Authors :
Presenting Author: Pauline Brandon Bravo Bruinsma, BS – Boston Children's Hospital
Aris Hadjinicolaou, MD – Division of Epilepsy and Clinical Neurophysiology – Boston Children’s Hospital; Rajsekar Rajaraman, MD – UCLA Mattel Children's Hospital; Shaun Hussain, MD – UCLA Mattel Children's Hospital; Darcy Krueger, MD, PhD – ] Division of Neurology, Department of Pediatrics – Cincinnati Children's Hospital Medical Center; Mustafa Sahin, MD, PhD – Division of Epilepsy and Clinical Neurophysiology – Boston Children’s Hospital; Hope Northrup, MD – Division of Medical Genetics, Department of Pediatrics – University of Texas Medical School at Houston; Brenda Porter, MD – ] Lucile Packard Children’s Hospital; Joyce Wu, MD – Division of Neurology & Epilepsy – Lurie Children’s Hospital of Chicago; Martina Bebin, MD – Department of Neurology – University of Alabama at Birmingham; Jurriaan Peters, MD, PhD – Division of Epilepsy and Clinical Neurophysiology – Boston Children’s Hospital
Rationale:
Interictal epileptiform discharges (''spikes'') in surveillance EEGs predict impending epilepsy in children with tuberous sclerosis complex (TSC), offering an opportunity for preventive treatment. Vigabatrin is highly effective for Epileptic Spasms (ES) in TSC, but carries a risk of irreversible retinal toxicity. To potentially prevent unwarranted vigabatrin exposure in children who may not develop ES, we determined whether quantification of spikes in these pre-seizure EEGs can discriminate impending ES from other seizure types (non-ES).
Methods:
Prospective multicenter observational study for the TSC Autism Center of Excellence Research Network (TACERN) of 156 children with TSC. We identified 44 children with EEGs prior to seizure onset, however only 16 children had eligible EEG data after data retrieval, harmonization, and quality control. Stage II sleep was scored in each EEG file to capitalize on sleep-associated spike augmentation and reduced artifact. Spike annotation was performed using a hybrid approach of highly sensitive automated spike detection (Persyst 14) followed by independent expert review by two board-certified clinical neurophysiologists. We calculated two spike metrics: (1) spike rate (spikes per minute) and (2) number of unique spike foci defined as a consistent morphology, field and local maximum for five or more spikes per focus. Results:
Sixteen children with seizures had eligible EEG data, recorded at a median age of 139 days. These were age-matched to 16 EEGs from children who did not develop epilepsy for the duration of the TACERN study. Mean duration of total EEG recording was 57 minutes (range 40-90) and 24 minutes during stage II sleep (range 6-50). Seven children had EEG data at a mean of 52 days prior to onset of ES and nine had EEG data 67 days prior to non-ES seizures. There was no association between total duration of EEG recording and number of spike foci detected in sleep.
In the sixteen children with subsequent epilepsy, ES and non-ES seizure groups were separated by a spike rate threshold of ≥2/per minute during sleep (no false positives, two false negatives), or when a threshold of ≥2 foci was applied (one false positive, one false negative). Of the sixteen control patients, one was falsely predicted to develop ES.
When thresholding the spike rate and number of spike foci for the prediction of ES to minimize false positives (i.e., to avoid undue exposure to vigabatrin in cases who would falsely be predicted to develop ES), the combination of (1) spike rate threshold of ≥2 (per minute) and (2) spike focus threshold of ≥2 was associated with a positive predictive value of 100% for impending ES, although with two false negatives (Table 1).
Conclusions:
Our pilot study suggests higher spike rates and a higher number of independently active spike foci are each associated with an elevated risk for ES, as compared to other seizure types. This EEG marker would allow for tailored clinical decisions regarding preventative treatment of epilepsy in TSC, pending larger-scale validation. Funding:
NIH U01-NS082320, P20-NS080199