Semiautomated electric source imaging determines epileptogenicity of encephaloceles in temporal lobe epilepsy.

OBJECTIVE: We aimed to assess the ability of semiautomated electric source imaging (ESI) from long-term video-electroencephalographic (EEG) monitoring (LTM) to determine the epileptogenicity of temporopolar encephaloceles (TEs) in patients with temporal lobe epilepsy. METHODS: We conducted a retrospective study involving 32 temporal lobe epilepsy patients with TEs as potentially epileptogenic lesions in structural magnetic resonance imaging scans. Findings were validated through invasive intracerebral stereo-EEG in six of 32 patients and postsurgical outcome after tailored resection of the TE in 17 of 32 patients. LTM (mean duration = 6 days) was performed using the 10/20 system with additional T1/T2 for all patients and sphenoidal electrodes in 23 of 32 patients. Semiautomated detection and clustering of interictal epileptiform discharges (IEDs) were carried out to create IED types. ESI was performed on the averages of the two most frequent IED types per patient, utilizing individual head models, and two independent inverse methods (sLORETA [standardized low-resolution brain electromagnetic tomography], MUSIC [multiple signal classification]). ESI maxima concordance and propagation in spatial relation to TEs were quantified for sources with good signal quality (signal-to-noise ratio > 2, explained signal > 60%). RESULTS: ESI maxima correctly colocalized with a TE in 20 of 32 patients (62.5%) either at the onset or half-rising flank of at least one IED type per patient. ESI maxima showed propagation from the temporal pole to other temporal or extratemporal regions in 14 of 32 patients (44%), confirming propagation originating in the area of the TE. The findings from both inverse methods validated each other in 14 of 20 patients (70%), and sphenoidal electrodes exhibited the highest signal amplitudes in 17 of 23 patients (74%). The concordance of ESI with the TE predicted a seizure-free postsurgical outcome (Engel I vs. >I) with a diagnostic odds ratio of 2.1. SIGNIFICANCE: Semiautomated ESI from LTM often successfully identifies the epileptogenicity of TEs and the IED onset zone within the area of the TEs. Additionally, it shows potential predictive power for postsurgical outcomes in these patients.

"What is this strange sensation?" A qualitative exploration of metaphors used to verbalise hard-to-describe experiences by people with epilepsy.

Mental health comorbidities are frequent in epilepsy. Consequently, psychotherapy is becoming increasingly important. To address the psychological needs of people with epilepsy (PwE) it is essential to understand the subjective experiences of seizures better. There is little research on how people report seizures, and which psychological representations they have. We conducted a thematic analysis based on 42 (micro-phenomenological) interviews with 15 participants on their experiences of seizures. In these interviews, we identified three categories of seizure descriptions: (1) phenomena related to the body and emotions; (2) the moments that are difficult to describe; and (3) the use of figurative language and metaphors. Paroxysmal physical and psychological sensations were often reported spontaneously by the participants. The moments that were difficult to describe were expressed, among other things, through the use of paradoxes or the report of a 'strange' feeling and led participants to use figurative language. As these metaphors can reveal important information about people's subjective experiences, they were analyzed in detail. We identified the three main types of metaphors that the participants used most frequently: (1) perception, (2) nature, and (3) battle. The theme of battle was most frequently used in different forms and was closely related to the metaphors from the fields of perception and nature, thus representing a key point in the personal experience of seizures. These findings can contribute to developing psychotherapeutic approaches for the treatment of seizure disorders.

Seizures as a Struggle between Life and Death: An Existential Approach to the Psychosocial Impact of Seizures in Candidates for Epilepsy Surgery.

INTRODUCTION: Mental health comorbidities such as depression and anxiety are common in epilepsy, especially among people with pharmacoresistant epilepsy who are candidates for epilepsy surgery. The Psychology Task Force of the International League Against Epilepsy advised that psychological interventions should be integrated into comprehensive epilepsy care. METHODS: To better understand the psychological impact of epilepsy and epileptic seizures in epilepsy surgery candidates, we analysed interviews with this subgroup of patients using Karl Jaspers' concept of limit situations, which are characterised by a confrontation with the limits and challenges of life. These are especially chance, randomness, and unpredictability, death and finitude of life, struggle and self-assertion, guilt, failure, and falling short of one's aspirations. RESULTS: In 43 interviews conducted with 15 people with drug-resistant epilepsy who were candidates for epilepsy surgery, we found that these themes are recurrent and have a large psychosocial impact, which can result in depression and anxiety. For some people, epileptic seizures appear to meet the criteria for traumatic events. CONCLUSION: Understanding epilepsy and seizures as existential challenges complements the neurobiological explanations for psychological comorbidities and can help tailor psychological interventions to the specific needs of people with epilepsy, especially those who are candidates for surgical treatment.

Detection of interictal epileptiform discharges in an extended scalp EEG array and high-density EEG-A prospective multicenter study.

OBJECTIVES: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). METHODS: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. RESULTS: Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. SIGNIFICANCE: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.

Diagnostic yield and limitations of in-hospital documentation in patients with epilepsy.

OBJECTIVE: To determine the diagnostic yield of in-hospital video-electroencephalography (EEG) monitoring to document seizures in patients with epilepsy. METHODS: Retrospective analysis of electronic seizure documentation at the University Hospital Freiburg (UKF) and at King's College London (KCL). Statistical assessment of the role of the duration of monitoring, and subanalyses on presurgical patient groups and patients undergoing reduction of antiseizure medication. RESULTS: Of more than 4800 patients with epilepsy undergoing in-hospital recordings at the two institutions since 2005, seizures with documented for 43% (KCL) and 73% (UKF).. Duration of monitoring was highly significantly associated with seizure recordings (p < .0001), and presurgical patients as well as patients with drug reduction had a significantly higher diagnostic yield (p < .0001). Recordings with a duration of >5 days lead to additional new seizure documentation in only less than 10% of patients. SIGNIFICANCE: There is a need for the development of new ambulatory monitoring strategies to document seizures for diagnostic and monitoring purposes for a relevant subgroup of patients with epilepsy in whom in-hospital monitoring fails to document seizures.

Electrocorticographic and neurochemical findings after local cortical valproate application in patients with pharmacoresistant focal epilepsy.

Because oral pharmacological treatment of neocortical focal epilepsy is limited due to common systemic side effects and relatively low drug concentrations reached at the epileptic foci locally, application of antiepileptic agents directly onto the neocortical focus may enhance treatment tolerability and efficacy. We describe the effects of cortically applied sodium valproate (VPA) in two patients with pharmacoresistant neocortical focal epilepsy who were selected for epilepsy surgery after a circumscribed epileptic focus had been determined by invasive presurgical evaluation using subdural electrodes. Local VPA modified epileptic activity as electrocorticographically recorded from the chronic focus in both patients. In addition, VPA induced local increase of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in cortical tissue samples, whereas the excitatory glutamate was possibly decreased. In this clinical pilot study, we could show antiepileptic effects of cortically applied VPA in humans by electrocorticographic and neurochemical parameters.

Can commercially available wearable EEG devices be used for diagnostic purposes? An explorative pilot study.

Electroencephalography (EEG) is a core element in the diagnosis of epilepsy syndromes and can help to monitor antiseizure treatment. Mobile EEG (mEEG) devices are increasingly available on the consumer market and may offer easier access to EEG recordings especially in rural or resource-poor areas. The usefulness of consumer-grade devices for clinical purposes is still underinvestigated. Here, we compared EEG traces of a commercially available mEEG device (Emotiv EPOC) to a simultaneously recorded clinical video EEG (vEEG). Twenty-two adult patients (11 female, mean age 40.2 years) undergoing noninvasive vEEG monitoring for clinical purposes were prospectively enrolled. The EEG recordings were evaluated by 10 independent raters with unmodifiable view settings. The individual evaluations were compared with respect to the presence of abnormal EEG findings (regional slowing, epileptiform potentials, seizure pattern). Video EEG yielded a sensitivity of 56% and specificity of 88% for abnormal EEG findings, whereas mEEG reached 39% and 85%, respectively. Interrater reliability coefficients were better in vEEG as compared to mEEG (ϰ = 0.50 vs. 0.30), corresponding to a moderate and fair agreement. Intrarater reliability between mEEG and vEEG evaluations of simultaneous recordings of a given participant was moderate (ϰ = 0.48). Given the limitations of our exploratory pilot study, our results suggest that vEEG is superior to mEEG, but that mEEG can be helpful for diagnostic purposes. We present the first quantitative comparison of simultaneously acquired clinical and mobile consumer-grade EEG for a clinical use-case.

Local brain activity persists during apparently generalized postictal EEG suppression.

OBJECTIVES: Postictal generalized EEG suppression (PGES) frequently occurs after generalized convulsive seizures (GCS) and may be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). It is usually determined using conventional scalp EEG which is likely to miss cerebral activity in deeper brain structures. Here, we examined intracranial EEG activity after GCS to unravel the pattern and extent of local brain activity during apparent PGES on scalp EEG (s-PGES). METHODS: We retrospectively reviewed electroencephalographic data of people with chronic epilepsy who had GCS during presurgical video-EEG monitoring using simultaneous intracranial and scalp EEG (10-20 system) electrodes. RESULTS: Twenty-five GCS (20 with s-PGES) of 15 patients with an average number of 88±42 intracranial electrode contacts were included. The majority of GCS with s-PGES (18 of 20) displayed persisting or reemerging intracranial EEG activity during apparent PGES on scalp EEG. Three patterns were identified: Pattern 1 (11 GCS, 6 patients) consisted of continuous local interictal activity; Pattern 2 (5 GCS, 5 patients) displayed suppressed EEG activity at all intracranial contacts in the early phase of s-PGES, but reemerging local brain activity before s-PGES dissolved; and Pattern 3 (2 GCS, 2 patients) showed persistent local ictal activity during s-PGES. Persisting intracranial EEG activity at PGES onset on scalp EEG was present in 10±14% (range: 0 to 42%) of all intracranial contacts and mostly in the temporal lobe. CONCLUSIONS: Our results reveal that, during apparently generalized postictal EEG suppression, local brain activity persists or reemerges in most GCS. Possible implications of this localized neuronal activity in the context of SUDEP are discussed in the paper.

Electroencephalographic findings in schizophreniform and affective disorders.

OBJECTIVE: Pathological findings in electroencephalography (EEG) are discussed as a possible marker of organic mental disorders and a therapeutic response to anticonvulsive medication under these conditions. METHODS: We compared the prevalence of EEG abnormalities in 100 patients with schizophrenia, 100 patients with schizoaffective disorder, 51 patients with acute polymorphic psychotic disorder, 100 patients with bipolar disorder, 100 patients with unipolar major depression and 76 healthy control subjects with the findings of a previous study using well-diagnosed, large control samples (13,658 pilots and aircrew personnel). RESULTS: We detected an increased number of pathological EEG findings with intermittent rhythmic delta or theta activity in 7% of patients with schizophrenia, 7% of patients with schizoaffective disorder, 5.9% of patients with acute polymorphic psychosis, 6% of patients with bipolar disorder, 4% of unipolar depressed patients and 3.9% of the own control group, compared to 1% of strictly controlled healthy subjects. One-sided logistic regression revealed an association between pathological EEGs and the diagnosis of schizophrenia (Wald W = 3.466, p = 0.0315), schizoaffective disorder (W = 3.466, p = 0.0315) and bipolar disorder (W = 2.862, p = 0.0455). CONCLUSIONS: We suggest that the previously developed local area network inhibition model for a potential paraepileptic pathomechanism can explain the relevance of such findings in different psychiatric disorders.

Latencies from intracranial seizure onset to ictal tachycardia: A comparison to surface EEG patterns and other clinical signs.

OBJECTIVE: Information on the relative timing of electroencephalography (EEG) seizure onset, ictal tachycardia (ITC), and first other clinical seizure manifestations is crucial for an understanding of the potential benefit of ITC-detection based closed-loop intervention systems for epilepsy treatment. This study analyzes the temporal relation of ITC, other clinical signs, and seizure onset in relation to intracranial and surface EEG. METHODS: Seventy-eight seizures with ITC from 13 patients undergoing invasive EEG recordings with simultaneous recordings of electrocardiography (ECG), intracranial EEG (iEEG) and surface EEG, and video recordings to determine clinical onset were analyzed. Latencies for ITC were calculated for thresholds of 100 bpm and for a 20% heart rate increase above baseline obtained 60 s prior to seizure onset on iEEG. Patient-based, seizure-based, and seizure origin-based analyses were performed. RESULTS: Mean latencies between seizure onset in invasive EEG and the following onset of ITC in the seizure- and patient-based analysis for both thresholds varied between 21.6 and 23.7 s, showing that ITC is an ictal rather a preictal phenomenon. In 10 of 13 patients and in 56 of 78 seizures, at least one of the thresholds for ITC was crossed before any other clinical sign. In the majority of cases, ITC also preceded ictal onset as determined in surface EEG. Latencies to ictal tachycardia were shorter for hippocampal than for extrahippocampal temporal seizure onset. ITC occurred earlier in right than in left temporal seizures. SIGNIFICANCE: iEEG preceded other seizure manifestations, but ictal tachycardia was an early sign particularly in mesial temporal and in right temporal seizure onset and often preceded not only other clinical manifestations but also first visible patterns in surface EEG. Detection of ictal tachycardia was thus the best noninvasively assessed marker for closed-loop interventions in this multimodally assessed patient group.

Long-term seizure outcome in 211 patients with focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasia (FCD) is currently recognized as the most common cause of neocortical pharmacoresistant epilepsy. Epilepsy surgery has become an increasingly successful treatment option. Herein, the largest patient cohort reported to date is analyzed regarding long-term outcome and factors relevant for long-term seizure control. METHODS: Two hundred eleven children and adults undergoing epilepsy surgery for histologically proven FCD and a follow-up period of 2-12 years were analyzed regarding the longitudinal course of seizure control, effects of FCD type, localization, magnetic resonance imaging (MRI), timing of surgery, and postoperative antiepileptic treatment. RESULTS: After 1 year, Engel class I outcome was achieved in 65% of patients and the percentage of seizure-free patients remained stable over the following (up to 12) years. Complete resection of the assumed epileptogenic area, lower age at surgery, and unilobar localization were positive prognostic indicators of long-term seizure freedom. Seizure recurrence was 12% after the first year, whereas 8% achieved late seizure freedom either following additional introduction of antiepileptic drugs (AEDs) (4%), a reoperation (2%), or a running down phenomenon (2%). Thirty-nine percent of patients had a reduction of AED from polytherapy to monotherapy or a complete cessation of AED treatment. Late seizure relapse was seen in nine patients during reduction of AEDs (i.e., in 12% of all patients with AED tapering); in four of them seizures persisted after reestablishment of antiepileptic medication. SIGNIFICANCE: Postoperative long-term seizure outcome was favorable in patients with FCD and remained stable in 80% of patients after the first postoperative year. Several preoperative factors revealed to be predictive for the postoperative outcome and may help in the preoperative counseling of patients with FCD and in the selection of ideal candidates for epilepsy surgery.

Transient global amnesia after the right temporal epilepsy surgery: A case report.

Transient global amnesia (TGA) is characterized by sudden and temporary memory impairment, while transient epileptic amnesia (TEA) represents amnestic attacks as the main manifestation of focal epilepsy with presumed temporal origin. We present a 48-year-old patient who experienced transient amnesia 10 weeks after right selective amygdalo-hippocampectomy for right temporal lobe epilepsy. Despite TEA being a plausible explanation for amnesia in patients with temporal lobe epilepsy, no epileptiform discharges were found during the amnestic episode and key features indicative of TGA, including long duration, isolated occurrence, and dense anterograde amnesia of the episode, argued against a diagnosis of TEA in this case. Notably, the patient has remained seizure-free (now 4,5 years) and stopped taking antiseizure medication 32 months after surgery. Although TGA clinical criteria formally exclude patients with recent active epilepsy, neurologists should be aware that TGA can occur after epilepsy surgery in the temporal lobe. Therefore, we consider it of high clinical relevance to establish a careful differential diagnosis between TGA and epileptic amnestic attacks after epilepsy surgery to avoid unnecessary reintroduction or continuation of antiseizure medication. Additionally, this case presents the first comparison of detailed neuropsychological test results before and after a presumed TGA episode, revealing a complete recovery of anterograde memory functions within 1 day. PLAIN LANGUAGE SUMMARY: A 48-year-old patient experienced an episode of transient amnesia 10 weeks after epilepsy surgery. Given the patient's history, an epileptic origin of the episode initially seemed likely. However, tests revealed no seizure activity during the episode and the characteristics matched a condition called transient global amnesia. This case highlights the importance of correctly diagnosing memory impairments after epilepsy surgery to prevent unnecessary treatment.

Somatotopic mapping of natural upper- and lower-extremity movements and speech production with high gamma electrocorticography.

Precise delineation of pathological and eloquent cortices is essential in pre-neurosurgical diagnostics of epilepsy. A limitation of existing experimental procedures, however, is that they critically require active cooperation of the patient, which is not always achievable, particularly in infants and in patients with insufficient cognitive abilities. In the present study, we evaluated the potential of electrocorticographic recordings of high gamma activity during natural, non-experimental behavior of epilepsy patients to localize upper- and lower-extremity motor and language functions, and compared the results with those obtained using electrocortical stimulation. The observed effects were highly significant and functionally specific, and agreed well with the somatotopic organization of the motor cortex, both on the lateral convexity and in the supplementary motor area. Our approach showed a similar specificity and sensitivity for extremity movements as previously obtained from experimental data. We were able to quantify, for the first time, sensitivity and specificity of high gamma underlying non-experimental lower-extremity movements in four patients, and observed values in the same range as for upper extremities (analyzed in six patients). Speech-related responses in the three investigated patients, however, exhibited only a very low sensitivity. The present findings indicate that localization of not only upper- but also lower-extremity movements congruent with electrocortical stimulation mapping is possible based on event-related high gamma responses that can be observed during natural behavior. Thus, non-experimental mapping may be usefully applied as adjunct to established clinical procedures for identification of both upper- and lower-extremity motor functions.

Is there evidence for clinical differences related to the new classification of temporal lobe cortical dysplasia?

PURPOSE: The new International League Against Epilepsy (ILAE) classification for focal cortical dysplasia (FCD) differentiates between patients with isolated FCD (type 1) and FCD with an associated hippocampal sclerosis (HS) (type 3a). In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis. We investigated in a cohort of 100 patients with exclusively temporal FCD if the new subdivision of FCD is reflected in clinical characteristics. METHODS: Thirty-one patients with FCD type 1 and 50 patients with FCD type 3a in the temporal lobe were included. In all patients MRI and histology of the FCD were available. Both patient groups were compared to 19 patients with temporal FCD type 2 with clearly different histologic appearance. KEY FINDINGS: Patients with FCD type 1 and type 3a presented with similar clinical features in many respects. In univariate analyses, no statistically significant differences were found as to age at epilepsy onset (p = 0.07) and epilepsy surgery (p = 0.14), a normal appearing neocortical temporal lobe (p = 0.08) or diagnosis of FCD by visual inspection of MRI (p = 0.08), preoperative seizure frequency (p = 0.06), and the predominance of an epigastric aura (p = 0.08). The postoperative outcome was nearly identical 1 year (p = 0.8) and 2 (p = 0.8), 3 (p = 0.8), 5 (p = 0.7), and 8 (p = 1.0) years postoperatively. Only febrile seizures (p = 0.025) and an aura (p = 0.03) were significantly more frequently reported in patients with FCD type 3a. Similar results were obtained from a multivariate logistic regression analysis. Patients with FCD type 2 were more different: Compared to FCD type 3a, age at epilepsy surgery was significantly lower (p = 0.004) and auras (p = 0.005) were significantly less frequently reported. Epigastric auras (p = 0.04) and febrile seizures (p = 0.025) occurred significantly less frequently in patients with FCD type 2 without HS compared to FCD type 3a. The diagnosis of an FCD was significantly more frequently made (p = 0.03) by visual inspection of the MRI compared to FCD type 1. SIGNIFICANCE: Clinical features did not allow to clear separation of temporal FCD types 1 and 3a. Statistically significant differences were seen in a history of febrile seizures and the occurrence of auras more common in FCD type 3a. However, FCD type 2 in the same localization but with different histology presented with further differences such as more frequent FCD diagnosis by visual inspection of MRI, earlier operation, and less frequent epigastric auras.

Occipital lobe epilepsy with fear as leading ictal symptom.

Ictal fear is a semiological feature which is commonly associated with mesial temporal lobe epilepsy. Here, we describe fear as a leading symptom in cryptogenic occipital lobe epilepsy. In a patient with negative MRI findings, intracranial EEG recordings documented a strict correlation between habitual ictal anxiety attacks and both spontaneous and stimulation-induced epileptic activity in a right occipital epileptogenic area with subsequent spreading to the symptomatogenic zone in the amygdala. Circumscribed occipital topectomy led to seizure freedom. Episodes of non-epileptic fear ceased shortly afterwards. This report provides insight into pathways of propagation of epileptic activity, illustrates different etiologies of pathologic fear and underlines the importance of ictal EEG recordings.

Electrode placement for SEEG: Combining stereotactic technique with latest generation planning software for intraoperative visualization and postoperative evaluation of accuracy and accuracy predictors.

BACKGROUND: Intracranial recordings with stereoelectroencephalography (SEEG) aims at defining the epileptogenic zone in patients with pharmacoresistant epilepsy. Currently used techniques for depth electrode implantation include stereotactic frame-based and navigated frameless applications, both either conventional or robot-assisted. Safety and diagnostic effectiveness depend on accuracy of implantation. OBJECTIVE: To evaluate the planning experience, accuracy of stereotactic electrode placement as well as accuracy predictors with the use of latest generation planning software. METHODS: Retrospective study of 15 consecutive patients who received depth electrodes using the Leksell stereotactic frame, after planning with Elements (Brainlab, Munich, Germany). For each electrode, we calculated the entry point error (EPE) as lateral deviation and target point error (TPE) both as lateral deviation and distance to tip. Multivariate regression analysis and computation of 95% confidence intervals using the bootstrap method were applied for statistical analysis and evaluation of accuracy predictors. RESULTS: The mean EPE, lateral deviation at TP and distance to tip at TP were 0.6 ±0.5 mm, 1.1 ±0.7 mm and 1.5 ±0.8 mm respectively. Order of implantation (1-6 vs. >6) is predictor for distance to tip at TP and length of electrode predictor for the lateral deviation at TP. Localization of electrode generally did not correlate to error, but insular electrodes were significantly less accurate than lobar ones. CONCLUSION: Combination of frame-based stereotaxy with latest generation planning software may offer a better planning and implantation experience. Accuracy predictors should be analyzed and be considered for the improvement of accuracy and safety of SEEG implantation methods.

Effects of cenobamate on cognitive performance of epilepsy patients.

PURPOSE: Cenobamate (CNB) is a new antiseizure medication (ASM) for the treatment of focal epilepsy in adults. While efficacy of CNB was confirmed in controlled clinical trials, its effects on cognition are unclear. Cognitive adverse effects of ASM affect quality of life and retention rate. Therefore, we investigated whether the adjunctive treatment with CNB is associated with changes in cognitive performance. METHOD: Efficacy and tolerability of CNB were investigated in an observational study. Fifty patients with pharmacoresistant focal epilepsy aged 18 to 71 years (Mdn = 37.5 years) were tested before (T0) and after reaching the first target dose of CNB, usually after three months (T1). Cognitive performance was assessed using the EpiTrack©, a change-sensitive screening tool for attention and executive functions. RESULTS: The median CNB dose at T1 was 125 mg/day (range: 50 - 250 mg/day). Most patients received 2-3 concomitant ASMs. Individual test scores remained stable in 72%, significantly improved in 16%, and significantly deteriorated in 12% of the patients from T0 to T1. The total group showed a significant improvement in EpiTrack scores (p < .01). Changes in EpiTrack performance from T0 to T1 occurred independently of CNB dose, changes in the total drug load or reduction in seizure frequency. CONCLUSION: Most of the patients showed stable or improved cognitive performance. Thus, there is preliminary evidence that adjunctive CNB is not associated with an increased risk of cognitive side effects for the majority of patients. These findings need to be confirmed in controlled trials encompassing higher doses.

Chronic high-frequency deep-brain stimulation in progressive myoclonic epilepsy in adulthood--report of five cases.

PURPOSE: To assess the efficacy and tolerability of chronic high-frequency deep brain stimulation (DBS) in adult patients with progressive myoclonic epilepsy (PME) syndromes. METHODS: Five adult patients (four male, 28-39 years) with PME underwent chronic high-frequency DBS according to a study protocol that had been approved by the local ethics committee. Electrodes were implanted in the substantia nigra pars reticulata (SNr)/subthalamic nucleus (STN) region in the first patient and additionally in the ventral intermediate nucleus (VIM) bilaterally in the following four cases. Follow-up took place in intervals of 3 months and DBS effects were compared with baseline frequency of passive and activation-induced myoclonic jerks and daily life performance 8 weeks prior to implantation. KEY FINDINGS: Follow-up periods ranged from 12-42 months (median 24 months). The best clinical effects were seen with SNr/STN DBS in all patients. VIM stimulation failed to achieve acute therapeutic effects and revealed low side-effect thresholds and even triggering of myoclonia. In all patients the reduction of myoclonic seizures was observed and ranged between 30% and 100% as quantified by a standardized video protocol. All patients reported clinically relevant improvements of various capabilities such as free standing and walking or improved fine motor skills. In one patient with an excellent initial response generalized tonic-clonic seizures increased after 3 months of stimulation following extensive trauma-related surgery. The best effect was seen in the least impaired patient. SIGNIFICANCE: DBS of the SNr/STN may be an effective treatment option for patients with PME. Less impaired patients may benefit more markedly.

Gamma activity and reactivity in human thalamic local field potentials.

Depth recordings in patients with Parkinson's disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of approximately 70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at approximately 70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep-wake cycle, being suppressed during slow wave sleep and re-emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle-eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at approximately 70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at approximately 70 Hz may be involved in movement and arousal.

Simultaneous Frame-assisted Stereotactic Placement of Subdural Grid Electrodes and Intracerebral Depth Electrodes.

BACKGROUND AND STUDY AIMS: In complex cases of drug-resistant focal epilepsy, the precise localization of the epileptogenic zone requires simultaneous implantation of depth and subdural grid electrodes. This study describes a new simple frame-assisted method that facilitates the simultaneous placement of both types of intracranial electrodes. MATERIAL AND METHODS: Ten consecutive patients were evaluated and divided into two groups. Group A included patients with simultaneous frame-assisted placement of depth and subdural grid electrodes. In group B, depth electrodes were implanted stereotactically; grid electrodes were implanted in a separate surgery. RESULTS: The placement of the subdural grid was accurate as individually designed by the epileptologists in all five patients from group A. In group B, one patient showed a slight and another one a significant deviation of the subdural grid position postoperatively. The mean surgical time in group A was shorter (280±62 minutes) compared with the mean duration of the surgical procedures in group B (336±51 minutes). CONCLUSION: The frame-assisted placement of subdural grid electrodes facilitates the surgical procedure for invasive video-electroencephalography monitoring in complex cases of drug-resistant focal epilepsy in which a combination of depth electrodes and subdural grid electrodes is needed, by reducing the surgical time and guaranteeing highly accurate electrode localizations.