Thomas Kral

Focal Cortical Dysplasia of Taylor's Balloon Cell Type: A Clinicopathological Entity with Characteristic Neuroimaging and Histopathological Features, and Favorable Postsurgical Outcome

Summary: Background and Purpose: Focal cortical dysplasia of Taylors balloon‐cell type (FCD‐BC) are a frequent cause of pharmacoresistant epilepsy in young patients. In order to characterize FCD‐BC, we coupled MRI and histopathology, and analyzed the clinical outcome following epilepsy surgery.

The CD34 epitope is expressed in neoplastic and malformative lesions associated with chronic, focal epilepsies.

Abstract The etiology and pathogenesis of complex focal lesions associated with chronic, intractable epilepsy are largely unknown. Some data indicate that malformative changes of the central nervous system may preceed the development of gangliogliomas and other epilepsy-associated neoplasms. In the present immunhistochemical study, we have examined epilepsy-associated lesions for CD34, a stem cell marker transiently expressed during early neurulation. Surprisingly, most tissue samples from patients with chronic epilepsy (n = 262) revealed neural cells immunoreactive for CD34. Prominent immunoreactivity was detected in gangliogliomas (74%), low-grade astrocytomas (62%) and oligodendrogliomas (59%). Only 52% of non-neoplastic, malformative pathologies, such as glio-neuronal hamartias or hamartomas showed solitary or small clusters of CD34-immunoreactive cells. None of the adult control tissues (n = 22), none of the specimens obtained from the developing human brain (n = 44) and none of those tumor samples from patients without epilepsy (n = 63) contained CD34-immunoreactive neural cells. However, a malignant teratoma with microscopic features of early neural differentiation displayed a focal CD34-immunoreactive staining pattern. The majority of CD34-immunoreactive cells co-localized with S-100 protein and a small subpopulation was also immunoreactive for neuronal antigens. CD34 may, thus, represent a valuable marker for the diagnostic evaluation of neoplastic and/or malformative pathological changes in epilepsy patients. The CD34 immunoreactivity of these lesions indicates an origin from dysplastic or atypically differentiated neural precursors. Further studies may elucidate the functional significance of CD34 expression during the pathogenesis of epilepsy-related focal lesions as well as during neurogenesis.

Outcome of epilepsy surgery in focal cortical dysplasia

Objective: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. Methods and subjects: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). Results: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. Conclusions: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies.

Analysis of different types of resection for pediatric patients with temporal lobe epilepsy.

OBJECTIVEResection strategies for the treatment of temporal lobe epilepsy (TLE) are a matter of discussion. Few data on the significance of resection type are available for pediatric patients with TLE. METHODSData for a series of 89 children who were surgically treated for TLE were analyzed. A first cohort of patients were mainly surgically treated with anterior temporal lobectomies. For a second cohort, resections were preoperatively “tailored” to the lesion and presumed epileptogenic area. RESULTSThe follow-up period was 46 months (range, 14–118 mo). Seventy-seven patients (87%) attained satisfactory seizure control (82% Engel Class I and 5% Class II). For 12 patients (13%), seizure control was unsatisfactory (8% Class III and 5% Class IV). Anterior temporal lobectomies resulted in 94% satisfactory seizure control (33 patients), whereas the success rates were only 74% (20 patients) for amygdalohippocampectomy (AH) (P = 0.023) and 77% (13 patients) for lesionectomy plus hippocampectomy (not significant). All patients who underwent purely lateral temporal lesionectomies became seizure-free (14 patients). Logistic regression revealed the factors of AH (P = 0.021) and left-side surgery (P = 0.017) as significant predictors of unsatisfactory seizure control. Satisfactory seizure control was not dependent on the histopathological diagnoses. There was a low rate of verbal memory deterioration after left-side operations. Neuropsychological deterioration was rare after right temporal resections. Attentional and contralateral functions improved after surgery. CONCLUSIONSurgery for the treatment of juvenile TLE is successful and safe, but the resection type may influence outcomes. Results after AHs were disappointing, probably because of difficulties in precise localization of the epileptogenic focus among children. Neuropsychological results demonstrated minimal rates of deterioration and significant improvements in contralateral functions. Surgical treatment of juvenile TLE should be encouraged, but the use of especially left AH should possibly be restricted.

Transsylvian keyhole functional hemispherectomy.

OBJECTIVETo describe the technical steps, advantages, and limitations of a quicker, minimal-exposure, functional hemispherectomy procedure developed from a hemispherical deafferentation technique previously described. METHODSThe surgical approach using the transsylvian/transsulcal passage to the ventricular system, with the anatomic orientation points and key features for planning of the small trepanation, is described. Through a linear incision, a craniotomy (4 × 4 to 4 × 5 cm) is placed over the sylvian fissure. Transsylvian exposure of the circular sulcus allows transcortical exposure of the entire ventricular system, from the frontal horn to the temporal horn encircling the insular cortex. The frontobasal and mesial white matter is disconnected via the intraventricular approach, with a callosotomy. An amygdalohippocampectomy completes the dissection. The experience with 20 patients who were treated using the transsylvian keyhole hemispherectomy technique is summarized. RESULTSThe operation time was significantly shorter (mean, 3.6 h) than with the Rasmussen technique (mean, 6.3 h) and 25% shorter than with the transcortical perisylvian technique (mean, 4.9 h). The proportion of patients requiring blood replacements was lower (15 versus 58%), as was the mean amount of transfused blood. The mean follow-up period was 46 months; 88% of patients were in Engel Outcome Class I, 6% in Class III, and 6% in Class IV. CONCLUSIONThe transsylvian keyhole procedure has been demonstrated to further reduce operation time and the need for blood replacement. It is most easily performed in cases with enlarged ventricles or perinatal ischemic cysts and is not recommended for hemimegalencephaly. The immediate seizure relief was satisfying. This minimal-exposure approach seems to be a satisfying alternative among possible functional hemispherectomy procedures.

Vagus nerve stimulation: clinical experience in a large patient series.

Summary During the last decade, intermittent electrical stimulation of the left cervical vagus nerve was established as a new add-on treatment of drug-resistant seizures. Particularly in Europe, the acceptance of vagus nerve stimulation (VNS) was tentative in the beginning because of unknown mechanisms of action. We report the outcome in a sample of 95 adult patients with drug-resistant seizures who have received implants since 1998. The last available follow-up data are included. Unavoidable medication changes (e.g., intoxication) were accepted to examine VNS under usual clinical conditions. Median percentage of reduction in seizure frequency as compared to baseline was 30%. The seizure responder rate (≥50% reduction) was 45%. Four patients experienced total release from seizures. Adverse effects were mild in general. Seizure outcome was positively correlated with VNS duration. No potential clinical factor (e.g., syndrome, cause, or lesion) could be identified as an indicator of favorable outcome. Patients with on stimulation-on periods of 30 seconds (standard cycle) had a better outcome than patients with stimulation-on periods of 7 seconds (rapid cycle). During an embedded, randomized, controlled trial, no evidence was found for a differential outcome of initial standard cycle versus initial rapid cycle stimulation conditions. Taking into account the good cost-benefit ratio as well as positive effects on well-being, VNS has to be considered an appropriate strategy for the add-on treatment of drug-resistant seizures, particularly in cases not suitable for epilepsy surgery.

Surgical Treatment for Refractory Temporal Lobe Epilepsy in the Elderly: Seizure Outcome and Neuropsychological Sequels Compared with a Younger Cohort

Summary:  Purpose: Surgical treatment of refractory temporal lobe epilepsy (TLE) is promising for selected patients, but only little experience has been acquired in operating on older patients, especially with limited resections. We intend to delineate clinical and surgical factors influencing outcome in patients older than 50 years at operation and to compare the results with those of a younger patient cohort.

Lesional mesial temporal lobe epilepsy and limited resections: prognostic factors and outcome

Objectives: To evaluate the influence of clinical, investigational, surgical, and histopathological factors on postoperative seizure relief in patients with mesial temporal lobe epilepsy (MTLE) due to lesions other than ammonshornsclerosis (AHS). Methods: Of 738 patients operated for TLE, 78 patients underwent limited resections for lesional MTLE (1990–2000). Seventy four patients with a follow up of more than one year were included. The preoperative clinical, neuropsychological, electroencephalogram, and neuroimaging characteristics were prospectively collected in a database. The histopathological material was re-examined. Results: The mean follow up was 49 months. Fifty eight patients were classified as seizure free (78.4% Class I), and six as almost seizure free (8.1% Class II), grouped together as satisfactory seizure control (64 patients, 86.5%). Five patients (6.8%) were categorised in Classes III and IV, respectively. These were grouped as unsatisfactory seizure control (10 patients, 13.5%). Surgical procedures were: 32 amygdalohippocampectomies (AH), 17 partial anterior AH, 15 AH plus polar resection, seven AH plus basal resection, and three AH plus extended temporal lesionectomy. There was no mortality and 2.7% mild permanent morbidity. Seizure relief did neither differ significantly with these approaches, nor with different classes of pathological findings (43 developmental tumours, 12 glial tumours, 10 dysplasias, and nine others). Even operation of dysplasias resulted in 80% satisfactory seizure control. Seizure onset during childhood proved to be a negative predictor for seizure relief (p = 0.020). MRI revealed 73 suspected lesions (98.6%), one dysembryoplastic neuroepithelial tumour was missed, in four cases no structural abnormalities could be confirmed with histopathological exam. Additionally, multifactorial regression revealed the factors “seizure onset after 10 years of age”, “presence of complex partial seizures”, “absence of a neurological deficit”, and a “correlating neuropsychological deficit” as predictive for satisfactory seizure control. Conclusions: “Preoperative tailoring” resulting in limit resections has proven to be safe and to provide a very good chance for satisfactory seizure relief in patients with lesional MTLE.

Focal cortical dysplasia: Long-term seizure outcome after surgical treatment

Background: Studies of long term outcome after epilepsy surgery for cortical malformations are rare. In this study, we report our experience with surgical treatment and year to year long term outcome for a subgroup of patients with focal cortical dysplasia (FCD). Methods: We retrospectively analysed the records of 49 patients (females n = 26; males n = 23; mean age 25 (11) years) with a mean duration of epilepsy of 18 years (range 1–45). Preoperative MRI, histological results based on the Palmini classification and clinical year to year follow-up according to the International League Against Epilepsy (ILAE) classification were available in all patients. Results: 98% of patients had a lesion on preoperative MRI. In addition to lobectomy (n = 9) or lesionectomy (n = 40), 14 patients had multiple subpial transections of the eloquent cortex. The resected tissue was classified as FCD type II b in 41 cases with an extratemporal (88%) and FCD type II a in 8 cases with a temporal localisation (100%). After a mean follow-up of 8.1 (4.5) years, 37 patients (76%) were seizure free, a subgroup of 23 patients (47%) had been completely seizure free since surgery (ILAE class 1a) and 4 patients (8%) had only auras (ILAE class 2). Over a 10 year follow-up, the proportion of satisfactory outcomes decreased, mainly within the first 3 years. During long term follow-up, 48% stopped antiepileptic drug treatment, 34% received a driver’s license and 57% found a job or training. Conclusion: Surgical treatment of epilepsy with FCD is not only successful in the short term but also has a satisfying long term outcome which remains constant after 3 years of follow-up but is not associated with better employment status or improvement in daily living.

Surgery to treat focal frontal lobe epilepsy in adults.

OBJECTIVE To report clinical, neuropathological, and outcome data for a series of adult patients with focal frontal lobe epilepsy (fFLE) who underwent nonlobar resection restricted to the frontal lobe. METHODS Sixty-eight adult cases (24 female and 44 male patients) were included in the study, on the basis of prospectively collected data that were retrospectively evaluated. There were 68 lesionectomies, 17 of which were combined with multiple subpial transection, with a mean follow-up period of 28.4 ± 23.3 months. Cases involving additional extrafrontal surgery were excluded. RESULTS Thirty-seven patients underwent invasive preoperative evaluations, and 31 underwent noninvasive evaluations. Intraoperative electrocorticography was used in 32% of cases. There were 24 tumors, 18 dysgenetic lesions, 14 gliotic lesions, and 10 vascular malformations. Fifteen tumors were of glial origin, one was a dysembryoplastic neuroepithelial tumor, and eight were gangliogliomas. The most common dysgenetic lesions were hamartomas (15 cases). Outcomes (classified into four Engel groups) were as follows: Class I, 54%; Class II, 19%; Class III, 15%; Class IV, 12%. Seizure-free rates were comparable for tumor and dysgenesis cases and were not as good for vascular malformation and gliosis cases. Outcome differences were not significant with respect to aura presence, side of surgery, age at the time of surgery, and age at seizure onset. There were 3 cases of surgical complications, 10 cases of transient neurological disturbances, and 1 case involving a permanent neurological deficit. No deaths occurred. CONCLUSION Outcomes with fFLE surgery have improved, compared with historical series. fFLE resections restricted to the frontal lobe did not yield seizure-free rates as good as those for comparable nonfocal frontal lobe epilepsy series. All fFLE cases demonstrated histological lesions. fFLE surgery was associated with a higher risk of transient neurological deficits, most likely because of the necessity for multiple subpial transection. The outcomes and higher rates of invasive evaluations and intraoperative electrocorticography indicate the special complexities of frontal lobe epilepsy. The permanent neurological disability rate was low in this series, and there were no deaths.