Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014.

OBJECTIVE: Surgical volumes at large epilepsy centers are decreasing. Pediatric cohorts, however, show a trend toward more resections and superior outcome. Differences in pediatric and adult epilepsy surgery were investigated in our cohort. METHODS: The Bethel database between 1990 and 2014 was retrospectively analyzed. RESULTS: A total of 1916 adults and 1300 children underwent presurgical workup. The most common etiologies were medial temporal sclerosis (35.4%) in adults, and focal cortical dysplasias (21.1%) and diffuse hemispheric pathologies (14.7%) in children. Only 1.4% of the total cohort had normal histopathology. A total of 1357 adults (70.8%) and 751 children (57.8%) underwent resections. Surgery types for children were more diverse and showed a higher proportion of extratemporal resections (32.8%) and functional hemispherectomies (20.8%). Presurgical evaluations increased in both groups; surgical numbers remained stable for children, but decreased in the adult group from 2007 on. The patients' decision against surgery in the adult nonoperated cohort increased over time (total = 44.9%, 27.4% in 1995-1998 up to 53.2% in 2011-2014; for comparison, in children, total = 22.1%, stable over time). Postsurgical follow-up data were available for 1305 adults (96.2%) and 690 children (91.9%) 24 months after surgery. The seizure freedom rate was significantly higher in children than in adults (57.8% vs 47.5%, P < 0.001) and significantly improved over time (P = 0.016). SIGNIFICANCE: Pediatric epilepsy surgery has stable surgical volumes and renders more patients seizure-free than epilepsy surgery in adults. A relative decrease in hippocampal sclerosis, the traditional substrate of epilepsy surgery, changes the focus of epilepsy surgery toward other pathologies.

Decreasing SUDEP incidence in a tertiary epilepsy center between 1981 and 2016: Effects of better patient supervision.

OBJECTIVE: The objective of this study was to investigate the incidence of sudden unexpected death in epilepsy (SUDEP) in a tertiary epilepsy center in the years 1981-2016 with an emphasis on patient supervision and nursing intervention in different departments. METHODS: We identified 14 SUDEP cases (probable, definite, definite plus). Patient-years (PY) and incidence were calculated for the periods of six years for the general epileptology wards (adults and children) and, in addition, for the epilepsy monitoring unit (EMU) since 1990. RESULTS: The incidence of SUDEP showed a decreasing trend over time (r = -0.81; p = 0.053, two-sided; Pearson correlation coefficient). This is especially true in children (no SUDEP occurred in pediatric general epileptology since 1992). Additionally, in the EMU (314 PY since the start of 1990), no SUDEP occurred. Sudden unexpected death in epilepsy incidence was highest (6.8/1000 PY) in the early time periods (1981-1992) and lowest (1.7/1000 PY) in the later time periods (1999-2010). In the general epileptology wards (3579 PY), the overall incidence was 3.9 per 1000 PY (95% confidence interval (CI): 2.1-6.6). CONCLUSIONS: We assume that the decreased SUDEP incidence is an effect of better supervision by the use of technical means (e.g., video cameras, pulse oximeters, seizure detection systems) and rooming-in of parents or family.

Psychiatric lifetime diagnoses are associated with a reduced chance of seizure freedom after temporal lobe surgery.

OBJECTIVE: To examine whether psychiatric comorbidity is a predictor of long-term seizure outcome following temporal lobe epilepsy surgery. METHODS: A sample of 434 adult patients who received temporal lobe resection to treat epilepsy between 1991 and 2009 and were psychiatrically assessed before surgery were followed for 2 years to assess seizure outcome. Stepwise multivariate logistic regression analyses were used to assess the impact of psychiatric variables on complete seizure freedom (Engel class IA), and freedom from disabling seizures (Engel class I). Lifetime histories of three psychiatric syndromes (PS: psychosis; depression; other) and five personality disorders (PD: DSM-IV Clusters A, B, and C; organic personality disorder; other) were considered as predictors, complemented by age at onset, duration of epilepsy, type of lesion (mesiotemporal sclerosis vs. other), and year of surgery. RESULTS: Seizure-freedom rates were significantly higher (p < 0.001) in patients with no history of PS or PD (N = 138; Engel class IA: 61.6%; Engel class I: 87.7%) than in those with any PS or PD (N = 296; Engel class IA: 39.5%; Engel class I: 58.8%). Particularly low seizure-freedom rates were found in patients with a diagnosis of psychosis (N = 32, Engel class IA: 21.9%; Engel class I: 40.6%), organic PD (N = 48, Engel class IA: 25.0%; Engel class I: 35.4%) or a double diagnosis of PS plus PD (N = 97; Engel class IA: 27.8%; Engel class I: 45.5%). No other variables emerged as significant risk factors in multivariate logistic regression analyses. SIGNIFICANCE: Patients with and without psychiatric comorbidities can benefit from temporal lobe epilepsy surgery; however, psychiatric comorbidities are negatively associated with postoperative seizure-freedom rates. Surgical outcome is related to the type and extent of preoperative psychiatric morbidity, which underscores the prognostic value of presurgical psychiatric evaluation. The data support the argument that there are common pathogenetic mechanisms underlying both epilepsy and psychiatric conditions.

Partial resection of presurgical fMRI activation is associated with a postsurgical loss of language function after frontal lobe epilepsy surgery.

We describe five patients with frontal lobe epilepsy who underwent electrocortical stimulation (ES) for language localization and language functional magnetic resonance imaging (fMRI) prior to epilepsy surgery. Six months after surgery, three patients suffered from a drop of verbal fluency. In all of them, frontal areas with presurgical language fMRI activity were resected. Our results suggest that resection in regions of areas with presurgical fMRI activation is not without risk for a postsurgical loss of function, even when ES results were negative for language function in these areas. Using fMRI activations might be specifically helpful to plan the resection when ES delivered inconclusive results.

Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes.

INTRODUCTION: Despite the success of epilepsy surgery, recent reports suggest a decline in surgical numbers. We tested these trends in our cohort to elucidate potential reasons. PATIENTS AND METHODS: Presurgical, surgical and postsurgical data of all patients undergoing presurgical evaluation in between 1990 and 2013 were retrospectively analysed. Patients were grouped according to the underlying pathology. RESULTS: A total of 3060 patients were presurgically studied, and resective surgery was performed in 66.8% (n=2044) of them: medial temporal sclerosis (MTS): n=675, 33.0%; benign tumour (BT): n=408, 20.0%; and focal cortical dysplasia (FCD): n=284, 13.9%. Of these, 1929 patients (94.4%) had a follow-up of 2 years, and 50.8% were completely seizure free (Engel IA). Seizure freedom rate slightly improved over time. Presurgical evaluations continuously increased, whereas surgical interventions did not. Numbers for MTS, BT and temporal lobe resections decreased since 2009. The number of non-lesional patients and the need for intracranial recordings increased. More evaluated patients did not undergo surgery (more than 50% in 2010-2013) because patients were not suitable (mainly due to missing hypothesis: 4.5% in 1990-1993 up to 21.1% in 2010-2013, total 13.4%) or declined from surgery (maximum 21.0% in 2010-2013, total 10.9%). One potential reason may be that increasingly detailed information on chances and risks were given over time. CONCLUSIONS: The increasing volume of the presurgical programme largely compensates for decreasing numbers of surgically remediable syndromes and a growing rate of informed choice against epilepsy surgery. Although comprehensive diagnostic evaluation is offered to a larger group of epilepsy patients, surgical numbers remain stable.

Secondarily generalized seizures in temporal lobe epilepsy.

PURPOSE: Secondarily generalized tonic-clonic seizure (SGTCS) may occur rarely in temporal lobe epilepsy (TLE), but SGTCS is the major risk factor for sudden death and for seizure-related fatal injuries. Our aim was to investigate clinical factors associated with the occurrence of SGTCS in TLE by addressing two questions: (1) What clinical features differentiate patients with TLE who regularly had SGTCS from those who did not? (2) Is there an association of secondarily generalized seizures with preceding seizure elements and clinical data? METHODS: We included 171 patients with TLE (mean age 34.4 ± 10) who participated in our presurgical evaluation program, which included continuous video-electroencephalography (EEG) and magnetic resonance imaging (MRI). Patients had a temporal lobectomy as a result of mesial or neocortical TLE. To reevaluate the archived seizures, we selected the consecutively recorded seizures of each patient. If the patient had more than three recorded seizures, then we reevaluated only the first three. Altogether video-recorded seizures of 402 patients were reanalyzed. KEY FINDINGS: A positive association between the presence of hippocampal sclerosis on the MRI and SGTCS in the patient history was found, whereas ictal speech and pedal automatism showed a negative association with a SGTCS history. The age of patients showed a positive association, whereas patient's reactivity before and during the seizure, oral/pedal automatisms, and vocalizations showed a negative association with secondary generalization of a focal-onset seizure during video-EEG monitoring. SIGNIFICANCE: Clinical features associated with SGTCS may help clinicians during presurgical monitoring identify high-risk patients for SGTCS. Our study may help in understanding the pathophysiology of secondary generalization.

Unilateral autoscopic phenomena as a lateralizing sign in focal epilepsy.

Positive autoscopic phenomena - autoscopy, heautoscopy and out-of-body experience - may occur in a variety of diseases and also in physiological conditions. They are a rare but probably underreported phenomenon in focal epilepsies. Here, we investigate whether ictal lateralized autoscopic phenomena give lateralizing information about the underlying epileptic focus. We present the cases of seven patients from our center who experienced ictal lateralized autoscopic phenomena and analyzed their focus lateralization and localization of the underlying brain lesion. In addition, we reviewed seven cases published in German and English language literature. In the total group of 14 patients with ictal lateralized autoscopic phenomena, 12 (85.7%) of them had a well-defined epileptic focus contralateral to the side of the autoscopic appearance. Therefore, the data point to an association between ictal lateralized autoscopy and contralateral epileptic focus.

Relative Source Power: A novel method for localizing epileptiform EEG discharges.

OBJECTIVE: To validate relative source power (RSP) imaging of extratemporal interictal epileptiform discharges (IEDs). METHODS: The accuracy of RSP was validated in a cohort of patients with extratemporal focal epilepsy and a confined epileptogenic lesion (<19 cm3) using distance to the lesion, concordance with resected area and postoperative outcome. Performance was compared with three conventional methods: voltage maps, equivalent current dipole and a distributed source model. RESULTS: Thirty-three of 41 consecutive patients (80%) had IED averages suitable for analysis. While the peak negativity in voltage maps localized above the epileptogenic lesion only in 18 cases, RSP-maps matched in 29 cases (88%, p < 0.0026). Source localization showed a median distance of 9.8 mm from the lesion. Source-regions with 20 mm radius included 98% of all source-to-lesion distances. In the 21 surgical cases, outcome showed a sensitivity of 82.35% and specificity of 50% without significant differences between the three source imaging methods. CONCLUSIONS: RSP-maps provide a rapid, intuitive and more accurate source estimation than voltage maps. At sublobar level, RSP localizes with an accuracy similar to conventional methods and results of previous studies. SIGNIFICANCE: The definition of a source region with 20 mm radius helps in guiding further exploration in extratemporal focal epilepsy.

Apical temporal lobe resection; "tailored" hippocampus-sparing resection based on presurgical evaluation data.

BACKGROUND: It is the aim of epilepsy surgery in patients with lesional epilepsy for the surgeon to not only remove the lesion itself, but also the epileptogenic zone. Here, we report our experience with a modified temporal resection technique confined to the apical temporal lobe, i.e., sparing the hippocampal formation in patients with epileptogenic lesions in the anterior part of the temporal lobe. This apical temporal lobe resection (aTLR) includes tailored lesionectomy, amygdalectomy, and resection of the mesial structures only in the apex of the temporal lobe. This paper presents our surgical technical details and the outcome of aTLR. METHODS: Between 2001 and 2008, aTLR was performed in 61 patients. All patients underwent comprehensive presurgical evaluation including video-EEG monitoring, magnetic resonance imaging (MRI), and neuropsychological testing. All patients had a lesion in the apex of the temporal lobe and a normal hippocampus as seen in MRI, as well as intact memory functions in neuropsychological examination. There were 33 males (54.1%) and 28 females (45.9%). The mean age in years at epilepsy onset was 20.2 ± 13.4, the mean age at epilepsy surgery was 32.1 ± 11.9, the mean preoperative epilepsy duration was 11.8 ± 8.8 years and the mean duration of follow-up was 2.1 ± 1.3 years (range 0.5-6 years). RESULTS: Fifty-four (88.5%) of 61 patients were in Engel Class 1 at 6 months, 38 (80.9%) of 47 at 2 years and nine (81.8%) of 11 at the 5 year follow-up. Histopathological examination showed tumors in 31 patients, FCD in ten patients, amygdala sclerosis in seven patients, cavernomas in six patients, unspecific reactions in eight patients, and gliosis in one patient. Surgical complications occurred in four patients: one had a permanent and three had transient complications which could be successfully treated. Fifty (82%) resections were considered to be complete resections as evaluated by serial postoperative MRI, seven patients (11.5%) had incomplete resection of the preoperative MRI lesion and in four patients (6.6%) it remained unclear. Fifteen patients (29.4%) were withdrawn from antiepileptic drugs for more than 2 years without relapse. Postoperative neuropsychological examination revealed worsening of memory performance in two patients (3.2%) and improved or no changes in the rest of the patients. CONCLUSIONS: Apical temporal resection sparing the mesial temporal structures is an effective procedure with good long-term seizure outcome in patients with refractory epilepsy due to lesions confined to the apex of the temporal lobe.

Deep Learning to Decipher the Progression and Morphology of Axonal Degeneration.

Axonal degeneration (AxD) is a pathological hallmark of many neurodegenerative diseases. Deciphering the morphological patterns of AxD will help to understand the underlying mechanisms and develop effective therapies. Here, we evaluated the progression of AxD in cortical neurons using a novel microfluidic device together with a deep learning tool that we developed for the enhanced-throughput analysis of AxD on microscopic images. The trained convolutional neural network (CNN) sensitively and specifically segmented the features of AxD including axons, axonal swellings, and axonal fragments. Its performance exceeded that of the human evaluators. In an in vitro model of AxD in hemorrhagic stroke induced by the hemolysis product hemin, we detected a time-dependent degeneration of axons leading to a decrease in axon area, while axonal swelling and fragment areas increased. Axonal swellings preceded axon fragmentation, suggesting that swellings may be reliable predictors of AxD. Using a recurrent neural network (RNN), we identified four morphological patterns of AxD (granular, retraction, swelling, and transport degeneration). These findings indicate a morphological heterogeneity of AxD in hemorrhagic stroke. Our EntireAxon platform enables the systematic analysis of axons and AxD in time-lapse microscopy and unravels a so-far unknown intricacy in which AxD can occur in a disease context.

Optimized set of criteria for defining interictal epileptiform EEG discharges.

OBJECTIVE: To find and validate the optimal combination of criteria that define interictal epileptiform EEG discharges (IEDs). Our target was a specificity over 95%, to avoid over-reading in clinical EEG. METHODS: We constructed 63 combinations of the six criteria from the operational definition of IEDs, recently issued in the EEG-glossary of the International Federation of Clinical Neurophysiology (IFCN). The diagnostic gold standard was derived from video-EEG recordings. In a testing EEG dataset from 100 patients, we selected the best performing combinations of criteria and then we validated them in an independent dataset from 70 patients. We compared their performance with subjective, expert-scorings and we determined inter-rater agreement (IRA). RESULTS: Without using criteria, the specificity of expert-scorings was lower than the pre-defined threshold (86%). The best performing combination of criteria was the following: waves with spiky morphology, followed by a slow-afterwave and voltage map suggesting a source in the brain. In the validation dataset this achieved a specificity of 97% and a sensitivity of 89%. IRA was substantial. CONCLUSIONS: The optimized set of criteria for defining IEDs has high accuracy and IRA. SIGNIFICANCE: Using these criteria will contribute to decreasing over-reading of EEG and avoid misdiagnosis of epilepsy.

Criteria for defining interictal epileptiform discharges in EEG: A clinical validation study.

OBJECTIVE: To define and validate criteria for accurate identification of EEG interictal epileptiform discharges (IEDs) using (1) the 6 sensor space criteria proposed by the International Federation of Clinical Neurophysiology (IFCN) and (2) a novel source space method. Criteria yielding high specificity are needed because EEG over-reading is a common cause of epilepsy misdiagnosis. METHODS: Seven raters reviewed EEG sharp transients from 100 patients with and without epilepsy (diagnosed definitively by video-EEG recording of habitual events). Raters reviewed the transients, randomized, and classified them as epileptiform or nonepileptiform in 3 separate rounds: in 2, EEG was reviewed in sensor space (scoring the presence/absence of each IFCN criterion for each transient or classifying unrestricted by criteria [expert scoring]); in the other, review and classification were performed in source space. RESULTS: Cutoff values of 4 and 5 criteria in sensor space and analysis in source space provided high accuracy (91%, 88%, and 90%, respectively), similar to expert scoring (92%). Two methods had specificity exceeding the desired threshold of 95%: using 5 IFCN criteria as cutoff and analysis in source space (both 95.65%); the sensitivity of these methods was 81.48% and 85.19%, respectively. CONCLUSIONS: The presence of 5 IFCN criteria in sensor space and analysis in source space are optimal for clinical implementation. By extracting these objective features, diagnostic accuracy similar to expert scorings is achieved. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IFCN criteria in sensor space and analysis in source space have high specificity (>95%) and sensitivity (81%-85%) for identification of IEDs.

Ictal vocalizations occur more often in temporal lobe epilepsy with dominant (left-sided) epileptogenic zone.

OBJECTIVE: To investigate the lateralization value of ictal vocalizations in temporal lobe epilepsy (TLE). METHODS: We reviewed video-recordings of 97 patients who had undergone presurgical evaluation programs with video-EEG (electroencephalography)-recorded complex partial seizures (CPS) and high-resolution magnetic resonance imaging (MRI). All patients had surgery due to TLE and became seizure-free. In 57 patients, determination of speech dominance was necessary by using Wada tests or functional MRI (fMRI). To reevaluate the archived seizures, we reviewed one to three consecutively recorded CPS of each patient. Altogether 223 archived seizures were analyzed. Ictal vocalization was considered to be present in a particular patient if it occurred in at least one of the recorded seizures. RESULTS: Ictal vocalizations occurred in 22 patients. They occurred in 37% of left-sided and in 11% of right-sided patients with TLE (p = 0.003). In patients with determined speech lateralization, ictal vocalizations occurred in 37% of the dominant and in 14% in patients with nondominant epileptogenic zone (p = 0.04). In patients with ictal vocalizations, epilepsy began at age 8.7 +/- 6, whereas in the remaining patients, epilepsy started at age 14.0 +/- 9 (p = 0.017). Logistic regression showed that both hemispheric dominance and age at onset were independently associated with pure ictal vocalization (PIV). CONCLUSIONS: Ictal vocalization is a frequent phenomenon, occurring in 23% of patients with TLE. It is more often associated with left-sided and early onset TLE. Our results may improve the lateralization of the epileptogenic zone and suggest that nonspeech vocalizations in humans are related to the dominant (left-sided) hemisphere. Our study is a further argument that there are different subtypes of TLE depending on the age at onset.

Long-term outcome after temporal lobe epilepsy surgery in 434 consecutive adult patients.

OBJECT: The aim of this study was to evaluate the long-term efficacy of temporal lobe epilepsy (TLE) surgery and potential risk factors for seizure recurrence after surgery. METHODS: This retrospective study included 434 consecutive adult patients who underwent TLE surgery at Bethel Epilepsy Centre between 1991 and 2002. RESULTS: Hippocampal sclerosis was found in 62% of patients, gliosis in 17.3%, tumors in 20%, and focal cortical dysplasia (FCD) in 6.9%. Based on a Kaplan-Meier analysis, the probability of Engel Class I outcome for the patients overall was 76.2% (95% CI 71-81%) at 6 months, 72.3% (95% CI 68-76%) at 2 years, 71.1% (95% CI 67-75%) at 5 years, 70.8% (95% CI 65-75%) at 10 years, and 69.4% (95% CI 64-74%) at 16 years postoperatively. The likelihood of remaining seizure free after 2 years of freedom from seizures was 90% (95% CI 82-98%) for 16 years. Seizure relapse occurred in all subgroups. Patients with FCD had the highest risk of recurrence (hazard ratio 2.15, 95% CI 0.849-5.545). Predictors of remission were the presence of hippocampal atrophy on preoperative MR imaging and a family history of epilepsy. Predictors of relapse were the presence of bilateral interictal sharp waves and versive seizures. Six-month follow-up electroencephalography predicted relapse in patients with FCD. Short epilepsy duration was predictive of seizure remission in patients with tumors and gliosis; 28.1% of patients were able to discontinue antiepileptic medications without an increased risk of seizure recurrence (hazard ratio 1.05, 95% CI 0.933-1.20). CONCLUSIONS: These findings highlight the role of etiology in prediction of long-term outcome after TLE surgery.

Outcome of frontal lobe epilepsy surgery in adults.

Our aim is to investigate seizure outcome and prognostic factors after pure frontal lobe epilepsy (FLE) surgery. We retrospectively studied the operative outcome in 97 consecutive adult patients who underwent resective surgery for intractable partial epilepsy between 1991 and 2005. Based on Kaplan-Meier, the probability of an Engel Class I outcome was found to be 54.6% (95% CI 44-64) at 6 months, 49.5% (95% CI 39.3-59.6) at 2 years, 47% (CI 34-59) at 5 years and 41.9% (CI 23.5-60.3) at 10 years. If the patient was seizure free at 2-year follow-up, the probability of remaining seizure free up to 10 years was 86% (95% CI 76-98). For 13.6% of the patients a running down of seizures could be shown. Factors predictive of poor long-term outcome were incomplete resection, using of subdural grids, IED in follow-up EEG, tonic seizures and an unspecific aura or a postoperative aura. Factors predictive of good long-term outcome were the presence of a well-circumscribed lesion in preoperative MRI, ipsilateral IED in preoperative EEG, surgery before age of 30 and short epilepsy duration prior to surgery. In the multivariate analysis, preoperative well-circumscribed lesion in MRI predicts seizure remission whereas persistent postoperative auras predict seizure relapse. FLE surgery should depend on restrictive patient selection to assure favorable outcome.

Long-term outcome of extratemporal epilepsy surgery among 154 adult patients.

OBJECT: The goal of this study was to evaluate the long-term outcome of patients who underwent extratemporal epilepsy surgery and to assess preoperative prognostic factors associated with seizure outcome. METHODS: This retrospective study included 154 consecutive adult patients who underwent epilepsy surgery at Bethel Epilepsy Centre, Bielefeld, Germany between 1991 and 2001. Seizure outcome was categorized based on the modified Engel classification. Survival statistics were calculated using Kaplan-Meier curves, life tables, and Cox regression models to evaluate the risk factors associated with outcomes. RESULTS: Sixty-one patients (39.6%) underwent frontal resections, 68 (44.1%) had posterior cortex resections, 15 (9.7%) multilobar resections, 6 (3.9%) parietal resections, and 4 (2.6%) occipital resections. The probability of an Engel Class I outcome for the overall patient group was 55.8% (95% confidence interval [CI] 52-58% at 0.5 years), 54.5% (95% CI 50-58%) at 1 year, and 51.1% (95% CI 48-54%) at 14 years. If a patient was in Class I at 2 years postoperatively, the probability of remaining in Class I for 14 years postoperatively was 88% (95% CI 78-98%). Factors predictive of poor long-term outcome after surgery were previous surgery (p = 0.04), tonic-clonic seizures (p = 0.02), and the presence of an auditory aura (p = 0.03). Factors predictive of good long-term outcome were surgery within 5 years after onset (p = 0.015) and preoperative invasive monitoring (p = 0.002). CONCLUSIONS: Extratemporal epilepsy surgery is effective according to findings on long-term follow-up. The outcome at the first 2-year follow-up visit is a reliable predictor of long-term Engel Class I postoperative outcome.

Lesional cerebellar epilepsy: a review of the evidence.

Classical teaching in epileptology localizes the origins of focal seizures solely in the cerebral cortex, with only inhibitory effects attributed to subcortical structures. However, electrophysiological and neuroimaging studies over the last decades now provide evidence for an initiation of epileptic seizures within subcortical structures. Intrinsic epileptogenicity of hypothalamic hamartoma has already been established in recognition of subcortical epilepsy, whereas a seizure-generating impact of dysplastic cerebellar lesions remains to be clarified. Herein, we examine the supportive evidence and clinical presentation of cerebellar seizures and review therapy options.

Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Frontal Lobe Epilepsy: A New Clinico-Pathological Entity.

The histopathological spectrum of human epileptogenic brain lesions is widespread including common and rare variants of cortical malformations. However, 2-26% of epilepsy surgery specimens are histopathologically classified as nonlesional. We hypothesized that these specimens include also new diagnostic entities, in particular when presurgical magnetic resonance imaging (MRI) can identify abnormal signal intensities within the anatomical region of seizure onset. In our series of 1381 en bloc resected epilepsy surgery brain specimens, 52 cases could not be histopathologically classified and were considered nonlesional (3.7%). An increase of Olig2-, and PDGFR-alpha-immunoreactive oligodendroglia was observed in white matter and deep cortical layers in 22 of these patients (42%). Increased proliferation activity as well as heterotopic neurons in white matter were additional histopathological hallmarks. All patients suffered from frontal lobe epilepsy (FLE) with a median age of epilepsy onset at 4 years and 16 years at epilepsy surgery. Presurgical MRI suggested focal cortical dysplasia (FCD) in all patients. We suggest to classify this characteristic histopathology pattern as "mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE)." Further insights into pathomechanisms of MOGHE may help to bridge the diagnostic gap in children and young adults with difficult-to-treat FLE.

Postoperative routine EEG correlates with long-term seizure outcome after epilepsy surgery.

We investigated the correlation of interictal epileptiform discharges (IED) in routine EEG 6 and 24 months after epilepsy surgery with regard to long-term seizure outcome. In 148 patients (74% temporal lobe epilepsy (TLE), 26% extratemporal epilepsy) EEG results (IED present or absent) were correlated with the postoperative outcome using the Engel classification 6 and 24 months after resection (PO6m and PO2y, respectively). Self-evaluation was conducted 3 and 5 years after resection (PO3y and PO5y, respectively). Ninety-one patients (62%) were seizure-free 5 years after resection; 88% of them showed no IED in PO6m. Twenty-eight patients (19%) displayed IED in routine EEG 6 months after resection; 61% of them had recurrent seizures at PO5y, whereas of 120 patients without IED only 33% had recurrent seizures at PO5y; p=0.01. Absence of IED in PO6m and PO2y correlated with good outcome: 71% without IED remained seizure-free, whereas only 25% with IED at PO6m and PO2y remained seizure-free; p=0.001. Seizure-free patients (Engel 1) and patients with less favourable outcome (Engel 3-4) at PO6m and PO2y rarely changed categories of outcome during the following years (p<0.001). Half of the patients with favourable seizure reduction (Engel 2) changed to seizure-free (Engel 1) or to a worse outcome category (Engel 3-4). Postoperative routine EEG is a good prognostic instrument for the prediction of long-term seizure outcome, especially for TLE. It predicts the running up and down of fits in patients with rare seizures (Engel 2).

Oscillatory dynamics track motor performance improvement in human cortex.

Improving performance in motor skill acquisition is proposed to be supported by tuning of neural networks. To address this issue we investigated changes of phase-amplitude cross-frequency coupling (paCFC) in neuronal networks during motor performance improvement. We recorded intracranially from subdural electrodes (electrocorticogram; ECoG) from 6 patients who learned 3 distinct motor tasks requiring coordination of finger movements with an external cue (serial response task, auditory motor coordination task, go/no-go). Performance improved in all subjects and all tasks during the first block and plateaued in subsequent blocks. Performance improvement was paralled by increasing neural changes in the trial-to-trial paCFC between theta ([Formula: see text]; 4-8 Hz) phase and high gamma (HG; 80-180 Hz) amplitude. Electrodes showing this covariation pattern (Pearson's r ranging up to .45) were located contralateral to the limb performing the task and were observed predominantly in motor brain regions. We observed stable paCFC when task performance asymptoted. Our results indicate that motor performance improvement is accompanied by adjustments in the dynamics and topology of neuronal network interactions in the [Formula: see text] and HG range. The location of the involved electrodes suggests that oscillatory dynamics in motor cortices support performance improvement with practice.