Neuropsychological features of mind wandering in left-, right- and extra temporal lobe epilepsy.

PURPOSE: Mind wandering, i.e. mental time-travelling and imagery unrelated to the current situation has recently been related to mesial temporal lobe (memory) function. In this regard we evaluated as to whether parameters of mind wandering are related to material specific memory in patients with a left-, right-, or extra- temporal lobe epilepsy. METHODS: In this prospective controlled study we analyzed mind wandering, material specific memory, and executive functions in 29 right-handed patients with right-, left-, or extra-temporal lobe epilepsies. Mind wandering was assessed with a sustained attention to response task containing embedded inquiries on mind wandering. In addition, verbal list learning and memory (VLMT), design list learning (DCS-R), and executive function (EpiTrack) were assessed. RESULTS: In patients with right temporal lobe epilepsy, the propensity to mind wander was positively related to verbal memory performance, while in left temporal lobe epilepsy, the propensity and future related mind wandering were positively correlated to the performance in visual/figural memory. Generally, the propensity of MW was related to executive function as well. CONCLUSION: The results suggest that mind wandering in lateralized temporal lobe epilepsy appears to be non-specifically driven by executive function and specifically by the mode and functionality of the memory system of the non-epileptic hemisphere. Repeated assessments would be required to discern as to how much such patterns depend on lesions versus epileptic dysfunction and whether they change with successful medical or surgical treatment.

Transcutaneous auricular vagus nerve stimulation induces stabilizing modifications in large-scale functional brain networks: towards understanding the effects of taVNS in subjects with epilepsy.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for subjects with refractory epilepsy. Its exact mechanism of action is not yet fully understood. We developed an examination schedule to probe for immediate taVNS-induced modifications of large-scale epileptic brain networks and accompanying changes of cognition and behaviour. In this prospective trial, we applied short-term (1 h) taVNS to 14 subjects with epilepsy during a continuous 3-h EEG recording which was embedded in two standardized neuropsychological assessments. From these EEG, we derived evolving epileptic brain networks and tracked important topological, robustness, and stability properties of networks over time. In the majority of investigated subjects, taVNS induced measurable and persisting modifications in network properties that point to a more resilient epileptic brain network without negatively impacting cognition, behaviour, or mood. The stimulation was well tolerated and the usability of the device was rated good. Short-term taVNS has a topology-modifying, robustness- and stability-enhancing immediate effect on large-scale epileptic brain networks. It has no detrimental effects on cognition and behaviour. Translation into clinical practice requires further studies to detail knowledge about the exact mechanisms by which taVNS prevents or inhibits seizures.

Laser interstitial thermotherapy (LiTT) in pediatric epilepsy surgery.

Laser interstitial thermotherapy (LiTT) is a novel stereotactic approach to the surgical treatment of severe drug-resistant focal epilepsies. This review extends our recent general review on this topic (Hoppe et al. Laser interstitial thermotherapy [LiTT] in epilepsy surgery. Seizure 2017; 48:45-52) with a focus on children (age <18 years). A PubMed search retrieved 25 uncontrolled case series reports that included a total of 179 pediatric patients as well as 7 review papers that specifically referred to using LiTT in pediatric epilepsy surgery (due August 31, 2018). Hypothalamic hamartomas (HH) represented the most frequent indication (64.2%) while therapeutic evidence for other more frequent etiologies underlying severe focal childhood epilepsies (e.g. focal cortical dysplasia, mesiotemporal sclerosis) is still scarce (n<20). For the published cases, the rate of severe complications was 3.4% and the overall complication rate was 23.5%. The seizure freedom rate (Engel class 1) was 57.5% (including patients with early follow-up and repeat thermoablations). None of the studies included the systematic evaluation of the cognitive outcome. Overall, the published evidence does not yet allow a scientific or clinical judgement on the utility of LiTT for pediatric epilepsy surgery. LiTT is likely to extend the neurosurgical toolbox with regard to deep brain lesions (e.g. HH). However, in cases that are equally accessible for both approaches therapeutic superiority of LiTT over open resective surgery still remains to be demonstrated. Recommendations for controlled though non-randomized outcome studies are provided.

Knowledge, expectations and fears of cannabis use of epilepsy patients at a tertiary epilepsy center.

INTRODUCTION: Medical cannabis is increasingly discussed as an alternative treatment option in neurological diseases, e.g. epilepsy. Supporters and opponents base their propositions mostly on subjective estimates, they confuse cannabis in whole versus extracts and botanical versus synthesized. METHODS: Two hundred seventy five patients with any kind of epilepsy (56% female, 44% seizure free, 91% on medication) answered a survey on the knowledge, expectations, fears, and willingness to be treated with medical cannabis. Data were analyzed with regard to patient characteristics and clinical data from patient files. RESULTS: Overall, 70.5% of the patients were familiar with the possibility of medical cannabis treatment, 36.7% with its use in epilepsy. A minority of 10.9% gained the information from their physicians. The majority knew about organic compared to synthetic cannabis. The interest in further information is high (71.3%). Regression analysis (explaining 53.8% of the variance) indicated that positive expectations (in the order of relevance) were seizure control, relaxation, mood, and tolerability whereas fears mostly concerned addiction and delirant intoxication. Men showed a greater interest than women. CONCLUSION: Many epilepsy patients knew about medical cannabis, were interested in this treatment, and wanted more information. Expectations, however, appear to be based on the connotations of the whole substance cannabis with tetrahydrocannabidiol and its commonly known effects. Unfortunately, patients did not get their information from physicians, but mostly by other sources. In order to avoid prejudices and potentially harmful self-medication, physicians and healthcare providers are called to become familiar with the substance and to inform patients adequately.

Laser interstitial thermotherapy (LiTT) in epilepsy surgery.

Besides other innovative stereotactic procedures (radiofrequency thermocoagulation, focused ultrasound, gamma knife) laser interstitial thermotherapy (LiTT) provides minimally invasive destruction of pathological soft tissues which could be especially relevant for epilepsy surgeries involving adult and pediatric patients. Unlike standard resections, no craniotomy is required; just a tiny borehole trepanation is sufficient. Damage to cortical areas when accessing deep lesions can be minimized or completely avoided, and treating epileptogenic foci near eloquent or even vital brain areas becomes possible. Here, we briefly describe the history and rationale of laser neurosurgery as well as the technical key features of the two currently available systems for magnetic resonance-guided LiTT (Visualase®, NeuroBlate®; CE marks pending for both). We also discuss the published clinical experience with LiTT in the field of epilepsy surgery (approximately 200 cases) with regard to complications, LiTT-induced, long-term brain structural alterations, seizure outcome, preliminary neuropsychological findings and first estimates of treatment costs. Overall, the seizure outcome appears to be slightly worse than for resective surgery. Due to insufficient research methods (e.g. non-established measures, lack of a control condition), the expected neuropsychological superiority over resective surgery has not been unambiguously demonstrated thus far. Also, the cost-benefit ratio requires further critical evaluation. Clinical, multi-center and adequately controlled outcome studies of high quality should also accompany the imminent introduction of LiTT into the field of epilepsy surgery and therewith permit critical scientific evaluation and rational, individual, clinical decisions.

Do surface DC-shifts affect epileptic hippocampal EEG activity?

Despite considerable research on EEG-feedback of slow cortical potentials (SCPs) for seizure control in epilepsy, the underlying mechanisms and the direct effects on intracerebral pathological activity within the focal area remain unclear. Intrahippocampal EEG recordings from four patients with temporal lobe epilepsy and implanted electrodes were analyzed with regard to spike activity and power in 10 frequency bands (0.5-148Hz) during SCP feedback based on surface recordings (position Cz). Trials with positive, negative and indifferent SCPs were contrasted. Three of the four patients showed changes in spike activity during SCPs, but these were inconsistent between patients, and resulted in increased and decreased activity in both positive and negative SCPs. Spectral analysis revealed that in all patients, positive surface shifts showed a bi-hemispheric higher power in the high-frequency activity above 40Hz. Two patients showed a higher power also during negative shifts, both in high-frequency activity and one in most other frequency bands. Feedback-related power effects did not differ between focal and non-focal side. The inconsistent change in spiking activity and the lack of decrease of power in pathology associated frequency bands during SCPs show that these SCPs do not decrease pathological activity within the epileptic focus. A possible relation of higher power in high-frequency activity during positive SCPs to cognitive processes, such as memory functions, is discussed.

Dose-dependent memory effects and cerebral volume changes after in utero exposure to valproate in the rat.

PURPOSE: Recent clinical studies raised concern of a cognitive teratogenicity of the major antiepileptic drug valproate. To investigate possible cerebral correlates, we established a forced self-application schedule by diluting valproate in the drinking water of pregnant Wistar rats. METHODS: After application of medium (MD) and high doses (HDs) with mean daily intakes of about 470 and 720 mg/kg during the entire pregnancy, we analyzed effects on offspring performance in a series of behavioral paradigms as well as brain volumetric changes by magnetic resonance imaging (MRI). RESULTS: While high dosages with peak serum concentrations slightly above 100 microg/ml induced early decrements in general activity and deficits in learning and memory, medium dosages led to improved watermaze performance in 30-day-old rats. MRI analyses indicated increased hippocampal volumes in the MD condition, whereas in the HD condition significantly decreased cortical and brainstem volumes were registered. Cortical volume reduction was correlated with spatial acuity in the watermaze. CONCLUSIONS: The results indicate that effects of valproate in utero on offspring cognitive capabilities might depend on total drug load differentially affecting cerebral development during adolescence in the rat.

Sensory gating in epilepsy - effects of the lateralization of hippocampal sclerosis.

OBJECTIVE: The role of the hippocampus in sensory gating is unresolved as yet. The current study was conducted in order to examine the effects of hippocampal lesions on the function of auditory sensory gating. METHODS: Epilepsy patients with unilateral and bilateral hippocampal sclerosis (HS) were investigated. Auditory-evoked potentials (AEPs) were recorded by multichannel scalp EEG in a double-click experiment. Gating was defined as the response decrease of the AEP components from 1st to 2nd click. RESULTS: Diagnosis (left vs. right vs. bilateral HS) did not affect the amplitudes or gating of the P50, N100 or P200 components. However, diagnosis had an impact on the topography of the N100 component after its peak maximum: In right HS patients, the N100 was left-lateralized, while it was nearly symmetrically distributed in patients with left HS and right lateralized in patients with bilateral HS. Besides the N100, the topography of the P200 component was affected by diagnosis. CONCLUSIONS: Findings suggest that auditory activity, as reflected in the N100 and P200 components, is modulated by the hippocampus, but not sensory gating in its classical definition. SIGNIFICANCE: Deficits in P50 gating in schizophrenia are unlikely to be explained by hippocampal deficits.

Human neocortical and hippocampal near-DC shifts are interconnected.

Hippocampal DC shifts have been observed under various physiological and pathological conditions. Here, we studied the interconnection of slow shifts (0.01 Hz high-pass) in surface EEG and hippocampal shifts as emerging in an event-related EEG biofeedback paradigm. Hippocampal EEG activity was monitored by depth electrodes implanted in four epilepsy patients for presurgical evaluation. Trials were sorted according to the near-DC shifts occurring at the surface position Cz, which was the feedback electrode, into positive, indistinct (i.e., small or biphasic) and negative shifts. We found significant hippocampal near-DC shifts being positively or negatively correlated to the shifts in surface EEG in all four patients. The amplitudes of the hippocampal near-DC shifts were several times larger than the surface shifts. The polarity of the shifts appears to depend on the location of the electrode contacts with respect to the hippocampal subfields. The finding that neocortical and hippocampal near-DC shifts are interconnected may open new perspectives for the prediction and control of mediotemporal lobe seizures.