Different Onset Patterns of Epileptic Seizures Have Different Mechanisms

At the beginning of an epileptic seizure, differing characteristics of brain tissue surrounding the seizure’s origin site may determine which of two main patterns of brain activity will be seen, according to a new study.

Electrical activity in the brain at the onset of an seizure in epilepsy usually follows either a “low amplitude fast” pattern or a “high amplitude slow” pattern.

Patients whose seizures follow the high amplitude slow pattern have a higher risk of continuing seizures after surgical treatment. However, the mechanisms underlying these different onset patterns are unclear.

Surrounding Tissue Excitability

To better understand the onset patterns, Yujiang Wang of Newcastle University, U.K., and colleagues used a previously developed computer model that can simulate brain activity at the start of a seizure. The model output suggested that the onset pattern of a seizure may be determined not by brain tissue at the site where the seizure originates, but by characteristics of the surrounding “healthy” brain tissue.

The simulation showed that the high amplitude slow pattern occurs when surrounding brain tissue has higher excitability; that is, the brain cells have a stronger response to stimulation and can react immediately to the initiation of a seizure. Meanwhile, the low amplitude fast pattern is associated with tissue of lower excitability, which is only slowly penetrated by seizure activity.

Effect of different parameters on seizure onset amplitude

Effect of different parameters on seizure onset amplitude.
(A) Seizure onset amplitude is shown (as the size and saturation of the circle markers) with respect to the parameters surround excitability (Psurround), percentage of minicolumns showing microseizure activity, and number of patches.
(B) Amplitude of onset is shown only for different values of the surround excitability Psurround. Essentially, the 3D parameter scan in (A) is shown here as a projection onto the parameter Psurround. The red shading indicates parameter ranges for which the surrounding is bistable (seizure and background states coexist).
(C) Two dimensional parameter scans of seizure onset amplitude for the parameters of percentage of minicolumns in microseizure activity, and number of patches. Top scan (green frame) is shown for a constant value of surround excitability (Psurround = −1.5), where the system is in a bistable state. Bottom scan (blue frame) is shown for a constant value of surround excitability (Psurround = −4), where the system is in a monostable background state. Both scans are essentially slices of the parameter space shown in (A), indicated by the green and blue frames. The top two small inset panels illustrate the concept of different number of patches for the same percentage of minicolumns in microseizure activity on the cortical sheet. Black indicates the location of the patches on the cortical sheet.
Credit: PLOS/Yujiang Wang, et al.

These findings suggest why the different onset patterns are associated with different treatment outcomes. Surgical removal of seizure-triggering brain tissue may be enough to prevent seizure activity in nearby low-excitability tissue.

However, high-excitability tissue may still be stimulated by alternative trigger sites after surgery, providing a possible explanation for the worse outcomes experienced by patients whose seizures follow the high amplitude slow pattern.

Next, the researchers plan to study seizure onset patterns in greater detail.

“We hope to contribute towards the overall goal of associating patterns seen in seizures with an understanding of the underlying mechanism,” Wang says. “This would not only help our understanding of seizures in general, but may be useful for patient stratification in terms of treatment options.”

Support for the research was provided by the CANDO project funded through the Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC). Other support came from the Human Green Brain project (http://www.greenbrainproject.org) funded through EPSRC, and the Portabolomics Project funded through EPSRC.

Wang Y, Trevelyan AJ, Valentin A, Alarcon G, Taylor PN, Kaiser M (2017)
Mechanisms underlying different onset patterns of focal seizures
PLoS Comput Biol 13(5): e1005475. https://doi.org/10.1371/journal.pcbi.1005475

Top Image: Simulated seizure activity on cortical tissue. Credit: Y. Wang