Dissociative seizures in the emergency room: room for improvement.

BACKGROUND: Dissociative seizures, also known as functional or psychogenic non-epileptic seizures, account for 11%-27% of all emergency seizure presentations. Misdiagnosis as epileptic seizures is common and leads to ineffective and potentially harmful treatment escalations. We assess the potential for diagnostic improvement at different stages of emergency workup and estimate the utility of benzodiazepines. METHODS: A retrospective study of all emergency presentations with a discharge diagnosis of acute dissociative seizures seen at a university hospital 2010-2022 was performed to assess clinical characteristics and emergency decision-making. RESULTS: Among 156 patients (73% female, median 29 years), 15% presented more than once for a total of 203 presentations. Half of seizures were ongoing at first medical contact; prolonged seizures and clusters were common (23% and 24%). Diagnostic accuracy differed between on-site emergency physicians and emergency department neurologists (12% vs 52%). Typical features such as eye closure, discontinuous course and asynchronous movements were common. Benzodiazepines were given in two-thirds of ongoing seizures, often in high doses and preferentially for major hyperkinetic semiology. Clinical response to benzodiazepines was mixed, with a minority of patients remaining either unaffected (16%) or becoming critically sedated (13%). A quarter of patients given benzodiazepines by emergency medical services were admitted to a monitoring unit, 9% were intubated. CONCLUSIONS: Improved semiological assessment could reduce early misdiagnosis of dissociative seizures. Although some seizures seem to respond to benzodiazepines, critical sedation is common, and further studies are needed to assess the therapeutic ratio.

Diagnostic challenges in patients with temporal lobe seizures and features of autoimmune limbic encephalitis.

BACKGROUND AND PURPOSE: Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neuronal antibodies (Abs), but it remains unclear which clinical features should prompt neuronal Ab screening in temporal lobe epilepsy patients. The aim of the study was to investigate whether patients with temporal lobe seizures associated with additional symptoms or signs of limbic involvement may harbor neuronal Abs, and which clinical features should prompt neuronal Ab screening in these patients. METHODS: We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal magnetic resonance imaging (MRI) hyperintensities or inflammatory cerebrospinal fluid (CSF). Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRI scans were assessed by two reviewers independently. RESULTS: Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), psychiatric symptoms in 27/42 (64%), and both in 19/42 patients (45%). Limbic T2/fluid-attenuated inversion recovery signal hyperintensities were found in 26/46 patients (57%; unilateral: n = 22, bilateral: n = 4). Standard CSF studies were abnormal in 2/37 patients (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 patients (17%) and were directed against neuronal cell-surface targets (leucine-rich glioma inactivated protein 1: n = 1, contactin-associated protein-2: n = 1, undetermined target: n = 3) or glutamic acid decarboxylase in its 65-kD isoform (n = 3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% vs. 18/38, 47%; p = 0.01, Fisher's exact test). CONCLUSIONS: In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% confidence interval 1.51-2.95).

Cortical thickness in default mode network hubs correlates with clinical features of dissociative seizures.

BACKGROUND: Dissociative seizures (DS) are a common subtype of functional neurological disorder (FND) with an incompletely understood pathophysiology. Here, gray matter variations and their relationship to clinical features were investigated. METHODS: Forty-eight patients with DS without neurological comorbidities and 43 matched clinical control patients with syncope with structural brain MRIs were identified retrospectively. FreeSurfer-based cortical thickness and FSL FIRST-based subcortical volumes were used for quantitative analyses, and all findings were age and sex adjusted, and corrected for multiple comparisons. RESULTS: Groups were not statistically different in cortical thickness or subcortical volumes. For patients with DS, illness duration was inversely correlated with cortical thickness of left-sided anterior and posterior cortical midline structures (perigenual/dorsal anterior cingulate cortex, superior parietal cortex, precuneus), and clusters at the left temporoparietal junction (supramarginal gyrus, postcentral gyrus, superior temporal gyrus), left postcentral gyrus, and right pericalcarine cortex. Dissociative seizure duration was inversely correlated with cortical thickness in the left perigenual anterior cingulate cortex, superior/middle frontal gyri, precentral gyrus and lateral occipital cortex, along with the right isthmus-cingulate and posterior-cingulate, middle temporal gyrus, and precuneus. Seizure frequency did not show any significant correlations. CONCLUSIONS: In patients with DS, illness duration inversely correlated with cortical thickness of left-sided default mode network cortical hubs, while seizure duration correlated with left frontopolar and right posteromedial areas, among others. Etiological factors contributing to neuroanatomical variations in areas related to self-referential processing in patients with DS require more research inquiry.

German translation and validation of the brief Epilepsy Anxiety Survey Instrument (brEASI).

BACKGROUND: Anxiety disorders remain undiagnosed in routine clinical practice in up to two thirds of affected patients with epilepsy despite their significant impact on medical and psychosocial outcomes. The study objective was to translate and validate the German 8-item "brief Epilepsy Anxiety Survey Instrument" (brEASI) to facilitate effective screening for the presence of anxiety disorders in German-speaking patients. METHODS: After expert translation into German, the brEASI was completed by consecutive adult inpatients with epilepsy hospitalized for seizures at an academic reference epilepsy center. Patients also completed the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), the Generalized Anxiety Disorder scale (GAD-7) for external validity, and underwent a standardized interview (Mini-DIPS-OA) as a gold standard to determine the presence of an ICD-10 anxiety disorder (generalized anxiety disorder (GAD), panic disorder, agoraphobia, and social phobia). Receiver operating characteristics (ROC) were calculated to determine the diagnostic accuracy of the brEASI, including the associated area under the curve (AUC) statistics to determine the potential of the brEASI to identify ICD-10 anxiety disorders diagnosed by interview. For comparative purposes, these analyses were also conducted for the GAD-7. RESULTS: Of 80 recruited adult inpatients with epilepsy, 18 (23 %) were found to have a current anxiety disorder through standardized interview. In this study, both brEASI and GAD-7 showed a better diagnostic performance at a cutoff of >5 than at the previously reported cutoff values of >6 and >9, respectively. The AUC of the German brEASI was outstanding (AUC = 0.90, 95 % confidence interval (CI) = 0.82-0.96) for detecting all anxiety disorders and excellent for detecting non-GAD disorders (AUC = 0.85, CI = 0.76-0.92) at a cutoff of >5. At this optimal cutoff of >5 the brEASI demonstrated better sensitivity and specificity (89 % and 84 %) for identifying anxiety disorders than the GAD-7 (83 % and 74 %). The final German version of the brEASI is free to download at https://www.v-neuro.de/veroeffentlichungen/. CONCLUSION: The German version of the brEASI represents a valid and reliable epilepsy-specific anxiety screening instrument. A positive screening result should be followed by further diagnostic procedures. Appropriate therapeutic steps should be initiated if the presence of an anxiety disorder or other psychiatric disorders is confirmed.

External validation of automated focal cortical dysplasia detection using morphometric analysis.

OBJECTIVE: Focal cortical dysplasias (FCDs) are a common cause of drug-resistant focal epilepsy but frequently remain undetected by conventional magnetic resonance imaging (MRI) assessment. The visual detection can be facilitated by morphometric analysis of T1-weighted images, for example, using the Morphometric Analysis Program (v2018; MAP18), which was introduced in 2005, independently validated for its clinical benefits, and successfully integrated in standard presurgical workflows of numerous epilepsy centers worldwide. Here we aimed to develop an artificial neural network (ANN) classifier for robust automated detection of FCDs based on these morphometric maps and probe its generalization performance in a large, independent data set. METHODS: In this retrospective study, we created a feed-forward ANN for FCD detection based on the morphometric output maps of MAP18. The ANN was trained and cross-validated on 113 patients (62 female, mean age ± SD =29.5 ± 13.6 years) with manually segmented FCDs and 362 healthy controls (161 female, mean age ± SD =30.2 ± 9.6 years) acquired on 13 different scanners. In addition, we validated the performance of the trained ANN on an independent, unseen data set of 60 FCD patients (28 female, mean age ± SD =30 ± 15.26 years) and 70 healthy controls (42 females, mean age ± SD = 40.0 ± 12.54 years). RESULTS: In the cross-validation, the ANN achieved a sensitivity of 87.4% at a specificity of 85.4% on the training data set. On the independent validation data set, our method still reached a sensitivity of 81.0% at a comparably high specificity of 84.3%. SIGNIFICANCE: Our method shows a robust automated detection of FCDs and performance generalizability, largely independent of scanning site or MR-sequence parameters. Taken together with the minimal input requirements of a standard T1 image, our approach constitutes a clinically viable and useful tool in the presurgical diagnostic routine for drug-resistant focal epilepsy.

Impaired emotional and behavioural awareness and control in patients with dissociative seizures.

BACKGROUND: Dissociative seizures (DS) are brief episodes of disrupted awareness and behavioural control that may resemble epileptic seizures. They are thought to arise in the context of impaired emotion processing and disinhibition. In a multi-perspective neuropsychological study, we aim to assess specific metacognitive traits and behavioural features involved in the affective and cognitive underpinnings of DS (emotion recognition and regulation, inhibition, interoception and sense of agency). METHODS: Twenty prospectively recruited patients with video-EEG-confirmed DS and 20 healthy controls underwent comprehensive neuropsychological and psychiatric testing using validated questionnaires and structured interviews. Behavioural experimental data was obtained using a custom-made emotional go/no-go task, a digital Libet clock setup and a heartbeat counting paradigm. RESULTS: Emotion recognition, as quantified in the emotional go/no-go task, was impaired in the DS group, and correlated with alexithymic traits. Behavioural inhibition, especially under conditions that would require emotion regulation, was also reduced in the emotional go/no-go task compared to controls and was correlated with neuropsychometric measures of emotion regulation. Data from the Libet clock experiment suggested impaired behavioural awareness in DS patients. No evidence of impaired interoceptive awareness was found in the heartbeat counting task. CONCLUSION: These results represent comprehensive experimental evidence for alterations in emotional and behavioural awareness and control in patients with DS that yield empirical evidence for current psychopathological models. Our findings offer a more detailed understanding of key pathogenic factors in DS and provide theoretical support for recently developed cognitive-behavioural therapies for DS.

Suggestive seizure induction for inpatients with suspected psychogenic nonepileptic seizures.

OBJECTIVE: To determine the utility of suggestive seizure induction for inpatient work-up of suspected psychogenic nonepileptic seizures (PNES). METHODS: Prospective study of epilepsy center inpatient admissions with suspected PNES. Patients were randomized to undergo suggestive induction first (group A) and then, if necessary, long-term video-electroencephalography (EEG) monitoring, or vice versa (group B). Diagnostic pathways were compared. Potential clinical predictors for diagnostic success were evaluated. RESULTS: Length of in-hospital stay did not significantly differ between groups. Suspicion of PNES was confirmed in 43 of 77 (56%) patients, evenly distributed between group A (22 of 39) and group B (21 of 38). In nine patients, recorded habitual seizures were epileptic and in 25 cases, no diagnostic event could be recorded. Diagnosis of PNES was ascertained primarily by recording a typical seizure through suggestive induction in 24 patients and through long-term monitoring in 19 patients. In group A (induction first), monitoring was not deemed necessary in 21% of cases. In group B (monitoring first), 13% would have remained inconclusive without suggestive induction. Patients who reported triggers to their habitual seizures were not more likely to have spontaneous or provoked PNES during monitoring or suggestive inducion, respectively. Patients with subjective seizure prodromes (auras) were significantly more likely to have a PNES during suggestive induction than those without (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.1-10.4). There was no significant difference in seizure frequency between patients with spontaneous PNES during long-term monitoring and those with nondiagnostic monitoring sessions. SIGNIFICANCE: Our results support the notion that suggestive seizure induction can reduce the number of inconclusive inpatient workups, and can obviate resource-intensive long-term monitoring in one fifth of cases. Patients who are aware of prodromes might have a higher chance of having seizures induced through suggestion.

Research on dissociative seizures: A bibliometric analysis and visualization of the scientific landscape.

Dissociative seizures are a common and often elusive differential diagnosis in epilepsy centers. Considering their high prevalence, long diagnostic delays, and disappointing rates of treatment response, scientific research dedicated to dissociative seizures is surprisingly scarce. In order to chart the scientific landscape of dissociative seizures and to visualize thematic clusters and trends in research, a comprehensive bibliometric analysis was performed. The Web of Science database was examined to identify relevant English language documents from the last half-century. A total of 1751 documents with titles referring to dissociative seizures were identified. Automated textual analysis of all titles and abstracts revealed that research clusters around three major topics: differential diagnosis in epilepsy centers, management and treatment, and psychopathology. Time analysis of term networks revealed that the focus of clinical research has moved from diagnostic procedures to treatment approaches. Furthermore, interest within etiological research is shifting from an emphasis on early life trauma and personality traits to the role of anxiety and emotion regulation. With respect to individual contributing authors, a relatively small network of prolific scientists with a remarkable degree of collaboration emerges. By mapping relevant publications, it becomes evident that dissociative seizures still represent a subject mostly within the realm of neurology and epileptology, with a tendency to settle in the latter domain. This analysis sheds light on an important niche subject and highlights trends in research focus and output.

Diagnosing psychogenic nonepileptic seizures: Video-EEG monitoring, suggestive seizure induction and diagnostic certainty.

Psychogenic nonepileptic seizures (PNES) can remain undiagnosed for many years, leading to unnecessary medication and delayed treatment. A recent report by the International League Against Epilepsy Nonepileptic Seizures Task Force recommends a staged approach to the diagnosis of PNES (LaFrance, et al., 2013). We aimed to investigate its practical utility, and to apply the proposed classification to evaluate the role of long-term video-EEG monitoring (VEEG) and suggestive seizure induction (SSI) in PNES workup. Using electronic medical records, 122 inpatients (mean age 36.0±12.9years; 68% women) who received the diagnosis of PNES at our epilepsy center during a 4.3-year time period were included. There was an 82.8% agreement between diagnostic certainty documented at discharge and that assigned retroactively using the Task Force recommendations. In a minority of cases, having used the Task Force criteria could have encouraged the clinicians to give more certain diagnoses, exemplifying the Task Force report's utility. Both VEEG and SSI were effective at supporting high level diagnostic certainty. Interestingly, about one in four patients (26.2%) had a non-diagnostic ("negative") VEEG but a positive SSI. On average, this subgroup did not have significantly shorter mean VEEG recording times than VEEG-positive patients. However, VEEG-negative/SSI-positive patients had a significantly lower habitual seizure frequency than their counterparts. This finding emphasizes the utility of SSI in ascertaining the diagnosis of PNES in patients who do not have a spontaneous habitual event during VEEG due to, for example, low seizure frequency.

Hyperventilation and photic stimulation are useful additions to a placebo-based suggestive seizure induction protocol in patients with psychogenic nonepileptic seizures.

The early and definitive diagnosis of psychogenic nonepileptic seizures is a common challenge in epileptology practice. Suggestive seizure induction is a valuable tool to aid the differentiation between epileptic and psychogenic nonepileptic seizures, especially when long-term video-EEG monitoring is inconclusive or unavailable. In this retrospective analysis, we compared the diagnostic yield of a classical, placebo-based induction protocol with that of an extended protocol that includes hyperventilation and photic stimulation as means of suggestion while also implementing more open, standardized patient information. We investigated whether the diversification of suggestive seizure induction has an effect on diagnostic yield and whether it preempts the administration of placebo. Data from 52 patients with confirmed psychogenic nonepileptic seizures were analyzed. While suggestive seizure induction using only placebo-based suggestion provoked a typical event in 13 of 20 patients (65%), the extended protocol was positive in 27 of 34 cases (84%); this improvement was not significant (p=0.11). Noninvasive suggestion techniques accounted for 78% of inductions, avoiding placebo administration in a majority of patients. Still, placebo remains an important part of suggestive seizure induction, responsible for 22% (6 out of 27) of successful inductions using our extended protocol. Our study demonstrates that the diversification of suggestive seizure induction is feasible and beneficial for both patients and diagnosticians.

Standardized hierarchical adaptive Lp regression for noise robust focal epilepsy source reconstructions.

OBJECTIVE: To investigate the ability of standardization to reduce source localization errors and measurement noise uncertainties for hierarchical Bayesian algorithms with L1- and L2-norms as priors in electroencephalography and magnetoencephalography of focal epilepsy. METHODS: Description of the standardization methodology relying on the Hierarchical Bayesian framework, referred to as the Standardized Hierarchical Adaptive Lp-norm Regularization (SHALpR). The performance was tested using real data from two focal epilepsy patients. Simulated data that resembled the available real data was constructed for further localization and noise robustness investigation. RESULTS: The proposed algorithms were compared to their non-standardized counterparts, Standardized low-resolution brain electromagnetic tomography, Standardized Shrinking LORETA-FOCUSS, and Dynamic statistical parametric maps. Based on the simulations, the standardized Hierarchical adaptive algorithm using L2-norm was noise robust for 10 dB signal-to-noise ratio (SNR), whereas the L1-norm prior worked robustly also with 5 dB SNR. The accuracy of the standardized L1-normed methodology to localize focal activity was under 1 cm for both patients. CONCLUSIONS: Numerical results of the proposed methodology display improved localization and noise robustness. The proposed methodology also outperformed the compared methods when dealing with real data. SIGNIFICANCE: The proposed standardized methodology, especially when employing the L1-norm, could serve as a valuable assessment tool in surgical decision-making.

Heartbeat evoked potentials and autonomic arousal during dissociative seizures: insights from electrophysiology and neuroimaging.

Introduction: Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness. However, the interplay between affective arousal and changes in interoceptive processing at the onset of dissociative seizures is not well understood. Methods: Using retrospective routine data obtained from video-electroencephalography telemetry in a university hospital epilepsy monitoring unit, we investigate ictal changes in cardiac indices of autonomic arousal and heartbeat evoked potentials (HEPs) in 24 patients with dissociative seizures. Results: Results show autonomic arousal during seizures with increased heart rate and a shift towards sympathetic activity. Compared with baseline, ictal HEP amplitudes over central and right prefrontal electrodes (F8, Fz) were significantly less pronounced during seizures, suggesting diminished cortical representation of interoceptive information. Significant correlations between heart rate variability measures and HEPs were observed at baseline, with more sympathetic and less parasympathetic activity related to less pronounced HEPs. Interestingly, these relationships weakened during seizures, suggesting a disintegration of autonomic arousal and interoceptive processing during dissociative seizures. In a subgroup of 16 patients, MRI-based cortical thickness analysis found a correlation with HEP amplitudes in the left somatosensory association cortex. Conclusions: These findings possibly represent an electrophysiological hint of how autonomic arousal could negatively impact bodily awareness in dissociative seizures, and how these processes might be related to underlying brain structure.

A multicenter randomized controlled feasibility trial of a digital self-management intervention for adults with epilepsy.

OBJECTIVE: Self-management interventions may enhance health-related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone-delivered self-care treatment program for adults with epilepsy. METHODS: The 12-week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting-list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy-related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE-31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi-structured interviews were conducted with a heterogeneous sample of participants to assess user-friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). RESULTS: Ninety-two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. SIGNIFICANCE: Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self-care apps. Feedback loops allow the participatory development of tailored interventions. PLAIN LANGUAGE SUMMARY: In this study, we investigated the effectiveness of an app-based self-help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one-fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options.

Co-localizing linguistic and musical syntax with intracranial EEG.

Despite general agreement on shared syntactic resources in music and language, the neuroanatomical underpinnings of this overlap remain largely unexplored. While previous studies mainly considered frontal areas as supramodal grammar processors, the domain-general syntactic role of temporal areas has been so far neglected. Here we capitalized on the excellent spatial and temporal resolution of subdural EEG recordings to co-localize low-level syntactic processes in music and language in the temporal lobe in a within-subject design. We used Brain Surface Current Density mapping to localize and compare neural generators of the early negativities evoked by violations of phrase structure grammar in both music and spoken language. The results show that the processing of syntactic violations relies in both domains on bilateral temporo-fronto-parietal neural networks. We found considerable overlap of these networks in the superior temporal lobe, but also differences in the hemispheric timing and relative weighting of their fronto-temporal constituents. While alluding to the dissimilarity in how shared neural resources may be configured depending on the musical or linguistic nature of the perceived stimulus, the combined data lend support for a co-localization of early musical and linguistic syntax processing in the temporal lobe.

Proposal for a magnetic resonance imaging protocol for the detection of epileptogenic lesions at early outpatient stages.

PURPOSE: Magnetic resonance imaging (MRI) is a key technology in the presurgical evaluation of patients with epilepsy. Already at early outpatient stages it can contribute to the identification of patients who are, in the case of pharmacoresistance, good candidates for epilepsy surgery. Yet, "standard head" MRI examinations often fail to displaying therapeutically relevant epileptogenic lesions. The purpose of this study is to identify an epilepsy-specific MRI protocol, which is likewise sensitive for even small epileptogenic lesions and economical enough to be applied outside specialized epilepsy centers. METHODS: Based on a large European presurgical epilepsy program comprising 2,740 patients we identified the spectrum of common epileptogenic lesions and determine the set of MRI sequences that are required for their reliable detection. Relying on a series of small, therapeutically particularly relevant lesions we determined the required slices thickness, slice angulations, and orientations for an epilepsy-specific MRI protocol. KEY FINDINGS: Indispensable for early outpatient epilepsy specific MRI are fluid attenuated inversion recovery (FLAIR), T(2) -weighted, T(1) -weighted, and hemosiderin/calcification-sensitive sequences. Slice thickness for T(2) and FLAIR must not exceed 3 mm. The T(1) image should be acquired in three-dimensional technique at 1 mm isotropic voxels size. For T(2) and FLAIR, at least two slice orientations each must be demanded in hippocampal angulation. We suggest no adaption to a clinical focus hypothesis. The resulting "essential 6" sequence protocol allows the detection of virtually all common epileptogenic lesion entities. SIGNIFICANCE: The creation of a broadly accepted and abundantly applied MRI protocol for epilepsy outpatients can contribute to improved and earlier identification of potential candidates for epilepsy surgery. Our systematic analysis of MRI requirements for the detection of epileptogenic lesions can serve as basis for protocol negotiations between epileptologists, radiologists, and health care funders.

The relationship of action, affect, and metacognition in functional seizures.

INTRODUCTION: Metacognition provides a lens through which individuals experience, interpret, and respond to their affective states and behavior; it might thus influence complex neuropsychiatric conditions such as functional seizures - events characterized by states of heightened affective arousal and the disinhibition of prepotent behavior. In this pilot study, we aimed to establish a better understanding of the role of metacognition in functional seizures and its relationship to affective arousal and behavioral disinhibition (i.e., problems in suppressing prepared behavior). We hypothesized that affective arousal is related to higher behavioral disinhibition as well as slower reaction times, that affect and action (performing vs. not performing a movement) are related to memory and metacognition, and that metacognition is related to illness characteristics. METHODS: We used a combination of an emotional go/no-go and a metacognitive recognition task with affectively valenced and neutral images in 18 patients with functional seizures. We compared markers of behavioral inhibition as well as indices for memory and metacognitive performance between affective (vs. neutral) and action/go (vs. inhibition/no-go) conditions. RESULTS: Contrary to our hypothesis, behavioral disinhibition was not different between conditions. However, we found slower reaction times for affectively valenced stimuli. Memory performance and metacognition were better for affectively valenced pictures and for pictures used in go trials (i.e., associated with action/performing the movement). Illness factors (illness duration, seizure frequency, levels of self-reported anxiety) were correlated with aspects of metacognition. CONCLUSIONS: This pilot study offers first insights into alterations in metacognition related to action and affect in patients with functional seizures; specifically, that affectively valenced stimuli and active engagement are related to enhanced memory and metacognition. This relationship was also found with respect to illness factors. These results provide insight into potentially underlying pathomechanisms, although the lack of a control group limits evaluating the specificity of these findings.

Validating EEG source imaging using intracranial electrical stimulation.

Electrical source imaging is used in presurgical epilepsy evaluation and in cognitive neurosciences to localize neuronal sources of brain potentials recorded on EEG. This study evaluates the spatial accuracy of electrical source imaging for known sources, using electrical stimulation potentials recorded on simultaneous stereo-EEG and 37-electrode scalp EEG, and identifies factors determining the localization error. In 11 patients undergoing simultaneous stereo-EEG and 37-electrode scalp EEG recordings, sequential series of 99-110 biphasic pulses (2 ms pulse width) were applied by bipolar electrical stimulation on adjacent contacts of implanted stereo-EEG electrodes. The scalp EEG correlates of stimulation potentials were recorded with a sampling rate of 30 kHz. Electrical source imaging of averaged stimulation potentials was calculated utilizing a dipole source model of peak stimulation potentials based on individual four-compartment finite element method head models with various skull conductivities (range from 0.0413 to 0.001 S/m). Fitted dipoles with a goodness of fit of ≥80% were included in the analysis. The localization error was calculated using the Euclidean distance between the estimated dipoles and the centre point of adjacent stimulating contacts. A total of 3619 stimulation locations, respectively, dipole localizations, were included in the evaluation. Mean localization errors ranged from 10.3 to 26 mm, depending on source depth and selected skull conductivity. The mean localization error increased with an increase in source depth (r(3617) = [0.19], P = 0.000) and decreased with an increase in skull conductivity (r(3617) = [-0.26], P = 0.000). High skull conductivities (0.0413-0.0118 S/m) yielded significantly lower localization errors for all source depths. For superficial sources (<20 mm from the inner skull), all skull conductivities yielded insignificantly different localization errors. However, for deeper sources, in particular >40 mm, high skull conductivities of 0.0413 and 0.0206 S/m yielded significantly lower localization errors. In relation to stimulation locations, the majority of estimated dipoles moved outward-forward-downward to inward-forward-downward with a decrease in source depth and an increase in skull conductivity. Multivariate analysis revealed that an increase in source depth, number of skull holes and white matter volume, while a decrease in skull conductivity independently led to higher localization error. This evaluation of electrical source imaging accuracy using artificial patterns with a high signal-to-noise ratio supports its application in presurgical epilepsy evaluation and cognitive neurosciences. In our artificial potential model, optimizing the selected skull conductivity minimized the localization error. Future studies should examine if this accounts for true neural signals.

Risks and benefits of invasive epilepsy surgery workup with implanted subdural and depth electrodes.

PURPOSE: In patients with pharmacoresistant focal-onset seizures, invasive presurgical workup can identify epilepsy surgery options when noninvasive workup has failed. Yet, the potential benefit must be balanced with procedure-related risks. This study examines risks associated with the implantation of subdural strip and grid, and intracerebral depth electrodes. Benefit of invasive monitoring is measured by seizure outcomes. Diagnostic procedures made possible by electrode implantation are described. METHODS: Retrospective evaluation of invasive workups in 242 epilepsy surgery candidates and additional 18 patients with primary brain tumors implanted for mapping only. Complications are scaled in five grades of severity. A regression analysis identifies risk factors for complications. Outcome is classified according to Engel's classification. KEY FINDINGS: Complications of any type were documented in 23% of patients, and complications requiring surgical revision in 9%. We did not find permanent morbidity or mortality. Major risk factor for complications was the implantation of grids and the implantation of electrode assemblies comprising strip and grid electrodes. Depth electrodes were significantly correlated with a lower risk. Tumors were not correlated with higher complication rates. Chronic invasive monitoring of 3-40 days allowed seizure detection in 99.2% of patients with epilepsy and additional extensive mapping procedures. Patients with epilepsy with follow-up >24 months (n = 165) had an Engel class 1a outcome in 49.7% if epilepsy surgery was performed, but only 6.3% when surgery was rejected. SIGNIFICANCE: The benefit of chronic invasive workup outweighs its risks, but complexity of implantations should be kept to a minimum.

Point-of-Care Testing Using a Neuropsychology Pocketcard Set: A Preliminary Validation Study.

Neurocognitive screening instruments usually require printed sheets and additional accessories, and can be unsuitable for low-threshold use during ward rounds or emergency workup, especially in patients with motor impairments. Here, we test the utility of a newly developed neuropsychology pocketcard set for point-of-care testing. For aphasia and neglect assessment, modified versions of the Language Screening Test and the Bells Test were validated on 63 and 60 acute stroke unit patients, respectively, against expert clinical evaluation and the original pen-and-paper Bells Test. The pocketcard aphasia test achieved an excellent area under the curve (AUC) of 0.94 (95% CI: 0.88−1, p < 0.001). Using an optimal cut-off of ≥2 mistakes, sensitivity was 91% and specificity was 81%. The pocketcard Bells Task, measured against the clinical neglect diagnosis, achieved higher sensitivity (89%) and specificity (88%) than the original paper-based instrument (78% and 75%, respectively). Separately, executive function tests (modified versions of the Trail Making Test [TMT] A and B, custom Stroop color naming task, vigilance 'A' Montreal Cognitive Assessment item) were validated on 44 inpatients with epilepsy against the EpiTrack® test battery. Pocketcard TMT performance was significantly correlated with the original EpiTrack® versions (A: r = 0.64, p < 0.001; B: r = 0.75, p < 0.001). AUCs for the custom Stroop task, TMT A and TMT B for discriminating between normal and pathological EpiTrack® scores were acceptable, excellent and outstanding, respectively. Quick point-of-care testing using a pocketcard set is feasible and yields diagnostically valid information.

Validating EEG, MEG and Combined MEG and EEG Beamforming for an Estimation of the Epileptogenic Zone in Focal Cortical Dysplasia.

MEG and EEG source analysis is frequently used for the presurgical evaluation of pharmacoresistant epilepsy patients. The source localization of the epileptogenic zone depends, among other aspects, on the selected inverse and forward approaches and their respective parameter choices. In this validation study, we compare the standard dipole scanning method with two beamformer approaches for the inverse problem, and we investigate the influence of the covariance estimation method and the strength of regularization on the localization performance for EEG, MEG, and combined EEG and MEG. For forward modelling, we investigate the difference between calibrated six-compartment and standard three-compartment head modelling. In a retrospective study, two patients with focal epilepsy due to focal cortical dysplasia type IIb and seizure freedom following lesionectomy or radiofrequency-guided thermocoagulation (RFTC) used the distance of the localization of interictal epileptic spikes to the resection cavity resp. RFTC lesion as reference for good localization. We found that beamformer localization can be sensitive to the choice of the regularization parameter, which has to be individually optimized. Estimation of the covariance matrix with averaged spike data yielded more robust results across the modalities. MEG was the dominant modality and provided a good localization in one case, while it was EEG for the other. When combining the modalities, the good results of the dominant modality were mostly not spoiled by the weaker modality. For appropriate regularization parameter choices, the beamformer localized better than the standard dipole scan. Compared to the importance of an appropriate regularization, the sensitivity of the localization to the head modelling was smaller, due to similar skull conductivity modelling and the fixed source space without orientation constraint.