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Seizure initiation in infantile spasms vs. focal seizures: proposed common cellular mechanisms
Roger D Traub1,2, Friederike Moeller3, Richard Rosch4
1IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
Insights
This study explores infantile spasms (IS) and focal seizures, finding shared EEG patterns but distinct evolutions. A unifying hypothesis emphasizes brain pH in explaining these seizure differences.
Area of Science:
- Neuroscience
- Epileptology
- Computational Biology
Background:
- Infantile spasms (IS) and focal onset seizures present distinct clinical features despite potential overlapping EEG findings.
- Identical pathologies can manifest as IS in younger patients and focal seizures in older individuals, suggesting age-dependent mechanisms.
- Understanding the cellular basis of seizure initiation is crucial for differentiating these epilepsy types.
Purpose of the Study:
- To investigate the similarities and differences in cellular mechanisms underlying seizure initiation in infantile spasms versus focal seizures.
- To correlate specific electroencephalography (EEG) patterns with underlying cellular processes in different seizure types.
- To propose a unifying mechanistic hypothesis for EEG signal variations in IS and focal seizures.
Main Methods:
- Analysis of common and distinct electroencephalography (EEG) features in infantile spasms (IS) and focal seizures.
- Utilizing in vitro data to elucidate cellular mechanisms for observed EEG patterns, including delta waves, very fast oscillations (VFO), electrodecrements (ED), and seizure bursts.
- Developing a mechanistic hypothesis to explain the observed EEG differences based on cellular activity and brain pH.
Main Results:
- Common EEG features include alpha-delta background, electrodecrement (ED), and preceding very fast oscillations (VFO).
- Infantile spasms show VFO coinciding with spasms, followed by ED reverting to slow waves.
- Focal seizures exhibit ED evolving into electrographic seizures with high-amplitude bursts and superimposed VFO.
Conclusions:
- A unifying mechanistic hypothesis, highlighting the role of brain pH, can explain the shared and divergent EEG characteristics of IS and focal seizures.
- Cellular mechanisms elucidated through in vitro studies provide insights into the generation of specific EEG patterns observed in different seizure types.
- Further research into brain pH regulation may offer novel therapeutic targets for epilepsy management.
Abstract:
Infantile spasms (IS) and seizures with focal onset have different clinical expressions, even when electroencephalography (EEG) associated with IS has some degree of focality. Oddly, identical pathology (with, however, age-dependent expression) can lead to IS in one patient vs. focal seizures in another or even in the same, albeit older, patient. We therefore investigated whether the cellular mechanisms underlying seizure initiation are similar in the two instances: spasms vs. focal. We noted that in-common EEG features can include (i) a background of waves at alpha to delta frequencies; (ii) a period of flattening, lasting about a second or more - the electrodecrement (ED); and (iii) often an interval of very fast oscillations (VFO; ~70 Hz or faster) preceding, or at the beginning of, the ED. With IS, VFO temporally coincides with the motor spasm. What is different between the two conditions is this: with IS, the ED reverts to recurring slow waves, as occurring before the ED, whereas with focal seizures the ED instead evolves into an electrographic seizure, containing high-amplitude synchronized bursts, having superimposed VFO. We used in vitro data to help understand these patterns, as such data suggest cellular mechanisms for delta waves, for VFO, for seizure-related burst complexes containing VFO, and, more recently, for the ED. We propose a unifying mechanistic hypothesis - emphasizing the importance of brain pH - to explain the commonalities and differences of EEG signals in IS versus focal seizures.
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