Short post-injection seizure duration is associated with reduced power of ictal brain perfusion SPECT to lateralize the seizure onset zone.

BACKGROUND: The aim of this study was to assess the impact of the post-injection electrical seizure duration on the identification of the seizure onset zone (SOZ) in ictal brain perfusion SPECT in presurgical evaluation of drug-resistant epilepsy. METHODS: 176 ictal SPECT performed with 99mTc-HMPAO (n = 140) or -ECD (n = 36) were included retrospectively. Visual interpretation of the SPECT images (together with individual MRI and statistical hyperperfusion maps) with respect to lateralization (right, left, none) and localization (temporal, frontal, parietal, occipital) of the SOZ was performed by 3 independent readers. Between-readers agreement was characterized by Fleiss' κ. An ictal SPECT was considered "lateralizing" if all readers agreed on right or left hemisphere. It was considered "localizing" if it was lateralizing and all readers agreed on the same lobe within the same hemisphere. The impact of injection latency and post-injection seizure duration on the proportion of lateralizing/localizing SPECT was tested by ANOVA with dichotomized (by the median) injection latency and post-injection seizure duration as between-subjects factors. RESULTS: Median [interquartile range] (full range) of injection latency and post-injection seizure duration were 30 [24, 40] (3-120) s and 50 [27, 70] (-20-660) s, respectively. Fleiss' κ for lateralization of the SOZ was largest for the combination of early (< 30 s) injection and long (> 50 s) post-injection seizure duration (κ = 0.894, all other combinations κ = 0.659-0.734). Regarding Fleiss' κ for localization of the SOZ in the 141 (80.1%) lateralizing SPECT, it was largest for early injection and short post-injection seizure duration (κ = 0.575, all other combinations κ = 0.329-0.368). The proportion of lateralizing SPECT was lower with short compared to long post-injection seizure duration (estimated marginal means 74.3% versus 86.3%, p = 0.047). The effect was mainly driven by cases with very short post-injection seizure duration ≤ 10 s (53.8% lateralizing). Injection latency in the considered range had no significant impact on the proportion of lateralizing SPECT (p = 0.390). The proportion of localizing SPECT among the lateralizing cases did not depend on injection latency or post-injection seizure duration (p ≥ 0.603). CONCLUSIONS: Short post-injection seizure duration is associated with a lower proportion of lateralizing cases in ictal brain perfusion SPECT.

Effects of midazolam on high-frequency oscillations in amygdala and hippocampus of epilepsy patients.

High-frequency oscillations (HFOs) are associated with normal brain function, but are also increasingly recognized as potential biomarkers of epileptogenic tissue. Considering the important role of interneuron activity in physiological HFO generation, we studied their modulation by midazolam (MDZ), an agonist of γ-aminobutyric acid type A (GABAA)-benzodiazepine receptors. Here, we analyzed 80 intracranial electrode contacts in amygdala and hippocampus of 13 patients with drug-refractory focal epilepsy who had received MDZ for seizure termination during presurgical monitoring. Ripples (80-250 Hz) and fast ripples (FRs; 250-400 Hz) were compared before and after seizures with MDZ application, and according to their origin either within or outside the individual seizure onset zone (SOZ). We found that MDZ distinctly suppressed all HFOs (ripples and FRs), whereas the reduction of ripples was significantly less pronounced inside the SOZ compared to non-SOZ contacts. The rate of FRs inside the SOZ was less affected, especially in hippocampal contacts. In a few cases, even a marked increase of FRs following MDZ administration was seen. Our results demonstrate, for the first time, a significant HFO modulation in amygdala and hippocampus by MDZ, thus giving insights into the malfunction of GABA-mediated inhibition within epileptogenic areas and its role in HFO generation.

Cell Size Contributes to Single-Cell Proteome Variation.

Accurate measurements of the molecular composition of single cells will be necessary for understanding the relationship between gene expression and function in diverse cell types. One of the most important phenotypes that differs between cells is their size, which was recently shown to be an important determinant of proteome composition in populations of similarly sized cells. We, therefore, sought to test if the effects of the cell size on protein concentrations were also evident in single-cell proteomics data. Using the relative concentrations of a set of reference proteins to estimate a cell's DNA-to-cell volume ratio, we found that differences in the cell size explain a significant amount of cell-to-cell variance in two published single-cell proteome data sets.

Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells.

Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how size influences cell physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be biochemically different. Here, we corroborate these results in mouse hepatocytes and extend our analysis using yeast. We find that size-dependent proteome changes are highly conserved and mostly independent of metabolic state. As eukaryotic cells grow larger, the dilution of the genome elicits a starvation-like proteome phenotype, suggesting that growth in large cells is limited by the genome in a manner analogous to a limiting nutrient. We also demonstrate that the proteomes of replicatively-aged yeast are primarily determined by their large size. Overall, our data suggest that genome concentration is a universal determinant of proteome content in growing cells.

Efficient colonic drug delivery in domestic pigs employing a tablet formulation with dual control concept.

Efficient and reproducible colonic drug delivery remains elusive. The aim of this study was to demonstrate specific colonic delivery in vivo in domestic pigs with a novel tablet formulation based on a dual release control concept using 5-aminosalicylic acid (5-ASA) and caffeine as drug substances. The developed controlled colonic release (CCR) tablet formulation employs a pH-sensitive coating based on Eudragit® FS 30 D to prevent drug release in the upper gastrointestinal tract, and a xyloglucan-based matrix to inhibit drug release after coating removal in the small intestine and to allow microbiome-triggered drug release by enzymatic action in the colon. CCR tablets were administered to domestic pigs and plasma concentration data was analyzed by physiologically based pharmacokinetic modeling to estimate absorbed amounts from small and large intestine and in vivo drug release rates by model-dependent deconvolution using immediate release (IR) tablets and intravenous solutions as reference. Peak concentration times (tmax) and values (cmax) of CCR 5-ASA and caffeine tablets indicated strongly delayed drug absorption and the deduced absorbed amount as a function of time confirmed absorption overwhelmingly from the large intestine. The microbially cleaved marker molecule sulfasalazine administered alone or together with caffeine in CCR tablets reported, in combination with telemetry measurements, gastrointestinal transit times and site of absorption. Drug release from CCR tablets was inferred to take place predominantly at the site of absorption at a release rate of caffeine that was much larger in the colon than in the small intestine indicating enzymatically triggered release by the colonic microbiome. Xyloglucanase activity in rectal and cecal samples was consistent with release data and compound recovery in fecal droppings was consistent with 5-ASA bioavailability. The results provide evidence that the developed formulation can prevent premature drug release and provide targeted colonic drug delivery. Clinical relevance based on the comparability between pig and man is discussed.

Tablet formulation with dual control concept for efficient colonic drug delivery.

Aim of this study was to develop a tablet formulation for targeted colonic drug release by implementing two control mechanisms: A pH-sensitive coating layer based on Eudragit® FS 30 D to prevent drug release in the upper gastrointestinal tract, combined with a matrix based on plant-derived polysaccharide xyloglucan to inhibit drug release after coating removal in the small intestine and to allow microbiome triggered drug release in the colon. In vitro dissolution tests simulated the passage through the entire gastrointestinal tract with a four-stage protocol, including microbial xyloglucanase addition in physiologically relevant concentrations as microbiome surrogate to the colonic dissolution medium. Matrix erosion was monitored in parallel to drug release by measurement of reducing sugar equivalents resulting from xyloglucan hydrolysis. Limited drug release in gastric and small intestinal test stages and predominant release in the colonic stage was achieved. The xyloglucan matrix controlled drug release after dissolution of the enteric coating through the formation of a gummy polysaccharide layer at the tablet surface. Matrix degradation was dependent on enzyme concentration in the colonic medium and significantly accelerated drug release resulting in erosion-controlled release process. Drug release at physiologically relevant enzyme concentration was completed within the bounds of colonic transit time. The dual control concept was applicable to two drug substances with different solubility, providing similar release rates in colonic environment containing xyloglucanase. Drug solubility mechanistically affected release, with diffusion of caffeine, but not of 5-ASA, contributing to the overall release rate out of the matrix tablet.

Delineation of proteome changes driven by cell size and growth rate.

Increasing cell size drives changes to the proteome, which affects cell physiology. As cell size increases, some proteins become more concentrated while others are diluted. As a result, the state of the cell changes continuously with increasing size. In addition to these proteomic changes, large cells have a lower growth rate (protein synthesis rate per unit volume). That both the cell's proteome and growth rate change with cell size suggests they may be interdependent. To test this, we used quantitative mass spectrometry to measure how the proteome changes in response to the mTOR inhibitor rapamycin, which decreases the cellular growth rate and has only a minimal effect on cell size. We found that large cell size and mTOR inhibition, both of which lower the growth rate of a cell, remodel the proteome in similar ways. This suggests that many of the effects of cell size are mediated by the size-dependent slowdown of the cellular growth rate. For example, the previously reported size-dependent expression of some senescence markers could reflect a cell's declining growth rate rather than its size per se. In contrast, histones and other chromatin components are diluted in large cells independently of the growth rate, likely so that they remain in proportion with the genome. Finally, size-dependent changes to the cell's growth rate and proteome composition are still apparent in cells continually exposed to a saturating dose of rapamycin, which indicates that cell size can affect the proteome independently of mTORC1 signaling. Taken together, our results clarify the dependencies between cell size, growth, mTOR activity, and the proteome remodeling that ultimately controls many aspects of cell physiology.

Increasing cell size remodels the proteome and promotes senescence.

Cell size is tightly controlled in healthy tissues, but it is unclear how deviations in cell size affect cell physiology. To address this, we measured how the cell's proteome changes with increasing cell size. Size-dependent protein concentration changes are widespread and predicted by subcellular localization, size-dependent mRNA concentrations, and protein turnover. As proliferating cells grow larger, concentration changes typically associated with cellular senescence are increasingly pronounced, suggesting that large size may be a cause rather than just a consequence of cell senescence. Consistent with this hypothesis, larger cells are prone to replicative, DNA-damage-induced, and CDK4/6i-induced senescence. Size-dependent changes to the proteome, including those associated with senescence, are not observed when an increase in cell size is accompanied by an increase in ploidy. Together, our findings show how cell size could impact many aspects of cell physiology by remodeling the proteome and provide a rationale for cell size control and polyploidization.

Face-induced gamma oscillations and event-related potentials in patients with epilepsy: an intracranial EEG study.

BACKGROUND: To examine the pathological effect of a mesial temporal seizure onset zone (SOZ) on local and inter-regional response to faces in the amygdala and other structures of the temporal lobe. METHODS: Intracranial EEG data was obtained from the amygdala, hippocampus, fusiform gyrus and parahippocampal gyrus of nine patients with drug-refractory epilepsy during visual stimulation with faces and mosaics. We analyzed event-related potentials (ERP), gamma frequency power, phase-amplitude coupling and phase-slope-index and compared the results between patients with versus without a mesial temporal SOZ. RESULTS: In the amygdala and fusiform gyrus, faces triggered higher ERP amplitudes compared to mosaics in both patient groups and higher gamma power in patients without a mesial temporal SOZ. In the hippocampus, famous faces triggered higher gamma power for both groups combined but did not affect ERPs in either group. The differentiated ERP response to famous faces in the parahippocampal gyrus was more pronounced in patients without a mesial temporal SOZ. Phase-amplitude coupling and phase-slope-index results yielded bidirectional modulation between amygdala and fusiform gyrus, and predominately unidirectional modulation between parahippocampal gyrus and hippocampus. CONCLUSIONS: A mesial temporal SOZ was associated with an impaired response to faces in the amygdala, fusiform gyrus and parahippocampal gyrus in our patients. Compared to this, the response to faces in the hippocampus was impaired in patients with, as well as without, a mesial temporal SOZ. Our results support existing evidence for face processing deficits in patients with a mesial temporal SOZ and suggest the pathological effect of a mesial temporal SOZ on the amygdala to play a pivotal role in this matter in particular.

Predicting the Outcome of Epilepsy Surgery by Covariance Pattern Analysis of Ictal Perfusion SPECT.

Previous studies on the utility of specific perfusion patterns in ictal brain perfusion SPECT for predicting the outcome of temporal lobe epilepsy surgery used qualitative visual pattern classification, semiquantitative region-of-interest analysis, or conventional univariate voxel-based testing, which are limited by intra- and interrater variability or low sensitivity to capture functional interactions among brain regions. The present study performed covariance pattern analysis of ictal perfusion SPECT using the scaled subprofile model for unbiased identification of predictive covariance patterns. Methods: The study retrospectively included 18 responders to temporal lobe epilepsy surgery (Engel I-A at 12 mo follow-up) and 18 nonresponders (≥Engel I-B). Ictal SPECT images were analyzed with the scaled subprofile model masked to group membership for unbiased identification of the 16 covariance patterns explaining the highest proportion of variance in the whole dataset. Individual expression scores of the covariance patterns were evaluated for predicting seizure freedom after temporal lobe surgery by receiver-operating-characteristic analysis. Kaplan-Meier analysis including all available follow-up data (up to 60 mo after surgery) was also performed. Results: Among the 16 covariance patterns only 1 showed a different expression between responders and nonresponders (P = 0.03). This favorable ictal perfusion pattern resembled the typical ictal perfusion pattern in temporomesial epilepsy. The expression score of the pattern provided an area of 0.744 (95% CI, 0.577-0.911, P = 0.004) under the receiver-operating-characteristic curve. Kaplan-Meier analysis revealed a statistical trend toward longer seizure freedom in patients with positive expression score (P = 0.06). The median estimated seizure-free time was 48 mo in patients with positive expression score versus 6 mo in patients with negative expression score. Conclusion: The expression of the favorable ictal perfusion pattern identified by covariance analysis of ictal brain perfusion SPECT provides independent (from demographic and clinical variables) information for the prediction of seizure freedom after temporal lobe epilepsy surgery. The expression of this pattern is easily computed for new ictal SPECT images and, therefore, might be used to support the decision for or against temporal lobe surgery in clinical patient care.

A deep learning approach to quantify auditory hair cells.

Hearing loss affects millions of people worldwide. Yet, there are still no curative therapies for sensorineural hearing loss. Frequent causes of sensorineural hearing loss are due to damage or loss of the sensory hair cells, the spiral ganglion neurons, or the synapses between them. Culturing the organ of Corti allows the study of all these structures in an experimental model, which is easy to manipulate. Therefore, the in vitro culture of the neonatal mammalian organ of Corti remains a frequently used experimental system, in which hair cell survival is routinely assessed. However, the analysis of the surviving hair cells is commonly performed via manual counting, which is a time-consuming process and the inter-rater reliability can be an issue. Here, we describe a deep learning approach to quantify hair cell survival in the murine organ of Corti explants. We used StarDist, a publicly available platform and plugin for Fiji (Fiji is just ImageJ), to train and apply our own custom deep learning model. We successfully validated our model in untreated, cisplatin, and gentamicin treated organ of Corti explants. Therefore, deep learning is a valuable approach for quantifying hair cell survival in organ of Corti explants. Moreover, we also demonstrate how the publicly available Fiji plugin StarDist can be efficiently used for this purpose.

No Evidence to Favor 99mTc-HMPAO or 99mTc-ECD for Ictal Brain Perfusion SPECT for Identification of the Seizure Onset Zone.

PURPOSE: Ictal brain perfusion SPECT with the tracer 99mTc-HMPAO or 99mTc-ECD is widely used for identification of the epileptic seizure onset zone (SOZ) in presurgical evaluation if standard pointers are uncertain or inconsistent. For both tracers, there are theoretical arguments to favor it over the other for this task. The aim of this study was to compare the performance of ictal brain perfusion SPECT between 99mTc-HMPAO and 99mTc-ECD in a rather large patient sample. PATIENTS AND METHODS: The study retrospectively included 196 patients from clinical routine in whom ictal perfusion SPECT had been performed with stabilized 99mTc-HMPAO (n = 110) or 99mTc-ECD (n = 86). Lateralization and localization of the SOZ were obtained by the consensus of 2 independent readers based on visual inspection of the SPECT images. RESULTS: The 99mTc-HMPAO group and the 99mTc-ECD group were well matched with respect to age, sex, age at first seizure, duration of disease, seizure frequency, history of previous brain surgery, and findings of presurgical MRI. The proportion of lateralizing ictal SPECT did not differ significantly between 99mTc-HMPAO and 99mTc-ECD (65.5% vs 72.1%, P = 0.36). Sensitivity of ictal perfusion SPECT (independent of the tracer) for correct localization of the SOZ in 62 patients with temporal lobe epilepsy and at least worthwhile improvement (Engel scale ≤ III) 12 months after temporal epilepsy surgery was 63%. CONCLUSIONS: This study does not provide evidence to favor 99mTc-HMPAO or 99mTc-ECD for identification of the SOZ by ictal perfusion SPECT.

Checkpoint-mediated DNA polymerase ε exonuclease activity curbing counteracts resection-driven fork collapse.

DNA polymerase ε (Polε) carries out high-fidelity leading strand synthesis owing to its exonuclease activity. Polε polymerase and exonuclease activities are balanced, because of partitioning of nascent DNA strands between catalytic sites, so that net resection occurs when synthesis is impaired. In vivo, DNA synthesis stalling activates replication checkpoint kinases, which act to preserve the functional integrity of replication forks. We show that stalled Polε drives nascent strand resection causing fork functional collapse, averted via checkpoint-dependent phosphorylation. Polε catalytic subunit Pol2 is phosphorylated on serine 430, influencing partitioning between polymerase and exonuclease active sites. A phosphormimetic S430D change reduces exonucleolysis in vitro and counteracts fork collapse. Conversely, non-phosphorylatable pol2-S430A expression causes resection-driven stressed fork defects. Our findings reveal that checkpoint kinases switch Polε to an exonuclease-safe mode preventing nascent strand resection and stabilizing stalled replication forks. Elective partitioning suppression has implications for the diverse Polε roles in genome integrity maintenance.

Resective epilepsy surgery in patients aged 50years and older - a retrospective study regarding seizure outcome, memory performance, and psychopathology.

PURPOSE: To assess clinical and demographic characteristics in two cohorts of elderly patients with drug-resistant focal epilepsy, undergoing resective epilepsy surgery (RES). Further, to determine seizure, neuropsychological, and mental health outcomes after RES and evaluate possible influencing factors. METHODS: Consecutive patients aged ≥50 years with temporal lobe epilepsy (TLE) who underwent curative RES in the Hamburg epilepsy surgery program (2004-2017) were identified. Data were retrospectively analyzed. Seizure outcome was classified according to ILAE and Engel outcome scales in patients with first-time surgeries and with reoperations. Previously reported predictors of the seizure outcome were evaluated using regression analyses. Changes in verbal memory were assessed for patients with complete pre- and postoperative datasets (n=30) using repeated-measures analysis of variance. For evaluation of possible predictors of psychopathologic changes after RES a regression analysis was conducted. RESULTS: Fifty-one elderly patients underwent RES of the temporal lobe, including twelve aged ≥60 years, and five with reoperations. After one year, 65% of the patients with first-time surgeries were seizure free and 91% had a favorable outcome. At last follow-up, 49% were seizure free since surgery. Three reoperated patients had an Engel I outcome. Seizure outcome was not dependent on age at surgery, duration of epilepsy, or other evaluated variables. There was no significant decline in the memory performance after surgery. Significant improvements in mental health were found. CONCLUSION: RES for drug-resistant TLE is safe, effective, and improves mental health also in patients aged ≥ 50 years. Thus, it should be evaluated as the treatment of choice also in this age group.

In-depth and 3-dimensional exploration of the budding yeast phosphoproteome.

Phosphorylation is one of the most dynamic and widespread post-translational modifications regulating virtually every aspect of eukaryotic cell biology. Here, we assemble a dataset from 75 independent phosphoproteomic experiments performed in our laboratory using Saccharomyces cerevisiae. We report 30,902 phosphosites identified from cells cultured in a range of DNA damage conditions and/or arrested in distinct cell cycle stages. To generate a comprehensive resource for the budding yeast community, we aggregate our dataset with the Saccharomyces Genome Database and another recently published study, resulting in over 46,000 budding yeast phosphosites. With the goal of enhancing the identification of functional phosphorylation events, we perform computational positioning of phosphorylation sites on available 3D protein structures and systematically identify events predicted to regulate protein complex architecture. Results reveal hundreds of phosphorylation sites mapping to or near protein interaction interfaces, many of which result in steric or electrostatic "clashes" predicted to disrupt the interaction. With the advancement of Cryo-EM and the increasing number of available structures, our approach should help drive the functional and spatial exploration of the phosphoproteome.

The Rad53CHK1/CHK2-Spt21NPAT and Tel1ATM axes couple glucose tolerance to histone dosage and subtelomeric silencing.

The DNA damage response (DDR) coordinates DNA metabolism with nuclear and non-nuclear processes. The DDR kinase Rad53CHK1/CHK2 controls histone degradation to assist DNA repair. However, Rad53 deficiency causes histone-dependent growth defects in the absence of DNA damage, pointing out unknown physiological functions of the Rad53-histone axis. Here we show that histone dosage control by Rad53 ensures metabolic homeostasis. Under physiological conditions, Rad53 regulates histone levels through inhibitory phosphorylation of the transcription factor Spt21NPAT on Ser276. Rad53-Spt21 mutants display severe glucose dependence, caused by excess histones through two separable mechanisms: dampening of acetyl-coenzyme A-dependent carbon metabolism through histone hyper-acetylation, and Sirtuin-mediated silencing of starvation-induced subtelomeric domains. We further demonstrate that repression of subtelomere silencing by physiological Tel1ATM and Rpd3HDAC activities coveys tolerance to glucose restriction. Our findings identify DDR mutations, histone imbalances and aberrant subtelomeric chromatin as interconnected causes of glucose dependence, implying that DDR kinases coordinate metabolism and epigenetic changes.

Characterization of an anti-FLAG antibody binding protein in V. cholerae.

FLAG-tags are commonly used for protein abundance measurements and for identification of protein-protein interactions in living cells. We have observed that the cholera pathogen Vibrio cholerae encodes a FLAG-antibody-reactive protein and identified this protein as an outer membrane porin, Porin4, which contains a sequence very similar to the 3xFLAG epitope tag. We have demonstrated the binding affinity of the conserved peptide sequence (called Porin 4 tag) in Porin4 against monoclonal anti-FLAG M2 antibody. In addition, we created a porin4 deletion mutant, which can be used for background-less FLAG antibody detection experiments.

Decision-making in temporal lobe epilepsy surgery based on invasive stereo-electroencephalography (sEEG).

In medical refractory temporal lobe epilepsy (TLE), the epileptogenic zone can be difficult to identify and therefore difficult to treat, especially in the absence of clear MRI pathologies and specific results from presurgical evaluation. Invasive monitoring with stereo-electroencephalography (sEEG) is a tool for a better determination of the epileptogenic zone. Here, we investigate the impact of sEEG on decision-making in temporal lobe epilepsy surgery. We reviewed patients with TLE who underwent further investigation with sEEG in our epilepsy unit. We examined specifically how sEEG findings influenced our decision regarding indication for a surgical procedure and resection volume. From 2013 to 2017, we performed 152 temporal resections in epilepsy patients. Twenty-one of these patients were designated for further preoperative investigation with sEEG due to incongruent findings in presurgical evaluation. Six patients were implanted bitemporally. In five cases, the hypothesis for the epileptogenic zone and localization had to be changed due to sEEG findings and resulted in a different tailored resection than intended. In three cases, sEEG findings led to the cancelation of the originally intended temporal resection as the epileptogenic zone was not definable or bilateral. In another three cases, the prognosis for reduction of seizures postoperatively had to be reduced due to the sEEG findings. However, the resection was performed after interdisciplinary discussion and informed consent of the patient. The examination by sEEG led to a change of plan for further treatment in 13 patients (61.9%) suffering TLE in total. Invasive monitoring with sEEG electrodes had a strong impact on decision-making for further treatment in patients suffering from temporal lobe epilepsy with incongruent findings in presurgical examination designated for epilepsy surgery. This applies to resection volumes as well as to prediction of seizure outcome.

Use of the mixed reality tool "VSI Patient Education" for more comprehensible and imaginable patient educations before epilepsy surgery and stereotactic implantation of DBS or stereo-EEG electrodes.

PURPOSE: It is unknown which patient education strategy before epilepsy surgery or stereotactic electrode implantation is best for patients. This prospective and randomized clinical study investigates whether the use of the mixed reality tool "VSI Patient Education" (VSI PE) running on HoloLens® glasses is superior to the use of a rubber brain model as a 3-dimensional tool for patient education before epilepsy surgery and stereotactic electrode implantation. MATERIAL AND METHODS: 17 patients with indication for epilepsy surgery or stereotactic electrode implantation were included in the study and randomized into two groups. All patients were informed with both comparative tools VSI PE (apoQlar®) and a rubber brain model (3B Scientific®) in a chronological order depending on group assignment. Afterwards, the patient and, if present, a relative (12) each filled out a questionnaire. For statistical analysis, Wilcoxon rank-sum tests were performed. RESULTS: Patients found their patient education highly significantly more comprehensible (p = 0.001**, r = 0.84) and almost significantly more imaginable (p=0.020, r = 0.57), when their doctor used VSI PE compared to the rubber brain model. The patients felt significantly less anxious as a result of VSI PE (p = 0.008*, r = 0.64). Highly significantly more patients chose VSI PE as the preferred patient education tool (p < 0.001**, r = 0.91), and almost significantly more patients decided VSI PE to be the future standard tool (p = 0.020, r = 0.56). Significantly more relatives chose VSI PE as the preferred patient education tool (p = 0.004*, r = 0.83), and significantly more relatives decided VSI PE to be the future standard tool (p = 0.002*, r = 0.91). CONCLUSION: VSI Patient Education is a promising new mixed reality tool for informing patients before epileptic surgery or stereotactic electrode implantation in order to enhance comprehension and imagination and reduce fear and worries. It might strengthen patient commitment and have a positive influence on patients' decisions in favor of medically indicated surgical operations.