The ancient “sacred disease”
The first descriptions of epileptic seizures date back thousands of years. Epilepsy was known in many parts of the ancient world, from Mesopotamia and Babylon, through China, to Greece and the Roman Empire. This mysterious condition was believed to be related to demons or gods. It was Hippocrates, in his work “On the Sacred Disease,” who suggested that seizures had nothing to do with magic or gods, and that their cause lay in the brain. Even so, for a long time, epilepsy continued to be treated as the result of a curse, and those affected were stigmatized and isolated from society.
Every year, 27,000 Poles find out that they have epilepsy. Treatment does not always produce satisfactory results. Thirty-eight percent of newly diagnosed adults suffer from a drug-resistant form of the disease. Scientists and doctors agree: the limited number of effective drug therapies results from insufficient knowledge and understanding of epileptic seizures.
How does an epileptic seizure occur?
Scientists decided to investigate the causes of epileptic seizures. How? Through realistic computer simulations. A Polish-Italian team led by Prof. Piotr Suffczyński from the Faculty of Physics at the University of Warsaw developed an innovative computational model. Using this model, the scientists were able to reproduce and understand the signals observed in epilepsy. They demonstrated that the electrical discharges leading to epileptic seizures are not caused, as long believed, by synapses, i.e., the connections between neurons, but by disturbances in potassium concentration in the extracellular space.
An increased concentration of this element raises the electrical potential across the cell membrane, thereby increasing neuronal excitability. The increase in neuronal activity then leads to further potassium accumulation. This feedback mechanism causes uncontrolled electrical discharges in the brain, leading to characteristic convulsions and loss of consciousness.
“Our biophysically realistic computational model consists of five cells: one inhibitory and four excitatory cells, glial cells, and the neuronal environment in which ion movement occurs. Using this model, we were the first to demonstrate the potential mechanism of seizure initiation by inhibitory neurons – the ‘trigger point’ or ‘spark’ that initiates the process is the accumulation of potassium outside the cells,” says Prof. Suffczyński.
The model also shows how the mechanism responsible for stopping seizures works. Researchers emphasize that this process is dependent on the potassium-sodium imbalance and the associated increase in activity of sodium-potassium pumps, which transport sodium and potassium, respectively, outside and inside the cell.
The hope lies in nanoparticles
This discovery by the physicists sets the direction for the search for more effective antiepileptic drugs. Researchers are focusing on how to control extracellular potassium levels in the brain.
Prof. Suffczyński’s team has proposed using nanomaterials for this purpose. Their role would be to mimic glial cells, known as astrocytes, which help regulate neuronal activity.
There are already gold nanoparticles capable of recognizing and absorbing various types of ions, including potassium. However, before nanotherapy can be used in humans, further research is needed, such as studies on its toxicity. The research conducted by biomedical physicists may help many patients. Understanding the mechanisms of the initiation and termination of epileptic seizures will be useful not only in the treatment of epilepsy, but also in other neurological conditions, such as brain hypoxia caused by stroke and migraines.
The text was originally published in Polish on the Serwis Naukowy UW website on February 17, 2025.
