The study included patients operated on at King's College Hospital between September 1999 and May 2004 for the treatment of medically refractory epilepsy. Four patients who had surgery for Landau–Kleffner syndrome within this period were excluded from the study, as the main aim of surgery in these patients was to improve language rather than the epilepsy. We have studied two patient populations: first, a group of 136 consecutive patients (70 male, 66 female, median age 33 years, age range 2 to 59 years) who were surgically treated for epilepsy at King's College Hospital within the recruiting period; and second, 105 consecutive patients assessed with chronically implanted intracranial electrodes within the same period (52 male, 53 female, median age 31 years, age range 1 to 58 years). Sixty patients belonged to both groups (they were assessed before surgery using chronically implanted intracranial electrodes and were then operated on). All 41 patients who had normal neuroimaging were assessed using intracranial electrodes. Among these 41 patients, 21 had been operated on at the time of analysis and 20 had not. The composition and interrelations of these patient populations can be seen in fig 1. In patients assessed using chronically implanted intracranial electrodes, the type, number, and position of the electrodes were determined by the location of the suspected epileptogenic zone in each patient, according to findings from clinical history, neuroimaging, neuropsychology, scalp electroencephalographic recordings, and videotelemetry. The selection criteria and implantation procedure have been described elsewhere11
and are summarised below.
Figure 1Composition and interrelations of the patient populations involved in the study: 136 patients had been operated on at the time of analysis and 105 had been assessed using intracranial recordings; 60 patients had been assessed with intracranial (more ...)
Among the 136 surgically treated patients, 101 had temporal lobe resections, 32 had extratemporal surgery, and three had a resection involving the temporal and occipital lobes. One hundred and twelve had a follow up period of at least 12 months at the time of analysis (83 temporal, 26 extratemporal, and three temporo‐occipital resections). For analysis, the three patients who had temporo‐occipital resections were considered as extratemporal.
Among the 105 patients assessed with intracranial electrodes, 63 proved to have temporal lobe epilepsy, 39 extratemporal epilepsy, and in three the source of their epilepsy remained unknown. Of the 105 patients, 60 were operated on (39 had temporal procedures, 19 had extratemporal procedures, and two had a temporo‐occipital resection). Among these 60 surgically treated patients, 53 had a follow up period of at least 12 months at the time of analysis (35 temporal, 16 extratemporal, and two temporo‐occipital resections). For analysis, the two patients who had temporo‐occipital resections were considered as extratemporal.
All patients with normal neuroimaging were assessed with intracranial electrodes.
Used electrodes were disposed of to prevent transmission of Creutzfeld–Jacob disease. Prophylactic antibiotics were prescribed (intravenous cefuroxime, 750 mg three times daily) during the period of recording with intracranial electrodes to minimise the risk of infection.
Resections were guided by preoperative subacute intracranial recordings or intraoperative electrocorticography and by intraoperative image guidance (Stealth, Medtronic, Houston, Texas, USA).
Indications for implantation of intracranial electrodes
The following two patient groups had surgery without studies with intracranial electrodes.
Lesionectomy—Patients with a discrete cerebral lesion demonstrated by neuroimaging at a non‐functionally eloquent site, with location concordant with seizure semiology, topography of interictal discharges, topography of ictal onset on the scalp EEG if known, distribution of background abnormalities in the interictal EEG, and neuropsychological findings.
Temporal lobectomy—Patients with a consistent single temporal site of seizure onset on scalp EEG telemetry, at or preceding clinical semiology, concordant with seizure semiology, distribution of background abnormalities in the interictal scalp EEG, neuroimaging, and neuropsychological findings.
Patients not fulfilling these criteria had studies with intracranial electrodes. These were patients in whom a hypothesis was available to explain findings to date, particularly any non‐convergence of evidence from different tests, and this hypothesis was testable with intracranial electrode implantation. The choice and placement of intracranial electrodes depended on the working hypothesis with regard to the site of seizure onset. As intracerebral (depth) electrodes are perceived to be more invasive that subdural recordings, the latter were generally preferred if possible. When temporal lobe seizures were suspected but laterality was uncertain, recordings with bilateral 8‐contact subtemporal strips inserted through frontotemporal burr holes were carried out. If this procedure yielded inconclusive results, a second intracranial recording was undertaken with bilateral temporal intracerebral electrodes implanted using a lateral approach. When seizures where thought to arise from the frontal lobes, but laterality was uncertain, bilateral intracerebral electrodes were used. When the seizures were thought to arise from the cerebral convexity, from the paracentral lobule, or from the supplementary motor area, mats or strips were used, usually implanted unilaterally.
Surgery was excluded in the following circumstances:
- the EEG showed predominantly generalised interictal EEG discharges in the absence of a discrete lesion on neuroimaging;
- independent sites of electrographic seizure onset were demonstrated in more than one lobe;
- generalised discharges were seen at or immediately preceding clinical seizure onset;
- a site of seizure onset was identified which could not be resected without unacceptable complications and was unsuitable for multiple subpial transection;
- bilateral or multilobar seizure onset was seen with intracranial recordings and there was no clear alternative hypothesis for further studies with intracranial recordings.
Subdural or intracerebral (depth) electrodes (supplied by AdTech Medical Instruments, Wisconsin, USA) were implanted in all 105 patients assessed with intracranial electrodes.
Subdural electrodes were either strips or mats. Each strip consisted of a single row of four to eight platinum disk electrodes spaced at 10 mm between centres. The disks were embedded in a 0.7 mm thick polyurethane strip which overlapped the edges, leaving a diameter of 2.3 mm exposed, and recessed approximately 0.1 mm from the surface plane. Mats contained rectangular arrays of 12, 16, 20, 32, or 64 similar platinum electrodes.
Intracerebral (depth) electrodes consisted of multicontact flexible bundles of electrodes, which were implanted stereotactically under MRI guidance. The electrodes consisted of six to 10 cylindrical 2.3 mm long platinum contacts separated by 5 mm between centres of adjacent electrodes of the same bundle.
Nine patients had depth electrodes in temporal structures only, five had depth electrodes in extratemporal regions only, 21 had temporal and extratemporal depth electrodes, 31 had subdural temporal strips, nine had subdural extratemporal strips, 29 had subdural temporal and extratemporal electrodes, and one had subdural and depth electrodes in temporal and extratemporal regions.
All patients had cerebral MRI. The MRI protocol included the following MRI sequences, which were used in all patients: (1) coronal fast spin echo T2 weighted (time of echo (TE)
85 ms, time of repetition (TR)
4300 ms), 3.5 mm slice thickness, 0.5 mm gap, perpendicular to temporal horn; (2) coronal FLAIR (fluid attenuated inversion recovery) (TE
115 ms, TR
8500 ms, inversion time (TI)
1900 ms), 3.5 mm slice thickness, 0.5 mm gap, perpendicular to temporal horn; (3) coronal IR prepped SPGR, T1 weighted (IR
inversion recovery, SPGR
spoiled gradient recalled), flip angle 30°, TE
2.8 ms, TR
14 ms, 1.5 mm partition; (4) axial fast spin echo T2 weighted (TE
75 ms, TR
3500 ms), 5 mm slice thickness, 2 mm gap, parallel to AC–PC line.
Hippocampal volumetry was not used regularly, as it is not widely accepted as routine clinical practice and visual assessment by experienced radiologists appears to be almost as good in detecting hippocampal atrophy.12
Unclear non‐specific changes of dubious significance were not considered as lesions. Thus patients showing only such changes were included in the group of normal neuroimaging. In equivocal cases, images were reformatted on an Advantage Windows workstation (GE Medical systems).
Computed tomography (CT) was not done routinely. Of the 136 surgically treated patients, 27 had CT, mainly to assess whether there was calcification in the lesion shown on MRI, or to check the position of intracranial electrodes or whether there was a haemorrhage as a complication of the implantation.
All resected specimens were fixed in formalin and serially sliced. The slices were processed to paraffin. In specimens with no macroscopic abnormality, all the slices were processed. When a macroscopic lesion was noted, blocks were taken from the lesion, from regions adjacent to the lesion, and from the margins of the specimen. Sections were stained with haematoxylin and eosin, luxol fast blue/cresyl violet, and the silver impregnation method of Glees and Marsland, and immunocytochemistry was carried out by the ABC method for glial fibrillary acidic protein (Dako polyclonal, 1:1250) and neurofilament 200KD (Dako monoclonal, 1:800). Archived slides from all the patients were reviewed.
Surgical outcome with regard to seizure control was determined at regular postoperative follow up assessments by GA and RS. Surgical outcome was classified in four grades according to the following criteria, which are largely based on Engel's classification13
: grade I, free of disabling seizures; grade II, almost seizure‐free (three or fewer diurnal or nocturnal seizures per year); grade III, worthwhile improvement (but more than three diurnal or nocturnal seizures per year); grade IV, no significant improvement. For analysis, grades I and II were considered a favourable surgical outcome, while grades III and IV were considered poor.
Two tailed χ2 testing with one degree of freedom was used to compare the proportion of patients with favourable outcome between the groups of patients with normal neuroimaging and with abnormal neuroimaging findings. When there were expected frequencies below 5, two tailed Fisher's exact test was used. Existence of significant differences was assumed if at p<0.05. A statistical trend was assumed at p>0.05 but <0.2.