A Focus On: Treatment of Pharmacoresistant Epilepsy

Fig. 3c.8 Left mesial temporal sclerosis. Note: shrinkage of the left hippocampus (arrow), destruction of its internal structure and increased volume of the temporal horn of the lateral ventricle, immediately lateral to the left hippocampus. T2 weighted full spin-echo sequence.Left mesial temporal sclerosis. Note: shrinkage of the left hippocampus (arrow), destruction of its internal structure and increased volume of the temporal horn of the lateral ventricle, immediately lateral to the left hippocampus. T2 weighted full spin-echo sequence. Reproduced from OSH Epilepsy by Gonzalo Alarcon, Lina Nashef, Helen Cross, Jennifer Nightingale, and Stuart Richardson. © 2009 Oxford University Press. DOI: 10.1093/med/9780198570738.001.0001


Forty percent of people with epilepsy have drug-resistant seizures. Despite the addition of almost 20 new antiseizure medications over the past 23 years, there has been little change in the percent of pharmacoresistance. Although basic research will no doubt lead to more effective future treatments, as well as prevention and cure, there are practical approaches that can be taken now to render more patients with epilepsy free of seizures, as well as serious comorbidities.


The goal of therapy for epilepsy is no seizures, and no side effects, as soon as possible.  The early control of seizures may be necessary to avoid adverse psychological and social consequences of epilepsy, as well as increased risk of injury and death.


Most types of epilepsy are easily treated, usually within the first or second antiseizure medicine tried. Pharmacoresistance is now defined as failure of adequate trials of two appropriate antiseizure medications, alone or in combination, to eliminate disabling seizures. The most common causes of persistent seizures after appropriate treatment are: nonadherence, lifestyle issues that provoke seizures, misdiagnosis of nonepileptic events, particularly psychogenic nonepileptic seizures, the wrong epilepsy diagnosis leading to the wrong drug treatment, or inadequate pharmacotherapy. 


When patients continue to have epileptic seizures that interfere with work, school, or interpersonal relations after trials of two appropriate antiseizure medications, timely referral to a full-service epilepsy center offers the best opportunity to render the patient seizure free and avoid a lifetime of disability. This is a grossly underutilized option; less than 1% of patients with pharmacoresistant seizures in the U.S. are referred for consultation at an epilepsy center.


Specialized epileptologists and staff at epilepsy centers can identify and correct nonadherence and lifestyle impediments to therapy. Evaluation on an epilepsy monitoring unit can diagnose nonepileptic events, seizure types, and syndromes that require specific treatment. Treatable causes of epilepsy may have been missed in the community, and patients can participate in experimental drug trials. 


In addition to resective surgical treatment, both noninvasive (vagus nerve stimulation and trigeminal nerve stimulation) and invasive (response neurostimulation) neuromodulation, as well as other treatments such as the ketogenic diet, may also greatly reduce seizure frequency and severity. 


Perhaps most importantly, whether or not epileptic seizures are eliminated, epilepsy centers provide psychiatric, psychological, and social diagnostic, they support services that can minimize disability and maximize quality of life.


Jerome Engel, Jr., MD, PhD, Jonathan Sinay Distinguished Professor of Neurology, Neurobiology, and Psychiatry and Biobehavioral Sciences Director, UCLA Seizure Disorder Center David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA



Further reading:


1. Cook M,  Lhatoo S. Oxford Textbook of Epilepsy and Epileptic Seizures. Oxford: Oxford University Press, 2013, 400 p.

2. Engel J Jr. Seizures and Epilepsy, 2nd Edition. Oxford: Oxford University Press, 2013, 706 p. 

3. IOM. Epilepsy across the Spectrum: Promoting Health and Understanding. Washington: The National Academic Press, 2012, pp 237.

4. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G, Moshé SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.  Epilepsia 51:1069-1077, 2010.

5. LaFrance WC, Wincze J. Treating Nonepileptic Seizures (paperback). Oxford: Oxford University Press, 2015 (estimated), 102 p.

6. Pohlmann-Eden B, Steinhoff BJ. Understanding Antiepileptic Drugs (paperback). Oxford: Oxford University Press, 2014, 184 p. 

7. Reiter JM, Andrews D, Reiter C, LaFrance, WC. Taking Control of Your Seizures. Oxford: Oxford University Press, 2015, 336 p.



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