The ANA Q&A: Dr. Kimford J. Meador | Epilepsy

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In recognition of National Epilepsy Awareness Month (November), we spoke with Kimford J. Meador, MD, FANA, FAAN, FAES, FRCPE, for this month's ANA Q&A. Dr. Meador is a Professor of Neurology and Neurosciences at Stanford University, and Clinical Director, Stanford Comprehensive Epilepsy Center. He discusses the cognitive and behavioral effects of epilepsy, its treatments, and more.

 

What does the public need to understand about epilepsy that it often doesn’t?

A seizure is the firing of the nerve cells in the brain, which occurs in an abnormal very fast and synchronous manner that can disrupt ongoing normal brain function. Depending on where the seizure starts and how it spreads, a seizure can produce many different symptoms (e.g., a recurrent odd feeling, staring with unresponsiveness, or convulsion). Any brain can seize, and 1 in 10 people have a seizure in their lifetime. Most of these seizures are provoked (e.g., low blood sugar, head trauma). However, some people have recurrent seizures that are not provoked or are provoked by something that should not cause a seizure. Epilepsy is a very common disorder affecting 1% of the population. It is not one disease, but is literally the result of thousands of different diseases (e.g., stroke, brain tumors, infection, genetic, congenital malformations of the brain). There are disorders that may mimic the symptoms of epilepsy (e.g., syncope, stroke, and functional neurological disorders), so an accurate diagnosis is important. Antiseizure medications remain the main treatment for epilepsy, and most people with epilepsy can be controlled well with medications, but over 30% of people are resistant to medical treatment. Drug resistant epilepsy is defined as failure of adequate trials of two antiseizure medications which were tolerated (not failed for side effects) and appropriately chosen and dosed for the type of epilepsy. Uncontrolled epilepsy can markedly reduce quality of life, and even lead to death (e.g., sudden unexplained death in epilepsy – SUDEP). Patients with drug resistant epilepsy should be referred to or informed of evaluation options at a comprehensive epilepsy center, where they may benefit from other evaluations or treatments (e.g., resective surgery or stimulation therapies).

 

How are treatment options for epilepsy different today from 10 years ago?

New antiseizure medications continue to be developed including those with novel mechanisms (e.g., cannabidiol, cenobamate, perampanel). In addition, surgical or stimulation therapies have continued to evolve over the last decade. Although first approved by the FDA for neurosurgery ablation in 2007, the use of MRI guided laser interstitial thermal therapy (LiTT) for focal epilepsy has markedly increased in the last decade. LiTT can provide seizure freedom with reduced morbidity compared to older resection techniques requiring craniotomies and larger areas of brain resection. Responsive neurostimulation (RNS) therapy was approved by the FDA in 2014, and Deep Brain Stimulation (DBS) in the anterior thalamus was approved by the FDA in 2018. These stimulation therapies are rapidly increasing in use and are revolutionizing the treatment of medically resistant epilepsy. Both RNS and DBS produce substantial reductions in seizures although less seizure freedom than resective surgeries. RNS is used when the focus is known but will produce unacceptable deficits if the region is resected; for example, when the focus is in critical language or motor areas, or if there are two foci that cannot both be resected such as when both hippocampi are epileptic). DBS is used when the focus cannot be localized or there are multiple foci. In addition, diagnostic techniques to guide therapeutic decisions have changed. Computer assisted stereotactic intracranial electrode implantation is being used much more commonly to record seizures and guide surgical treatments in place of subdural grids which can have more morbidity and cannot sample potentially critical deeper structures. In addition, long-term video EEG monitoring has expanded and is being used routinely in many ICUs to diagnosed non-convulsive status, whose recognition and treatment improve patient outcomes.

 

What promising research is poised to change the standard of treatment for epilepsy?

Development of new antiseizure medications continues, particularly for medications based on new mechanisms. However, the development of truly antiepileptic medications (i.e., drugs that interfere with epileptogenesis and the emergence of epilepsy) is needed for high-risk populations (e.g., severe head trauma). Early studies on direct intracranial medication delivery systems suggest that they could offer improved efficacy without systemic side effects. The aforementioned stimulation therapies are just at their inception, and only the surface of their possibilities has been scratched. Many questions as to how best to stimulate and where to stimulate for a variety of different epilepsies remain to be answered and are likely to improve their application to the control of epilepsy. Stimulation therapies also have the potential to not only control epilepsy but also to treat comorbid disorders such as depression and cognitive disorders. The role of LiTT vs. standard open resections is still being defined. Other techniques less invasive than standard open resections are also being explored (e.g., ultrasonic lesioning). Both surgical and stimulation therapeutic outcomes are improved when a structural lesion is found. Our constantly emerging neuroimaging techniques are likely to continue to improve lesion detection (e.g., voxel-based MRI morphometric analysis). Multiple recent investigations are seeking to better understand epileptic networks, which could lead to a better understanding of epilepsy and its comorbidities as well as improved therapeutic choices and better targeting of therapies. Similarly, bioinformatics and machine learning algorithms could enhance epilepsy care by improving assess and understanding of data. Improved long-term outpatient seizure monitoring techniques are developing which are likely to improve detection and diagnosis; they could also potentially be incorporated into methods to predict seizures. Advances in our understanding of the genetics of epilepsy have been rapid over the past decade, improving our knowledge of genetic risks and of epileptogenesis. Future advances in this regard are likely to ultimately lead to improved diagnosis, prevention, and targeted therapeutics in epilepsy.

 

What work is your research group undertaking to move understanding or treatment for epilepsy forward?

Our group’s research has been focused on the cognitive and behavioral effects of epilepsy and its treatments. At the present, we are investigating potential cognitive enhancers for people with epilepsy, exploring novel non-invasive predictors of surgical resection risks for cognitive deficits, and investigating the mechanisms of altered consciousness in epilepsy and other disorders. For many years, we have been examining the cognitive and behavioral effects of antiseizure medications, and are now targeting the newer meds. This line of research led us to investigate the effects of fetal antiseizure medications on the child’s ultimate neuropsychological outcomes. This work spans several decades, and our studies have delineated differential risks of fetal exposure across multiple antiseizure medications, although much work remains as the data for many medications are inadequate or absent. Concomitant with our investigations of the child outcomes, we have also been examining maternal pregnancy outcomes (e.g., seizures, depression, OB outcomes).

 

How has the ANA supported your career and/or work in this area? 

The ANA provides excellent opportunities for education, access to publications on cutting-edge clinical neuroscience, and a rich network of interactions with others involved in research and care of patients with neurological disorders. The ANA also provides a strong voice for clinical neuroscience research and neurologists at a time when misinformation is directed at science and medicine

 

Want to learn about more of the groundbreaking research being conducted by ANA members? Read past editions of The ANA Q&A.