Eeg-driven Insights into SYNGAP1 Developmental and Epileptic Encephalopathy: Bridging Biomarkers and Therapeutic Targets
Abstract number :
2.531
Submission category :
3. Neurophysiology / 3C. Other Clinical EEG
Year :
2024
Submission ID :
1443
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Joshua Chang, MD – University of Chicago
Mohamed Taha, MD – University of Chicago
Douglas Nordli, MD – University of Chicago
Douglas Nordli, MD – University of Chicago
Rationale:
The EEG signature of SYNGAP1 developmental and epileptic encephalopathy (DEE) is an emerging focus due to its distinctive electroclinical features. These include drug-resistant seizures of various types, such as eyelid myoclonia with absence and eating-induced seizures. Additionally, patients often experience significant developmental delays. As with other DEEs, treatment aims not only at controlling seizures but also at preserving neurodevelopment. This study specifically explores the natural evolution of EEG patterns in SYNGAP1-DEE and aims to identify biomarkers that can guide treatment strategies.Methods:
We identified four patients with pathogenic SYNGAP1 variants and conducted a detailed analysis of their EEG findings. For each patient, we examined background activity, interictal and ictal features, and documented their seizure control, neurocognitive status, and concurrent therapies. These analyses were then systematically compared.Results:
Common findings across all patients included background disorganization and slowing, along with degradation of sleep structures on quantitative sleep EEG analysis (qEEG). Younger patients exhibited occipital intermittent rhythmic delta activity (OIRDA), which evolved into biparietal theta as they aged. Occipitally predominant interictal epileptiform discharges (IEDs) also increased with age. Eye closure sensitivity was observed in all patients. In two cases, slow eye closure triggered eyelid myoclonia with atypical absence seizures. The oldest patient experienced eating-induced atypical absence, characterized by occipitally predominant spike-and-wave discharges that crescendoed into a generalized pattern. The youngest patient, who began Perampanel at age two, showed neurocognitive improvement despite only modest seizure reduction. Serial EEGs revealed the natural evolution mentioned above, along with significant improvement in the asleep background. An association between cognitive delay and qEEG sleep analysis was observed. Specifically, a patient with a normal sleep background had mild cognitive delay, while another with infrequent seizures but significant cognitive delay exhibited a markedly abnormal sleep background.Conclusions:
SYNGAP1-DEE is a distinct condition with identifiable EEG biomarkers that differentiate it from unspecified DEE. These biomarkers provide an opportunity to conduct focused studies that explore the syndrome's response to various therapies, as well as its long-term outcomes. In our review, common features included background slowing and disorganization, occipitally predominant IEDs, OIRDA evolving into biparietal theta, and eye closure sensitivity. An association between qEEG FFT spectrogram analysis and cognitive disability was also observed. This review represents an initial step in addressing an important question, as further understanding of the unique EEG signature of SYNGAP1 could lead to improved seizure control and proactive management aimed at optimizing neurocognitive development.Funding: No funding to report.
Neurophysiology