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.

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.

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.

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.

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.

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.

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.

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.

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.

Epileptic monocular nystagmus and ictal diplopia as cortical and subcortical dysfunction.

We present the case of a patient with ictal monocular nystagmus and ictal diplopia who became seizure-free after resection of a right frontal focal cortical dysplasia (FCD), type 2B. Interictal neuroophthalmological examination showed several beats of a monocular nystagmus and a spasm of the contralateral eye. An exclusively ictal monocular epileptic nystagmus could be an argument for an exclusively cortical involvement in monocular eye movement control. The interictal findings in our patient, however, argue for an irregular ictal activation of both the cortical frontal eye field and the brainstem.

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.

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.

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.

Analysis of reoperation in mesial temporal lobe epilepsy with hippocampal sclerosis.

BACKGROUND: Most patients do well after epilepsy surgery for mesial temporal lobe sclerosis, and in only 8 to 12% of all operations, the outcome is classified as not improved. OBJECTIVE: To analyze the outcome of reoperation in cases of incomplete resection of mesial temporal lobe structures in patients with mesial temporal lobe sclerosis in temporal lobe epilepsy. METHODS: We analyzed 22 consecutive patients who underwent reoperation for mesial temporal lobe sclerosis (follow-up, 23-112 months; mean, 43.18 months) by evaluating noninvasive electroencephalographic/video monitoring before the first and second surgeries (semiology, interictal epileptiform discharges, ictal electroencephalography with special attention to the secondary contralateral evolution of the electroencephalographic seizure pattern after the initial regionalization), and magnetic resonance imaging (resection indices after the first and second surgeries on the amygdala, hippocampus, lateral temporal lobe). In 18 of 22 patients T2 relaxometry of the contralateral hippocampus was performed. RESULTS: Nine of 22 patients became seizure free; another 4 patients had a decrease in seizures and eventually became seizure free (range, 16-51 months; mean, 30.3). Recurrence of seizures is associated with (1) ictal electroencephalography with later evolution of an independent pattern over the contralateral temporal lobe (0 of 5 patients seizure free vs 5 of 7 patients non-seizure free; P = .046) and (2) a smaller amount of lateral temporal lobe resection in the second surgery (1.06 ± 0.59 cm vs 2.18 ± 1.37 cm; P = .019). No significant correlation with outcome was found for lateralization of interictal epileptiform discharges, change in semiology, other resection indices, T2 relaxometry, onset and duration of epilepsy, duration of follow-up, and side of surgery. CONCLUSION: Patients have a less favorable outcome with a reoperation if they show ictal scalp electroencephalography with secondary contralateral propagation and if only a small second resection of the lateral temporal lobe is performed.

Absolute spike frequency and etiology predict the surgical outcome in epilepsy due to amygdala lesions.

PURPOSE: To identify surgical prognostic factors for temporal lobe epilepsy (TLE) due to amygdala lesions. METHODS: We included 42 patients (mean age: 31.4 ± 11) who underwent presurgical evaluation including long-term video-EEG and in whom the high-resolution MRI showed amygdala lesions without hippocampal abnormalities. All patients had apical temporal lobe resection without hippocampectomy. We distinguished patients with frequent spikes (spike frequency ≥ 60/h) and with non-frequent spikes (< 60 spikes/h). RESULTS: At the 2-year postoperative evaluation, 30 patients (71%) were seizure-free. The presence of infrequent spikes (p = 0.013), tumor on the MRI (p = 0.027), and no epilepsy history in the family (p = 0.027) were independently associated with 2-year seizure-free outcome. Of 33 patients with infrequent spikes, 79% became seizure-free, while of 9 patients with frequent spikes only 4 had a favorable surgical outcome (44%). CONCLUSION: In TLE patients due to amygdala lesions, high spike frequency and family history of epilepsy predicted an unfavorable, while tumoral etiology a favorable outcome after apical temporal lobe resection without hippocampectomy. Seventy-one percent of patients with amygdalar epilepsy who underwent this novel type of epilepsy surgery became seizure-free. This is comparable with results of "classical" anterior temporal lobe resections where hippocampus is NOT spared. Moreover, the surgical outcome may be predictable.

Vagus nerve stimulation: outcome and predictors of seizure freedom in long-term follow-up.

OBJECTIVES: To present long-term outcome and to identify predictors of seizure freedom after vagus nerve stimulation (VNS). METHODS: All patients who had undergone VNS implantation in the Epilepsy Centre Bethel were retrospectively reviewed. There were 144 patients who had undergone complete presurgical evaluation, including detailed clinical history, magnetic resonance imaging, and long-term video-EEG with ictal and interictal recordings. After implantation, all patients were examined at regular intervals of 4 weeks for 6-9 months. During this period the antiepileptic medication remained constant. All patients included in this study were followed up for a minimum of 2 years. RESULT: Ten patients remained seizure-free for more than 1 year after VNS implantation (6.9%). Seizures improved in 89 patients (61.8%) but no changes were observed in 45 patients (31.3%). The following factors were significant in the univariate analysis: age at implantation, multifocal interictal epileptiform discharges, unilateral interictal epileptiform discharge, cortical dysgenesis, and psychomotor seizure. Stepwise multivariate analysis showed that unilateral interictal epileptiform discharges (IEDs), P=0.014, HR=0.112 (95% CIs, 0.019-0.642), cortical dysgenesis P=0.007, HR=0.065 (95% CIs, 0.009-0.481) and younger age at implantation P=0.026, HR=7.533 (95% CIs 1.28-44.50) were independent predictors of seizure freedom in the long-term follow-up. CONCLUSION: VNS implantation may render patients with some forms of cortical dysgenesis (parietooccipital polymicrogyria, macrogyria) seizure-free. Patients with unilateral IEDs and earlier implantation achieved the most benefit from VNS.

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.