Epilepsy surgery : overview Of forty years experience.
Although many patients with epilepsy achieve control of their seizures with medication, a substantial number ultimately develop intractable epilepsy. Patients with intractable epilepsy form the group for whom surgical procedures may be beneficial. We retrospectively analyzed the clinical profile and outcome of 141 patients operated for intractable epilepsy at Vellore between 1949 and 1990. The operative procedures done for suprasylvian epilepsy were topectomy (24 cases) and lobectomy (2 cases). For temporal lobe epilepsy the surgical procedures done were topectomy (28 cases), temporal lobectomy with amygdalectomy (25 cases), temporal lobectomy with amygdalectomy and hippocampectomy (10 cases), amygdalectomy (15 cases) and topectomy with amygdalectomy in one case. Hemispherectomy was done for 12 cases with multilobe epilepsy. For multifocal epilepsy, four patients underwent stereotactic ansotomy. Post operative complications included infections (10 cases) and acute post operative haematoma in one patient. There was transient neurological deterioration in ten patients. Three patients operated prior to 1960 died due to peri operative complications. Follow up data of 80 patients, ranging from 1 to 42 years (mean 10 years) was analysed. Total or near total seizure control was obtained in 53% patients and a worthwhile outcome in 20% patients. Mental retardation, pre operative scalp electroencephalography and post excision electrocorticography has been shown to be predictors of outcome with respect to seizures.
Epilepsy surgery is considered for patients with intractable epilepsy, patients with uncontrolled seizures or intolerable side effects that interfere with the function or quality of life despite maximally tolerated trials of one or more anti epileptic drugs (AED). Many controlled studies done earlier have clearly demonstrated the efficacy of surgical methods in the management of intractable epilepsy., The past decade has witnessed a dramatic increase in the number of comprehensive epilepsy surgery centres and surgical procedures for epilepsy. This growth reflects technological advances like video EEG with on line computer analysis, positron emission tomography, and quantitative MR imaging, which precisely defines abnormal areas. In carefully selected patients, epilepsy surgery is effective. Despite these advances in technology and newer surgical procedures, there exists a discrepancy between the number of surgeries performed and the number of good surgical candidates. This is because of failure to educate patients about epilepsy surgery, lack of funds, medical resources and preference of some to tolerate seizures and side effects than to undergo surgery.
The present paper focuses on the results of surgeries done for intractable epilepsy in the first forty years of our Epilepsy surgery program.
Between 1949 and 1990, we operated 141 patients of intractable epilepsy. Their case records, operation records and the outpatient records were studied. Their present status was documented by latest outpatient clinic visits or by letters. There were 108 male and 33 female patients. Their ages ranged from 1 to 49 (mean 18.6) years. The duration of seizures ranged from 1 to 38 years (mean 10.06 yrs, median 8.5 yrs). Age at onset of seizures ranged from 0-39 yrs (mean 8.68 yrs, median 7 yrs) with 95 out of the 141 patients having seizure onset in the first decade of life. In majority of patients no identifiable aetiology for the seizure disorder could be found [Table I].
1. Selection of surgical candidates : Indications for a surgical procedure for refractory epilepsy have changed over the years; however all patients had been found to be refractory to adequate trial of drugs that were available at the time of surgery. Appropriate radiological investigations available were used to rule out tumours and vascular malformations.
2. Localisation of seizure focus : The epileptiform abnormality was localised with the aid of seizure characteristics, neurological deficits, scalp EEGs (including sphenoidal electrode studies) and neuropsychological tests.
The patients were divided into four groups based on the localisation of the epileptiform abnormalities [Table II]. In the suprasylvian group, we included patients with epileptiform abnormality above the sylvian fissure. This group was subdivided into i) frontal, ii) central (sensori motor strip), iii) parietal and iv) occipital. The patients with abnormalities mainly in the temporal lobe formed a different group as the surgical procedures differed from those in the suprasylvian group and they formed a major group. In the multilobe (unilateral) group all patients had large atrophic lesions involving one hemisphere which had already produced weakness of contralateral limbs with or without hemianopia. The multifocal (bilateral) group was a small minority where patients had persistent multifocal epileptiform abnormality.
Local anaesthesia was favoured during the first decade and a half. It had many advantages such as good electrocorticographic recordings and the option of using cortical stimulation in mapping sensory, motor and language areas and induction of seizures intra-operatively. General anaesthesia was used more often in later years as it was less cumbersome, more comfortable for the patient and was the anaesthesia of choice for noncooperative or mentally retarded adults and children.
In the suprasylvian group, a large craniotomy was done based on the area to be resected, with a view to expose important landmarks like the central sulcus and the sylvian fissure. Eloquent cortices were mapped either by using known landmarks or by cortical stimulation (under local or light general anaesthesia). Recently, evoked potentials were used to map the central sulcus. The epileptogenic area was clearly localised and resected if this did not involve eloquent cortex. A post excision electrocorticogram (ECoG) was done and resection continued till all electrocorticographic activity had ceased. Epileptiform foci in the eloquent areas were left behind. In this group of 23 patients, there were 24 topectomies and two frontal lobectomies.
Similar techniques of localisation were used for the temporal lobe group. In addition depth electrode studies to detect foci within the amygdala and the hippocampus were also done (from 1960 onwards). Temporal lobe resections were done based on the scalp EEG, sphenoidal studies, neuropsychological assessment and the intraoperative ECoG and depth electrode studies. A total of 105 surgical procedures had been carried out in the 102 patients in this group. In cases where there were no depth foci, a topectomy was done (28 cases). When both depth and surface foci were present, the operative procedures were temporal lobectomy with amygdalectomy (25 cases), temporal lobectomy with amygdalectomy and hippocampectomy (10 cases) and topectomy with amygdalectomy (one case). When only depth foci were detected, amygdalectomy was done, (unilateral in 13 cases and bilateral in 2 cases). Patients in the multilobe (unilateral) group underwent a standard structural hemispherectomy. One patient had a partial hemispherectomy and eleven patients had either a one or two staged total hemispherectomy. Four patients in the multifocal (bilateral) group underwent stereotactic ansotomy in the early seventies after which this procedure was not done. In 1991, we started corpus callosotomy for this group but these patients have not been included the present study.
The reports of the biopsy of the resected tissues were reviewed. Most of the biopsies were normal and the abnormalities detected included gliosis (13), chronic infection (3), degenerative lesions and infarction (1 each).
Complications [Table III] Eleven patients (7.3%) had non neurological morbidity of which ten had post operative infection which was treated successfully with antibiotics. One had a surface haematoma which needed evacuation. Ten patients (6.7%) who had new or increased neurological deficits post operatively were found to have completely improved within three months. Three patients (2.1%) died in the immediate post operative period. All the three had undergone total hemispherectomy prior to 1960. Two of these patients had hypovolaemic shock due to persistent bleeding from the superior sagittal sinus. One patient had a fulminant post operative meningitis.
The inpatient case records and outpatient follow up charts were studied to determine the results following surgery. Patients who could not come to the clinic for follow up and review, were contacted through letters of a standard format and the seizure outcome was determined from the replies. The seizure outcome was obtained based on the Engel Jr. seizure outcome classification.11 Only patients with at least one year of follow up were included for analysis of results. Patients who on follow up for at least one year had remained free of disabling seizures were included in class I. Class II included patients who had rare disabling seizures. Patients who had worthwhile improvement were put into Class III. Patients who either had no improvement or when improvement was not considered to be worthwhile, were included in Class IV. There were thus 80 patients who had adequate follow up and were therefore included in the analysis of results [Figure.1]. The duration of follow up of these patients ranged from one to forty two years (mean 10 years, median 4 years). In the suprasylvian group, out of total of 19 patients, 7 (37%) were seizure free, one patient (5%) had rare seizures, 6 (32%) had worthwhile improvement and 5 (26%) had no worthwhile improvement. Out of 58 patients in the temporal lobe group, 27 (47%) were seizure free, 6 (10%) had rare seizures, 9 (16%) had worthwhile improvement and 16 (27%) had no worthwhile improvement. Of the 3 patients who had adequate follow up in the multilobe group, two (67%) patients were seizure free and one (33%) patient had a worthwhile improvement.
Analysis of factors influencing outcome
Various factors in the history, seizure characteristics, EEG and intraoperative findings that could have some bearing on the seizure outcome were analysed. For analysis we considered patients in Class I and II (Engel Jr. Seizure outcome classification) as having a good outcome and compared the group with patients in Class III and IV who were considered to have a poor outcome. Chi square test with Yates correction was used for the statistical analysis.
Of the 26 mentally retarded patients, only 5 (19%) had a good outcome, whereas 38 (70%) of the 54 non retarded patients had a good outcome. This was found to be statistically highly significant (p=0.0000). Based on the pre operative scalp EEG the patients were divided into two groups for analysis. There were 52 patients who had strictly focal EEG abnormality, restricted to the area that was planned to be resected and of them 38 (73%) patients had a good outcome. Patients who had epileptiform abnormality in other lobes of the brain in addition to the one resected (e.g. bitemporal epileptiform abnormality with predominance of one temporal lobe which was resected) were put into one group (relatively focal epilepsy). Of the 28 patients in this group only 5 (15%) had a good outcome. This was found to be highly significant (p=0.0000).
Following resective surgery, a post excision ECoG was done where ever technically feasible. 31 patients had no residual focus on the post excision ECoG. 25 (81%) of these had a good outcome. Of the 18 patients with residual focus, only 4 (22%) had a good outcome. Statistical analysis showed that this was significant (p=0.0001). Comparison between topectomy, lobectomy and lobectomy with excision of medial structures in the temporal lobe group did not reveal any statistically significant difference in the outcome. Other factors like age, age at onset of epilepsy, type of epilepsy and aetiology had no statistical significance on the outcome.
In this study majority of patients who had adequate followup had undergone focal resections. Hence the discussion will focus on the results of focal resections of the temporal lobe and the suprasylvian areas.
Suprasylvian epilepsy : The Montreal Neurological Institute (MNI) has by far published the most informative studies on extrahippocampal neocortical epilepsy. In a study from MNI, in which outcome was available for 216 cases, 22 (10%) were seizure free, 28 (13%) became seizure free after a few early seizures, 26 (12%) had rare seizures after initially being seizure free for 3-20 years, 42 (19%) had a marked reduction to 1-2% of pre operative frequency and 94 (44%) had moderate or no reduction of seizure frequency. From Zurich, Hajek and Weiser reported 30 patients operated for extratemporal epilepsy. Among them 6 (20%) were seizure free, 14 (47%) had a marked improvement (auras or rare seizures), 4 (13%) had improvement in terms of seizure frequency and severity and 6 (20%) had no improvement. Most of the other studies had fewer cases and often included mainly structural lesions. In the present study where only nontumoural cases were included, out of a total of 19 patients, 7 (37%) were seizure free, one (5%) patient had rare seizures, 6 (32%) had worthwhile improvement and 5 (26%) had no worthwhile improvement.
The surgical outcome for intractable neocortical focal epilepsy remains suboptimal for many reasons. Invasive localisation of seizures carries a significant risk and the nature of epilepsy is often diffuse as compared to the temporal lobe epileptic group. Available strategies for seizure localisation can be unsatisfactory due to misleading scalp EEG. Neocortical seizure spread may be rapid and may produce false localising clinical signs. The epileptogenic zone may be hidden in the depths of sulci or may be only to be seen later over a disappointingly widespread area. Rasmussen found that most patients with neocortical extrahippocampal epilepsy have sizeable epileptogenic zone and are not helped with small resections. Seizures may begin in or near eloquent cortex where adequate resection would result in unacceptable disability. In the present series results of resections of extratemporal focus were marginally inferior to the results of temporal lobe series. Eloquent cortices showing epileptogenic focus often limited the extent of resection, which ultimately led to a poorer outcome. Specific protocols need to be developed for specific lobes like those existing for temporal lobe epilepsy. In this sub set of intractable epilepsy, multiple subpial trasections are certainly worth a close look and further investigation are required to see if the encouraging results of Morell et al can be substantiated.
Temporal lobe epilepsy : Jensen extensively reviewed the world literature on the outcome following temporal lobectomy between 1928 and 1973 and reported that 43.6% were seizure free, 18% had >75% reduction in seizure frequency, 16.5% had 50-75% reduction and 17.3% had no change in seizure frequency. In 1983, Rasmussen reported 894 patients operated between 1928 and 1980, in which 22% were seizure free since discharge, 15% were seizure free after some early attacks, 13% had occasional attacks, 13% had a marked reduction of seizures and 37% a moderate reduction of seizure frequency. At the 1986 International Conference on the surgical treatment of epilepsy, 40 centres completed a survey of their surgical results in patients operated between 1949 and 1984. This report included outcome for 2336 patients. 55.5% were reported to be seizure free for at least 2 years with or without auras, 27.7% had a worthwhile improvement and 16.8% had no improvement. In our series of 58 patients having undergone temporal lobe surgery for nontumoural epilepsy, 47% were seizure free, 10% had rare seizures, 16% had worthwhile improvement and 27% had no improvement. It is quite obvious from comparison of results from various centres,,,,,,,,,, that although the results show a remarkable similarity, there is a wide range in the outcome.
Factor influencing outcome with respect to seizures Pre operative factors : Patients with brain damage are more seizure prone than healthy individuals and are less likely to go into remission. Retarded patients with seizures have higher rates of intractable epilepsy than the non retarded patients. Patients with full scale intelligence quotients under 70 are usually not considered for resective surgery in most centers because there are often diffuse or multifocal lesions and surgical outcome is less favourable. Our study also concurs with these results in that the surgical outcome with respect to seizures was far inferior in the mentally retarded group when compared to the non retarded group. Keeping these in mind one must consider that mental retardation does not constitute an absolute contraindication for surgery. It has been said that alleviation of seizures does not significantly improve the life style of severely retarded patients though this view has never been substantiated. We are however of the view that in a developing country, reduction of seizure frequency to any degree and reduction in AED dosages if possible will help in the rehabilitation of the severely retarded patient and will also greatly help the family members involved in the care of the patient. Retarded patients however must be able to cooperate with the presurgical evaluation at least to a bare minimum degree and therefore their referral for epilepsy surgery should be considered on an individual basis.
Pre operative EEG findings, both ictal and interictal as predictors of outcome have been evaluated in several reports., There is a good deal of experimental evidence to support the view that if a certain area always generated the interictal spikes, that area probably also generates the habitual seizures. Numerous clinical reports have also been published suggesting that this assumption may be false.,, The study of Dodrill et al identified a highly localised interictal scalp EEG focus as a predictor of outcome. In our study we found that the scalp EEG used in association with semi invasive EEG (for temporal lobe epilepsy) localised the epileptiform abnormality strictly to one lobe, which was also a predictor of outcome.
Perioperative Factors : Irrespective of the mode of anaesthesia, ECoG can be used to `tailor' the resection as is frequently done in many centres. The surgeons at Montreal Neurological Institute tended to `chase spikes' on the lateral cortical margins of resections. They noted the interesting phenomenon of `activation by partial excision'. Areas that were quiet on the first ECOG sometimes became active after resection of the temporal tissue. Bengzon et al correlated the presence of these persistent ECoG abnormalities with a less favourable outcome. Gloor stated that the relationship of persistent spiking and adverse outcome is `of a statistical nature and the predictive value of the post excision electrocorticogram for a given individual patient is relative'. Falconer's group also felt that post excision spikes did not correlate with adverse outcome as long as the main discharges had been anterior. The study of Wyllie et al recently showed no correlation between spikes on the post excision ECoG and less favourable outcome. We follow the policy of tailoring the resection based on the ECoG and cortical stimulation or evoked potential mapping. Any residual spikes are then resected if possible without incurring unacceptable deficits. In our study we found that the post excision persistent spikes did adversely influence the outcome.
Surgery for intractable non tumoural epilepsy in this study yielded total or near total seizure control in 53% of patients and 20% had a worthwhile improvement. The fact that factors like mental retardation and pre operative scalp EEG influence seizure outcome, underscores the need for careful case selection for surgery, when the limits of medical management for epilepsy have been reached. Electrocorticography is a useful means to `tailor' the resection in focal onset epilepsy and post excision spikes should be `chased' as it has been shown that residual post excision spikes adversely influence the outcome. As health care economics assumes greater importance in medicine, there is a need to define the relative costs and benefits of epilepsy surgery to the individual and society. Changes in social functioning, employment status and quality of life after epilepsy surgery need to be more carefully studied.