Brain health and national neurological societies: Results of the European Academy of Neurology survey on brain health awareness and areas of implementation for European countries.

BACKGROUND AND PURPOSE: The European Academy of Neurology (EAN) has adhered to the global plan for reducing the burden of neurological disorders and promoting brain health launched by the World Health Organisation (WHO), the WHO Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders. This study reports the results of an EAN survey among national neurological societies (NNSs) on their awareness of brain health policies. METHODS: The EAN survey on the current state of national brain health policies was conducted among the 47 presidents of the NNSs affiliated with the EAN, with the aim of developing the best strategy for close collaboration among stakeholders. RESULTS: From June 2023 to February 2024, 36/47 responses (77%) were collected. Among respondents, 67% were in contact with their Ministry of Health and 78% were aware of and in contact with one or more national neurological patient organisation, while 17% had no contacts with any association. Ninety-two percent declared a high to medium degree of awareness of the need to support brain health and of brain health plans and strategies in their country. CONCLUSIONS: Our findings suggest good awareness of the importance of brain health and of the strategies implemented at the national level among the EAN-affiliated NNSs and representatives. Efforts towards improvement may be directed towards cooperation between NNSs and political institutions, as well as patient organisations, to optimise brain and global public health and neurological care in each country.

European Academy of Neurology: First 10 years.

The European Academy of Neurology (EAN) was founded in May 2014 as the scientific society of all neurologists and all national neurological societies in Europe. The creation of EAN was based on the conscious decision of two predecessor societies (the European Federation of Neurological Societies and the European Neurological Society) to have a unique society for this continent with its 53 countries according to the World Health Organization and with the EU as the most important continental political decision level. In this report, the important milestones and the motivations of the decision-makers during the first 10 years are described. The development of the annual congress, the broad educational agenda, and the scientific groundwork including the European guidelines for the practise of neurology are described. Collaboration with and work for the national neurological societies is an important task for EAN. The political representation of neurology in Brussels and collaboration with the scientific societies of neighbouring medical disciplines and patient organizations are other major tasks on the agenda of the organization. EAN's goal is to reduce the burden of neurological diseases and to be the "home of neurology" in Europe for physicians, patients, and society. EAN communicates and interacts with its members, patients, partners, politicians, and the public through different channels. EAN is the owner of the scientifically independent European Journal of Neurology. EAN is based in Vienna, where its head office is located, but is also strongly represented in Brussels.

Unravelling the origin of the reward positivity: a human intracranial event-related brain potential study.

The reward positivity (RewP) is an event-related brain potential (ERP) component that emerges approximately 250 to 350 milliseconds (ms) after receiving reward-related feedback stimuli and is believed to be important for reinforcement learning and reward processing. Although numerous localization studies have indicated that the anterior cingulate cortex (ACC) is the neural generator of this component, other studies have identified sources outside of the ACC, fuelling a debate about its origin. Because the results of EEG and MEG source localization studies are severely limited by the inverse problem, we addressed this question by leveraging the high spatial and temporal resolution of intracranial EEG. We predicted that we would identify a neural generator of the RewP in the caudal ACC. We recorded intracranial EEG in 19 refractory epilepsy patients who underwent invasive video-EEG monitoring at Ghent University Hospital, Belgium. Participants engaged in the virtual T-maze task (vTMT), a trial-and-error task known to elicit a canonical RewP, while scalp and intracranial EEG were simultaneously recorded. The RewP was identified using a difference wave approach for both scalp and intracranial EEG. The data were aggregated across participants to create a virtual "meta-participant" that contained all the recorded intracranial ERPs (iERPs) with respect to their intracranial contact locations. We used both a hypothesis-driven (focused on ACC) and exploratory (whole-brain analysis) approach to segment the brain into regions of interest (ROI). For each ROI, we evaluated the degree to which the time course of the absolute current density (ACD) activity mirrored the time course of the RewP, and confirmed the statistical significance of the results using permutation analysis. The grand average waveform of the scalp data revealed a RewP at 309 ms after reward feedback with a frontocentral scalp distribution, consistent with the identification of this component as the RewP. The meta-participant contained iERPs recorded from 582 intracranial contacts in total. The ACD activity of the aggregated iERPs were most similar to the RewP in left caudal ACC, left dorsolateral prefrontal cortex, left frontomedial cortex, and left white matter, with the highest score attributed to caudal ACC, as predicted. To our knowledge, this is the first study that uses intracranial EEG aggregated across multiple human epilepsy patients and current source density analysis to identify the neural generator(s) of the RewP. These results provide direct evidence that the ACC is a neural generator of the RewP.

Imagined speech event detection from electrocorticography and its transfer between speech modes and subjects.

Speech brain-computer interfaces aim to support communication-impaired patients by translating neural signals into speech. While impressive progress was achieved in decoding performed, perceived and attempted speech, imagined speech remains elusive, mainly due to the absence of behavioral output. Nevertheless, imagined speech is advantageous since it does not depend on any articulator movements that might become impaired or even lost throughout the stages of a neurodegenerative disease. In this study, we analyzed electrocortigraphy data recorded from 16 participants in response to 3 speech modes: performed, perceived (listening), and imagined speech. We used a linear model to detect speech events and examined the contributions of each frequency band, from delta to high gamma, given the speech mode and electrode location. For imagined speech detection, we observed a strong contribution of gamma bands in the motor cortex, whereas lower frequencies were more prominent in the temporal lobe, in particular of the left hemisphere. Based on the similarities in frequency patterns, we were able to transfer models between speech modes and participants with similar electrode locations.

Investigating the Working Mechanism of Transcranial Direct Current Stimulation.

BACKGROUND: Transcranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates tDCS-induced modulation of the corticospinal excitability and the underlying MOA. By anesthetizing the scalp before applying tDCS and by stimulating the cheeks, we investigated whether stimulation of peripheral and/or cranial nerves contributes to the effects of tDCS on corticospinal excitability. MATERIALS AND METHODS: In a randomized cross-over study, four experimental conditions with anodal direct current stimulation were compared in 19 healthy volunteers: 1) tDCS over the motor cortex (tDCS-MI), 2) tDCS over the motor cortex with a locally applied topical anesthetic (TA) on the scalp (tDCS-MI + TA), 3) DCS over the cheek region (DCS-C), and 4) sham tDCS over the motor cortex(sham). tDCS was applied for 20 minutes at 1 mA. Motor evoked potentials (MEPs) were measured before tDCS and immediately, 15, 30, 45, and 60 minutes after tDCS. A questionnaire was used to assess the tolerability of tDCS. RESULTS: A significant MEP amplitude increase compared with baseline was found 30 minutes after tDCS-MI, an effect still observed 60 minutes later; no time∗condition interaction effect was detected. In the other three conditions (tDCS-MI + TA, DCS-C, sham), no significant MEP modulation was found. The questionnaire indicated that side effects are significantly lower when the local anesthetic was applied before stimulation than in the other three conditions. CONCLUSIONS: The significant MEP amplitude increase observed from 30 minutes on after tDCS-MI supports the modulatory effect of tDCS on corticospinal neurotransmission. This effect lasted one hour after stimulation. The absence of a significant modulation when a local anesthetic was applied suggests that effects of tDCS are not solely established through direct cortical stimulation but that stimulation of peripheral and/or cranial nerves also might contribute to tDCS-induced modulation.

Long-term evaluation of anterior thalamic deep brain stimulation for epilepsy in the European MORE registry.

OBJECTIVE: Short-term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) were reported for people with drug-resistant focal epilepsy (PwE). Because long-term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT-DBS. METHODS: In this multicenter registry, PwE with ANT-DBS were followed up for safety, efficacy, and battery longevity. Follow-up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. RESULTS: Of 170 eligible PwE, 104, 62, and 49 completed the 3-, 4-, and 5-year follow-up, respectively. Most discontinuations (68%) were due to planned study closure as follow-up beyond 2 years was optional. The 5-year follow-up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5-year follow-up (p < .001), with most-pronounced effects on focal-to-bilateral tonic-clonic seizures (n = 15, 77% reduction, p = .008). At last follow-up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (p = .035) and a negative history of epilepsy surgery (p = .002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS-related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT-DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. SIGNIFICANCE: MORE provides further evidence for the long-term application of ANT-DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management.

Exploration of Theta Burst-Induced Modulation of Transcranial Magnetic Stimulation-Evoked Potentials Over the Motor Cortex.

OBJECTIVES: This study investigates the way theta burst stimulation (TBS) applied to the motor cortex (M1) affects TMS-evoked potentials (TEPs). There have been few direct comparisons of continuous TBS (cTBS) and intermittent TBS (iTBS), and there is a lack of consensus from existing literature on the induced effects. We performed an exploratory trial to assess the effect of M1-cTBS and M1-iTBS on TEP components. MATERIALS AND METHODS: In a cross-over design, 15 participants each completed three experimental sessions with ≥one week in between sessions. The effect of a single TBS train administered over M1 was investigated using TEPs recorded at the same location, 20 to 30 minutes before and in the first 10 minutes after the intervention. In each session, a different type of TBS (cTBS, iTBS, or active control cTBS) was administered in a single-blinded randomized order. For six different TEP components (N15, P30, N45, P60, N100, and P180), amplitude was compared before and after the intervention using cluster-based permutation (CBP) analysis. RESULTS: We were unable to identify a significant modulation of any of the six predefined M1 TEP components after a single train of TBS. When waiving statistical correction for multiple testing in view of the exploratory nature of the study, the CBP analysis supports a reduction of the P180 amplitude after iTBS (p = 0.015), whereas no effect was observed after cTBS or in the active control condition. The reduction occurred in ten of 15 subjects, showing intersubject variability. CONCLUSIONS: The observed decrease in the P180 amplitude after iTBS may suggest a neuromodulatory effect of iTBS. Despite methodologic issues related to our study and the potential sensory contamination within this latency range of the TEP, we believe that our finding deserves further investigation in hypothesis-driven trials of adequate power and proper design, focusing on disentanglement between TEPs and peripherally evoked potentials, in addition to indicating reproducibility across sessions and subjects. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05206162.

Vagus nerve stimulation enhances remyelination and decreases innate neuroinflammation in lysolecithin-induced demyelination.

BACKGROUND: Current treatments for Multiple Sclerosis (MS) poorly address chronic innate neuroinflammation nor do they offer effective remyelination. The vagus nerve has a strong regulatory role in inflammation and Vagus Nerve Stimulation (VNS) has potential to affect both neuroinflammation and remyelination in MS. OBJECTIVE: This study investigated the effects of VNS on demyelination and innate neuroinflammation in a validated MS rodent model. METHODS: Lysolecithin (LPC) was injected in the corpus callosum (CC) of 46 Lewis rats, inducing a demyelinated lesion. 33/46 rats received continuously-cycled VNS (cVNS) or one-minute per day VNS (1minVNS) or sham VNS from 2 days before LPC-injection until perfusion at 3 days post-injection (dpi) (corresponding with a demyelinated lesion with peak inflammation). 13/46 rats received cVNS or sham from 2 days before LPC-injection until perfusion at 11 dpi (corresponding with a partial remyelinated lesion). Immunohistochemistry and proteomics analyses were performed to investigate the extend of demyelination and inflammation. RESULTS: Immunohistochemistry showed that cVNS significantly reduced microglial and astrocytic activation in the lesion and lesion border, and significantly reduced the Olig2+ cell count at 3 dpi. Furthermore, cVNS significantly improved remyelination with 57.4 % versus sham at 11 dpi. Proteomic gene set enrichment analyses showed increased activation of (glutamatergic) synapse pathways in cVNS versus sham, most pronounced at 3 dpi. CONCLUSION: cVNS improved remyelination of an LPC-induced lesion. Possible mechanisms might include modulation of microglia and astrocyte activity, increased (glutamatergic) synapses and enhanced oligodendrocyte clearance after initial injury.

Ketogenic dietary therapy utilization in Kenya: A qualitative exploration of dietitian's perceptions.

This study utilized a qualitative design to explore dietitians' perceptions regarding Ketogenic Diet Therapy (KDT) for patients with drug-resistant epilepsy in Kenya. Dietitians from Kenya were selected and consented. Audio-recorded interviews were conducted, followed by thematic analysis of verbatim transcripts to identify recurring patterns. The study enrolled 18 dietitians, fourteen of whom correctly described their understanding of KDT for managing drug-resistant epilepsy. There was a lack of confidence in their capacity to initiate the KDT with all expressing the need for further training and facilitation. Only one dietitian reported having initiated and maintained KDT. There was an overall positive view regarding KDT and willingness to implement KDT for patients with drug-resistant epilepsy. Dietitians expressed concerns regarding the availability of national policies, inadequate staffing to support families who require KDT, and the cost of implementing this intervention. Dietitians expressed interest in virtual training to enhance their understanding of KDT. Dietitians in Kenya are mostly aware of KDT utilization for the management of drug-resistant epilepsy. However, they cited poor capability and various barriers to implementation. There is a need for policies to facilitate KDT as a treatment option for the benefit of patients with drug-resistant epilepsy.

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.

General neurology: Current challenges and future implications.

BACKGROUND AND PURPOSE: In the coming decades, the world will face an increasing burden of neurological disorders (ND) and an urgent need to promote brain health. These challenges contrast with an insufficient neurological workforce in most countries, as well as decreasing numbers of general neurologists and neurologists attracted to work in general neurology (GN). This white paper aims to review the current situation of GN and reflect on its future. METHODS: The European Academy of Neurology (EAN) task force (TF) met nine times between November 2021 and June 2023. During the 2023 EAN annual meeting, attendees were asked to answer five questions concerning the future of GN. The document was sent for suggestions and eventually approval to the board and the presidents of the 47 national societies of the EAN. RESULTS: The TF first identified four relevant current and future challenges related to GN: (i) definition, (ii) practice, (iii) education, and (iv) research. The TF then identified seven initiatives to further develop GN at both the academic and community level. Finally, the TF formulated 16 recommendations to promote GN in the future. CONCLUSIONS: GN will remain essential in the coming decades to provide rapid, accessible, and comprehensive management of patients with ND that is affordable and cost-effective. There is also a need for research, education, and other initiatives aiming to facilitate improved working conditions, recognition, and prestige for those pursuing a career in GN.

Current extent and future opportunities for living shorelines in Australia.

Living shorelines aim to enhance the resilience of coastlines to hazards while simultaneously delivering co-benefits such as carbon sequestration. Despite the potential ecological and socio-economic benefits of living shorelines over conventional engineered coastal protection structures, application is limited globally. Australia has a long and diverse coastline that provides prime opportunities for living shorelines using beaches and dunes, vegetation, and biogenic reefs, which may be either natural ('soft' approach) or with an engineered structural component ('hybrid' approach). Published scientific studies, however, have indicated limited use of living shorelines for coastal protection in Australia. In response, we combined a national survey and interviews of coastal practitioners and a grey and peer-reviewed literature search to (1) identify barriers to living shoreline implementation; and (2) create a database of living shoreline projects in Australia based on sources other than scientific literature. Projects included were those that had either a primary or secondary goal of protection of coastal assets from erosion and/or flooding. We identified 138 living shoreline projects in Australia through the means sampled starting in 1970; with the number of projects increasing through time particularly since 2000. Over half of the total projects (59 %) were considered to be successful according to their initial stated objective (i.e., reducing hazard risk) and 18 % of projects could not be assessed for their success based on the information available. Seventy percent of projects received formal or informal monitoring. Even in the absence of peer-reviewed support for living shoreline construction in Australia, we discovered local and regional increases in their use. This suggests that coastal practitioners are learning on-the-ground, however more generally it was stated that few examples of living shorelines are being made available, suggesting a barrier in information sharing among agencies at a broader scale. A database of living shoreline projects can increase knowledge among practitioners globally to develop best practice that informs technical guidelines for different approaches and helps focus attention on areas for further research.

Increased Dentate Gyrus Excitability in the Intrahippocampal Kainic Acid Mouse Model for Temporal Lobe Epilepsy.

The intrahippocampal kainic acid (IHKA) mouse model is an extensively used in vivo model to investigate the pathophysiology of mesial temporal lobe epilepsy (mTLE) and to develop novel therapies for drug-resistant epilepsy. It is characterized by profound hippocampal sclerosis and spontaneously occurring seizures with a major role for the injected damaged hippocampus, but little is known about the excitability of specific subregions. The purpose of this study was to electrophysiologically characterize the excitability of hippocampal subregions in the chronic phase of the induced epilepsy in the IHKA mouse model. We recorded field postsynaptic potentials (fPSPs) after electrical stimulation in the CA1 region and in the dentate gyrus (DG) of hippocampal slices of IHKA and healthy mice using a multielectrode array (MEA). In the DG, a significantly steeper fPSP slope was found, reflecting higher synaptic strength. Population spikes were more prevalent with a larger spatial distribution in the IHKA group, reflecting a higher degree of granule cell output. Only minor differences were found in the CA1 region. These results point to increased neuronal excitability in the DG but not in the CA1 region of the hippocampus of IHKA mice. This method, in which the excitability of hippocampal slices from IHKA mice is investigated using a MEA, can now be further explored as a potential new model to screen for new interventions that can restore DG function and potentially lead to novel therapies for mTLE.

Chronic subthreshold cortical stimulation: A promising therapy for motor cortex seizures.

Chronic subthreshold cortical stimulation (CSCS) is a form of neurostimulation consisting of continuous or cyclic, open-loop, subthreshold electrical stimulation of a well-defined epileptogenic zone (EZ). CSCS has seen limited clinical use but could be a safe and effective long-term treatment of focal drug resistant epilepsy, in particular when the EZ is located in the motor cortex. We present a case of a 49-year-old woman suffering from debilitating focal motor seizures. Treatment with CSCS resulted in significant clinical improvement, enabling her to walk unaided for the first time in years.

Neurostimulation for childhood epilepsy.

The experience with neurostimulation for childhood epilepsy is far less extensive than for adults. Nevertheless, the implementation of these techniques could be of great value, especially considering the detrimental effects of ongoing seizures on the developing brain. In this review, we discuss the available evidence for neurostimulation for childhood epilepsy. Vagus nerve stimulation (VNS) is the most studied neurostimulation modality in children. Based on mostly retrospective, open-label studies, we can conclude that VNS has a similar safety and efficacy profile in children compared to adults. Although there is little available evidence for deep brain stimulation (DBS) and responsive neurostimulation (RNS) in children, both DBS and RNS show promise in reducing seizure frequency with few complications. The implementation of non-invasive techniques with a more appealing safety profile has gained interest. Small randomized control trials and open-label studies have investigated transcranial direct current simulation for childhood epilepsy, demonstrating promising but inconsistent findings.

A strategic neurological research agenda for Europe: Towards clinically relevant and patient-centred neurological research priorities.

BACKGROUND AND PURPOSE: Neurological disorders constitute a significant portion of the global disease burden, affecting >30% of the world's population. This prevalence poses a substantial threat to global health in the foreseeable future. A lack of awareness regarding this high burden of neurological diseases has led to their underrecognition, underappreciation, and insufficient funding. Establishing a strategic and comprehensive research agenda for brain-related studies is a crucial step towards aligning research objectives among all pertinent stakeholders and fostering greater societal awareness. METHODS: A scoping literature review was undertaken by a working group from the European Academy of Neurology (EAN) to identify any existing research agendas relevant to neurology. Additionally, a specialized survey was conducted among all EAN scientific panels, including neurologists and patients, inquiring about their perspectives on the current research priorities and gaps in neurology. RESULTS: The review revealed the absence of a unified, overarching brain research agenda. Existing research agendas predominantly focus on specialized topics within neurology, resulting in an imbalance in the number of agendas across subspecialties. The survey indicated a prioritization of neurological disorders and research gaps. CONCLUSIONS: Building upon the findings from the review and survey, key components for a strategic and comprehensive neurological research agenda in Europe were delineated. This research agenda serves as a valuable prioritization tool for neuroscientific researchers, as well as for clinicians, donors, and funding agencies in the field of neurology. It offers essential guidance for creating a roadmap for research and clinical advancement, ultimately leading to heightened awareness and reduced burden of neurological disorders.

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.