Abstracts

Early Recognition of Unique Neonatal Seizures Caused by KCNQ3 and SCN2A Mutations Helping Precision Medicine Therapy

Abstract number : 3.146
Submission category : 3. Neurophysiology / 3C. Other Clinical EEG
Year : 2021
Submission ID : 1825679
Source : www.aesnet.org
Presentation date : 12/9/2021 12:00:00 PM
Published date : Nov 22, 2021, 06:44 AM

Authors :
Juan Appendino, MD, CSCN (EEG), FAES - Alberta Children's Hospital; Judith Pijpers, MD – Resident, Department of Pediatric Neurology, Leiden University Medical Center, The Netherlands; Ping Y. Au, MD – Assistant Professor, Department of Medical Genetics, Alberta Children's Hospital; Linda de Vries, MD – Department of Neonatology – Leiden University Medical Center, The Netherlands; Elke Jacobs, MD – Pediatric Neurologist, Department of Pediatric Neurology, Erasmus Medical Center, The Netherlands; Liesbeth Smit, MD – Pediatric Neurologist, Department of Pediatric Neurology, Erasmus Medical Center, The Netherlands; Sylke Steggerda, MD – Department of Neonatology – Leiden University Medical Center, The Netherlands; Alla Vein, MD – Department of Clinical Neurophysiology – Leiden University Medical Center, The Netherlands; Ana Vilan, MD – Neonatologist, Department of Neonatology, University of Porto, Portugal; Lauren Weeke, MD – Neonatologist, Department of Neonatology, Erasmus Medical Center, The Netherlands; Cacha M.P.C. Peeters, MD – Department of Pediatric Neurology – Leiden University Medical Center, The Netherlands

Rationale: Early recognition of neonatal seizures secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications (ASM), but respond well to sodium channel blockers. Recently, a distinctive ictal amplitude-integrated electroencephalogram (aEEG) pattern was described in newborns with KCNQ2 mutations. In this descriptive study of neonatal seizures caused by SCN2A and KCNQ3 pathogenic variants, we report a similar (a)EEG pattern supporting the existing literature as well as adding regular EEG description; therefore expanding the utility of this unique pattern in clinical bedside management.

Methods: International multicentre descriptive study, reporting clinical characteristics, aEEG and conventional EEG findings of 9 newborns with seizures secondary to pathogenic variants in SCN2A and KCNQ3 genes.

Results: Seizures started in the first postnatal week. Seizure semiology typically included tonic posturing with apnea and desaturation. The aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral suppression in the conventional EEG at onset, followed by rhythmic discharges ending in several seconds of post-ictal amplitude attenuation. Interictally, aEEG and conventional EEG activity showed wide degree of findings, ranging from normal to severe encephalopathy. The majority of patients became seizure free upon initiation of a sodium channel blocker.

Conclusions: Neonatal seizures caused by SCN2A and KCNQ3 mutations can be recognized by a characteristic ictal aEEG pattern and clinical semiology previously reported only in KCNQ2-associated epilepsy, extending these unique features to other channelopathies. Awareness of this pattern facilitates the prompt initiation of targeted therapy with sodium channel blockers before genetic test results are available.

Funding: Please list any funding that was received in support of this abstract.: None.

Neurophysiology