WONOEP appraisal: Development of epilepsy biomarkers—What we can learn from our patients?

Abstract

Summary Objective Current medications for patients with epilepsy work in only two out of three patients. For those medications that do work, they only suppress seizures. They treat the symptoms, but do not modify the underlying disease forcing patients to take these drugs with significant side effects often for the rest of their lives. A major limitation in our ability to advance new therapeutics that permanently prevent, reduce the frequency of, or cure epilepsy comes from a lack of understanding of the disease coupled with a lack of reliable biomarkers that can predict who has or who will get epilepsy. Methods The main goal of this report is to present a number of approaches on how we may be able to identify reliable biomarkers from observing patients with brain disorders that have a high probability of producing epilepsy. Results A given biomarker, or more likely a profile of biomarkers, will have both a quantity and a time course during epileptogenesis that can be used to predict who will get the disease, to confirm epilepsy as a diagnosis, to identify co-existing pathologies, and monitor the course of treatments. Significance Additional studies in patients and animal models could identify common and clinically valuable biomarkers as a means to successfully translate animal studies into new and effective clinical trials.

Age at onset and response to antiepileptic drugs in patients with various subtypes of idiopathic generalized epilepsy - preliminary investigation for the prevention of epilepsy

“…To justify AED treatment before the onset of epilepsy, biomarkers should be identified to predict future onset of epilepsy and detect patients at ever higher risk. Magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and EEG are currently used to examine biomarkers for epilepsy [34]. Among these, EEG is the most established and frequently used tool for the diagnosis of epilepsy.…”

Epileptogenesis, traumatic brain injury, and biomarkers

“…As only 15-to 25% of patients undergoing moderate to severe TBI develop PTE, and seizures can begin years after injury, clinical trials would need to involve extremely large subject populations followed for long periods of time, making them prohibitively expensive (20). Consequently, research into fundamental mechanisms of epileptogenesis following TBI is also directed at identifying biomarkers of epileptogenesis (20)(21)(22)(23). Biomarkers that could reliably indicate a high likelihood of developing PTE following TBI would permit enrichment of the subject population.…”

“…Much work has been published in recent years on putative imaging, electrophysiological, molecular, and cellular biomarkers of epileptogenesis following TBI (20)(21)(22)(23). Predictive power will likely require a combination of electrophysiological, neuroimaging, and molecular biomarkers measured at different post-injury time points, to diagnose with high sensitivity and specificity ongoing epileptogenesis independent of the severity of brain damage.…”

Prevention of epileptogenesis as a future strategy for the treatment of epilepsy

“…It is likely that a profile of biomarkers will be required for most clinical applications in addition to electroencephalogram (EEG) [51], which will improve the accuracy of epilepsy prediction [52][53][54][55][56][57]. Compared to electrophysiological methods, MRI has higher spatial resolution and provides valuable contrasting of grey and white matter.…”