A recently published review has discovered that considering genetic data for individuals who are suffering from drug-resistant focal epilepsy has led to the definition of novel illness entities and enhanced clinical decision making. Drug-resistant focal epilepsy, as defined by the International League Against Epilepsy, usually occurs when an individual has failed to stay free of seizures with sufficient trials of 2 ASMs (anti-seizure medication). The disease is often caused by brain lesions such as glioneural tumors.
These drugs must have been specifically chosen for the individual’s type of seizures and tried in combination with other seizure medications or on their own. Epilepsy surgery can be a curative treatment option for some patients.
Physicians usually identify these lesions using intracerebral electroencephalogram and magnetic resonance imaging (“MRIs”). However, these techniques lack the accuracy and specificity required to the lesions.
This led the research team to develop a tumor classifier that utilizes epigenetic profiling. The brain tumor classifier utilizes CpG sites in identifying different tumor groups and has shown to be useful in recognizing multiple tumor entities, including isomorphic diffuse glioma, glioneural tumors with nuclear clusters and primary mismatch repair-deficient IDH-mutant astrocytoma. These lesions, among many others, are difficult to diagnose without using molecular approaches and are usually morphologically heterogeneous.
In their report, the authors of the review discuss the different types of lesions that are linked to particular molecular markers. These lesions are brought about by a combination of germline and somatic variants, and they often impact glycosylation, receptor tyrosine kinase/mitogen-activate protein kinase (RTK/MPAK) signaling and mechanistic target of rapamycin (“mTOR”) signaling. These lesions can also be evaluated using cell-free DNA, without conducting a biopsy. This can be done using a cerebrospinal fluid sample that has been collected by a dural puncture.
However, the authors note in their report that this particular technique may require additional validation. Methylation profiles evaluated from peripheral blood can also be used to diagnose epilepsy, but studies on methylation in epilepsy are scarce at the moment. In addition, more studies and samples are required to assess the potential of DNA methylation in drug-resistant focal epilepsy.
The authors of the review conclude that molecular approaches are altering the diagnostic process for individuals suffering from this particular type of epilepsy. They note that the approaches could potentially be used by physicians to accurately give diagnoses of causal lesions based off of data collected using procedures that are less-invasive.