Abstract 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.
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.
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.
PHQ-9 was translated to Kinyarwanda using translation-back translation and validated by a discussion group. For validation, PwE of greater than or equal to15 years of age were administered the PHQ-9 ...and Hamilton Depression Rating Scale (HDRS) by trained psychiatry staff at Visit 1. A random sample of 20% repeated PHQ-9 and HDRS after 14 days to assess temporal stability and intra-rater reliability. Internal structure, reliability and external validity were assessed using confirmatory factor analysis, reliability coefficients and HDRS-correlation, respectively. Maximal Youden's index was considered for cut-offs. Four hundred and thirty-four PwE, mean age 30.5 years (SD ±13.3), were included of whom 33.6%, 37.9%, 13.4%, and 15.1% had no, mild, moderate and severe depression, respectively. PHQ-9 performed well on a one-factor model (unidimensional model), with factor loadings of 0.63-0.86. Reliability coefficients above 0.80 indicated strong internal consistency. Good temporal stability was observed (0.79 95% CI: 0.68-0.87). A strong correlation (R = 0.66, p = 0.01) between PHQ-9 and HDRS summed scores demonstrated robust external validity. The optimal cut-off for the PHQ-9 was similar (greater than or equal to5) for mild and moderate depression and greater than or equal to7 for severe depression. PHQ-9 validation in Kinyarwanda creates the capacity to screen PwE in Rwanda at scores of greater than or equal to5 for mild or moderate and greater than or equal to7 for severe depression. The availability of validated tools for screening and diagnosis for depression is a forward step for holistic care in a resource-limited environment.
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.
Neurostimulation is becoming an increasingly accepted treatment alternative for patients with drug-resistant epilepsy (DRE) who are unsuitable surgery candidates. Standardized guidelines on when or ...how to use the various neurostimulation modalities are lacking. We conducted a systematic review on the currently available neurostimulation modalities primarily with regard to effectiveness and safety.
For vagus nerve stimulation (VNS), there is moderate-quality evidence for its effectiveness in adults with drug-resistant partial epilepsies. Moderate-to-low-quality evidence supports the efficacy and safety of deep brain stimulation (DBS) and responsive neurostimulation (RNS) in patients with DRE. There is moderate-to-very low-quality evidence that transcranial direct current stimulation (tDCS) is effective or well tolerated. For transcutaneous vagus nerve stimulation (tVNS), transcranial magnetic stimulation (TMS) and trigeminal nerve stimulation (TNS), there are insufficient data to support the efficacy of any of these modalities for DRE. These treatment modalities, nevertheless, appear well tolerated, with no severe adverse events reported.
Head-to-head comparison of treatment modalities such as VNS, DBS and RNS across different epileptic syndromes are required to decide which treatment modality is the most effective for a given patient scenario. Such studies are challenging and it is unlikely that data will be available in the near future. Additional data collection on potentially promising noninvasive neurostimulation modalities like tVNS, TMS, TNS and tDCS is warranted to get a more precise estimate of their therapeutic benefit and long-term safety.
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.
Summary
This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League ...Against Epilepsy (CEA‐ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures‐Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patient's representatives. Discussions should include a careful risk–benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first‐line treatment for focal epilepsy. (5) Valproate may be offered as a first‐line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic–clonic seizures. (6) Valproate may be offered as a first‐line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls taking valproate require regular follow‐up for ongoing consideration of the most appropriate treatment regimen.
Today, neuroimaging techniques are frequently used to investigate the integration of functionally specialized brain regions in a network. Functional connectivity, which quantifies the statistical ...dependencies among the dynamics of simultaneously recorded signals, allows to infer the dynamical interactions of segregated brain regions. In this review we discuss how the functional connectivity patterns obtained from intracranial and scalp electroencephalographic (EEG) recordings reveal information about the dynamics of the epileptic brain and can be used to predict upcoming seizures and to localize the seizure onset zone. The added value of extracting information that is not visibly identifiable in the EEG data using functional connectivity analysis is stressed. Despite the fact that many studies have showed promising results, we must conclude that functional connectivity analysis has not made its way into clinical practice yet.
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.
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.
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.
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.
PDF
