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.

Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222.

BACKGROUND: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma. METHODS: To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls. RESULTS: The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10(-24), minor allele frequency ~0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown. CONCLUSION: Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3'-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma.

A comprehensive analysis of early outcomes and complication rates after 769 craniotomies in pediatric patients.

PURPOSE: Perioperative complications following craniotomy in pediatric neurosurgery have received little attention. We analyzed perioperative complications and early outcomes following craniotomy in a large cohort of pediatric patients. METHODS: A retrospective chart review identified 769 operations (27 % epilepsy surgery, 26 % trauma, 21 % tumor, 7 % vascular, 4 % infections, 14 % other, and 88 % supratentorial) in 641 patients <16 years (mean age 8.5 years). We recorded all perioperative complications and functional outcomes 30 days after surgery. RESULTS: Excluding epilepsy surgery cases, 17.5 % patients had emergency surgery. There were 38 new major neurological deficits (5.0 %; excluding deficits incurred as part of the surgical strategy). New neurological deficits occurred more frequently following operations for brain tumors, when compared to other surgeries (P < 0.001), and after surgery for infratentorial lesions (P < 0.001). Local complications occurred in 3.9 %, systemic complications in 2.5 % of patients. Ventricular shunting or endoscopic ventriculostomy was necessary in 87 patients (11.3 %). Surgical mortality was 2.0 % (including moribund patients after trauma or vascular incidence). Preoperative Karnofsky Performance Index (KPI) and the incurrence of new neurological deficits proved the most powerful predictors of functional outcome. Emergency surgery or repeat craniotomies were not correlated with increased rates of local complications. CONCLUSIONS: Craniotomies for pediatric patients carry a low morbidity and mortality. Systemic complications seem to occur less often in the pediatric than in the adult population. Good surgical outcomes require a proper balance between local pediatric neurosurgical care for emergency cases and centralized treatment of more difficult cases.

Training charter in epilepsy surgery added competence.

The present Training Charter in Epilepsy Surgery Added Competence constitutes the third stage of a program initiated by the European Society for Stereotactic and Functional Neurosurgery (ESSFN) and substantiated in close collaboration with the Union Européennedes Médecins Spécialists (UEMS) and the European Association of Neurosurgical Societies (EANS). This program aims to raise the standards of clinical practice by guiding education and quality control concepts. The particular sections of this Charter include: definitions and standards of added competence training, relations of the Epilepsy Unit with the Neurosurgical Department, duration of epilepsy surgery fellowship, institution and training program director requirements, operative totals for epilepsy surgery, educational program, individual requirements, and evaluation and qualification of the trainees. The specification of all these requirements is expected to improve harmonisation and quality of epilepsy surgery practice across Europe, and enhance the clinical activity and the scientific productivity of existing neurosurgical centres.

Pediatric functional hemispherectomy: outcome in 92 patients.

BACKGROUND: The revival of epilepsy surgery after the introduction of modern presurgical evaluation procedures has led to an increase in hemispherectomy or hemispherotomy procedures. Since a large part of our pediatric series was done using a newer hemispherotomy technique, we focus mainly on the outcomes after a recently developed hemispherotomy technique (transsylvian keyhole). METHODS: Ninety-six pediatric patients (aged 4 months to 18 years, mean 7.3) were operated on between 1990 and 2009; 92 were available with follow-up. RESULTS: The most frequent diagnosis was porencephaly in 46 % of all patients. Progressive etiologies were present in 20 % and developmental etiologies in 22 %. At last available outcome (LAO), 85 % of the patients were seizure free (ILAE class 1). Year-to-year outcome was rather stable; usually over 80 % were class 1 for up to 13 years (n = 24). Of 92 assessable patients, 71 were treated with the transsylvian keyhole technique, with 89 % being seizure free. The overall shunt rate was 5.3 % for the whole series and 3 % for the keyhole technique subgroup. Mortality was 1 of 96 patients. Excluding patients with hemimegalencephaly (HME), patients with the shortest duration of epilepsy and the lowest age at seizure onset had the highest rates of seizure freedom. The etiology does influence outcome, with HME patients having the poorest seizure outcome and patients with Sturge-Weber syndrome and porencephaly having excellent seizure control. CONCLUSION: Hemispherotomies/functional hemispherectomies are very effective and safe procedures for treating drug-resistant epilepsy with extensive unihemispheric pathology. Etiology and surgery type clearly influence seizure outcome.

Seizure outcome, functional outcome, and quality of life after hemispherectomy in adults.

BACKGROUND: Functional hemispherectomy is a well-established method in childhood epilepsy surgery with only a few reports on its application in adults. METHODS: We report on 27 patients (median age 30 years, range 19-55) with a follow-up of more than 1 year (median 124 months, range 13-234). Etiology was developmental in two (one schizencephaly, one hemimegalencephaly), acquired in 21 (two hemiatrophy, 17 porencephaly, two postencephalitic), and progressive in four (Rasmussen's encephalitis). RESULTS: At last available follow-up, 22 patients were seizure free (81 % ILAE class 1), one had auras (4 % ILAE class 2), one had no more than three seizures per year (4 % ILAE class 3). Thirty-seven percent were without antiepileptic drugs. Seventeen patients of 20 responding patients stated improved quality of life after surgery, one patient reported deterioration, and two patients reported no difference. Additionally, a self-rated postoperative functional status and changes compared to the pre-operative status was assessed. Six patients improved in gait, ten remained unchanged, and four deteriorated. Three patients improved in speech, none deteriorated. Hand function got worse five times, and in 15 cases remained unchanged. There was no mortality, one bone flap infection, and one subdural hematoma. Hydrocephalus was seen in three cases (12 %). CONCLUSIONS: It is possible to achieve good seizure outcome results despite long-standing epilepsy across a variety of etiologies, comparable to epilepsy surgery in pediatric patients. Adult patients do not have to expect more problems with new deficits, appear to cope quite well, and mostly profit from surgery in several quality of life domains.

Cerebral cavernous malformations and intractable epilepsy: the limited usefulness of current literature.

BACKGROUND: Cerebral cavernous malformations (CCM) are known to be highly epileptogenic lesions. A number of studies on CCM surgery deal with CCM-associated seizures and/or epilepsy. In order to counsel patients with CCM-associated epilepsy, clear results from such studies would be highly useful. This study reviews the current literature with the aim to assess its usefulness for presurgical decision-making with emphasis on differentiating outcomes in different epilepsy types. METHODS: A systematic Medline search identified 27 studies between 1991 and 2009 through the keywords "cavernomas, cavernous, hemangioma, AND epilepsy, AND surgery". They were analysed with regard to clarity of definition of epilepsy subtypes, precision of definition of drug-resistant epilepsy, information on surgical procedure and presurgical workup, seizure outcome and length of follow-up. RESULTS: Twenty studies included only surgically treated patients. Three types of epilepsy were defined: drug-resistant epilepsy, epilepsy or single/sporadic seizures. In 12 of 27 studies, at least one of these categories remained unclear. The classic definition of drug-resistant epilepsy was not used in the vast majority of studies, with many groups using their own definition. In 30%, the surgical procedure was not described precisely, although 52% of studies used a differentiated preoperative evaluation. Seizure outcome was described using a widely accepted classification in only 48% of series, and in over half of the studies outcome results contained cases with insufficient length of follow-up. CONCLUSIONS: A large proportion of recent studies on surgery for CCM-associated epilepsy are not using criteria and definitions for the classification of epilepsy and outcome that are commonly used by epileptologists or epilepsy surgeons. This results in the limited usefulness of a large part of the literature for the purpose of preoperative counselling a patient with CCM-associated epilepsy.

Insular lesionectomy for refractory epilepsy: management and outcome.

Surgical treatment of deep-seated insular lesions causing refractory epilepsy is thought to be difficult due to the complicated accessibility and close proximity of eloquent areas. Here we report our experience with insular lesionectomies. Twenty-four patients (range 1-62 years, mean 27) who underwent epilepsy-surgery for a lesion involving the insular region, were identified from the epilepsy surgery data bank. We analysed pre-surgical diagnostics, surgical strategy and postoperative follow up concerning functional morbidity and seizure outcome (range 12-168 months, mean 37.5). Eight patients had pure insular lesions, in 16 cases the lesion extended either to the frontal (n = 3) or temporal lobe (n = 8) or was multilobar (n = 5). Sixteen resections (66.7%) were done on the right side. Six patients required invasive EEG-recording, three patients received intra-operative electrocorticography. In seven patients only subtotal resection of the insular lesion was possible due to involvement of eloquent areas. Thirteen patients suffered from glial/glioneural tumours (WHO grades I-III), 11 from non-neoplastic lesions. Postoperatively, one patient had a hemihypesthesia and one patient had a deterioration of a pre-existing hemiparesis; two patients had a hemianopia as calculated deficit (mild permanent morbidity 16.6%). According to the ILAE-classification, 15 patients were completely seizure free (62.5%, ILAE 1). Around 79.2% had satisfactory seizure outcome (ILAE 1-3). In selected patients an individually tailored lesionectomy of insular lesions can be performed, which is acceptably safe and provides a high rate of satisfactory seizure relief. Even subtotal resection can result in good seizure control.

Cognitive outcome of pediatric epilepsy surgery across ages and different types of surgeries: A monocentric 1-year follow-up study in 306 patients of school age.

OBJECTIVE: The neuropsychological outcome of pediatric epilepsy surgery has been reported before, but only few studies compared different major types of surgery in differentially located epilepsies. METHODS: Neuropsychological performance of 306 children and adolescents (ages 6-17 years) were assessed before and one year after epilepsy surgery. Individual impairments, changes into and out of impairment, as well as intraindividually meaningful positive or negative changes were examined. Regression analyses addressed the effects of site, side, pathology, type of surgery, seizure outcome, and drug change on the cognitive and behavioral domains. RESULTS: Preoperatively 85% of the patients had cognitive impairments in at least one domain, 71% had behavioral problems. Postoperatively the number of impaired patients dropped considerably: 21-50% of the patients changed from impaired to unimpaired, individually significant gains were registered in 16-42%. Seizure freedom was achieved in 81% of all patients. The number of antiepileptic drugs decreased significantly. Seizure freedom, a younger age at evaluation, a later age at onset, a lower antiepileptic drug load, and less baseline damage predict better cognitive and behavioral outcomes. Gender, pathology, localization, and lateralization had little or no impact. CONCLUSION: Differentially located and lateralized epilepsies hardly differed in cognition and behavior indicating nonspecific developmental rather than domain specific impairments. Childhood epilepsy surgery is very successful and the functional improvements one year after surgery confirm the general relevance of baseline damage, mental reserve capacities, functional plasticity, the preservation of functional tissues and the functional release due to seizure freedom and drug load reduction.

Intraoperative preservation of corticospinal function in the brainstem.

BACKGROUND: The corticospinal tract features a largely exposed course through the brainstem, and is therefore at risk in many brainstem-related procedures. No large case series on motor-evoked potential (MEP) monitoring during brainstem surgery have been reported as yet. OBJECTIVE: To understand intraoperative MEP changes during brainstem-related surgery, and to explore the value of MEP monitoring for preventing permanent new paresis. METHODS: Myogenic MEPs after transcranial electrical train stimulation were monitored in 70 cases of intraparenchymal (n = 39) and extraparenchymal (n = 31) brainstem-related tumours and vascular lesions. MEP recordings failed in another five cases. Motor outcome and intraoperative MEP results were documented prospectively and correlated for this study. RESULTS: Significant MEP changes occurred in 46% of cases. Stable and only reversibly deteriorated MEPs warranted unimpaired motor outcome (n = 50, 71% of all cases). Irreversible deterioration and reversible loss (n = 19, 27%) indicated a 37% risk for transient deficit. Irreversible loss (one case, 1.5%) predicted permanent paresis. MEPs and motor outcome correlated equally well in intra- and extraparenchymal lesions. Somatosensory-evoked potentials (SEPs) did not reliably reflect motor outcome. Permanent motor deficit occurred in one out five cases (20%) with failed MEP recordings. CONCLUSIONS: MEP monitoring-as opposed to SEPs-is a valid indicator of corticospinal function in brainstem-related surgery, independent from the type of lesion operated on. New deficit occurs only after more pronounced MEP changes than in supratentorial surgery, but complete loss as in spinal surgery is not required. MEPs may help to prevent permanent new paresis.

Epilepsy surgery for insular lesions.

OBJECTIVE: Due to the proximity of eloquent areas of the brain, the surgical treatment of insular lesions causing refractory epilepsy is considered difficult. We report here on our experience in this field. METHODS: We identified 24 patients (age: 1-62 years, mean 27) who underwent epilepsy surgery for an insular lesion from the epilepsy surgery data bank. We analyzed the preoperative diagnostics, surgical strategy and postoperative follow-up (duration: 12-168 months, mean 37.5) for functional morbidity and seizure outcome. RESULTS: Eight patients had strictly insular lesions while, in 16 cases, the lesion extended into the frontal (n=3) or temporal (n=8) lobe, or was multilobar (n=5). Sixteen resections (66.7%) were right-sided. Six patients required invasive EEG with implanted electrodes, while three had the aid of intraoperative electrocorticography. In 12 patients, continuous electrophysiological monitoring was used intraoperatively (phase reversal, motor evoked potentials) and, in seven, neuronavigation. In seven patients, only subtotal resection of the insular lesion was possible due to involvement of eloquent areas, and two patients required repeat surgery to complete the resection. Thirteen patients had glial/glioneural tumours (WHO grades I-III), 11 from non-neoplastic lesions. Postoperatively, two patients (8.3%) had a transient neurological deficit (hemiparesis and dysphasia, respectively). One patient had permanent hemihypaesthesia, another had permanent deterioration of preexistent hemiparesis and two had hemianopia as calculated deficit (16.6% rate of mild permanent morbidity). According to the International League against Epilepsy (ILAE) classification, 15 patients were totally seizure-free (62.5%, ILAE 1) and 79.2% had a satisfactory seizure outcome (ILAE 1-3). CONCLUSION: In selected patients, an individually tailored lesionectomy of insular lesions can be performed, with acceptable safety, to provide a high rate of satisfactory seizure relief. Indeed, even subtotal resection can result in effective seizure control.

Frequent loss of chromosome 9, homozygous CDKN2A/p14(ARF)/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas.

The molecular pathogenesis of pleomorphic xanthoastrocytoma (PXA), a rare astrocytic brain tumor with a relatively favorable prognosis, is still poorly understood. We characterized 50 PXAs by comparative genomic hybridization (CGH) and found the most common imbalance to be loss on chromosome 9 in 50% of tumors. Other recurrent losses affected chromosomes 17 (10%), 8, 18, 22 (4% each). Recurrent gains were identified on chromosomes X (16%), 7, 9q, 20 (8% each), 4, 5, 19 (4% each). Two tumors demonstrated amplifications mapping to 2p23-p25, 4p15, 12q13, 12q21, 21q21 and 21q22. Analysis of 10 PXAs with available high molecular weight DNA by high-resolution array-based CGH indicated homozygous 9p21.3 deletions involving the CDKN2A/p14(ARF)/CDKN2B loci in six tumors (60%). Interphase fluorescence in situ hybridization to tissue sections confirmed the presence of tumor cells with homozygous 9p21.3 deletions. Mutational analysis of candidate genes on 9q, PTCH and TSC1, revealed no mutations in PXAs with 9q loss and no evidence of TSC1 promoter methylation. However, PXAs consistently showed low TSC1 transcript levels. Taken together, our study identifies loss of chromosome 9 as the most common chromosomal imbalance in PXAs and suggests important roles for homozygous CDKN2A/p14(ARF)/CDKN2B deletion as well as low TSC1 mRNA expression in these tumors.

Peri-operative glucocorticoid replacement therapy in transsphenoidal pituitary adenoma surgery: a prospective controlled study.

BACKGROUND: We set out to prospectively study the peri-operative changes of the hypothalamic-pituitary-adrenal axis (HPA), and to test the hypothesis that the peri-operative corticoid replacement regimen used at the authors' institution in patients with impaired HPA undergoing transsphenoidal pituitary adenoma surgery is adequate. METHOD: Thirty seven patients (21 females, 16 males, mean age 50.6 years) underwent transsphenoidal pituitary adenoma surgery (mean tumour diameter 20.6 mm, 13 tumours hormone-secreting). The HPA functions of these patients were classified as impaired (group A, n = 15) or preserved (group B, n = 22) according to the results of a pre-operative corticotrophin releasing-hormone test (CRHT). Eleven patients (9 female, 2 male, mean age 53.6 years) without pituitary adenomas and with a preserved HPA (as assessed by medical history and morning serum cortisol (MSC) measurements), undergoing decompressive surgery for degenerative lumbar disc disease, were also studied (group C). On the day of surgery, the patients of group A received 100 mg hydrocortisone (HC) replacement therapy, which was thereafter gradually tapered off in a standardised fashion. The patients of groups B and C were not treated with corticoids. Pre-operative, intra-operative and post-operative variables of these three patient groups were compared. FINDINGS: The urinary free cortisol excretion (UFC) in group A declined from 6732 +/- 7683 microg/d on the day of surgery to 305 +/- 358 microg/d on the 10(th) post-operative day. In group B, the respective UFC values were 12,851 +/- 16,278 microg/d and 223 +/- 235 microg/d. In both of these groups, the mean UFC did not fall into the normal range during the first ten post-operative days. On none of the post-operative days, was there a significant difference between the UFC of groups A and B. The UFC values of group C dropped from 177 +/- 157 microg/d on the day of surgery to 87 +/- 61 microg/d on post-operative day six, reaching the normal range from the 2(nd) post-operative day onwards. All UFC values of group C were significantly lower than those of group A and B. None of the evaluated clinical, laboratory and MRI parameters, as disclosed by uni- and multivariate analysis, showed any significant influence on the peri-operative UFC values. CONCLUSIONS: The peri-operative UFC of pituitary adenoma patients with preserved HPA was very high, as compared to patients with degenerative lumbar disc disease. The present study showed for the first time, that the proposed regimen of peri-operative corticoid replacement therapy used in patients with pituitary adenomas and impaired HPA raised cortisol levels to match the physiological increase of UFC in patients with pituitary adenoma surgery and preserved HPA. However, although statistically not significant, the UFC of patients with pituitary adenomas and preserved HPA seemed considerably higher on the day of surgery than in patients with pituitary adenomas and HPA impairment. Although there is no evidence to make it mandatory, administration of 150 mg instead of 100 mg HC substitution on the day of pituitary adenoma surgery in patients with HPA impairment may be prudent.

Comparison of two different measurement techniques of hippocampal resection length in temporal lobe epilepsy: results of a prospective study.

BACKGROUND: Magnetic resonance imaging (MRI) volumetry has evolved to a highly sensitive method for presurgical detection of hippocampal sclerosis in temporal lobe epilepsy (TLE). Seizure resolution and neuropsychological sequelae are believed to correlate with extent of resection. Therefore an easy volumetric method to determine extent of resection is desirable. The purpose of this work is to evaluate and compare two different measurement techniques for hippocampal resection length. METHODS: Sixty-one patients with a mean seizure history of 25.1 years and medically intractable TLE were included. They underwent MRI with sagittal acquired 3D T1-weighted spoiled gradient recalled echo sequence in 1 mm(3) isotropic voxel. Hippocampal resection length was calculated with two different methods. In the slice counting method (SCM) the number of consecutive 1-mm-thick slices containing resected hippocampus formation was counted. In the vector method (VM) the sum of the oblique and thus longer distances between the centre points of segmented hippocampal areas on each MRI slice were calculated. RESULTS: Since the hippocampus is a curved body, the resection lengths measured with VM were always larger than measured with SCM. The comparison of resection length expressed in "percent of total length" showed good agreement between the two methods, because unlike the absolute values of resection length, the percentage values are unaffected by the three-dimensional shape of the hippocampus. CONCLUSION: The easier and quicker method of "slice counting" may be used to determine resection length expressed in "percent of total length", giving reliable values for resection length but causing less volumetric work.

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.

Stroke prevention during surgery for deep-seated gliomas.

AIMS OF THE STUDY: New motor deficit after surgery for deep-seated gliomas can occur from subcortical ischemia of the pyramidal tract. Motor evoked potentials (MEPs) validly indicate impending motor tract ischemia in cerebrovascular surgery. This study determines the feasibility and clinical utility of MEP monitoring for ischemic complication avoidance during surgery for deep-seated, specifically insular gliomas. METHODS: MEPs were recorded during 100 operations of insular gliomas. Intraoperative MEP results were correlated with postoperative clinical and imaging results. RESULTS: Useful MEP monitoring was possible in 89/100 cases, 88 of which were assessable since one patient died early postoperatively. Stable recordings warranted unimpaired motor outcome in 47/88 cases (53%). Surgical intervention reversed MEP attenuation in 26 of the remaining 41 cases (30% of the overall series) to prevent motor deficit except transient paresis in 12 (14%). Irreversible MEP changes without loss in eight cases (9%) resulted in only transient new deficit in seven cases, except one with permanent new paresis. Permanent paresis also occurred in seven cases (8%) where complete MEP loss could not be prevented. Permanent paresis arose exclusively through stroke of the deep motor pathways, whereas transient deficit typically corresponded to transitory ischemia of the pyramidal tract. MEP changes attributable to ischemic events frequently occurred spatially and temporally uncorrelated to resection in critical proximity of the motor tract. CONCLUSIONS: Ischemia in deep-seated glioma surgery usually occurs uncorrelated to resection close to the pyramidal tract. MEP monitoring efficiently helps detect ischemia early and to avert definite stroke and permanent new paresis in part of these cases.

Interinstitutional variance of postoperative radiotherapy and follow up for meningiomas in Germany: impact of changes of the WHO classification.

OBJECTIVE: To document and critically analyse the impact of the revised WHO 2000 histological classification for meningiomas on postoperative radiotherapy/radiosurgery indications and MRI follow up protocols. METHODS: The current (2000) WHO classification was used to grade 57 meningiomas treated surgically at one institution. These had been reviewed previously in 1999. All German neurosurgical departments carrying out intracranial microsurgery were asked to detail their guidelines for radiation therapy and follow up for meningiomas of different WHO grades. RESULTS: Use of the current criteria downgraded seven of 15 atypical meningiomas (WHO grade II, MII) to grade I (MI), and four of six anaplastic tumours (WHO grade III, MIII) to grade II. Indications for radiotherapy/radiosurgery and MRI follow up protocols varied substantially with the histological grade and between institutions--for example, after an incomplete resection, radiotherapy/radiosurgery recommendations differed between MI and MII in 30 of 58 units (52%), and between MII and MIII in 34 of 56 units (61%). CONCLUSIONS: Correlative studies combining treatment and outcome data with a standardised histopathological analysis are warranted to define properly the indications for radiotherapy/radiosurgery and follow up protocols after surgery for meningiomas of different histological grades. The use of changing grading paradigms during recent years renders decision making based on local and published experience difficult. The relatively large number of meningiomas classified as atypical/WHO grade II in current practice would argue against an uncritically aggressive approach to these tumours.

Firing pattern and calbindin-D28k content of human epileptic granule cells.

In the hippocampus of chronic temporal lobe epilepsy, many abnormalities in structure and function have been described but their pathophysiological relevance often is poorly understood. In this study, we asked whether there may be a link between changes in the firing pattern and the loss of the calcium binding protein calbindin-D28k in epileptic hippocampal granule cells. Using the perforated patch-clamp technique, we investigated granule cells in slices prepared from human hippocampi removed for the treatment of pharmacoresistant temporal lobe epilepsy. Granule cells in hippocampi without significant signs of structural damage (lesion group) displayed a firing pattern indistinguishable from that of rodent granule cells and were strongly labeled with anti-calbindin-D28k antibodies. In contrast, half of granule cells in sclerotic hippocampi (HS group) showed an altered firing pattern and a severe loss of calbindin-D28k. While these cells show passive membrane properties comparable to cells of the rodent and lesion group, they lack the medium afterhyperpolarization and display only a weak spike frequency adaptation. On the other hand, granule cells in the HS group have an increased action potential threshold and an enlarged fast afterhyperpolarization. Applying post-recording immunohistochemistry to individual electrophysiologically characterized granule cells, we show that the loss of calbindin-D28k is not causally related to any of the changes in firing pattern. Both alterations seem to occur during the course of temporal lobe epilepsy, with the firing pattern being affected earlier than the calbindin-D28k content. In conclusion, we propose that it is the combination of the altered intrinsic excitability of granule cells with the amplified and prolonged synaptic input from perforant path fibers previously described in the epileptic dentate area which promotes tonic, non-adapting, high frequency firing of granule cells and thereby strongly augments the excitability of the hippocampus.

Greater functional recovery after temporal lobe epilepsy surgery in children.

The purpose of our study is to evaluate whether children recover better than adults from memory deficits as a consequence of temporal lobe surgery. We compared 3 and 12 month outcomes obtained in children and adults with medically refractory epilepsy. Each candidate underwent temporal lobe resection for seizure control and children were matched with regard to pathology, onset of epilepsy, side of surgery and type of surgery with adults (N = 30 for each group, mean age at surgery 13 versus 30 years). Three months after surgery, both left-resected groups displayed a significant decline in verbal learning capacity. During the following 9 months, only the children recovered and were able to reach their preoperative level 1 year after surgery. The left-resected adults remained, for the most part, on their low level and one year after surgery, they were still significantly worse than at the time of their preoperative examination. The right-resected adults experienced a deterioration in visual memory 1 year after surgery relative to the results of the short-term follow-up; the children improved. The children also had a better outcome with regard to attentional functions and, as a trend, a better seizure outcome (Engel Outcome I--1 year after surgery: 63% adults, 80% paediatric patients). Our neuropsychological data provide evidence of greater plasticity and compensational capacity in childhood. The results can be taken as a strong argument for early surgical intervention.

PTEN mutations in gliomas and glioneuronal tumors.

Cytogenetic and loss of heterozygosity studies have suggested the presence of at least one tumor suppressor gene on chromosome 10 involved in the formation of high grade gliomas. Recently, the PTEN gene, also termed MMAC1 or TEP1, on chromosomal band 10q23 has been identified. Initial studies revealed mutations of PTEN in limited series of glioma cell lines and glioblastomas. In order to systematically evaluate the involvement of PTEN in gliomas, we have analysed the entire PTEN coding sequence by SSCP and direct sequencing in a series of 331 gliomas and glioneuronal tumors. PTEN mutations were detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas. No PTEN mutations were detected in 52 astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas, four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for the presence of homozygous deletions of the PTEN gene; these were detected in 7 glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur in approximately 20% of glioblastomas but are rare in lower grade gliomas. These findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas.