Gray-White Matter Blurring of the Temporal Pole Associated With Hippocampal Sclerosis: A Microstructural Study Involving 3 T MRI and Ultrastructural Histopathology.

Hippocampal sclerosis (HS) is often associated with gray-white matter blurring (GMB) of the anterior temporal lobe. In this study, twenty patients with unilateral temporal lobe epilepsy and HS were studied with 3 T MRI including T1 MP2RAGE and DTI/DMI sequences. Anterior temporal lobe white matter T1 relaxation times and diffusion measures were analyzed on the HS side, on the contralateral side, and in 10 normal controls. Resected brain tissue of three patients without GMB and four patients with GMB was evaluated ultrastructurally regarding axon density and diameter, the relation of the axon diameter to the total fiber diameter (G-ratio), and the thickness of the myelin sheath. Hippocampal sclerosis GMB of the anterior temporal lobe was related to prolonged T1 relaxation and axonal loss. A less pronounced reduction in axonal fraction was also found on imaging in GMB-negative temporal poles compared with normal controls. Contralateral values did not differ significantly between patients and normal controls. Reduced axonal density and axonal diameter were histopathologically confirmed in the temporopolar white matter with GMB compared to temporal poles without. These results confirm that GMB can be considered an imaging correlate for disturbed axonal maturation that can be quantified with advanced diffusion imaging.

Flashbulb memory recall in healthy adults - a functional magnetic resonance imaging study.

The present study investigated neural activations related to flashbulb memory (FM) recall and examined whether the amygdala and hippocampus are involved in FM recall. 20 healthy adults completed a block design with an FM-condition, where the reception events for a number of potential FM events had to be recalled, and a control condition (FMC) comprising reception events lacking FM characteristics. A definition naming task was used as an implicit baseline. The individual emotional reaction to the FM events (EMO) and self-rated retrieval success were included in the SPM model as modulating parameters. The main contrast of interest were FM > FMC and activations associated with EMO. ROI-analyses on mesiotemporal regions were performed. FM > FMC yielded activations in line with the autobiographical memory network, with mostly left sided-activations. EMO was associated with a more bilateral activation pattern. ROI-analysis revealed activations for EMO in the right amygdala and HATA. FM > FMC was associated with right hippocampal activations. The present findings are compatible with previous research into autobiographical memory, but also show activations for FM recall different from ordinary, not highly emotional autobiographical memories, as EMO is associated with a more bilateral network. Moreover, the amygdala seems to be involved in FM recall.

[Mobile seizure monitoring in epilepsy patients]. / Mobiles Anfallsmonitoring bei Epilepsiepatienten.

Wearables are receiving much attention from both epilepsy patients and treating physicians, for monitoring of seizure frequency and warning of seizures. They are also of interest for the detection of seizure-associated risks of patients, for differential diagnosis of rare seizure types and prediction of seizure-prone periods. Accelerometry, electromyography (EMG), heart rate and further autonomic parameters are recorded to capture clinical seizure manifestations. Currently, a clinical use to document nocturnal motor seizures is feasible. In this review the available devices, data on the performance in the documentation of seizures, current options for clinical use and developments in data analysis are presented and critically discussed.

High Frequency Oscillations in the Ripple Band (80-250 Hz) in Scalp EEG: Higher Density of Electrodes Allows for Better Localization of the Seizure Onset Zone.

High frequency oscillations (HFO) are known as markers of epileptic areas in intracranial EEG and possibly scalp EEG. We compared distributions of HFO in the ripple band (80-250 Hz) in intracranial and scalp EEG with either a conventional 10-20-montage (10-20-EEG) or a high density recording using 128 electrodes (HD-EEG). HFO were visually identified, in all intracranial EEG channels (80-500 Hz) and all channels of the 10-20-EEG (scalp EEG 80-250 Hz). For the HD-EEG, HFO were analyzed in regions of interest using areas with HFO as seen on the 10-20-EEG as well as areas in the clinically-defined seizure onset zone (SOZ). 13 patients were included in the study, of whom 12 showed HFO in the ripple band. In 8 patients HD-EEG revealed additional regions of ripples compared to the 10-20-EEG. With HD-EEG, areas of highest ripple rates were corresponding between scalp and intracranial EEG in 7 patients (58%) and 8 (67%) patients showed highest ripple rates over the SOZ. In contrast, with 10-20-EEG only 2 patients (17%) had corresponding areas of highest ripple rates and only 3 patients (23%) showed highest ripple rates over the SOZ. HD-EEG proved to be better to identify scalp HFO in the ripple band compared to standard 10-20-EEG. Moreover, ripples in 10-20-EEG seem to lead to false localization of epileptic areas. In contrast ripples detected with HD-EEG were located over the seizure onset zone and maybe a promising tool to localize epileptic tissue in the future.

[Differential diagnosis of dissociative seizures]. / Differenzialdiagnose dissoziativer Anfälle.

Patient history taking and semiology provide seminal clues to the diagnosis of dissociative seizures. Openness and alertness of the treating physician are essential. Video-electroencephalogram(EEG)-based analyses of the events are crucial to establish the correct diagnosis, particularly in complex cases. The patient-doctor relationship is of particular importance in order to successfully motivate the patient for psychotherapeutic treatment. Coexisting psychiatric morbidity as well as other functional somatic symptoms must be actively explored. Current changes in the established diagnostic manuals, including ICD-11, reflect the ongoing vivid interest and controversial discussions in the field of dissociative disorders.

The role of blood vessels in high-resolution volume conductor head modeling of EEG.

Reconstruction of the electrical sources of human EEG activity at high spatio-temporal accuracy is an important aim in neuroscience and neurological diagnostics. Over the last decades, numerous studies have demonstrated that realistic modeling of head anatomy improves the accuracy of source reconstruction of EEG signals. For example, including a cerebro-spinal fluid compartment and the anisotropy of white matter electrical conductivity were both shown to significantly reduce modeling errors. Here, we for the first time quantify the role of detailed reconstructions of the cerebral blood vessels in volume conductor head modeling for EEG. To study the role of the highly arborized cerebral blood vessels, we created a submillimeter head model based on ultra-high-field-strength (7T) structural MRI datasets. Blood vessels (arteries and emissary/intraosseous veins) were segmented using Frangi multi-scale vesselness filtering. The final head model consisted of a geometry-adapted cubic mesh with over 17×10(6) nodes. We solved the forward model using a finite-element-method (FEM) transfer matrix approach, which allowed reducing computation times substantially and quantified the importance of the blood vessel compartment by computing forward and inverse errors resulting from ignoring the blood vessels. Our results show that ignoring emissary veins piercing the skull leads to focal localization errors of approx. 5 to 15mm. Large errors (>2cm) were observed due to the carotid arteries and the dense arterial vasculature in areas such as in the insula or in the medial temporal lobe. Thus, in such predisposed areas, errors caused by neglecting blood vessels can reach similar magnitudes as those previously reported for neglecting white matter anisotropy, the CSF or the dura - structures which are generally considered important components of realistic EEG head models. Our findings thus imply that including a realistic blood vessel compartment in EEG head models will be helpful to improve the accuracy of EEG source analyses particularly when high accuracies in brain areas with dense vasculature are required.

[Invasive stimulation procedures and EEG diagnostics in epilepsy]. / Invasive Stimulationsverfahren und EEG-Diagnostik bei Epilepsien.

Stimulation has been performed experimentally and in small case series to treat epilepsy since the 1970s. Since the introduction of vagus nerve stimulation in 1997 and intracranial stimulation methods in 2011 into patient care, invasive stimulation has become a rapidly developing but infrequently used therapeutic option in Europe. Whereas vagus nerve stimulation is frequently used, particularly in the USA, intracranial stimulation differs in its regional availability. In order to improve the efficacy of stimulation, develop criteria for its use and assure low complication rates, a concentration on experienced centers and multicenter data acquisition and sharing are needed.Invasive electroencephalographic (EEG) monitoring with subdural electrodes and especially with stereotactically implanted depth electrodes have been used increasingly more often for presurgical evaluation in recent years. They are applied when non-invasive diagnostics show insufficient results to exactly identify the location and extent of the epileptogenic zone or cannot be adequately distinguished from eloquent cortex areas. Complications include intracranial hemorrhage, infections and increased intracranial pressure but lasting deficits or even death are rare (≤2 %). The outcome of invasive monitoring is inferior to non-invasive monitoring because of the higher degree of complexity of the cases; however, it is far superior to the seizure-free rates achieved by anticonvulsant drug treatment alone.

[Perampanel as a therapy option in patients with epilepsy]. / Perampanel als Therapieoption bei Epilepsiepatienten.

BACKGROUND: This article describes a monocentric retrospective analysis of clinical experience with the latest antiepileptic drug perampanel with non-competitive modulation of postsynaptic AMPA receptors. MATERIAL AND METHODS: Evaluation of electronic medical charts of patients newly treated with perampanel between 2012 and 2014 at the epilepsy center of the University Hospital Freiburg regarding effectiveness and tolerability. RESULTS: A total of 85 patients (45 male, mean age 37.4 years, range 14-80 years) with therapy resistance to an average of 6 antiepileptic medications were newly treated with add-on perampanel. Of the patients 35 % experienced a relevant reduction in seizures. The most commonly reported side effects were tiredness (32.5 %), dizziness (24.5 %) and irritability (10.5 %). The dosages resulting in a significant reduction in seizures which varied between patients from 4 to 12 mg/day. Even multidrug-resistant patients who had not benefited from vagus nerve and deep brain stimulation, profited from add-on treatment with perampanel. CONCLUSION: In this cohort, even epilepsy patients who did not respond to multiple previous antiepileptic treatment profited from add-on therapy with the new mode of action of perampanel.

[Epilepsy-associated tumors of the central nervous system: Epilepsy surgery and oncological aspects]. / Epilepsieassoziierte Tumoren des Zentralnervensystems : Epilepsiechirurgische und onkologische Aspekte.

BACKGROUND: Among the tumors associated with chronic epilepsy, dysembryoplastic neuroepithelial tumor and ganglioglioma are the most common besides angiocentric glioma, pleomorphic xanthoastrocytoma and pilocytic astrocytoma. These tumors are usually considered as being benign. OBJECTIVE: To determine the best conservative and surgical treatment of tumors associated with epilepsy. MATERIAL AND METHODS: This article presents case reports of malignant transformation of a dysembryoplastic neuroepithelial tumor and of a tumor initially diagnosed as a ganglioglioma based on magnetic resonance imaging (MRI) criteria. Description of references in the literature on epilepsy surgery and the neuro-oncology of epilepsy-associated tumors. RESULTS: In the case of the initially histopathologically diagnosed dysembryoplastic neuroepithelial tumor, a malignant transformation occurred 5 years after incomplete resection. The differentiation from a glioblastoma was possible through the analysis of the methylation profile. In another case a tumor assumed to be a ganglioglioma showed an increase in size after 6 years. Initial histopathological results revealed a glioblastoma. The analysis of the methylation profile suggested the diagnosis of an anaplastic pleomorphic xanthoastrocytoma and as a differential diagnosis an anaplastic ganglioglioma. Tumor progress correlated with the worsening of seizures. CONCLUSION: Recent studies have shown that in the treatment of predominantly benign epilepsy-associated tumors neuro-oncological aspects should also be taken into account in addition to the epileptological considerations. In the case of malignant transformation epigenetic screening (methylation profiles) can help to classify the tumor entity more precisely.

Verbal fluency in focal epilepsy: a systematic review and meta-analysis.

Testing of verbal fluency is currently part of standard presurgical neuropsychological assessment for patients with focal epilepsy. However, to date no systematic review has been conducted on semantic (SVF) and phonemic verbal fluency (PVF) in this patient group. The present review compares verbal fluency between healthy control subjects and subgroups of adult presurgical patients with focal epilepsy according to lateralisation and localisation of the dysfunction. PubMed was searched with a comprehensive search string. Abstracts of all studies and full-texts of potentially relevant studies were screened. Study quality was assessed by independent raters according to predefined criteria. 39 studies were included. Meta-analyses were performed to compare SVF and PVF across groups of patients with temporal (TLE) and frontal lobe epilepsy (FLE) as well as healthy controls (HC). Both patients with left- and right sided TLE were impaired on SVF and PVF compared to HC. Patients with left-sided TLE were slightly more impaired than patients with right-sided TLE. Patients with FLE showed a larger impairment in PVF than patients with TLE, whereas on SVF there was no difference between FLE and TLE. For TLE comparisons the study pool seems to have been sufficient, whereas more studies are needed to verify results for FLE. Semantic verbal fluency might not differentiate between FLE and TLE. While verbal fluency impairment was anticipated, especially in left-sided TLE and FLE patients, the impairment in patients with right-sided TLE was larger than expected. Results are discussed with regard to neuropsychological theory and practice.

Scalp EEG is not a blur: it can see high frequency oscillations although their generators are small.

High frequency oscillations (HFOs) are emerging as biomarkers of epileptogenicity. They have been shown to originate from small brain regions. Surprisingly, spontaneous HFOs can be recorded from the scalp. To understand how is it possible to observe these small events on the scalp, one avenue is the analysis of the cortical correlates at the time of scalp HFOs. Using simultaneous scalp and intracranial recordings of 11 patients, we studied the spatial distribution of scalp events on the cortical surface. For typical interictal epileptiform discharges the subdural distributions were, as expected, spatially extended. On the contrary, for scalp HFOs the subdural maps corresponded to focal sources, consisting of one or a few small spatial extent activations. These topographies suggest that small cortical areas generated the HFOs seen on the scalp. Similar scalp distributions corresponded to distinct distributions on a standard 1 cm subdural grid and averaging similar scalp HFOs resulted in focal subdural maps. The assumption that a subdural grid "sees" everything that contributes to the potential of nearby scalp contacts was not valid for HFOs. The results suggest that these small extent events are spatially undersampled with standard scalp and grid inter-electrode distances. High-density scalp electrode distributions seem necessary to obtain a solid sampling of HFOs on the scalp. A better understanding of the influence of spatial sampling on the observation of high frequency brain activity on the scalp is important for their clinical use as biomarkers of epilepsy.

Flashbulb memories in patients with temporal lobe epilepsy.

PURPOSE: Flashbulb memories (FMs) are vivid and stable autobiographical memories associated with learning surprising news of high emotional impact. Patients with temporal lobe epilepsy (TLE) can have autobiographical memory deficits. This is the first investigation of FMs in TLE applying a consistency measure of FM quality controlling for confabulation. METHOD: A sample of 12 patients with TLE and a matched group of 15 healthy controls (HCs) were tested on an FM test including a retest procedure. Scores of FM consistency were obtained by comparing answers across both testing occasions. RESULTS: In patients with TLE, FM consistency scores were significantly lower than in HCs. Exploratory subgroup analyses revealed FM deficits in both patients with left TLE and patients with right TLE compared with HCs. CONCLUSION: The present study indicates that the FMs of patients with TLE are less consistent than those of healthy control subjects. Future investigations with larger samples are desirable, especially regarding separate analyses of patients with left TLE and patients with right TLE.

[Treatment of epilepsy: peripheral and central stimulation techniques]. / Epilepsiebehandlung: Periphere und zentrale Stimulationsverfahren.

The efficacy of electrical stimulation in the treatment of epileptic seizures was demonstrated experimentally even in the 1970s. Clinical studies have proven the efficacy of vagus nerve stimulation and in recent years also of stimulation of the trigeminal nerve, the anterior nucleus of the thalamus and of the epileptic focus in treating focal epilepsy. Mechanisms of action depend on the stimulation site and parameters and include activation of endogenous antiepileptic nuclei, modulation of propagation of epileptic activity and suppression of ictal activity at the site of generation. Based on available data the tolerability of peripheral and central brain stimulation appears to be good but experiences from wider clinical use are still lacking.

[Dissociative seizures: a manual for neurologists for communicating the diagnosis]. / Dissoziative Anfälle : Ein Manual für Neurologen zur Diagnosemitteilung.

The great physical resemblance between epileptic and dissociative seizures and a diagnosis of epilepsy that had been made years ago and usually had been treated unsuccessfully makes it difficult for both physician and patient to communicate the diagnosis of dissociative seizures. A direct referral to psychotherapy treatment is rarely accepted by patients. Intermediate steps, which are based on cooperation between neurologists and psychotherapists, are necessary. The approach that we use to communicate diagnosis and motivation for psychotherapeutic treatment includes eight steps: 1. Welcome and introduction; 2. Jointly watching a video of documented seizures; 3. The message that the seizures are not of epileptic origin, 4. Development of an alternative disease concept; 5. Motivation for a conversation with a representative from psychosomatics; 6. Responding to the fear of "going crazy"; 7. If necessary, briefly touching on the subject of sexual violence; 8. More recommendations and conclusion of the conversation. The manual was discussed and practiced with the attending neurologist in two sessions and is now being regularly used by two neurologists with concomitant supervision.

[Slow release versus immediate release oxcarbazepine in difficult-to-treat focal epilepsy: a multicenter, randomized, open, controlled, parallel group phase III study]. / Retardiertes vs. schnell freisetzendes Oxcarbazepin bei therapierefraktärer fokaler Epilepsie : Eine offene multizentrische, randomisierte kontrollierte Studie.

BACKGROUND: The aim of the study was an assessment of the tolerability and efficacy of slow release oxcarbazepine (OXC-MR) versus immediate release OXC (OXC-IR) after forced titration in patients with focal epileptic seizures with and without secondary generalization who had previously not become seizure-free under OXC-IR with or without concomitant antiepileptic drugs. The primary study variable was to assess the maximum tolerated dosage with OXC-MR and OXC-IR. PATIENTS AND METHODS: This was designed as a multicenter, randomized, open, controlled, parallel group phase III study. After randomization patients received OXC-MR or OXC-IR for a study period of 26 days. The initial dosage of 900 mg, 1,200 mg or 1,500 mg OXC was increased every 5 days by 300 mg up to a maximum daily dosage of 2,700 mg. In cases of intolerable adverse events dosage could be reduced by 150 mg 2 days after an increase. Adverse events and executive abilities were assessed with the questionnaire "Adverse Event Profile plus" and with the Epitrack® test protocol. Serum concentrations of OXC and its active metabolite were measured in a part of the patient group. RESULTS: The 71 patients (54% male, age: 19-70 years) enrolled in the study were randomized. The maximum mean daily OXC dosage at the end of the study period was 1,950 mg with OXC-MR and thus statistically significantly higher than in OXC-IR group (1,650 mg, p = 0.022). The number of causally related adverse events was lower in the OXC-MR group (n = 104 versus n = 138 with OXC-IR) and CNS-related adverse events such as dizziness, tremor, somnolence and headache occurred significantly less often with OXC-MR (OXC-MR 65.7%, OXC-IR 88.9%, p = 0.01). Fluctuations of serum concentrations of the active metabolite were less pronounced under the OXC-MR regimen. CONCLUSIONS: Due to better tolerability OXC-MR allowed higher maintenance dosages to be reached than OXC-IR. In spite of a higher mean daily dosage adverse events and especially CNS-related adverse events occurred less often than with OXC-IR.

Interpretable functional specialization emerges in deep convolutional networks trained on brain signals.

Objective.Functional specialization is fundamental to neural information processing. Here, we study whether and how functional specialization emerges in artificial deep convolutional neural networks (CNNs) during a brain-computer interfacing (BCI) task.Approach.We trained CNNs to predict hand movement speed from intracranial electroencephalography (iEEG) and delineated how units across the different CNN hidden layers learned to represent the iEEG signal.Main results.We show that distinct, functionally interpretable neural populations emerged as a result of the training process. While some units became sensitive to either iEEG amplitude or phase, others showed bimodal behavior with significant sensitivity to both features. Pruning of highly sensitive units resulted in a steep drop of decoding accuracy not observed for pruning of less sensitive units, highlighting the functional relevance of the amplitude- and phase-specialized populations.Significance.We anticipate that emergent functional specialization as uncovered here will become a key concept in research towards interpretable deep learning for neuroscience and BCI applications.

First long term in vivo study on subdurally implanted micro-ECoG electrodes, manufactured with a novel laser technology.

A novel computer aided manufacturing (CAM) method for electrocorticography (ECoG) microelectrodes was developed to be able to manufacture small, high density microelectrode arrays based on laser-structuring medical grade silicone rubber and high purity platinum. With this manufacturing process, we plan to target clinical applications, such as presurgical epilepsy monitoring, functional imaging during cerebral tumor resections and brain-computer interface control in paralysed patients, in the near future. This paper describes the manufacturing, implantation and long-term behaviour of such an electrode array. In detail, we implanted 8-channel electrode arrays subdurally over rat cerebral cortex over a period of up to 25 weeks. Our primary objective was to ascertain the electrode's stability over time, and to analyse the host response in vivo. For this purpose, impedance measurements were carried out at regular intervals over the first 18 weeks of the implantation period. The impedances changed between day 4 and day 7 after implantation, and then remained stable until the end of the implantation period, in accordance with typical behaviour of chronically implanted microelectrodes. A post-mortem histological examination was made to assess the tissue reaction due to the implantation. A mild, chronically granulated inflammation was found in the area of the implant, which was essentially restricted to the leptomeninges. Overall, these findings suggest that the concept of the presented ECoG-electrodes is promising for use in long-term implantations.

Local area network inhibition: a model of a potentially important paraepileptic pathomechanism in neuropsychiatric disorders.

Electroencephalographic abnormalities in the absence of any other major laboratory or imaging findings are a frequently encountered phenomenon in many psychiatric disorders. In some cases, clear-cut interictal epileptiform EEG abnormalities in patients with classic primary psychiatric disorders lead to referrals to epilepsy departments for diagnostic evaluation. Although video/EEG telemetry in these cases generally proves that there is no direct temporal link between the EEG pathologies and psychiatric symptoms, and therefore the psychiatric syndrome cannot be regarded as epilepsy, the relevance of the EEG abnormalities remains open to discussion. In this article we put forward the model of a paraepileptic pathomechanism, which might explain the pathogenetic role of such EEG pathologies, at least in subgroups of such patients. We propose that ictal or nonictal epileptic neurophysiological activity can lead to local area neuronal network inhibition (LANI). In this model clinical symptoms are related not to the excitatory epileptiform abnormalities themselves, but to the extent, site, and dynamics of the resulting local neuronal network inhibition. The LANI hypothesis is capable of explaining the complex relationship between EEG abnormalities and clinical symptoms in different neuropsychiatric syndromes and can be verified and falsified in empirical research.

Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection--Part 2: volumetric resection extent and subgroup analyses.

BACKGROUND: This paper is addressing outcome differences in interesting subgroups from a previous randomized controlled trial of the extent of mesial temporal lobe resection (TLR) for drug-resistant epilepsy, by looking at effects of randomization, intended resection group, center, and true resection extent on seizure outcome. METHODS: One hundred and seventy-nine cases with volumetrically assessed resection extent were used. Analyses of the extent of resection and subgroups and within subgroups for the two treatment arms will be performed, looking for confounding factors and using statistical methods (chi-square test, logistic regression analysis, and two-factorial ANOVA). RESULTS: True resection extent varied considerably. Outcome comparison for right versus left resections, subgroups with mesial temporal sclerosis (MTS), or largest and smallest resections revealed no remarkable difference, compared to overall class I outcome. The intent-to-treat analyses within these subgroups revealed differences for class I outcome, albeit lacking in significance, except for better TLR outcome. Small true resection volume differences or randomization into the two resection groups could not explain the outcome differences between the selective amygdalohippocampectomy (SAH) and TLR subgroups. Logistic regression analysis showed an interaction between intended resection length and surgery type, confirming the impression of different impacts of the intended resection length under the two surgery types. The outcome difference between SAH and TLR was more likely explained by a center effect. In a two-factorial ANOVA for resected hippocampal volume, Engel outcome class I, and resection type, the outcome was not found to be correlated with true resection volume. A multifactorial logistic regression showed a mild interaction between the resection type with center on the Engel outcome class, extent of resection, and surgery type interacted, as did the extent of resection and center. CONCLUSION: Patients with quite similar extent of resection can be seizure free or non-seizure free. In this cohort, seizure freedom rates fell again when the extent of mesial resection was maximized. Differences in class I outcome for SAH and TLR were not due to erroneous randomization, true resection extent, or presence of MTS, but were influenced by a center effect. Subgroup analyses did not help to provide arguments to favor one surgery type over the other.

Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection in temporal lobe epilepsy--Part 1: intent-to-treat analysis.

BACKGROUND: Only one prospective randomized study on the extent of mesial resection in surgery for temporal lobe epilepsy (TLE) exists. This randomized controlled trial (RCT) examines whether 3.5-cm mesial resection is leading to a better seizure outcome than a 2.5-cm resection. METHODS: Three epilepsy surgery centers using similar MRI protocols, neuropsychological tests, and resection types for TLE surgery included 207 patients in a RCT with pre- and postoperative volumetrics. One hundred and four patients were randomized into a 2.5-cm resection group and 103 patients into a 3.5-cm resection group, i.e., an intended minimum resection length of 25 versus 35 mm for the hippocampus and parahippocampus. Primary outcome measure was seizure freedom Engel class I throughout the first year. The study was powered to detect a 20% difference in class I outcome. Seizure outcome was available for 207 patients, complete volumetric results for 179 patients. Outcome analysis was restricted to control of successful randomization and an intent-to-treat analysis of seizure outcome. RESULTS: The mean true resection volumes were significantly different for the 2.5-cm and 3.5-cm resection groups; thus, the randomization was successful. Median resection volume in the 2.5-cm group was 72.86% of initial volume and 83.44% in the 3.5-cm group. At 1 year, seizure outcome Engel class I was 74% in the 2.5-cm and 72.8% in the 3.5-cm resection group. CONCLUSIONS: The primary intent-to-treat analysis did not show a different seizure freedom rate for the more posteriorly reaching 3.5-cm resection group. It appears possible that not maximal volume resection but adequate volume resection leads to good seizure freedom.