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Rates and predictors of seizure freedom in resective epilepsy surgery: an update

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Abstract

Epilepsy is a debilitating neurological disorder affecting approximately 1 % of the world’s population. Drug-resistant focal epilepsies are potentially surgically remediable. Although epilepsy surgery is dramatically underutilized among medically refractory patients, there is an expanding collection of evidence supporting its efficacy which may soon compel a paradigm shift. Of note is that a recent randomized controlled trial demonstrated that early resection leads to considerably better seizure outcomes than continued medical therapy in patients with pharmacoresistant temporal lobe epilepsy. In the present review, we provide a timely update of seizure freedom rates and predictors in resective epilepsy surgery, organized by the distinct pathological entities most commonly observed. Class I evidence, meta-analyses, and individual observational case series are considered, including the experiences of both our institution and others. Overall, resective epilepsy surgery leads to seizure freedom in approximately two thirds of patients with intractable temporal lobe epilepsy and about one half of individuals with focal neocortical epilepsy, although only the former observation is supported by class I evidence. Two common modifiable predictors of postoperative seizure freedom are early operative intervention and, in the case of a discrete lesion, gross total resection. Evidence-based practice guidelines recommend that epilepsy patients who continue to have seizures after trialing two or more medication regimens should be referred to a comprehensive epilepsy center for multidisciplinary evaluation, including surgical consideration.

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Acknowledgement

We would like to thank the practitioners of the UCSF Comprehensive Epilepsy Center for their tireless dedication to the patients and to advancing care.

Disclosures

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. UCSF Comprehensive Epilepsy Center, University of California, San Francisco, CA, USA

    Dario J. Englot & Edward F. Chang

  2. Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, Box 0112, M779, San Francisco, CA, 94143-0112, USA

    Dario J. Englot

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  1. Dario J. Englot
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Correspondence to Dario J. Englot.

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Comments

Hartmut Vatter and Christian E. Elger, Bonn, Germany

Recently, convincing data by Engel et al. are available, which demonstrate the superiority of early resective epilepsy surgery compared with conservative treatment. Accordingly, the recommendations of the International League against Epilepsy and several national neurological societies are supporting an earlier referral of patients with drug-resistant epilepsy in high-volume centers for pre-surgical evaluation and, if suitable, for epilepsy surgery. In spite of these recommendations, neither the number of referrals to specialized centers nor the number of epilepsy surgery increased significantly.

Therefore, this excellent review article by Englot and Chang is hopefully a sufficient instrument to support the operative treatment of epilepsy in specialized centers. The authors report in a concise form about the essential literature, the recent data, and their own experience as a “high-volume center” for resective epilepsy surgery. The review is clearly structured in the most important morphological changes underlying epilepsy. The expected rates of seizure reduction/freedom and the outcome predictors are clearly given in tables for each etiology.

Some important topics could be even more emphasized. The first is the impressing development of the pre-surgical diagnostic opportunities including functional neuroimaging, white matter tractography, and further sophisticated MRI sequences. These methods will more and more precisely define potential epileptic brain areas in correlation with eloquent cortex areas and tracts. The proof of the epilepsy origin of such areas could significantly be improved by the development of invasive electrophysiological investigations, which enable measurements even on a single-cell level. The accurate placement of these probes and the following observation is, however, standard in any specialized epilepsy center. Another significant development is the possibility of an accurate control of the resection of the pre- and/or intraoperatively defined brain tissue by intraoperative MRI. The inclusion of these new developments in the standardized pre- and intra-surgical workup will facilitate specialized centers to perform epilepsy surgery as a well-tailored lesionectomy, in which the personal facilities of the patient, the burden of the seizures, and the etiology of the epilepsy could be taken into account, comparably.

These topics may be added to further support the educational character of this excellent article and to improve the ranking of invasive diagnostic and surgical treatment of drug-resistant epilepsy.

Karl Schaller, Geneva, Switzerland

The present review is coming from one of the most eminent North American epilepsy surgical centers. The authors have outlined the present state of knowledge on epidemiology, underlying pathology and diagnosis of epilepsy on the one hand, and on the presently available options of resective epilepsy surgical procedures and on its potential benefits and outcomes. They have to be commended for the important and comprehensive work they have done in that regard; without doubt, this review will serve as a standard reference on the matter for years to come. As they had restricted themselves to an analysis of the body of literature in the field of resective epilepsy surgery, it is tempting for a commentator to provide some further reflections on the concept of epilepsy surgery as a whole. Epilepsy surgery may have a high socioeconomic impact because there is proof that the mortality rate of epileptics is clearly elevated when compared with person-years of an age-matched control population.

I do fully agree with the authors that, given the right indication, neurosurgical interventions in pediatric epilepsy may improve or normalize the psychomotor development. Concerning the pathogenesis of temporal epilepsy, I would like to add that there is evidence that the particular ontogenetic zytoarchitectonics of the temporal lobe may in part be held responsible for epileptogenesis. This concerns the mesocortical regions, which are connecting the lateral isocortex with the mesial temporal lobe and the limbic system in particular. Thus, it is presumed that this specific zytoarchitecture may facilitate the occurrence of malformations of cortical development and the scattering of ectopic neurons with epileptogenic potential on the one side and the genesis and growth of intrinsic and long-term epilepsy-associated tumors on the other side. These neuropathological specifics in temporal epilepsy seem to be contributive to better long-term epileptological outcome following additional temporo-polar resection in pediatric temporal lobe epilepsy, when compared with the results of more selective temporo-mesial resection. This may be due to the presence of ectopic neurons in the temporal pole of epileptic children, whereas in adult temporal lobe epilepsy, mesio-temporal sclerosis plays a by far more important role. The seizure freeness rates in adults do not differ between standard anterior temporal lobectomies and more selective temporo-mesial approaches, as has been highlighted by the authors

Epilepsy surgery can be considered an asset and a luxury for a given society. This is reflected by the fact that there are important variations between societies with different socioeconomic status with regard to the existence of epilepsy surgical centres. This may even differ from state to state and with the insurance status of the affected population, according to recent North American comparative studies. It is a subspecialty, which is embedded in the setting of pluridisciplinary evaluation and research, which requires important financial funding, and the surgical partner cannot function on his own in a proper way. Only the close cooperation between clinicians, epileptologists, neurosurgeons, neuropsychologists, and neuroradiologists, together with fundamental neuroscientists and signal analysts, allows for profound evaluation of epilepsy disorders and of potential epilepsy surgery candidates. This holds particularly true for the evaluation of extra-temporal and cryptogenic epilepsies. This close cooperation between subspecialized clinicians and researchers from various fields has triggered important knowledge about the function of the human brain, including contributions to modern neuroscientific concepts about memory, behavior, awareness, and the human self. It is thus important that the community with an interest in epilepsy diagnostics and epilepsy surgery will work into the direction of more precise spatial allocation of the epileptogenic zone, be it by a combination of signal analysis and imaging or by co-registration of various morphologic, functional, and metabolic imaging modalities in order to further improve the long-term outcome. There is still considerable room for improvement when looking at the present rates for seizure freeness, which have been outlined by the authors of this review, which are in the range of 60–70 % for temporal lobe epilepsy surgical procedures and clearly lesser for extra-temporal epilepsy surgical procedures. Deep brain stimulation for modulation of neuronal circuits and, experimentally, possibly by optogenetics, will further improve our knowledge and potential clinical outcome in this fascinating field of applied clinical neuroscience.

Antonio Gonçalves-Ferreira, Lisbon, Portugal

The authors present a comprehensive review of rates and predictors of seizure freedom after resective epilepsy surgery based on an extensive class I evidence meta-analyses and the experience of their own institution, the UCSF Comprehensive Epilepsy Center. They divide this subject into four main categories—mesial temporal lobe sclerosis, brain tumors, malformations of cortical development, and vascular malformations—that are indeed the major causes of refractory epilepsy. Nevertheless, other lesions like extrinsic neoplasms, namely, meningeomas are also important epileptogenic pathologies that stay out of the scope of this review, but cannot be forgotten.

The discussion about the surgical management of epilepsy for the lesions focused in each chapter is well elaborated and includes the most significant aspects that must be taken into consideration by those who are involved in this practice. As the title indicates, nothing is mentioned about other kinds of surgical treatment of epilepsy such as radiosurgery or the different forms of palliative surgery, namely, calosotomy or other more recent disconnection procedures; these treatments, as well as the neuromodulation techniques (VNS, DBS), represent nowadays an important contribution for the treatment of refractory epilepsy, although seldom resulting in a complete seizure freedom.

As the authors point in their own “Limitations” comment, they do not present any detailed information about the surgical complications, a matter of great concern for the neurosurgeons. The postoperative quality of life including neuropsychological and psychiatric implications is equally assumed as out of focus in this text.

The conclusions highlight the two main predictors of seizure freedom that are modifiable in the natural history of this kind of epilepsies: the early surgical intervention and the gross total removal of the epileptogenic zone.

Globally considered, it is a very interesting review on this subject, pleasant to read, and providing important updated information for all people engaged in the surgical treatment of epilepsy, notably the young doctors.

This manuscript has not been previously published in whole or in part and is not currently submitted elsewhere for review.

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Englot, D.J., Chang, E.F. Rates and predictors of seizure freedom in resective epilepsy surgery: an update. Neurosurg Rev 37, 389–405 (2014). https://doi.org/10.1007/s10143-014-0527-9

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