Predictors and reasons for epilepsy patients to decline surgery: a prospective study

Background: In patients with drug-resistant focal epilepsy, resective surgery is the most successful treatment option to achieve seizure freedom. However, a surprisingly high rate of patients declines their physicians' recommendation to undergo removal of the seizure focus or-if necessary-further video-EEG monitoring (VEM). Methods: In this prospective study, consecutive patients in presurgical assessment with at least one scalp VEM between 2016 and 2018 were included. We assessed both epilepsy-related and psychosocial variables as well as decision-making of physicians and patients, including reasons for decline in the latter. Results: Out of 116 patients with a total of 165 VEM, 20 patients were eventually found to be ineligible for resection, 51 declined, and 45 agreed on recommendations for resection or further VEM diagnostics. Patients most frequently declined due to general fear of brain surgery (n = 30, 59%) and currently lower seizure frequency (n = 11, 22%). An independent predictor of patients' decline was less epilepsy-related fear (OR 0.43; p = 0.02) assessed in a standardised questionnaire. Conclusion: Half of the patients potentially eligible for resective surgery decline the operation or further VEM procedures. Patients who decline are more fearful of brain surgery than of ongoing disabling seizures. More insight is needed to improve counselling of patients

Camera-based Prospective Motion Correction in Paediatric Epilepsy Patients Enables EEG-fMRI Localization Even in High-motion States

BACKGROUND: EEG-fMRI is a useful additional test to localize the epileptogenic zone (EZ) particularly in MRI negative cases. However subject motion presents a particular challenge owing to its large effects on both MRI and EEG signal. Traditionally it is assumed that prospective motion correction (PMC) of fMRI precludes EEG artifact correction. METHODS: Children undergoing presurgical assessment at Great Ormond Street Hospital were included into the study. PMC of fMRI was done using a commercial system with a Moiré Phase Tracking marker and MR-compatible camera. For retrospective EEG correction both a standard and a motion educated EEG artefact correction (REEGMAS) were compared to each other. RESULTS: Ten children underwent simultaneous EEG-fMRI. Overall head movement was high (mean RMS velocity < 1.5 mm/s) and showed high inter- and intra-individual variability. Comparing motion measured by the PMC camera and the (uncorrected residual) motion detected by realignment of fMRI images, there was a five-fold reduction in motion from its prospective correction. Retrospective EEG correction using both standard approaches and REEGMAS allowed the visualization and identification of physiological noise and epileptiform discharges. Seven of 10 children had significant maps, which were concordant with the clinical EZ hypothesis in 6 of these 7. CONCLUSION: To our knowledge this is the first application of camera-based PMC for MRI in a pediatric clinical setting. Despite large amount of movement PMC in combination with retrospective EEG correction recovered data and obtained clinically meaningful results during high levels of subject motion. Practical limitations may currently limit the widespread use of this technology

Utility of 18F-fluorodeoxyglucose positron emission tomography in presurgical evaluation of patients with epilepsy: A multicenter study

OBJECTIVE: 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used in presurgical assessment in patients with drug-resistant focal epilepsy (DRE) if magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) do not localize the seizure onset zone or are discordant. METHODS: In this multicenter, retrospective observational cohort study, we included consecutive patients with DRE who had undergone FDG-PET as part of their presurgical workup. We assessed the utility of FDG-PET, which was defined as contributing to the decision-making process to refer for resection or intracranial EEG (iEEG) or to conclude surgery was not feasible. RESULTS: We included 951 patients in this study; 479 had temporal lobe epilepsy (TLE), 219 extratemporal epilepsy (ETLE), and 253 epilepsy of uncertain lobar origin. FDG-PET showed a distinct hypometabolism in 62% and was concordant with ictal EEG in 74% in TLE and in 56% in ETLE (p < .001). FDG-PET was useful in presurgical decision-making in 396 patients (47%) and most beneficial in TLE compared to ETLE (58% vs. 44%, p = .001). Overall, FDG-PET contributed to recommending resection in 78 cases (20%) and iEEG in 187 cases (47%); in 131 patients (33%), FDG-PET resulted in a conclusion that resection was not feasible. In TLE, seizure-freedom 1 year after surgery did not differ significantly (p = .48) between patients with negative MRI and EEG-PET concordance (n = 30, 65%) and those with positive MRI and concordant EEG (n = 46, 68%). In ETLE, half of patients with negative MRI and EEG-PET concordance and three quarters with positive MRI and concordant EEG were seizure-free postsurgery (n = 5 vs. n = 6, p = .28). SIGNIFICANCE: This is the largest reported cohort of patients with DRE who received presurgical FDG-PET, showing that FDG-PET is a useful diagnostic tool. MRI-negative and MRI-positive cases with concordant FDG-PET results (with either EEG or MRI) had a comparable outcome after surgery. These findings confirm the significance of FDG-PET in presurgical epilepsy diagnostics

evaluation of hypothermia

Einleitung: Erworbene Hirnläsionen infektiöser, traumatischer oder vaskulärer Genese oder ein Status epilepticus (SE) können zur Entwicklung einer Epilepsie führen. Eine der großen Herausforderungen in der Epilepsie-Forschung ist, die Entwicklung einer Epilepsie nach einer Hirnläsion zu verhindern oder diese zumindest in ihrem Verlauf abzuschwächen. Bisher konnte die Epileptogenese weder in transienten pharmakologischen Interventionen nach Hirnläsionen bei Patienten noch im Tiermodell verhindert oder wesentlich beeinflusst werden. Ziel dieser experimentellen Studie ist die Evaluation der Hypothermie hinsichtlich ihres antiepileptogenen Potenzials. Methode: In einem chronischen Epilepsie-Tiermodell mit Ratten wurden die antiepileptogenen Eigenschaften einer 3-Std.-Kühlung auf 25°C direkt nach Beendigung eines elektrisch induzierten selbst-erhaltenden Status epilepticus (SSSE; self-sustaining status epilepticus) untersucht. Insgesamt gab es drei Versuchsgruppen, denen allen intrazerebrale Elektroden implantiert wurden (Ableitelektrode im Gyrus dentatus, Stimulationselektrode im Tractus perforans). Zwei Gruppen wurden elektrisch stimuliert mit nachfolgendem SSSE und im direkten Anschluss entweder mit Hypothermie (25°C) oder mit Normothermie (37°C) behandelt, bei der dritten Gruppe wurden den Tieren Elektroden implantiert, ohne dass diese elektrisch stimuliert wurden, die Tiere entwickelten somit keinen SSSE. Diese Kontrollgruppe sollte den Einfluss der Elektrodenimplantation kontrollieren. Das Auftreten spontaner Anfälle und die Anfallsstärke nach SSSE (1, 2, 4 und 8 Wochen) wurden mit 48-Stunden Epochen im Video – bei einigen Tiere ergänzend auch mittels EEG - untersucht. Weiterhin wurden zu mehreren Zeitpunkten nach SSSE elektrophysiologisch die inhibitorischen und exzitatorischen Parameter im Gyrus dentatus mit Hilfe des Paired-Pulse-Paradigmas erfasst. Ergebnisse: Hypothermie nach SSSE konnte das Auftreten von epileptischen Anfällen bei keinem der Tiere verhindern. Acht Wochen nach SSSE zeigte sich ein Trend zu weniger stark ausgeprägten Anfällen nach Kühlung (4,0±0,6) im Vergleich zu den normothermen Kontrollen (4,8±0,2), der jedoch nach Korrektur für Mehrfachvergleiche nicht signifikant war. Ein frühzeitiger Inhibitionsverlust, der typischerweise nach SSSE beobachtet wird, war bei den gekühlten Tieren drei Stunden nach SSSE etwas abgeschwächt. Dies drückte sich durch eine kleinere Paired-Puls-Ratio (PPR; 0,16±0,21) gegenüber den normothermen Kontrollen (0,54±0,21) aus, auch dieser Unterschied war nicht signifikant. Die Latenz zwischen Stimulusartefakt und exzitatorischen post-synaptischem Potential war 3 Stunden nach SSSE in Tieren, die gekühlt wurden (8,29±2,45 ms) im Vergleich zu normothermen Kontrollen (4,82±0,66 ms), verlängert. Dieser Unterschied war aber nach Korrektur für Mehrfach-Vergleiche nicht signifikant. Schlussfolgerung: Zusammenfassend konnte mittels der hier vorgestellten Experimente nicht gezeigt werden, dass kurzfristige Kühlung direkt im Anschluss an einen SSSE die Epileptogenese verhindert oder beeinflusst.Introduction: Aquired brain insult of infectious, traumatic or vascular origin can lead to the development of chronic epilepsy. In epilepsy research, one of the major challenges is to prevent or at least mitigate development of epilepsy following acquired brain insult by early, but transient therapeutic interventions. So far, all pharmacological antiepileptogenic treatment approaches were largely unsuccessful in clinical trials and in experimental animal studies. Aim of this study is the evaluation of hypothermia regarding its antiepileptogenic properties. Methods: In a rat model of chronic epilepsy following electrically induced self-sustaining status epilepticus (SSSE), we assessed the antiepileptogenic properties of 3-h-cooling to 25°C induced directly after the end of SSSE. Altogether there were three studygroups, all of whom were implanted with intracerebral electrodes (recording in dentate gyrus, stimulating in perforant path). Two groups underwent stimulation with SSSE treated subsequently with either hypothermia (25°C) or normothermia (37°C), the third group remained unstimulated and controlled for influence of electrodes. Occurrence of spontaneous seizures and seizure severity after SSSE were examined in 48h epochs with video and, additionally, some animals with EEG (1, 2, 4 and 8 weeks). Furthermore, electrophysiological parameters assessing inhibition and excitation in the dentate gyrus were assessed at multiple time points using the paired-pulse-paradigm. Results: Post SSSE hypothermia did not prevent the occurrence of seizures in any animal. Eight weeks after SSSE, Racine motor seizures trended to be less severe following cooling (4.0±0.6) compared with normothermic controls (4.8±0.2) but the difference was not significant when correcting for multiple comparisons. Early loss of inhibition that is typically seen following SSSE, was to some degree attenuated in hypothermically treated animals 3 h after SSSE as expressed by smaller paired-pulseratios (PPR; 0.16±0.21) compared with normothermic controls (0.54±0.21) but this difference was not significant either. Latency between stimulus artefact and excitatory post-synaptic potential 3 h after SSSE, reciprocally reflecting neuronal excitation, was higher in animals that underwent hypothermia (8.29±2.45 ms) compared with controls (4.82±0.66 ms), however, the difference was not significant after correction for multiple comparisons. Conclusion: In summary, the current experiments were not able to demonstrate prevention or mitigation of epileptogenesis with immediate short- term cooling following SSSE

Bildgebung in der prächirurgischen Epilepsiediagnostik

While two thirds of patients with epilepsy become seizure-free with antiseizure medications, 30% remain drug-resistant. In drug-resistant focal epilepsy, epilepsy surgery offers an approximately 65% chance of becoming seizure-free; however, for a successful outcome of surgery a seizure focus must be precisely located, for which imaging techniques are essential. In recent years, the proportion of patients with apparently inconspicuous findings in magnetic resonance imaging (MRI) in the presurgical evaluation has increased. The sensitivity of MRI can be increased using special MRI sequences and MRI postprocessing techniques. Ictal and interictal source localization based on electroencephalography (EEG) and magnetencephalography (MEG) aim at determining the onset of interictal discharges and seizures. Nuclear medicine imaging techniques such as interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) can detect chronic or acute seizure-related changes in brain metabolism and can indicate an epileptogenic focus even if MRI is inconspicuous. The results of these techniques are used to plan invasive EEG recordings and subsequently surgery. Concordant findings are associated with better surgical outcomes and show significantly higher rates of seizure freedomin the long-term seizure outcome

Editorial: Advances in diagnosing and treating new-onset refractory status epilepticus (NORSE).

info:eu-repo/semantics/publishe

Automatic and manual segmentation of the piriform cortex: Method development and validation in patients with temporal lobe epilepsy and Alzheimer's disease.

The piriform cortex (PC) is located at the junction of the temporal and frontal lobes. It is involved physiologically in olfaction as well as memory and plays an important role in epilepsy. Its study at scale is held back by the absence of automatic segmentation methods on MRI. We devised a manual segmentation protocol for PC volumes, integrated those manually derived images into the Hammers Atlas Database (n = 30) and used an extensively validated method (multi-atlas propagation with enhanced registration, MAPER) for automatic PC segmentation. We applied automated PC volumetry to patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE; n = 174 including n = 58 controls) and to the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 151, of whom with mild cognitive impairment (MCI), n = 71; Alzheimer's disease (AD), n = 33; controls, n = 47). In controls, mean PC volume was 485 mm3 on the right and 461 mm3 on the left. Automatic and manual segmentations overlapped with a Jaccard coefficient (intersection/union) of ~0.5 and a mean absolute volume difference of ~22 mm3 in healthy controls, ~0.40/ ~28 mm3 in patients with TLE, and ~ 0.34/~29 mm3 in patients with AD. In patients with TLE, PC atrophy lateralised to the side of hippocampal sclerosis (p < .001). In patients with MCI and AD, PC volumes were lower than those of controls bilaterally (p < .001). Overall, we have validated automatic PC volumetry in healthy controls and two types of pathology. The novel finding of early atrophy of PC at the stage of MCI possibly adds a novel biomarker. PC volumetry can now be applied at scale