Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: experience at an epilepsy centre.

OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Estereoelectroencefalografía en la evaluación prequirúrgica de epilepsias focales refractarias: experiencia de un centro de epilepsia / Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: Experience at an epilepsy centre

Objetivo: La estereoelectroencefalografía (E-EEG) es una técnica de evaluación prequirúrgica en pacientes con epilepsia focal refractaria de difícil localización (EFRDL) que permite explorar con electrodos profundos regiones cerebrales de difícil acceso y la profundidad de la corteza. Esta técnica, en auge en centros internacionales, apenas se ha desarrollado en España. Describimos nuestra experiencia con la E-EEG en la evaluación de pacientes con EFRDL. Material y métodos: En los últimos 8 años, 71 pacientes con EFRDL fueron evaluados con E-EEG en nuestro centro. Analizamos prospectivamente los resultados obtenidos en la localización, los resultados quirúrgicos y las complicaciones asociadas a la técnica. Resultados: La mediana de edad fue de 30 años (rango 4-59 años), 27 pacientes eran mujeres (38%). La RM cerebral fue negativa en 45 pacientes (63,4%). Se implantaron 627 electrodos (mediana de 9 electrodos por paciente, rango 1-17), con un 50% de implantaciones multilobares. En 64 (90,1%) pacientes se localizó la zona epileptógena (ZE), siendo extratemporal o temporal plus en el 66% de los casos. En 55 pacientes de los 61 intervenidos el seguimiento fue superior al año: en el último año de seguimiento 32/55 pacientes (58,2%) estaban libres de crisis (Engel I) siendo los resultados favorables (Engel I-II) en el 76,4% de las intervenciones. Tres pacientes (4,2%) presentaron una hemorragia cerebral. Conclusión: La E-EEG permite localizar la ZE en pacientes en quienes anteriormente no era posible, ofreciendo unos resultados quirúrgicos superiores a otras técnicas invasivas y una tasa de complicaciones relativamente baja. (AU)

Objective: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. Material and methods: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. Results: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. Conclusion: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications. (AU)

Hippocampal Sclerosis Detection with NeuroQuant Compared with Neuroradiologists.

BACKGROUND AND PURPOSE: NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant analysis with visual MR imaging analysis by neuroradiologists with expertise in epilepsy in identifying hippocampal sclerosis. MATERIALS AND METHODS: We reviewed 144 adult patients who underwent presurgical evaluation for temporal lobe epilepsy. The reference standard for hippocampal sclerosis was defined by having hippocampal sclerosis on pathology (n = 61) or not having hippocampal sclerosis on pathology (n = 83). Sensitivities, specificities, positive predictive values, and negative predictive values were compared between NeuroQuant analysis and visual MR imaging analysis by using a McNemar paired test of proportions and the Bayes theorem. RESULTS: NeuroQuant analysis had a similar specificity to neuroradiologist visual MR imaging analysis (90.4% versus 91.6%; P = .99) but a lower sensitivity (69.0% versus 93.0%, P < .001). The positive predictive value of NeuroQuant analysis was comparable with visual MR imaging analysis (84.0% versus 89.1%), whereas the negative predictive value was not comparable (79.8% versus 95.0%). CONCLUSIONS: Visual MR imaging analysis by a neuroradiologist with expertise in epilepsy had a higher sensitivity than did NeuroQuant analysis, likely due to the inability of NeuroQuant to evaluate changes in hippocampal T2 signal or architecture. Given that there was no significant difference in specificity between NeuroQuant analysis and visual MR imaging analysis, NeuroQuant can be a valuable tool when the results are positive, particularly in centers that lack neuroradiologists with expertise in epilepsy, to help identify and refer candidates for temporal lobe epilepsy resection. In contrast, a negative test could justify a case referral for further evaluation to ensure that false-negatives are detected.

Epileptic Patient with Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia and Epilepsy (MOGHE): A Case Report and Review of the Literature.

INTRODUCTION: There is an emerging interest in the literature about MOGHE (Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia and Epilepsy). We report the case of an epileptic patient with MOGHE. CASE REPORT: A 33-year-old male patient was suffering from refractory focal epilepsy since adolescence. MRI demonstrated increased T2/FLAIR signal intensity of right frontal lobe. Presurgical evaluation led to definition of epileptogenic network in a specific area of right frontal lobe. The resected specimen revealed MOGHE. Discussion. MOGHE appears to be a brain entity which shares some unique histopathological features. Review of the literature is in accordance with our patient's findings. The major neuropathological finding consists of areas with blurred gray-white matter boundaries due to heterotopic neurons in white matter and increased numbers of subcortical oligodendroglial cells with increased proliferation. MR abnormalities are present in T2/FLAIR sequences. It concerns patients with refractory frontal lobe epilepsy and appears to associate with unfavourable postsurgical outcome in seizure control. CONCLUSION: More cases are needed in order to establish more data about this distinct entity in frontal lobe epilepsy. This could be valuable knowledge to patients and doctors concerning expectations or management of undesirable outcome in frontal lobe epilepsy surgery.

Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: Experience at an epilepsy centre. / Estereoelectroencefalografía en la evaluación prequirúrgica de epilepsias focales refractarias: experiencia de un centro de epilepsia.

OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Review: Challenges in the histopathological classification of ganglioglioma and DNT: microscopic agreement studies and a preliminary genotype-phenotype analysis.

Low-grade epilepsy-associated brain tumours (LEAT) are the second most common cause for drug-resistant, focal epilepsy, that is ganglioglioma (GG) and dysembryoplastic neuroepithelial tumours (DNT). However, molecular pathogenesis, risk factors for malignant progression and their frequent association with drug-resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular-genetic basis and targeted treatment options in diffuse gliomas. The Neuropathology Task Force of the International League Against Epilepsy examined available literature to identify common obstacles in diagnosis and research of LEAT. Analysis of 10 published tumour series from epilepsy surgery pointed to poor inter-rater agreement for the histopathology diagnosis. The Task Force tested this hypothesis using a web-based microscopy agreement study. In a series of 30 LEAT, 25 raters from 18 countries agreed in only 40% of cases. Highest discordance in microscopic diagnosis occurred between GG and DNT variants, when oligodendroglial-like cell patterns prevail, or ganglion cells were difficult to discriminate from pre-existing neurons. Suggesting new terminology or major histopathological criteria did not satisfactorily increase the yield of histopathology agreement in four consecutive trials. To this end, the Task Force applied the WHO 2016 strategy of integrating phenotype analysis with molecular-genetic data obtained from panel sequencing and 450k methylation arrays. This strategy was helpful to distinguish DNT from GG variants in all cases. The Task Force recommends, therefore, to further develop diagnostic panels for the integration of phenotype-genotype analysis in order to reliably classify the spectrum of LEAT, carefully characterize clinically meaningful entities and make better use of published literature.

Review: The international consensus classification of Focal Cortical Dysplasia - a critical update 2018.

The Diagnostic Methods commission of the International League against Epilepsy (ILAE) released a first international consensus classification of Focal Cortical Dysplasia (FCD) in 2011. Since that time, this FCD classification has been widely used in clinical diagnosis and research (more than 740 papers cited in Pubmed between 1/1/2012 and 7/1/2017). Herein, we review the new data that will inform and revise the FCD classification. Many recent papers described molecular-genetic characteristics in FCD type II including multiple mutations in the mTOR pathway. In addition, the electro-clinico-imaging phenotype and surgical outcomes of FCD type II (in particular type IIb) were further defined and validated. These results pave the way for the design of an integrated clinico-pathological and genetic classification system, as recently recommended by the WHO for the classification of malignant brain tumours. On the other hand, little new information was acquired on FCD types I and III. Focal cortical dysplasia type I subtypes are still lacking a comprehensive description of clinical phenotypes, reproducible imaging characteristics, and specific molecular/genetic biomarkers. Associated FCD III subtypes also became rare in published literature. Despite temporal lobe epilepsy being the most common focal epilepsy in adults, we have not identified neurophysiological, imaging, histopathological and/or genetic biomarkers to reliably classify FCD III with or without hippocampal sclerosis. In respect of pathogenesis, FCD adjacent to a non-developmental, postnatally acquired lesion is difficult to explain and perhaps does not exist. This update may help foster shared efforts towards a better understanding of FCD, potential future updates of classification and novel targeted treatments.

Epigenetics in epilepsy.

Approximately 50 million people have epilepsy, making it the most common chronic and severe neurological disease worldwide, with increased risk of mortality and psychological and socioeconomic consequences impairing quality of life. More than 30% of patients with epilepsy have inadequate control of their seizures with drug therapy. Any structural brain lesion can provoke epilepsy. However, progression of seizure activity as well as the development of drug-resistance remains difficult to predict, irrespective of the underlying epileptogenic condition, i.e., traumatic brain injury, developmental brain lesions, brain tumors or genetic inheritance. Mutated DNA sequences in genes encoding for ion channels or neurotransmitter receptors have been identified in hereditary focal or generalized epilepsies, but genotype-phenotype correlations are poor, arguing for additional factors determining the effect of a genetic predisposition. The dynamics of epigenetic mechanisms (e.g. DNA methylation, histone modifications, chromatin remodelling, and non-coding RNAs) provide likely explanations for common features in epilepsy and other complex diseases, including late onset, parent-of-origin effects, discordance of monozygotic twins, and fluctuation of symptoms. In addition, many focal epilepsies, including focal cortical dysplasias (FCDs), glio-neuronal tumors (e.g. ganglioglioma), or temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), do not seem to primarily associate with hereditary traits, suggesting other pathogenic mechanisms. Herein we will discuss the many faces of the epigenetic machinery, which provides powerful tools and mechanisms to propagate epileptogenicity and likely also contribute to the epileptogenic memory in chronic and difficult-to-treat epilepsies.

Epigenetic control of epilepsy target genes contributes to a cellular memory of epileptogenesis in cultured rat hippocampal neurons.

Hypersynchronous neuronal excitation manifests clinically as seizure (ictogenesis), and may recur spontaneously and repetitively after a variable latency period (epileptogenesis). Despite tremendous research efforts to describe molecular pathways and signatures of epileptogenesis, molecular pathomechanisms leading to chronic epilepsy remain to be clarified. We hypothesized that epigenetic modifications may form the basis for a cellular memory of epileptogenesis, and used a primary neuronal cell culture model of the rat hippocampus to study the translation of massive neuronal excitation into persisting changes of epigenetic signatures and pro-epileptogenic target gene expression. Increased spontaneous activation of cultured neurons was detected 3 and 7 days after stimulation with 10 µM glutamate when compared to sham-treated time-matched controls using calcium-imaging in vitro. Chromatin-immunoprecipitation experiments revealed short-term (3 h, 7 h, and 24 h) and long-term (3 d and 2 weeks) changes in histone modifications, which were directly linked to decreased expression of two selected epilepsy target genes, e.g. excitatory glutamate receptor genes Gria2 and Grin2a. Increased promoter methylation observed 4 weeks after glutamate stimulation at respective genes suggested long-term repression of Gria2 and Grin2a genes. Inhibition of glutamatergic activation or blocking the propagation of action potentials in cultured neurons rescued altered gene expression and regulatory epigenetic modifications. Our data support the concept of a cellular memory of epileptogenesis and persisting epigenetic modifications of epilepsy target genes, which are able to turn normal into pro-epileptic neurons and circuits.

Clinico-pathological subtypes of hippocampal sclerosis in temporal lobe epilepsy and their differential impact on memory impairment.

Hippocampal anatomy and network organization are capable to generate drug-resistant temporal lobe epilepsy (TLE) in humans and particularly vulnerable to segmental neuronal cell loss. Surgical hippocampectomy has been proven successful in treatment and available human tissue specimens allow systematic clinico-pathological examination. Different patterns of hippocampal cell loss have been identified in TLE patients and are recently classified by the International League against Epilepsy (ILAE) into four distinct subtypes in order to stratify the heterogenous group of TLE patients also with respect to postsurgical outcome. Another important aim of the international consensus classification system of hippocampal sclerosis (HS) is to gain further insights into the morpho-functional organization of human memory frequently compromised in TLE patients.

Interictal magnetoencephalography used in magnetic resonance imaging-negative patients with epilepsy.

PURPOSE: This study aims to investigate the contributions of magnetoencephalography (MEG) in magnetic resonance imaging (MRI)-negative patients. METHODS: A total of 18 MRI-negative patients diagnosed with refractory epilepsy, subjected to MEG investigation, and subsequently underwent surgery were selected for retrospective analysis. A 1.5-tesla Magnetom Sonata with an eight-channel head array coil was used. MEG data were obtained using a 74/248-channel system. RESULTS: A total of 16 patients (16/18) had positive MEG results, comprising 12 patients with monofocal localizations, five with multifocal localizations, and one with unremarkable results in MEG. In addition, 12 patients had indicative single photon-emission computed tomography (SPECT), five had indicative fluorodeoxyglucose positron emission tomography (FDG-PET), and all the patients had intracranial electroencephalography (EEG) (14 with subdural electrodes and four with electrocorticography). The intracranial EEG recordings of nine patients were guided by MEG informative results. Among these 18 patients, 10 exhibited good postoperative outcomes (Engel I and II), four of which were completely seizure-free. All these ten patients had clear monofocal localization in MEG, including nine with accordant indicative metabolic changes in either SPECT or FDG-PET, or both. None of the five patients with multifocal localizations achieved good postoperative outcomes. CONCLUSION: For cases with negative MRI findings, epilepsy surgery may be an alternative option for pharmaco-resistant patients if epileptogenic focus localizations by MEG are present in multimodal evaluation.

[Neuropathology and etiology of focal epilepsy]. / Neuropathologie und Ätiologie fokaler Epilepsien.

In 2010 the International League against Epilepsy published a new classification of epilepsies. A major advance of this classification system is the acknowledgment of a genetic or pathologic-anatomic basis of epilepsy as important predictors of outcome (cause matters). This applies in particular to structural-metabolic lesions, which were frequently recognized in surgical specimens obtained from patients with drug-resistant focal epilepsy, i.e. hippocampal sclerosis, glioneuronal tumors, focal cortical dysplasias, vascular malformations, ischemia, intracerebral hemorrhage, glial scars or inflammation. A better understanding and classification of the etiopathology as well as the underlying molecular mechanisms will help to anticipate and appreciate the clinical course of a disease as well as to develop new and targeted drug treatment. Surgically available human brain tissue will be most helpful to support this approach but will also need careful neuropathological evaluation with accurate classification systems and use of terminology.

Neuropathological work-up of focal cortical dysplasias using the new ILAE consensus classification system - practical guideline article invited by the Euro-CNS Research Committee.

FCDs are increasingly recognized in patients with drug-resistant epilepsies, and many patients benefit from tailored resection strategies. Yet, postsurgical seizure control cannot be sufficiently predicted and specification of FCD variants remains difficult during presurgical monitoring. The International League against Epilepsy (ILAE) has published a new consensus classification system for focal cortical dysplasias (FCDs). Based on a review of imaging data, electroclinical features and postsurgical seizure control correlation with neuropathological findings specify three clinico-pathological FCD subtypes: FCD Type I is characterized by aberrant radial (FCD Type Ia) or tangential lamination of the neocortex (FCD Type Ib) affecting one or multiple lobes. FCD Type II is characterized by cortical dyslamination and dysmorphic neurons without (Type IIa) or with balloon cells (Type IIb). It is important to note, that these types should not be associated with any other structural brain lesion (isolated FCD). In contrast, a new FCD Type III is introduced, which occurs in combination with hippocampal sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas FCD Type IIId can be diagnosed in association with other epileptogenic lesions obtained in early life (i.e., traumatic injury, ischemic injury or encephalitis). Histopathological features are very similar to those observed in FCD Type I, but likely present postnatal development and maturation failures acquired by the principal lesion. This first international consensus classification may encourage neuropathologists to focus their attention onto this important histopathological group. Addressing more precisely defined clinico-pathological entities will also help to clarify underlying pathomechanisms and, thereby, improve treatment strategies for patients with difficult-to-treat epilepsies.

[New developments in epileptogenesis and therapeutic perspectives]. / Neue Entwicklungen der Epileptogenese und therapeutische Perspektiven.

Epileptogenesis describes the mechanisms of how epilepsies are generated. We have chosen four areas in which significant progress has been achieved in understanding epileptogenesis. Those are (1) inflammatory processes which play an increasingly important role for the generation of temporal lobe epilepsy with hippocampal sclerosis (TLE with HS), (2) disturbances of intrinsic properties of neuronal compartments, in particular acquired defects of ion channels of which those in dendrites are described here for TLE with HS, (3) epigenetic effects, which affect for example the methylation of promoters and secondarily can change the expression of specific genes in TLE with HS, and finally (4) the epileptogenesis of idiopathic epilepsies which are caused by inborn genetic alterations affecting mainly ion channels. Apart from aspects of basic research, we will describe clinical consequences and therapeutic perspectives.

No effect of the PPAR-gamma agonist rosiglitazone on ACTH or cortisol secretion in Nelson's syndrome and Cushing's disease in vitro and in vivo.

OBJECTIVE: Surgical tumor resection remains the primary treatment strategy in ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD) and Nelson's syndrome (NS). However, an effective long-term pharmacological regime is not available in patients with persistent ACTH-hypersecretion. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) is abundantly expressed in most pituitary adenomas. First encouraging data reported that the PPAR-gamma ligand rosiglitazone antagonizes ACTH hypersecretion and exerts also antiproliferative effects in pituitary cell lines. Herein, we studied the potential therapeutical effects of rosiglitazone in patients with ACTH-secreting pituitary adenomas in vitro and in vivo. MATERIALS AND METHODS: Seven patients with persistent ACTH-hypersecretion (3 with NS, 4 with persistent CD) were treated 5 months with rosiglitazone (4 - 16 mg/day). In vitro assays were performed in primary cell cultures obtained from eight additional patients with ACTH-secreting pituitary adenomas applying 80 microM rosiglitazone repeatedly over a time period of 14 days. RESULTS: Our long-term clinical trial with the PPAR-gamma activator rosiglitazone showed no amelioration of clinical symptoms nor an inhibiting effect on ACTH-secretion in vivo. In vitro, rosiglitazone treatment led to a statistically significant decrease of ACTH levels in 2 out of 8 primary cell cultures after 14 days compared to untreated controls. CONCLUSION: In contrast to the initially promising laboratory data gathered in pituitary cell line experiments and nude mice models, our experimental data obtained in primary human ACTH-expressing pituitary adenoma cell cultures as well as our clinical experience with a long-term rosiglitazone trial in approved antidiabetic doses support the recently reported disappointing reports on acute or short-term medical treatment of ACTH-hypersecretion with PPAR-gamma activators.

Evidence for a progenitor cell population in the human pituitary.

The ability to isolate and propagate adult stem/progenitor cells from the human brain opens novel avenues for cell replacement therapy. This will also apply to the pituitary gland, i.e., following tumor induced endocrine deficiency. Herein, we examine autopsy derived pituitaries to unravel a putative stem/progenitor cell population in humans. In tissue sections of the anterior lobe nestin immunoreactive cells co-expressing smooth muscle actin (SMA) were identified in the perivascular space, indicating a pericytic differentiation. Under clonal conditions, this particular cell population generated primary and secondary cell aggregates (spheres). Pituitary cell cultures maintained a stable cell cycle length with a doubling time of 10 days for over eight months. Forskolin treatment induced a prolactin-expressing phenotype in the majority of cell progenies as well as few betaIII-tubulin (Tuj1) expressing cells of putative neuronal lineage. The presence of sphere-forming, nestin-immunoreactive cells and their ability to generate differentiated cell lineages indicates the existence of a progenitor cell population persisting in the adult human pituitary. Further studies are needed to characterize this cell population in more detail and to clarify their potential to initiate neoplastic transformation for example in the cellular pathogenesis of pituitary adenoma.

Clinical prediction of postoperative seizure control: structural, functional findings and disease histories.

OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) constitutes a heterogenic entity with different clinical histories, pathomorphological hippocampal findings and varying postoperative outcome. METHOD: 64 patients with MTLE, scheduled for hippocampal resection, were included. Initial precipitating injuries (IPI), structural and functional findings and neuropathological classification of hippocampal specimens were related to prediction of surgical outcome. RESULTS: Patients with severe hippocampal sclerosis (mesial temporal sclerosis (MTS) type 1b) became completely seizure free (80% Engel Ia) significantly more often compared with approximately 40% of seizure freedom in other types of MTS or in patients without hippocampal cell loss (non-MTS), irrespective of the extent of hippocampal resection. Age at IPI was found to be related to MTS variants (p<0.01) and significantly correlated with cell loss in the CA1 sector and the dentate gyrus (p<0.05). Presurgical MRI discriminated between MTS and non-MTS, but did not discriminate between different MTS subtypes. The most reliable predictors of MTS type 1b were the Wada memory scores combined with interictal and ictal EEG. CONCLUSIONS: A particular cohort of MTLE patients benefit most from surgical treatment. These patients are clinically best recognised as presenting with (1) very early IPI; (2) a silent period of about 5 years; (3) unequivocal unilateral EEG localisation; (4) MRI signs of MTS; and (5) Wada Test indicates contralateral memory compensation and ipsilateral reduced memory capacity. MTS type 1b, characterised by severe cell loss in all hippocampal subfields including the dentate gyrus, and associated with optimal postoperative seizure control, was preoperatively clinically best differentiated from other MTS types by the Wada Memory Test.