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Surgery for Epilepsy

ILAE Commission on Neurosurgery
– H.G. Wieser, Chair

The non-pharmacological treatment of the epilepsies consists of epilepsy surgery, behavioral therapies, and dietetic measures. In recent time some ‘experimental’ methods or treatments ‘in evaluation’ have enriched the armamentarium, such as radiosurgery, in particular Gamma-Knife, deep brain stimulation (DBS), transcranial magnet stimulation and transplantation surgery.

Epilepsy surgery has met with an increased interest but is still underutilized in most countries, particularly third-world countries. In so-called developed countries the availability of advanced non-invasive diagnostic tools to delineate epileptogenic lesions and epilepsy related functional deficits, and to prove epileptogenicity, has partly improved this situation. These modern diagnostic tools, together with improved surgical techniques, have translated into better postsurgical outcome figures and into a larger population of difficult-to-treat patients profiting from surgical therapy. In parallel one can recognize an important role of epilepsy surgery within the modern neuroscience field.

Epilepsy Surgery

The classical ‘open’ epilepsy surgery can be (and was) described at three levels. The first category differentiates between ‘lesion-oriented surgery’, ‘epilepsy-oriented lesional surgery’ and ‘epilepsy surgery sensu stricto’. The second category differentiates between individually ‘tailored’ and ‘standardized’ procedures, such as anterior temporal lobe resection, selective amygdalohippocampectomy, and anterior callosotomy. It is obvious that also so-called standardized operations are most often somewhat tailored, based on preoperative findings as well as on intraoperative electrocorticography (ECoG) and other intraoperative neurophysiological tests (functional mapping). Individually tailored operations comprise topectomies and larger resections.

The third category differentiates between ‘curative (causative)’ and ‘palliative" surgeries. ‘Curative’ means that the goal of the operation is complete freedom of seizures, i.e., the intention is the complete resection of the seizure generating area. ‘Palliative’ means that an amelioration of the seizure tendency, but no cure, is expected, because the seizure generating area cannot be entirely resected. Into the latter category fall the transection of pathways important for spread of the seizure discharges (as is the case in corpus callosum section, and the multiple subpial transection (MST, Morrel-Whisler), and the resection of secondary ‘amplifier structures’ (as is the case in palliative amygdalohippocampectomy). Also the vagus nerve stimulation (VNS) can be included here.

Curative, Resective Surgery

The efficacy of resective epilepsy surgery in temporal lobe epilepsy and some forms of extratemporal epilepsy surgery in patients with focal epilepsy uncontrolled by antiepileptic drugs is undisputed. Uncontrolled epilepsy is associated with progressive cortical and hippocampal atrophy, substantial cognitive and psychosocial morbidity, and increased mortality. Seizure freedom is required to reverse such morbidity and mortality. Surgery is vastly superior to medical therapy for patients with chronic, refractory temporal lobe seizures, and is now the standard of care for these patients.

Evidence from a recent randomized controlled trial of surgical versus medical therapy of temporal lobe epilepsy proves that antero-mesial resection is safe and more effective than medical therapy. The number of patients needed to treat for one patient to become free of disabling seizures is two, which is superior to most interventions in neurology. A meta-analysis of non-randomized trials gives almost identical results; about
two-thirds of patients become seizure-free, compared with only 8% with medical therapy. The results are remarkably similar among studies from different parts of the world. Quality of life improves early after epilepsy surgery, the improvements are both statistically and
clinically significant, and they are sustained. Surgical morbidity with clinically important permanent sequelae is 2%. Nevertheless, epilepsy surgery remains underutilized in developed countries and it does not exist in all but a few developing countries. Current randomized trials are underway to explore the effect of early surgery versus optimum medical therapy on the prevention of disability in patients with mesial temporal lobe epilepsy, and to examine the effectiveness of novel interventions, such as minimally invasive surgery and brain stimulation. Although the concept of early surgery requires further exploration and definition and, at present, there is no robust, direct evidence to support early epilepsy surgery, case series and cohort studies report an association between earlier surgery and better outcomes.

Outcome predictors: Extensive reviews of the literature since 1990 on the effectiveness of surgery for antero-mesial temporal lobe exist (Engel et al. 2003; McIntosh et al. 2001) and many of the more recent studies tried to identify variables (outcome predictors / risk factors) associated with postoperative outcome. In the systematic literature review of 126 articles published between January 1991 and April 2000 on temporal lobe surgery outcome, McIntosh et al. (2001) found that 97 studies tested the relationship of at least one factor with outcome by using statistical analysis. Preoperative variables (aggregated into six major groups according to general subject) were clinical features, electroencephalographical (EEG and ECoG), preoperative magnetic resonance imaging (MRI), preoperative functional imaging, histopathology findings, and operative factors. Such studies on predictors of epilepsy surgery outcome have helped to better advise patients at an early stage of their disease.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most important type of epilepsy in surgical series. At the May 2002 expert Meeting in Istanbul on MTLE-HS (Wieser 2004) experts discussed in depth the underlying causes and how to diagnose and treat this syndrome. Concerning treatment it was concluded that in the presence of unilateral MTLE-HS the extent of mesial resection correlates positively with seizure outcome. However, ‘extent’ of mesial resection needs precision. Surgical series where only the anterior part of the hippocampal formation (pes) or no hippocampus was removed indicate less seizure control than when most of the hippocampal body along with the pes and parahippocampal gyrus is removed. Except for the study of Wyler et al. (1997) direct comparisons of different surgical resections have not been done in a prospective surgical series to compare seizure control (short-and long-term, and for differences in neurocognitive skills). In the prospective, randomized, blinded clinical trial of Wyler et al. seizure and neuropsychological outcomes from anterior temporal lobectomies were compared between two groups of patients. One group underwent hippocampal resection posteriorly to the anterior edge of the cerebral peduncle (partial hippocampectomy). In the other group, the hippocampus was removed further to the level of the superior colliculus (total hippocampectomy). The amount of lateral cortical resection was the same between groups. At 1 year postoperatively, the total hippocampectomy group had a statistically superior seizure outcome compared with the partial hippocampectomy group (69% versus 38% seizure-free), and examination of time to first seizure revealed significantly superior outcomes associated with total hippocampectomy. There was no increased neuropsychological morbidity associated with the more extensive hippocampal resection. Therefore, if there is evidence for the presence of MTLE-HS the hippocampal formation and in most instances the anterior parahippocampal gyrus should be resected after careful evaluation of the remaining functions of the to-be-resected structures. However, the amount of amygdala that needs to be resected in MTLE-HS is unknown.

Outcome for MTLE-HS might be associated with the severity and type of HS (‘classical’ HS with neuron cell loss and gliosis in CA1, CA3, and the granule cell layer of the dentate gyrus, with relative sparing of the CA2 region versus ‘nonclassical’ (diffuse) HS, sometimes extending into temporal polar regions) patients, but further studies are necessary to provide convincing evidence and possible confounding variables have to be taken into account (Wieser et al. 2003).

There is controversy about the need to resect lateral temporal cortex in the presence of MTLE-HS. From the systematic review of McIntosh et al. (2001) there is no indication that extent of lateral neocortical resections correlates with seizure outcome. Consequently several centers no longer resect neocortical lateral temporal cortex and claim that seizure outcomes with restricted mesial resections are at least as good as with more extensive temporal lobe resections. However, until now no convincing studies exist that show that more selective mesial resections are correlated with better neuropsychological outcomes, although this has been claimed and might be the case. It is likely that the more selective surgery causes less memory problems than standard two-thirds anterior temporal lobe resection. However potential collateral cortical damage due to the approach must be considered a potential source of additional memory impairment in highly selective mesial resections. The cognitive consequences of sparing not only the lateral cortex but also mesial structures apart from the hippocampus or of tailored hippocampal resections are not yet known. Likewise there is controversy whether tailored resections using pre-/post intraoperative recording improves seizure outcome.

In the presence of circumscribed foreign tissue lesions, such as ganglioglioma, DNET and other low-grade tumors a lesionectomy might suffice in certain instances. If there is evidence for ‘secondary’ HS or ‘dual pathology’, it is recommended to resect both the foreign
tissue lesion and the gliotic hippocampus. In patients with dual pathology, removal of both the lesion and the atrophic hippocampus is the best surgical approach and should be considered whenever possible since hippocampectomy alone and removal of the lesion alone yield unsatisfactory results. An accepted definition of dual pathology is, however, still lacking. Therefore, the concept of ‘dual pathology’ needs further clarification.
Seizure outcome in MRI-negative patients and in patients without histopathological abnormalities in the resected specimen is poor. Outcome may be good in MRI-negative patients with temporal hypometabolism on FDG-PET, who usually do show histopathologic abnormalities. Long-term actuarial analysis of outcome is a necessary next step for future studies. Thus, while not optimal, cryptogenic cases (defined as no significant pathology on imaging and histology) are still surgical candidates if the risk-benefit analysis is acceptable to the patient and family.

The actuarial analysis of Berkovic et al. (1995) showed that outcome at postoperative year 5 is different for MTLE-HS compared to other forms of temporal lobe epilepsy: 5 years after surgery 21% with normal MRI had no postoperative seizures versus 50% with hippocampal sclerosis, and 69% of patients with foreign tissue lesions. Similarly, an eventual seizure-free state of 2 years or more, whether the patient was seizure-free since surgery or not, was achieved by 36% of those with normal MRI, versus 62% of those with HS, and 80% of patients with foreign tissue lesions.

Long-term relapse. More research is needed to determine if patients with HS are more likely to experience late seizure recurrence. Data previously published from patients with long-term follow-up analyzed up to 1996 found that medial temporal resections had a higher rate of long-term relapse, but this remains open to further prospective studies.

Extratemporal Epilepsy Surgery

Extratemporal epilepsy surgery is usually a tailored
surgery and very often associated with lesions. Frontal epilepsy surgery prevails in this category. Non-lesional extratemporal epilepsy surgery usually requires extensive invasive presurgical evaluation, which differs from patient to patient according to the non-invasive findings. Invasive EEG with grid- strip- and depth-electrodes, often in combination, is necessary to delineate the epileptogenic seizure onset zone. Results in extratemporal epilepsy surgery are inferior to temporal lobe surgery. From the data collected by Engel et al. (1993) at the 2nd Palm Desert Conference out of a total of 8234 operations only 13% were extratemporal. In non-lesional extratemporal epilepsies circumscribed topectomies are rarely successful; more often rather extensive resections are required to render a patient seizure-free. The complete resection of the epileptogenic zone is very often hindered by the fact that the epileptogenic seizure-generating zone extends into indispensable functional cortex. In such instances
multiple subpial transection can be considered.


Today standard anatomical hemispherectomy has given place to the so-called ‘functional hemispherectomy’ (Adams 1983; Rasmussen 1973, 1983; Villemure et al. 1993). Rasmussen’s ‘functional hemispherectomy’ technique is a subtotal hemispherectomy, i.e., removal of the temporal lobe and central region, and disconnection of the residual frontal and parieto-occipital lobes from the rest of the brain. Schramm et al. (2001) described the so-called ‘transsylvian keyhole functional hemispherectomy’.

Indications for hemispherectomy are severe unilateral epilepsies of childhood with unilateral neurological deficits (hemiparesis and hemianopia), hemimegaloencephaly, infantile type hemiplegia and seizures (HHE), Rasmussen’s encephalitis, and Sturge-Weber-Syndrome. Marked preoperative neurological deficits should be present before considering this radical operation. If performed early and with appropriate indication results of functional hemispherectomy are in general very gratifying, i.e., most children profit quite a lot.

Corpus Callosotomy (CCT)

Callosotomy is based on the principle of preventing generalization of seizures. It should be considered in pharmacoresistant epileptic conditions where no circumscribed cortical excision is possible because of extended badly localized epileptogenic seizure generating zone(s). Ictal EEG findings are, however, lateralized with rapid generalization (so-called ‘secondary bilateral synchrony’). Clinically, candidates for callosotomy suffer usually multiple seizure types, but those with severe sudden falls are said to respond best to this surgical approach.

CCT using Gamma Knife is possible as shown by the Graz group. However, further studies are necessary to define the role of classically performed CCT versus Gamma Knife CCT versus VNS.

Multiple Subpial Transection (MST)

In a meta-analysis Spencer et al. (2002) collected 211 patients from 6 large epilepsy centers operated on with MST, but only 53 had no additional resection (MST-). In patients with MST and resection (MST+) in 87% a >95% seizure reduction was obtained for generalized seizures, a 68% reduction for psychomotor seizures and a 68% seizure reduction for simple partial seizures. For MST results were less good. A >95% seizure reduction was obtained for generalized seizures in 71%, for psychomotor in 62% and for simple partial seizures in 63%. EEG localization, age at onset of epilepsy, duration of epilepsy, and localization of MST were not significantly correlated with the result. Surgery related neurological deficits were present in 47 patients, in MST+ (23%) in MST- (19%).

Experimental Procedures or Epilepsy Surgical Techniques in Evaluation.

Besides intermittent vagal nerve stimulation (VNS), transcranial magnetic stimulation and deep brain stimulation, as well as attempts of transplantation of fetal or genetically engineered inhibitory active cells into the epileptogenic focus have been started.

Whereas stereotactic procedures – with the exception of amygdalotomy in the extremely rare amygdalar seizure onset epilepsies – are no longer generally accepted, some subthalamic and thalamic targets have been recently rediscovered within the field of deep brain stimulation (DBS). Some tumor-associated focal epilepsies of delicate locations (insula of Reil and hypothalamic hamartoma) may profit from radiosurgical approaches, such as the Gamma Knife and interstitial 125-iodine radiosurgery of low-grade gliomas by seed-implantation. Arguments for radiosurgery are lower mortality and morbidities with equal efficacy with regard to seizure outcome and quality of life. In principle today Gamma Knife, linear accelerator and Cyclotron techniques are available and competing. In the field of so-called non-lesional (non-tumoral) epilepsy surgery only with the Gamma Knife technique has a reasonable experience accumulated with at least some – albeit limited – long-term data. Studies are presently conducted to define the role of Gamma Knife for the treatment of MTLE-HS.

Concluding Remarks

Epilepsy surgery is playing an increasingly important role in the epileptologist's therapeutic armamentarium. In one part this is due to the considerable improvement in structural and functional imaging and electrophysiological techniques, particularly EEG long-term monitoring. The other reasons are a better understanding of the pathophysiology of those epileptic conditions, which are amenable to surgery, and refinements in surgical (and radiosurgical) techniques. Today reasonably reliable prognosis can be made prior to the recommendation of surgery based on worldwide collected inclusion and outcome data.

Whereas careful and knowledgeable presurgical evaluation of candidates of epilepsy surgery still remains the most important step, there is no doubt that today a
considerable number of patients can undergo successful surgery without invasive intracranial presurgical procedures, resulting in an improved cost-effectiveness and in a growing utilization of this kind of therapy in countries with limited resources.

Whereas for years epilepsy surgery has been considered a kind of ‘last resort’ for many doctors, surgical treatment for epilepsy is nowadays an evolving and accepted discipline. It is hoped that the resulting growth in basic research on the epileptic human brain and improved surgical techniques result in further improvement in the treatment of certain types of epilepsy. On the other hand, experience shows that quality control in epilepsy surgery is very important. Worldwide collaboration and the establishment of national centers of reference for epilepsy surgery are probably the best way to guarantee observation of high and accepted standards. The ILAE Commission on Neurosurgery for Epilepsy is challenged!


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