Temporal lobe surgery in Germany from 1988 to 2008: diverse trends in etiological subgroups.

BACKGROUND AND PURPOSE: In the epilepsy community, there is talk that the number of classical patients with early onset temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS) is decreasing. This is counterintuitive, considering the success story of epilepsy surgery, improved diagnostic methods and the current recommendation of early admission to surgery. In order to recognize trends, the development of temporal lobe surgery over 20 years in three major German epilepsy centers was reviewed. METHODS: Age at surgery and duration of epilepsy, which was differentiated according to histopathology (AHS, developmental, tumor, vascular), year of surgery and center, were evaluated in a cohort of 2812 patients from three German epilepsy centers who underwent temporal lobe surgery between 1988 and 2008. The analysis was carried out for the pooled cohort as well as for each center separately. RESULTS: Of all patients, 52% showed AHS. Compared with other pathologies, the AHS group had the earliest epilepsy onset and the longest duration of epilepsy. Across five time epochs, the diagnosis of AHS increased in the first epoch, remaining constant thereafter. Contrary to the trends in other pathologies, in the AHS group the mean age of patients at surgery increased by 7 years and the duration of epilepsy until surgery increased by 5 years. This trend could be replicated in all three centers. As initially hypothesized for all groups, age and duration of epilepsy in other pathology groups remained constant or indicated earlier submission to surgery. CONCLUSIONS: During the first few years studied, most probably due to progress in brain imaging, the proportion of patients with AHS increased. However, despite stable numbers over time, and contrary to the trends in other pathology groups, age and duration of epilepsy in mesial TLE with AHS (mTLE + AHS) increased over time. This supports the hypothesis of a decreasing incidence of AHS. This trend is discussed with respect to disease-modifying factors which have changed the incidence of classical mTLE + AHS or, alternatively, to recent developments in antiepileptic drug treatment, the appraisal of surgery and economic incentives for treatment options other than surgery.

Prognostic factors for surgery of neocortical temporal lobe epilepsy.

OBJECTIVES: In the current classification of epilepsies two forms of temporal lobe epilepsy (TLE) were included: mesial and lateral (neocortical) TLE. We aimed at identifying prognostic factors for the surgical outcome of lesional neocortical TLE. METHODS: We included consecutive patients who had undergone presurgical evaluation including ictal video-EEG and high-resolution MRI, who had TLE due to neocortical lateral epileptogenic lesions, who had a lesionectomy and who had >2-year follow-up. RESULTS: There were 29 patients who met the inclusion criteria. Twenty of them became postoperatively seizure-free. Patients' mean age was 34.8+/-9 years (range 18-52). The age at epilepsy onset was 20.1+/-8 years. We found that left-sided surgery (p=0.048) and focal cortical dysplasia (FCD) on MRI (p=0.005) were associated with non-seizure-free outcome, while lateralized/localized EEG seizure pattern (p=0.032), tumors on the MRI (p=0.013), and a favorable seizure situation at the 6-month postoperative evaluation were associated with 2-year postoperative seizure-freedom (p<0.001). Multivariate analysis indicated that the side of surgery was not an independent predictor. CONCLUSION: More than two-thirds of the patients with neocortical TLE became seizure-free postoperatively. Lateralized/localized EEG seizure pattern and tumors on the MRI were associated with postoperative seizure-freedom, while FCD were associated with a poor outcome. The 6-month postoperative outcome is a reliable predictor for the long-term outcome.

Failed surgery for temporal lobe epilepsy: predictors of long-term seizure-free course.

OBJECTIVES: To identify prognostic factors which predict the outcome 2 years after TLE surgery in those patients who were not seizure-free at the 6-month postoperative examination. METHODS: We included 86 postoperative TLE patients who had undergone presurgical evaluation, including video-EEG and high-resolution MRI, and who had seizures between the second and sixth postoperative months. RESULTS: 32% of patients were seizure-free in the second postoperative year. We found that normal MRI findings and secondarily generalized seizures (SGTCS) preoperatively were associated with a non-seizure-free outcome, while rare postoperative seizures and ipsilateral temporal IED with seizure-free outcome. Newly administered levetiracetam showed a significant positive effect on the postoperative outcome independent of other prognostic factors. Five of seven patients who received levetiracetam became seizure-free (p = 0.006). CONCLUSION: One-third of patients who did not become seizure-free immediately after surgery, eventually achieved long-term seizure freedom. We suggest watching for long-term seizure freedom after failed epilepsy surgery especially in patients who had rare postoperative seizures, focal MRI abnormality, ipsilateral temporal spikes, or no SGTCS preoperatively. Levetiracetam may have a positive effect on postsurgical seizures.

Vagus nerve stimulation: predictors of seizure freedom.

OBJECTIVES: To identify predictive factors for the seizure-free outcome of vagus nerve stimulation (VNS). METHODS: All 47 patients who had undergone VNS implantation at one centre and had at least one year of follow up were studied. They underwent complete presurgical evaluation including detailed clinical history, magnetic resonance imaging, and long term video-EEG with ictal and interictal recordings. After implantation, adjustment of stimulation parameters and concomitant antiepileptic drugs were at the discretion of the treating physician. RESULTS: Mean (SD) age of the patients was 22.7 (11.6) years (range 7 to 53). Six patients (13%) became seizure-free after the VNS implantation. Only two variables showed a significant association with the seizure-free outcome: absence of bilateral interictal epileptiform discharges (IED) and presence of malformation of cortical development (MCD). Epilepsy duration showed a non-significant trend towards a negative association with outcome. By logistic regression analysis, only absence of bilateral IED correlated independently with successful VNS treatment (p<0.01, odds ratio = 29.2 (95% confidence interval, 2.4 to 353)). Bilateral IED (independent or bilateral synchronous) was found in one of six seizure-free patients and in 33 of 41 non-seizure-free patients. When bilateral IED were absent, the sensitivity for seizure-free outcome was 0.83 (0.44 to 0.97), and the specificity was 0.80 (0.66 to 0.90). CONCLUSIONS: Bilateral IED was independently associated with the outcome of VNS. These results are preliminary because they were based on a small patient population. They may facilitate prospective VNS studies enrolling larger numbers of patients to confirm the results.

Temporal lobe epilepsy with hippocampal sclerosis: predictors for long-term surgical outcome.

Temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS) is the type of epilepsy most frequently operated on. The predictors for long-term seizure freedom after surgery of TLE-HS are unknown. In this study, we aimed to identify prognostic factors which predict the outcome 6 months and 2, 3 and 5 years after epilepsy surgery of TLE-HS. Our working hypothesis was that the prognostic value of potential predictors depended on the post-operative time interval for which the assessment was made. We included 171 patients (100 females and 71 males, aged 16-59 years) who had undergone presurgical evaluation, including video-EEG, who had had MRI-defined HS, and who had undergone temporal lobectomy. We found that secondarily generalized seizures (SGTCS) and ictal dystonia were associated with a worse 2-year outcome. Both these variables together with older age and longer epilepsy duration were also related to a worse 3-year outcome. Ictal limb dystonia, older age and longer epilepsy duration were associated with long-term surgical failure evaluated 5 years post-operatively. In order to determine the independent predictors of outcomes, we calculated multivariate analyses. The presence of SGTCS and ictal dystonia independently predicted the 2-year outcome. Longer epilepsy duration and ictal dystonia predicted the 3-year outcome. Longer epilepsy duration (P = 0.003) predicted a poor 5-year outcome. Conclusively, predictors for the long-term surgical results of TLE with HS are different from those variables that predict the short-term outcome. Epilepsy duration is the most important predictor for long-term surgical outcome. Our results strongly suggest that surgery for TLE-HS should be performed as early as possible.

Characterization of a fast transient outward current in neocortical neurons from epilepsy patients.

A-type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A-type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole-cell voltage-clamp technique. The A-type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about -70 mV. The voltage-dependent activation was fitted with a Boltzmann function, with a half-maximal conductance at -14.8 +/- 1.8 mV (n = 5) and a slope factor of 17.0 +/- 0.5 mV (n = 5). The voltage of half-maximal steady-state inactivation was -98.9 +/- 8.3 mV (n = 5), with a slope factor of -6.6 +/- 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 +/- 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4-aminopyridine or 100 microM flecainide resulted in a reduction of A-type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 microM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A-type current with properties similar to those described for animal tissues.

MRI and EEG findings in surgically treated patients with partial seizures due to neuronal migration disorders, their relations to each other and to surgery outcome.

OBJECTIVES: To evaluate magnetic resonance imaging (MRI) and electro-encephalogram (EEG) findings of patients with therapy-resistant partial seizures due to neuronal migration disorders (NMD), and compare them with each other and with surgery outcome. MATERIAL AND METHODS: The MRI, interictal and ictal EEG findings, and their relations to each other in 41 patients with NMD were compared with class IA surgery outcome. RESULTS: The patients showed an MRI lesion in decreasing frequency from the frontal to the occipital areas. A predominantly extratemporal location of the interictal EEG foci (73.3%) and ictal patterns (82.4%) was therefore apparent, also showing a diminishing frequency from the anterior to the posterior areas. Comparing the EEG foci with the MRI lesions, the same location of the interictal foci was found in 68.4% and of the ictal foci in 52.7%, including several cases with a more widespread EEG focus or MRI lesion. The same location of interictal as well as ictal foci was evident in 85.7%. The most favourable surgery outcome (class IA) was, on average, apparent in patients with an MRI lesion (28.6% vs 25%), a main interictal EEG focus (50% vs 18%) and an ictal seizure pattern (37.5% vs 16.7%) located in the temporal area; likewise, if the interictal focus (30.8% vs 18.2%) and the ictal pattern (31.8% vs 12.5%) showed the same location as the MRI lesion, as well as when the interictal and ictal EEG changes had an equal location (30% vs 20%). CONCLUSION: MRI and EEG recordings show relatively close relations to each other and might be important methods to predict surgery outcome in NMD patients.

Stimulus-induced patterns of bioelectric activity in human neocortical tissue recorded by a voltage sensitive dye.

Stimulus-induced pattern of bioelectric activity in human neocortical tissue was investigated by use of the voltage sensitive dye RH795 and a fast optical recording system. During control conditions stimulation of layer I evoked activity predominantly in supragranular layers showing a spatial extent of up to 3000 microm along layer III. Stimulation in white matter evoked distinct activity in infragranular layers with a spatial extent of up to 3000 microm measured along layer V. The mean amplitude of optical signals close to the stimulated sites in layer I and white matter determined 25 ms following the stimulus, decreased by 50% at a lateral distance of approximately 900 microm and 1200 microm, respectively. Velocity of spread along the vertical stimulation axis reached 0.24 m/s in the supragranular layers (layers I to III) and then decreased to 0.09 m/s following layer I activation; stimulation of white matter induced a velocity of spread in layer V of 0.38 m/s, which slowed down to 0.12 m/s when passing the lower border of lamina IV. The horizontal velocities of spread determined from the stimulation site to a lateral distance of 500 microm reached 0.26-0.28 m/s and 0.28-0.35 m/s for layer I and white matter stimulation, respectively. At larger distances velocity of spread decreased. Increased excitability (Mg(2+)-free solution) had no significant effect on the spatio-temporal distribution of evoked activity as compared with control conditions. There were also no obvious differences between the results obtained in slices, which generated spontaneously sharp waves and those which were not spontaneously active. About 30% of the slices (n=7) displayed a greatly different response pattern, which seemed not to be related in a simple way to the stimulation as was the case in the majority of the investigated slices. The activity pattern of those slices appeared atypical in regard to their deviations of the vertical and horizontal extent of activity, to their reduced spatial extent of activity during increased excitability, to their layer-related distribution of activity, and to the appearance of afterdischarges.Concluding, in 30% of the human temporal lobe slices atypical activity pattern occurred which obviously reflect intrinsic epileptiform properties of the resected tissue. The majority of slices showed stereotyped activity pattern without evidence for increased excitability.

Optical monitoring of neuronal activity during spontaneous sharp waves in chronically epileptic human neocortical tissue.

Functional changes in neuronal circuitry reflected in spontaneously occurring synchronous sharp field potentials (SSFP) have been reported to occur in human brain suffering from chronic epileptogenicity but not in primary nonepileptic tissue from peritumoral resectates. Voltage sensitive dyes and fast imaging were used to visualize spontaneously occurring rhythmic depolarizations correlated to SSFP in chronically epileptic human neocortical slices obtained during epilepsy surgery. Localized and spatially inhomogeneous neuronal depolarizations were found to underlie spontaneous SSFP, which remained unchanged and spatially restricted to foci <750 micrometer diam even under epileptogenic (low-Mg(2+)) conditions. In cases where ictaform paroxysmal activity occurred in low-Mg(2+) medium, neuronal depolarizations were wide-spread but still spatially inhomogeneous, and the events were preferentially initiated at distinct foci. The findings suggest that small neuronal networks are able to establish and maintain synchronous rhythmic and epileptiform activity.

Evaluation with subdural plates in children and adolescents.

Noninvasive EEG examination is not always adequate for the determination of the epileptogenic area. In such cases invasive methods are required. The authors report on their experience with the implantation of subdural plates for the precise ictal and inter-ictal determination of the epileptogenic areal and the stimulation of the eloquent cortex. From December 1992 to December 1997, 97 patients were evaluated in the Bethel epilepsy center using subdural plates. Of these patients, 44 were children or adolescents, who underwent 45 resections. In order to be able to draw differentiated conclusions on the use of subdural plates in children and adolescents, these patients were divided into three age groups: Group 1, 0-5 years (n = 12); Group 2, 6-11 years (n = 13 + 1 repeat evaluation and resection); Group 3, 12-18 years (n = 19). In the groups of children and adolescents examined there were no complications or progress impediments which might give reason to assume that the application of these techniques involves risks or hazards. This has been verified by the results, in which 75% of age Groups 1 and 3 were categorized as 1 a/b or 2d according to the Engel classification.

Minimally invasive lesionectomies through a stereotactically guided working sleeve.

The authors report on their experience of lesionectomies close to or in the thalamus, basal ganglia, third ventricle and in the temporal lobe. The resection itself is performed stereotactically, MRI or CT guided, either microscopically or endoscopically through a sleeve designed by one of the authors and named PAN working sleeve. Over the last four years this new minimally invasive technique has been successfully applied in 39 cases. Eighteen patients with 11 astrocytoma (6AA, 5All), 5 cavernoma and 2 metastases (melanoma, adenocarcinoma) of the basal ganglion-thalamus area and the trigonum were resected by means of a frontal or an occipital burr-hole, whereby in some cases there were subtotal resections. With four of these patients an existing hemiparesis increased by one degree (according to the proposal of the British Medical Research Council I-V). Seventeen patients with lesions in the foramen Monroi and in the third ventricle also underwent operation by means of frontal access, and in each case there was a total resection. Two of the patients required a shunt due to a persistent hydrocephalus internus. In one of these cases there was intraventricular bleeding which necessitated an intra-operative craniotomy. Four patients with intractable epilepsy were operated through a burr-hole in the anterior area of the os zygomaticum. Three patients were submitted to a selective resection of mesial structures and one to an anterior temporal lobe resection. To date the four patients have had no further seizures and no deficits have been observed.

[Fractionated afterloading irradiation as a new procedure for treating inoperable brain tumors]. / Fraktionierte Afterloading-Bestrahlung als neues Verfahren zur Therapie inoperabler Hirntumoren.

A method is shown for fractionated afterloading therapy of inoperable cerebral tumors. A 3 mm thick, tube-form applicator of noble metal which is closed at the front side is implanted into the tumor by a stereotaxic technique and firmly screwed together with the osseous calotte. It remains there up to two weeks, giving full mobility to the patient. The afterloading therapy with a moving iridium source is performed one or two times per day with individual doses of 2 Gray. Thus, the chronological and--to a certain extent--also the spatial dose distribution is variable when applying this method.