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Neuroimaging technique helps understand effects of epilepsy on the brain

A Unicamp study evaluated the brains of more than 3,8 volunteers in search of anatomical changes specific to each subtype of the disease

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An international research consortium analyzed, using neuroimaging techniques, the brains of more than 3,8 volunteers from different countries. It is the largest study of its kind ever carried out. The objective was to investigate anatomical similarities and differences present in the brains of individuals with different types of epilepsy and, thus, search for markers that assist in prognosis and treatment.

The multicenter research included the participation of the Institute for Research on Neurosciences and Neurotechnology (BRAINN), a FAPESP Research, Innovation and Dissemination Center (CEPID) based at Unicamp. The results were disclosed in the international journal Brain.

“Advances in neuroimaging techniques have made it possible to detect structural changes in the brain of people with epilepsy that previously went unnoticed,” said Fernando Cendes, professor at Unicamp and coordinator of BRAINN.

“However, there were many discrepancies in previous studies, which included a few dozen or hundreds of volunteers. Our goal was to do this type of analysis on a really large series of patients to get more robust data,” he said.

The term epilepsy covers a set of neurological disorders whose common feature is the temporary change in brain functioning without an apparent cause, such as high fever or use of psychoactive drugs.

For a few moments, part of the brain starts to emit incorrect signals, which may be restricted to one location or spread throughout the entire organ. These processing failures cause epileptic seizures, which can range from distortions in perception and uncontrolled movements to convulsions and loss of consciousness.

The frequency and severity of seizures – as well as the response to drug therapy – vary depending on the part of the brain affected and other factors that are not yet fully understood. Data from the scientific literature indicate that approximately one third of patients do not respond well to antiepileptic drugs. Studies show that these individuals are more likely to develop cognitive and behavioral changes over the years.

The new research was conducted within the framework of an international consortium called ENIGMA (an acronym for Improving Genetic Neuroimaging by Meta-Analysis), dedicated to studying various neurological and psychiatric diseases. 24 centers from different countries participated in this study, linked to the subgroup of the consortium that treats epilepsy.

Photo: Perri
Professor Fernando Cendes, coordinator of BRAINN: “Advances in neuroimaging techniques have made it possible to detect structural changes in the brain of people with epilepsy that previously went unnoticed”

“Each center was responsible for collecting and analyzing data from its patients. Then, all the material was sent to the Imaging Genetics Center, at the University of Southern California, in the United States, the center responsible for consolidating the results in a meta-analysis”, said Cendes.

In total, data from 2.149 people with epilepsy and 1.727 control individuals (without neurological or psychiatric disease) were included. Unicamp was the center with the largest sample: 291 patients and 398 controls.

All participants underwent MRI scans. As Cendes explained, a specific protocol was used to acquire the image in three dimensions. “This allows, with the help of computer programs, post-processing of the images. They are segmented into thousands of anatomical points, which are evaluated and compared one by one,” she explained.

The objective of the quantitative analysis, according to the researcher, was to identify regions of the brain that are atrophied, that is, areas in which cortical thickness is reduced compared to the control group.

The patients included in the study were divided into four subgroups: mesial temporal lobe epilepsy with left hippocampal sclerosis; mesial temporal lobe epilepsy with right hippocampal sclerosis; genetic generalized epilepsy; and a fourth group that encompassed several less common subtypes of the disease.

“Temporal lobe epilepsy is a focal form of the disease, that is, it affects a specific region of the brain. It is also the most common subtype of treatment-refractory epilepsy in adults. We know that when it affects the left hemisphere it produces a different and more serious condition than when it affects the right hemisphere. They are different diseases”, explained Cendes.

The generalized genetic form, although it affects the organ in a diffuse manner, is usually more easily controllable through drugs and has a less harmful evolution for the patient, said Cendes.

“Common MRI exams do not reveal anatomical changes in cases of genetic generalized epilepsy. One of the objectives of this study was to confirm whether there were areas of atrophy in these patients, and we saw that there were,” he said.

First analysis

Initially, the researchers evaluated data from the four subgroups of patients together and compared them with the control. The objective was to investigate whether there were anatomical changes common to all forms of epilepsy. The analysis included both patients who have been living with the disease for many years as well as those recently diagnosed.

“It was possible to notice that the four subgroups present atrophy in regions of the motor-sensory cortex and also in some areas of the frontal lobe,” said Cendes.

According to the researcher, this data shows that, in the case of mesial temporal lobe epilepsy, there are changes that go beyond the area where the epileptic seizures are generated (hippocampus, parahippocampus and amygdala). The damage to the brain, therefore, is even greater than previously imagined.

“Patients with longer illness had a larger area of ​​the brain affected. This reinforces the hypothesis that, as the disease progresses, more brain regions become atrophied and more cognitive impairment appears”, commented Cendes.

The next step was to analyze the subgroups of patients separately, looking for changes characteristic of each form of the disease. The results confirmed, for example, that mesial temporal lobe epilepsy with left-sided hippocampal sclerosis presents changes in neuronal circuits distinct from those affected by mesial temporal lobe epilepsy with right-sided hippocampal sclerosis.

“One disease is not simply the mirror of another. When the left hemisphere is affected, the involvement is more intense and more diffuse. It was previously believed that this happened because the left hemisphere is dominant for language, but it appears to be something more than that. It is somehow more vulnerable than the law”, said Cendes.

In the genetic generalized epilepsy subgroup, it was possible to notice atrophies in regions of the thalamus, located in the deep central region of the human brain, above the hypothalamus, as well as the motor cortex. “It is a subtle change, but present in comparison to control individuals,” said Cendes.

In the opinion of the BRAINN coordinator, the findings published in the article should benefit research in the area and, in the future, will also have implications for the diagnosis of the disease. In parallel to the analysis of anatomical changes, the group is evaluating genetic changes that could possibly explain certain hereditary patterns in the context of brain atrophies. The results of the genetic analyzes should be published soon.

“Knowing that there is a more or less specific signature for each subtype of the disease, instead of looking for changes throughout the brain, we can focus on suspicious areas, reducing cost, time and increasing the statistical power of the analyses. It will then be possible to correlate these changes with cognitive dysfunctions or behavioral changes,” said Cendes.

 

THE ARTICLE
 

The article Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study (https://doi.org/10.1093/brain/awx341), by Christopher D Whelan and collaborators, can be read at:https://academic.oup.com/brain/article/141/2/391/4818311



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