic diet (one patient) or levetiracetam at a dose of 30 mg/kg/day (two patients). The patient initially treated with the ketogenic diet was subsequently switched to levetiracetam due to lack of response. The patients, who showed no evidence of NCSE, did not receive any treatment.
Results:
Three out of six patients (50%) were diagnosed with NCSE. EEGs in these patients revealed continuous spike-wave discharges. In the remaining three, EEG showed the classical pattern of AS without evidence of NCSE [4]. Treatment with levetiracetam resulted in EEG normalization and marked clinical improvement in all patients with NCSE. In one case, NCSE was associated with increased seizure frequency, which returned to baseline following treatment.
Conclusions:
NCSE in AS may present solely as functional decline. Proactive EEG screening enables early detection and effective treatment. All children regained lost abilities, underscoring the reversibility of NCSE-related regression. Larger, multicenter studies are needed to confirm these findings and define best practices.
References:
- Worden L, et al. Diazepam for outpatient treatment of nonconvulsive status epilepticus in pediatric patients with Angelman syndrome. Epilepsy Behav 2018;82:74–80.
- Ohtsuka Y, et al. Relationship between severity of epilepsy and developmental outcome in Angelman syndrome. Brain Dev 2005;27(2):95–100.3.
- Melikishvili G, et al. Nonconvulsive status epilepticus in Angelman syndrome: rapid resolution following ketogenic diet. Seizure. 2022;97:43–47.
- Valente KD, et al. Angelman syndrome: difficulties in EEG pattern recognition and possible misinterpretations. Epilepsia. 2003;44(8):1051–1063.
Figure 1. EEG tracings.
(A, B, C) - Montage-longitudinal bipolar, Sensitivity 10mkv/mm; Speed 30 mm/s, LPF-0.5 Hz, HPF- 70hz.
(D)- Montage-longitudinal bipolar, Sensitivity 20mkv/mm; Speed 30 mm/s, LPF-0.5 Hz, HPF- 70hz.
(A) Patient 1, Female, 2 years 7 months, awake, Continuous spike-wave discharges.
(B) Patient 2, Female, 5 years 7 months, Continuous spike-wave discharges.
(C, D) Patient 3, Female, 2 years 2 months, Continuous spike-wave discharges.
Funding: None.