Challenges to epilepsy management in Rwandan women living with epilepsy.

BACKGROUND AND PURPOSE: In Rwanda, epilepsy prevalence ranges between 29‰ and 49‰. Many women living with epilepsy (WwE) are of childbearing age. Epilepsy characteristics and management, contraception, pregnancy, puerperium and stigma in WwE presenting at the neurology clinic of Ndera, Rwanda, were investigated. METHODS: This prospective cross-sectional study investigated demographics, epilepsy characteristics, treatment, contraception, folic acid use, pregnancy, puerperium and stigma in WwE aged ≥18 years. Subgroups were analysed by status of any pregnancy and time of epilepsy diagnosis relative to pregnancy, with significant differences expected. RESULTS: During December 2020 and January 2021, a hundred WwE were enrolled (range 18-67 years). Fifty-two women had never been pregnant, 39 women had epilepsy onset before pregnancy and nine were diagnosed after pregnancy. No significant differences in age, marital status or occupation were observed. Contraception was used by 27%, of whom 50% were taking enzyme-inducing anti-epileptic medication. Valproate was used by 46% of WwE of reproductive age. Thirty-nine women with epilepsy onset before pregnancy reported 91 pregnancies, with 14% spontaneous abortions. None used folic acid before conception, and 59% only during pregnancy. Five of 78 newborns were preterm. No offspring had major congenital malformations. Nearly 25% of WwE were not compliant with their anti-epileptic medication schedule during pregnancy or breastfeeding. Internalized stigma was observed in more than 60%. Up to 25% had been discriminated against at school or work. CONCLUSION: A comprehensive strategy considering the reproductive health and societal challenges of WwE is needed to drive optimal epilepsy management, reproductive health outcomes and societal inclusion.

The 2022 European postgraduate (residency) programme in neurology in a historical and international perspective.

BACKGROUND AND PURPOSE: Neurology residency programmes, which were first established at the beginning of the 20th century, have become mandatory all over Europe in the last 40-50 years. The first European Training Requirements in Neurology (ETRN) were published in 2005 and first updated in 2016. This paper reports the most recent revisions of the ETRN. METHODS: Members of the EAN board performed an in depth revision of the ETNR 2016-version, which was reviewed by members of the European Board and Section of Neurology of the UEMS, the Education and Scientific Panels, the Resident and Research Fellow Section and the Board of the EAN, as well as the presidents of the 47 European National Societies. RESULTS: The new (2022) ETRN suggest a 5-year training subdivided in three phases: a first phase (2 years) of general neurology training, a second phase (2 years) of training in neurophysiology/neurological subspecialties and a third phase (1 year) to expand clinical training (e.g., in other neurodisciplines) or for research (path for clinical neuroscientist). The necessary theoretical and clinical competences as well as learning objectives in diagnostic tests have been updated, are newly organized in four levels and include 19 neurological subspecialties. Finally, the new ETRN require, in addition to a programme director, a team of clinician-educators who regularly review the resident's progress. The 2022 update of the ETRN reflects emerging requirements for the practice of neurology and contributes to the international standardization of training necessary for the increasing needs of residents and specialists across Europe.

Very high epilepsy prevalence in rural Southern Rwanda: The underestimated burden of epilepsy in sub-Saharan Africa.

OBJECTIVES: Up to 85% of people living with epilepsy (PwE) reside in low-and middle-income countries. In sub-Saharan Africa, the lifetime prevalence of epilepsy is 16 per 1000 persons. In Northern rural Rwanda, a 47.7 per 1000 prevalence has been reported. As variations in prevalence across geographical areas have been observed, we studied the prevalence in Southern rural Rwanda using the same robust methodology as applied in the North. METHODS: We conducted a three-stage, cross-sectional, door-to-door survey in two rural villages in Southern Rwanda from June 2022 to April 2023. First, trained enumerators administered the validated Limoges questionnaire for epilepsy screening. Second, neurologists examined the persons who had screened positively to confirm the epilepsy diagnosis. Third, cases with an inconclusive assessment were separately reexamined by two neurologists to reevaluate the diagnosis. RESULTS: Enumerators screened 1745 persons (54.4% female, mean age: 24 ± 19.3 years), of whom 304 (17.4%) screened positive. Epilepsy diagnosis was confirmed in 133 (52.6% female, mean age: 30 ± 18.2 years) and active epilepsy in 130 persons. Lifetime epilepsy prevalence was 76.2 per 1000 (95% CI: 64.2-89.7‰). The highest age-specific rate occurred in the 29-49 age group. No gender-specific differences were noted. In 22.6% of the PwE, only non-convulsive seizures occurred. The treatment gap was 92.2%, including a diagnosis gap of 79.4%. CONCLUSION: We demonstrated a very high epilepsy prevalence in Southern rural Rwanda, with over 20% of cases having only non-convulsive seizures, which are often underdiagnosed in rural Africa. In line with previous Rwandan reports, we reiterate the high burden of the disease in the country. Geographic variation in prevalence throughout Africa may result from differences in risk and aetiological factors. Case-control studies are underway to understand such differences and propose adapted health policies for epilepsy prevention.

Corrigendum: Long-Term Impact of Single Epilepsy Training on Knowledge, Attitude and Practices: Comparison of Trained and Untrained Rwandan Community Health Workers.

[This corrects the article DOI: 10.3389/ijph.2021.645598.].

Epilepsy-Related Direct Medical and Direct Non-Medical Cost in Adult Patients Living with Epilepsy at a Tertiary Neurology Center in Rwanda.

Objective: Up to one in four patients living with epilepsy (PwE) mentions financial constraints as a reason for loss to follow-up at the Ndera tertiary neuropsychiatry hospital. Therefore, we evaluated the annual direct medical cost (DMC) and direct non-medical cost (DnMC) of epilepsy and calculated costs assuming different follow-up frequency. Materials and Methods: DMC data were obtained from a descriptive retrospective study of medical records, pharmacy dispensation and hospital logs of PwE, following their initial consultation in 2018 and who adhered to the normal clinical practice of monthly consultations for one year. DnMC data were collected through structured interviews of PwE in a cross-sectional cohort in August 2020. DnMC included biomedical care costs (eg, transportation, hospitality) and non-biomedical costs (traditional healer visits). We report weighted means for total costs, health insurance costs, and out-of-pocket costs (OoP). Results: Mean annual total cost was 389.4 US$, of which 226.2 US$ was covered by the Rwandan Health Insurance co-payment for DMC and 163.2 US$ was OoP paid by patients. Mean weighted annual DMC (n = 55) was 248.9 US$. Mean weighted annual DMC for medical consultations and antiseizure medication accounted for 30.7 US$ and 161.7 US$, respectively. Based on structured interviews (n = 69), mean weighted annual DnMC for biomedical care was 73.0 US$. Mean DnMC for traditional healer care was 67.6 US$. Weighted annual total OoP was 163.2 US$ or 20% of the GDP per capita. OoP consisted of 14% DMC co-payment, 45% biomedical DnMC, and 41% traditional healer DnMC. Conclusion: Epilepsy-related costs at a tertiary center are an important economic burden for PwE and Rwandan Health Insurance. Biomedical and traditional healer DnMC constitute 86% of total OoP. Future prospective studies should evaluate outcomes and costs of reduced visit frequency, indirect costs, and costs of comorbidities.

Effectiveness of community health workers on identification and mobilization of persons living with epilepsy in rural Rwanda using a validated screening tool.

INTRODUCTION: Engagement and training of community health workers (CHWs) have demonstrated their value in different conditions. Despite repeat epilepsy trainings of CHWs in Northern Rwanda, the treatment gap remained high. We hypothesized that effectiveness of CHWs on mobilization of patients living with epilepsy (PwE) could be improved using a validated tool for epilepsy screening. METHODS: CHWs associated with health centers (HCs) of Gataraga, Kimonyi and Karwasa attended a 1-day training on epilepsy and Limoges epilepsy screening questionnaire (Kinyarwanda version). Thereafter, CHWs screened households in their villages for persons with one or more positive answer. CHWs then accompanied positively screened persons to a consultation for clinical evaluation and diagnosis by neurologists, and demographic data were collected. CHW variables were collected retrospectively. RESULTS: A total of 1308 persons were screened positive by 281 CHWs. Clinical diagnosis of epilepsy was confirmed in 589 and in 93 additional unscreened PwE, presenting voluntarily at the consultation. Pre-intervention number of 48 PwE increased to 682 after, a 14.2-fold increase. The overall treatment gap amounted to 93.0%. The age distribution of male PwE preponderance at younger age inverted to females at older age. CHW characteristics showed non-significant differences within and across HCs. Logistic regression did not relate CHW age, gender, and experience to screening results. DISCUSSION: Equipping CHWs with a validated screening tool was effective in identifying and mobilizing PwE in a short time frame and offers opportunity for future scaling. Nonetheless, barriers to sustainability of care will need to be addressed before.

Personalizing Repetitive Transcranial Magnetic Stimulation Parameters for Depression Treatment Using Multimodal Neuroimaging.

Repetitive transcranial magnetic stimulation (rTMS) is a tool that can be used to administer treatment for neuropsychiatric disorders such as major depressive disorder, although the clinical efficacy is still rather modest. Overly general stimulation protocols that consider neither patient-specific depression symptomology nor individualized brain characteristics, such as anatomy or structural and functional connections, may be the cause of the high inter- and intraindividual variability in rTMS clinical responses. Multimodal neuroimaging can provide the necessary insights into individual brain characteristics and can therefore be used to personalize rTMS parameters. Optimal coil positioning should include a three-step process: 1) identify the optimal (indirect) target area based on the exact symptom pattern of the patient; 2) derive the cortical (direct) target location based on functional and/or structural connectomes derived from functional and diffusion magnetic resonance imaging data; and 3) determine the ideal coil position by computational modeling, such that the electric field distribution overlaps with the cortical target. These TMS-induced electric field simulations, derived from anatomical and diffusion magnetic resonance imaging data, can be further applied to compute optimal stimulation intensities. In addition to magnetic resonance imaging, electroencephalography can provide complementary information regarding the ongoing brain oscillations. This information can be used to determine the optimal timing and frequency of the stimuli. The heightened benefits of these personalized stimulation approaches are logically reasoned, but speculative. Randomized clinical trials will be required to compare clinical responses from standard rTMS protocols to personalized protocols. Ultimately, an optimized clinical response may result from precision protocols derived from combinations of personalized stimulation parameters.

Long-Term Impact of Single Epilepsy Training on Knowledge, Attitude and Practices: Comparison of Trained and Untrained Rwandan Community Health Workers.

Objectives: To close the epilepsy treatment gap and reduce related stigma, eradication of misconceptions is importantIn 2014, Community Health Workers (CHWs) from Musanze (Northern Rwanda) were trained on different aspects of epilepsy. This study compared knowledge, attitude and practices (KAPs) towards epilepsy of trained CHWs 3 years after training, to untrained CHWs from Rwamagana (Eastern Rwanda). Methods: An epilepsy KAP questionnaire was administered to 96 trained and 103 untrained CHWs. Demographic and intergroup KAP differences were analysed by response frequencies. A multivariate analyses was performed based on desired and undesired response categories. Results: Epilepsy awareness was high in both groups, with better knowledge levels in trained CHWs. Negative attitudes were lowest in trained CHWs, yet 17% still reported misconceptions. Multivariate analysis demonstrated the impact of the training, irrespective of age, gender and educational level. Knowing someone with epilepsy significantly induced more desired attitudes. Conclusion: Despite demographic differences between trained and untrained CHWs, a single epilepsy training resulted in significant improvement of desired KAPs after 3 years. Nation-wide CHW training programs with focus on training-resistant items, e.g., attitudes, are recommended.

High prevalence of epilepsy in Northern Rwanda: Exploring gender differences.

INTRODUCTION: In sub-Saharan Africa (SSA), the prevalence of lifetime epilepsy varies widely between subregions and is higher in rural compared to urban regions. Observed versus expected numbers of patients with epilepsy (PwE) in the northern province of Rwanda did not match the prevalence of 49‰ reported in 2005 in Rwanda. We report a confirmatory prevalence study focused on gender-specific observations. METHODS: A cross-sectional door-to-door approach was used in three rural villages. First, epilepsy screening using the Kinyarwanda version of the Limoges questionnaire was performed. Second, confirmation of epilepsy diagnosis was completed by trained physicians. RESULTS: In total, 2681 persons (56.14% female) were screened. Of 168 positively screened, 128 persons were diagnosed with epilepsy confirming the prevalence of lifetime epilepsy of 47.7‰ (CI 39.8-56.8). The diagnosis gap was 62.5% with 80 newly diagnosed. The overall female:male ratio was 1.61:1.00. A male preponderance below 9 years of age inverted to a female preponderance above 20 years of age. Female PwE had an older age at first seizure, reported different reasons for not seeking care, and differed from male PwE in possible etiology. For previously diagnosed PwE, the treatment gap was more than 77%. CONCLUSION: A high prevalence in rural areas was confirmed, with an observed female/male ratio among the highest of published door-to-door surveys in SSA. Gender differences in associated co-morbidities and age at first seizure warrant future research of underlying etiologies and possible survival bias. A better understanding and focus on gender-associated care-seeking patterns, education, and specific needs are recommended.

Letter to the Editor in response to Professor Josef Finsterer.

•Future actions to improve SUDEP reporting include training of healthcare professionals.•Future actions to improve SUDEP reporting include development of easy to use tools that ensure complete case reporting.

Mortality of all causes and sudden unexplained death in epilepsy (SUDEP) in a cohort of 235 persons living with epilepsy in Rwanda using WHO Verbal Autopsy Questionnaire.

INTRODUCTION: Mortality in persons living with epilepsy (PwE) is 1.6-9.3-fold higher than in the general population. Mortality from definite/probable Sudden Unexpected Death in EPilepsy (SUDEP) is estimated at 1.2 per 1000 person-years. We report mortality and SUDEP rate in a cohort of Rwandan PwE. METHODS: PwE presenting for a first visit at the Ndera epilepsy center between January and June 2016 were followed-up prospectively. For PwE who did not attend their follow-up visit, home visits were organized. Deaths were assessed using World Health Organization Verbal Autopsy Standards age-specific questionnaires. RESULTS: Of 235 PwE enrolled, home visits were organized for 81 (34.4%) PwE who did not return for their follow-up consultation. Seven fatalities (mortality 16.7/1000 patient-years [CI 6.7-34.3]) were recorded (aged 2-80 years). Four had an identified cause. Three were classified as probable SUDEP, resulting in a probable SUDEP rate of 7.1/1000 patient-years (CI 1.47-20.86). Probable SUDEP occurred in PwE (age: 2, 21, 34 years) showing no symptoms of illness while receiving antiepileptic treatment; in two cases, death occurred during sleep. CONCLUSION: Although autopsies were absent, the high mortality and probable SUDEP rates warrant future studies to establish causes of epilepsy-related deaths in Rwanda and sub-Saharan Africa.

Validity, Reliability, and Diagnostic Cut-off of the Kinyarwandan Version of the Hamilton Depression Rating Scale in Rwanda.

Introduction: In Rwanda, major depressive disorder affects 11.9% of the population and up to 35% of genocide survivors. Mental health services remain underutilized due to stigma and lack of awareness. Increasing the ability and capacity to diagnose and treat mental disorders is considered important to close this gap. We describe the translation, validity, and reliability assessment of the Hamilton Depression Rating Scale (HDRS) as a diagnostic tool for moderate to severe depression in Rwanda. Methods: The HDRS-21 was translated by a multi-group taskforce. We validated the translation against expert assessment in a comparative study on a sample of patients living with depression and of healthy volunteers. Psychometric properties, namely internal structure, reliability, and external validity were assessed using confirmatory factor analysis, three reliability calculations, and correlation analysis, respectively. Maximized Youden's index was used for determining diagnostic cut-off. Results: The translated version demonstrated a kappa of 0.93. We enrolled 105 healthy volunteers and 105 patients with confirmed mild to severe depression. In the confirmatory factor analysis, HDRS had good factor loadings of 0.32-0.80. Reliability coefficients above 0.92 indicated strong internal consistency. External validity was shown by good sensitivity (0.95) and specificity (0.94) to differentiate depression from absence of depression. At a cut-off point of 17 for the diagnosis of depression, sensitivity and specificity were both 0.95 relative to gold standard. Conclusion: The validated HDRS in Kinyarwanda with diagnostic cut-off provides mental healthcare staff with an accurate tool to diagnose moderate to severe depression, enabling closure of the diagnosis and treatment gap.

Focal application of accelerated iTBS results in global changes in graph measures.

Graph analysis was used to study the effects of accelerated intermittent theta burst stimulation (aiTBS) on the brain's network topology in medication-resistant depressed patients. Anatomical and resting-state functional MRI (rs-fMRI) was recorded at baseline and after sham and verum stimulation. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). Using various graph measures, the different effects of sham and verum aiTBS were calculated. It was also investigated whether changes in graph measures were correlated to clinical responses. Furthermore, by correlating baseline graph measures with the changes in HDRS in terms of percentage, the potential of graph measures as biomarker was studied. Although no differences were observed between the effects of verum and sham stimulation on whole-brain graph measures and changes in graph measures did not correlate with clinical response, the baseline values of clustering coefficient and global efficiency showed to be predictive of the clinical response to verum aiTBS. Nodal effects were found throughout the whole brain. The distribution of these effects could not be linked to the strength of the functional connectivity between the stimulation site and the node. This study showed that the effects of aiTBS on graph measures distribute beyond the actual stimulation site. However, additional research into the complex interactions between different areas in the brain is necessary to understand the effects of aiTBS in more detail.

Involvement of fast-spiking cells in ictal sequences during spontaneous seizures in rats with chronic temporal lobe epilepsy.

See Lenck-Santini (doi:10.1093/awx205) for a scientific commentary on this article. Epileptic seizures represent altered neuronal network dynamics, but the temporal evolution and cellular substrates of the neuronal activity patterns associated with spontaneous seizures are not fully understood. We used simultaneous recordings from multiple neurons in the hippocampus and neocortex of rats with chronic temporal lobe epilepsy to demonstrate that subsets of cells discharge in a highly stereotypical sequential pattern during ictal events, and that these stereotypical patterns were reproducible across consecutive seizures. In contrast to the canonical view that principal cell discharges dominate ictal events, the ictal sequences were predominantly composed of fast-spiking, putative inhibitory neurons, which displayed unusually strong coupling to local field potential even before seizures. The temporal evolution of activity was characterized by unique dynamics where the most correlated neuronal pairs before seizure onset displayed the largest increases in correlation strength during the seizures. These results demonstrate the selective involvement of fast spiking interneurons in structured temporal sequences during spontaneous ictal events in hippocampal and neocortical circuits in experimental models of chronic temporal lobe epilepsy.

Autonomic nervous system functioning associated with psychogenic nonepileptic seizures: Analysis of heart rate variability.

OBJECTIVE: Psychogenic nonepileptic seizures (PNESs) resemble epileptic seizures but originate from psychogenic rather than organic causes. Patients with PNESs are often unable or unwilling to reflect on underlying emotions. To gain more insight into the internal states of patients during PNES episodes, this study explored the time course of heart rate variability (HRV) measures, which provide information about autonomic nervous system functioning and arousal. METHODS: Heart rate variability measures were extracted from double-lead electrocardiography data collected during 1-7days of video-electroencephalography monitoring of 20 patients with PNESs, in whom a total number of 118 PNESs was recorded. Heart rate (HR) and HRV measures in time and frequency domains (standard deviation of average beat-to-beat intervals (SDANN), root mean square of successive differences (RMSSD), high-frequency (HF) power, low-frequency (LF) power, and very low-frequency (VLF) power) were averaged over consecutive five-minute intervals. Additionally, quantitative analyses of Poincaré plot parameters (SD1, SD2, and SD1/SD2 ratio) were performed. RESULTS: In the five-minute interval before PNES, HR significantly (p<0.05) increased (d=2.5), whereas SDANN (d=-0.03) and VLF power (d=-0.05) significantly decreased. During PNES, significant increases in HF power (d=0.0006), SD1 (d=0.031), and SD2 (d=0.016) were observed. In the five-minute interval immediately following PNES, SDANN (d=0.046) and VLF power (d=0.073) significantly increased, and HR (d=-5.1) and SD1/SD2 ratio (d=-0.14) decreased, compared to the interval preceding PNES. CONCLUSION: The results suggest that PNES episodes are preceded by increased sympathetic functioning, which is followed by an increase in parasympathetic functioning during and after PNES. Future research needs to identify the exact nature of the increased arousal that precedes PNES.

Are Epilepsy-Related fMRI Components Dependent on the Presence of Interictal Epileptic Discharges in Scalp EEG?

Spatial independent component analysis (ICA) is increasingly being used to extract resting-state networks from fMRI data. Previous studies showed that ICA also reveals independent components (ICs) related to the seizure onset zone. However, it is currently unknown how these epileptic ICs depend on the presence of interictal epileptic discharges (IEDs) in the EEG. The goal of this study was to explore the relation between ICs obtained from fMRI epochs during the occurrence of IEDs in the EEG and those without IEDs. fMRI data sets with co-registered EEG were retrospectively selected of patients from whom the location of the epileptogenic zone was confirmed by outcome of surgery (n = 8). The fMRI data were split into two epochs: one with IEDs visible in scalp EEG and one without. Spatial ICA was applied to the fMRI data of each part separately. The maps of all resulting components were compared to the resection area and the EEG-fMRI correlation pattern by computing a spatial correlation coefficient to detect the epilepsy-related component. For all patients, except one, there was a remarkable resemblance between the epilepsy-related components selected during epochs with IEDs and those without IEDs. These findings suggest that epilepsy-related ICs are not dependent on the presence of IEDs in scalp EEG. Since these epileptic ICs showed partial overlap with resting-state networks of healthy volunteers (n = 10), our study supports the need for new ways to classify epileptic ICs.

Resting-state networks and dissociation in psychogenic non-epileptic seizures.

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are epilepsy-like episodes which have an emotional rather than organic origin. Although PNES have often been related to the process of dissociation, the psychopathology is still poorly understood. To elucidate underlying mechanisms, the current study applied independent component analysis (ICA) on resting-state fMRI to investigate alterations within four relevant networks, associated with executive, fronto-parietal, sensorimotor, and default mode activation, and within a visual network to examine specificity of between-group differences. METHODS: Twenty-one patients with PNES without psychiatric or neurologic comorbidities and twenty-seven healthy controls underwent resting-state functional MR imaging at 3.0T (Philips Achieva). Additional neuropsychological testing included Raven's Matrices test and dissociation questionnaires. ICA with dual regression was used to identify resting-state networks in all participants, and spatial maps of the networks of interest were compared between patients and healthy controls. RESULTS: Patients displayed higher dissociation scores, lower cognitive performance and increased contribution of the orbitofrontal, insular and subcallosal cortex in the fronto-parietal network; the cingulate and insular cortex in the executive control network; the cingulate gyrus, superior parietal lobe, pre- and postcentral gyri and supplemental motor cortex in the sensorimotor network; and the precuneus and (para-) cingulate gyri in the default-mode network. The connectivity strengths within these regions of interest significantly correlated with dissociation scores. No between-group differences were found within the visual network, which was examined to determine specificity of between-group differences. CONCLUSIONS: PNES patients displayed abnormalities in several resting-state networks that provide neuronal correlates for an underlying dissociation mechanism.

Neurophysiological correlates of dissociative symptoms.

OBJECTIVE: Dissociation is a mental process with psychological and somatoform manifestations, which is closely related to hypnotic suggestibility and essentially shows the ability to obtain distance from reality. An increased tendency to dissociate is a frequently reported characteristic of patients with functional neurological symptoms and syndromes (FNSS), which account for a substantial part of all neurological admissions. This review aims to investigate what heart rate variability (HRV), EEG and neuroimaging data (MRI) reveal about the nature of dissociation and related conditions. METHODS: Studies reporting HRV, EEG and neuroimaging data related to hypnosis, dissociation and FNSS were identified by searching the electronic databases Pubmed and ScienceDirect. RESULTS: The majority of the identified studies concerned the physiological characteristics of hypnosis; relatively few investigations on dissociation related FNSS were identified. General findings were increased parasympathetic functioning during hypnosis (as measured by HRV), and lower HRV in patients with FNSS. The large variety of EEG and functional MRI investigations with diverse results challenges definite conclusions, but evidence suggests that subcortical as well as (pre)frontal regions serve emotion regulation in dissociative conditions. Functional connectivity analyses suggest the presence of altered brain networks in patients with FNSS, in which limbic areas have an increased influence on motor preparatory regions. CONCLUSIONS: HRV, EEG and (functional) MRI are sensitive methods to detect physiological changes related to dissociation and dissociative disorders such as FNSS, and can possibly provide more information about their aetiology. The use of such measures could eventually provide biomarkers for earlier identification of patients at risk and appropriate treatment of dissociative conditions.

EEG-fMRI correlation patterns in the presurgical evaluation of focal epilepsy: a comparison with electrocorticographic data and surgical outcome measures.

EEG-correlated functional MRI (EEG-fMRI) visualizes brain regions associated with interictal epileptiform discharges (IEDs). This technique images the epileptiform network, including multifocal, superficial and deeply situated cortical areas. To understand the role of EEG-fMRI in presurgical evaluation, its results should be validated relative to a gold standard. For that purpose, EEG-fMRI data were acquired for a heterogeneous group of surgical candidates (n=16) who were later implanted with subdural grids and strips (ECoG). The EEG-fMRI correlation patterns were systematically compared with brain areas involved in IEDs ECoG, using a semi-automatic analysis method, as well as to the seizure onset zone, resected area, and degree of seizure freedom. In each patient at least one of the EEG-fMRI areas was concordant with an interictally active ECoG area, always including the early onset area of IEDs in the ECoG data. This confirms that EEG-fMRI reflects a pattern of onset and propagation of epileptic activity. At group level, 76% of the BOLD regions that were covered with subdural grids, were concordant with interictally active ECoG electrodes. Due to limited spatial sampling, 51% of the BOLD regions were not covered with electrodes and could, therefore, not be validated. From an ECoG perspective it appeared that 29% of the interictally active ECoG regions were missed by EEG-fMRI and that 68% of the brain regions were correctly identified as inactive with EEG-fMRI. Furthermore, EEG-fMRI areas included the complete seizure onset zone in 83% and resected area in 93% of the data sets. No clear distinction was found between patients with a good or poor surgical outcome: in both patient groups, EEG-fMRI correlation patterns were found that were either focal or widespread. In conclusion, by comparison of EEG-fMRI with interictal invasive EEG over a relatively large patient population we were able to show that the EEG-fMRI correlation patterns are spatially accurate at the level of neurosurgical units (i.e. anatomical brain regions) and reflect the underlying network of IEDs. Therefore, we expect that EEG-fMRI can play an important role for the determination of the implantation strategy.