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.

The COVID-19 pandemic and neurology: A survey on previous and continued restrictions for clinical practice, curricular training, and health economics.

BACKGROUND AND PURPOSE: The COVID-19 pandemic has significantly impacted health systems worldwide. Here, we assessed the pandemic's impact on clinical service, curricular training, and financial burden from a neurological viewpoint during the enforced lockdown periods and the assumed recovery by 2023. METHODS: An online 18-item survey was conducted by the European Academy of Neurology (EAN) NeuroCOVID-19 Task Force among the EAN community. The survey was online between February and March 2023. Questions related to general, demographic, clinical, work, education, and economic aspects. RESULTS: We collected 430 responses from 79 countries. Most health care professionals were aged 35-44 years, with >15 years of work experience. The key findings of their observations were as follows. (i) Clinical services were cut back in all neurological subspecialties during the most restrictive COVID-19 lockdown period. The most affected neurological subspecialties were services for patients with dementia, and neuromuscular and movement disorders. The levels of reduction and the pace of recovery were distinct for acute emergencies and in- and outpatient care. Recovery was slow for sleep medicine, autonomic nervous system disorders, neurorehabilitation, and dementia care. (ii) Student and residency rotations and grand rounds were reorganized, and congresses were converted into a virtual format. Conferences are partly maintained in a hybrid format. (iii) Affordability of neurological care and medication shortage are emerging issues. CONCLUSIONS: Recovery of neurological services up to spring 2023 has been incomplete following substantial disruption of neurological care, medical education, and health economics in the wake of the COVID-19 pandemic. The continued limitations for the delivery of neurological care threaten brain health and call for action on a global scale.

The European Academy of Neurology NeuroCOVID-19 Task Force: A lesson for the future.

BACKGROUND: The COVID-19 pandemic has made its mark on world history forever causing millions of deaths, and straining health systems, economies, and societies worldwide. The European Academy of Neurology (EAN) reacted promptly. A special NeuroCOVID-19 Task Force was set up at the beginning of the pandemic to promote knowledge, research, international collaborations, and raise awareness about the prevention and treatment of COVID-19-related neurological issues. METHODS: Activities carried out during and after the pandemic by the EAN NeuroCOVID-19 Task Force are described. The main aim was to review all these initiatives in detail as an overarching lesson from the past to improve the present and be better prepared in case of future pandemics. RESULTS: During the pandemic, the Task Force was engaged in several initiatives: the creation of the EAN NEuro-covid ReGistrY (ENERGY); the launch of several surveys (neurological manifestations of COVID-19 infection; the pandemic's impact on patients with chronic neurological diseases; the pandemic's impact of restrictions for clinical practice, curricular training, and health economics); the publication of position papers regarding the management of patients with neurological diseases during the pandemic, and vaccination hesitancy among people with chronic neurological disorders; and the creation of a dedicated "COVID-19 Breaking News" section in EANpages. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force was immediately engaged in various activities to participate in the fight against COVID-19. The Task Force's concerted strategy may serve as a foundation for upcoming global neurological emergencies.

Joint European Academy of Neurology-European Pain Federation-Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment.

BACKGROUND AND PURPOSE: In these guidelines, we aimed to develop evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain (NeP). METHODS: We systematically reviewed studies providing information on the sensitivity and specificity of screening questionnaires, and quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy. We also analysed how functional neuroimaging, peripheral nerve blocks, and genetic testing might provide useful information in diagnosing NeP. RESULTS: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I-DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, and S-LANSS (self-administered LANSS) and PainDETECT weak recommendations for their use in the diagnostic pathway for patients with possible NeP. We devised a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials in the NeP diagnosis. Trigeminal reflex testing received a strong recommendation in diagnosing secondary trigeminal neuralgia. Although many studies support the usefulness of corneal confocal microscopy in diagnosing peripheral neuropathy, no study specifically investigated the diagnostic accuracy of this technique in patients with NeP. Functional neuroimaging and peripheral nerve blocks are helpful in disclosing pathophysiology and/or predicting outcomes, but current literature does not support their use for diagnosing NeP. Genetic testing may be considered at specialist centres, in selected cases. CONCLUSIONS: These recommendations provide evidence-based clinical practice guidelines for NeP diagnosis. Due to the poor-to-moderate quality of evidence identified by this review, future large-scale, well-designed, multicentre studies assessing the accuracy of diagnostic tests for NeP are needed.

Association between CSF biomarkers of Alzheimer's disease and neuropsychiatric symptoms: Mayo Clinic Study of Aging.

INTRODUCTION: We examined the association between cerebrospinal fluid (CSF)-derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms (NPS) in older non-demented adults. METHODS: We included 784 persons (699 cognitively unimpaired, 85 with mild cognitive impairment) aged ≥ 50 years who underwent CSF amyloid beta (Aß42), hyperphosphorylated tau 181 (p-tau), and total tau (t-tau) as well as NPS assessment using Beck Depression and Anxiety Inventories (BDI-II, BAI), and Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS: Lower CSF Aß42, and higher t-tau/Aß42 and p-tau/Aß42 ratios were associated with BDI-II and BAI total scores, clinical depression (BDI-II ≥ 13), and clinical anxiety (BAI ≥ 10), as well as NPI-Q-assessed anxiety, apathy, and nighttime behavior. DISCUSSION: CSF Aß42, t-tau/Aß42, and p-tau/Aß42 ratios were associated with NPS in community-dwelling individuals free of dementia. If confirmed by a longitudinal cohort study, the findings have clinical relevance of taking into account the NPS status of individuals with abnormal CSF biomarkers.

The Importance of Subjective Cognitive Decline Recognition and the Potential of Molecular and Neurophysiological Biomarkers-A Systematic Review.

Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are early stages of Alzheimer's disease (AD). Neurophysiological markers such as electroencephalography (EEG) and event-related potential (ERP) are emerging as alternatives to traditional molecular and imaging markers. This paper aimed to review the literature on EEG and ERP markers in individuals with SCD. We analysed 30 studies that met our criteria, with 17 focusing on resting-state or cognitive task EEG, 11 on ERPs, and two on both EEG and ERP parameters. Typical spectral changes were indicative of EEG rhythm slowing and were associated with faster clinical progression, lower education levels, and abnormal cerebrospinal fluid biomarkers profiles. Some studies found no difference in ERP components between SCD subjects, controls, or MCI, while others reported lower amplitudes in the SCD group compared to controls. Further research is needed to explore the prognostic value of EEG and ERP in relation to molecular markers in individuals with SCD.

Mapping of European activities on the integration of sex and gender factors in neurology and neuroscience.

BACKGROUND: Neurological disorders pose a profound unmet medical need for which new solutions are urgently needed. The consideration of both biological (sex) and socio-cultural (gender) differences between men and women is necessary to identify more efficacious, safer and tailored treatments. Approaches for putting sex and gender medicine into practice have gathered momentum across Europe, but it is currently unclear to what extent they have been implemented in the field of neurology and neuroscience. METHODS: We mapped current activities in research, funding and education aimed at integrating sex and gender consideration in neuroscience and neurology in Europe. We examined and analyzed data gathered from (1) literature searches, (2) policy documents and reports by the European Commission and national funding agencies, (3) web-based searches, (4) "Web of Science", and (5) searches of project databases of funding agencies. An informative / non-systematic search was performed for sections on policies and funding, education, basic research, while a systematic literature and database review was conducted forquantitative analysis of research output and funded projects in terms of sex and gender analysis. RESULTS: Our mapping shows that there is a growing interest and attention towards sex and gender consideration in neurological fields, both from funding agencies and researchers. However, most activities, especially for education, are limited to the individual motivation of researchers and are not organically built within curricula and strategic research priorities. DISCUSSION: We recommend actions that might help increase the consideration of sex and gender specifically in the field of neuroscience and neurology.

COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper.

BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course. METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation. RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.

European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases.

BACKGROUND AND PURPOSE: Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. METHODS: A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. RESULTS: The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. CONCLUSIONS: This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

Diagnosis, management and impact on patients' lives of cancer-related neuropathic pain (CRNP): A European survey.

OBJECTIVE: This study assessed the impact of cancer-related neuropathic pain (CRNP) on patients and the importance of the patient-healthcare professional (HCP) relationship in diagnosis and management. METHODS: A quantitative online survey was conducted involving adult patients from 13 European countries who had been diagnosed with treatable cancer and experienced symptoms of peripheral neuropathy. RESULTS: Of 24,733 screened respondents, 549 eligible persons met the inclusion criteria and completed the questionnaire. Among individuals still experiencing pain, 75% rated it as 'severe' or 'moderate'. In addition, 61% reported a negative impact on day-to-day activities, and 30% said they had stopped working as a result. A third of respondents had received no diagnosis of CRNP despite reporting painful symptoms to an HCP. HCPs spending enough time discussing pain and understanding the impact on patients' lives were each associated with an increased likelihood of a formal CRNP diagnosis. Compared with individuals currently in active cancer treatment, cancer survivors were less likely to have a diagnosis of CRNP or regular pain conversations with HCPs. CONCLUSION: CRNP remains under-recognised despite its substantial impact on patients' lives. Clinical practice may be improved by strengthening patient-HCP relationships around pain discussions and increasing the focus on pain management among cancer survivors.

Awakening to sleep disorders in Europe: Survey on education, knowledge and treatment competence of European residents and neurologists.

OBJECTIVES: Sleep-wake disorders are common in the general population and in most neurological disorders but are often poorly recognized. With the hypothesis that neurologists do not get sufficient training during their residency, the Young European Sleep Neurologist Association (YESNA) of the European Academy of Neurology (EAN) performed a survey on postgraduate sleep education. METHODS: A 16-item questionnaire was developed and distributed among neurologists and residents across European countries. Questions assessed demographic, training and learning preferences in sleep disorders, as well as a self-evaluation of knowledge based on five basic multiple-choice questions (MCQs) on sleep-wake disorders. RESULTS: The questionnaire was completed by 568 participants from 20 European countries. The mean age of participants was 31.9 years (SD 7.4 years) and was composed mostly of residents (73%). Three-quarters of the participants reported undergraduate training in sleep medicine, while fewer than 60% did not receive any training on sleep disorders during their residencies. Almost half of the participants (45%) did not feel prepared to treat neurological patients with sleep problems. Only one-third of the participants correctly answered at least three MCQs. Notably, 80% of participants favoured more education on sleep-wake disorders during the neurology residency. CONCLUSIONS: Education and knowledge on disorders in European neurological residents is generally insufficient, despite a strong interest in the topic. The results of our study may be useful for improving the European neurology curriculum and other postgraduate educational programmes.

A plea for equitable global access to COVID-19 diagnostics, vaccination and therapy: The NeuroCOVID-19 Task Force of the European Academy of Neurology.

Coronavirus disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID-19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID-19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long-term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID-19 Task Force intends to raise awareness of the potential impact of COVID-19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.

Association of Cortical and Subcortical ß-Amyloid With Standardized Measures of Depressive and Anxiety Symptoms in Adults Without Dementia.

OBJECTIVE: The purpose of this study was to test the hypothesis that subcortical ß-amyloid (Aß) deposition was associated with elevated scores on standardized measures of depressive and anxiety symptoms when compared with cortical (Aß) deposition in persons without dementia. METHODS: The authors performed a cross-sectional study, derived from the population-based Mayo Clinic Study of Aging, comprising participants aged ≥70 years (N=1,022; 55% males; 28% apolipoprotein E [APOE] ε4 carriers; without cognitive impairment, N=842; mild cognitive impairment; N=180). To assess Aß deposition in cortical and subcortical (the amygdala, striatum, and thalamus) regions, participants underwent Pittsburgh Compound B positron emission tomography (PiB-PET) and completed the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). The investigators ran linear regression models to examine the association between PiB-PET standardized uptake value ratios (SUVRs) in the neocortex and subcortical regions and depressive and anxiety symptoms (BDI-II and BAI total scores). Models were adjusted for age, sex, education level, and APOE ε4 carrier status and stratified by cognitive status (without cognitive impairment, mild cognitive impairment). RESULTS: Cortical PiB-PET SUVRs were associated with depressive symptoms (ß=0.57 [SE=0.13], p<0.001) and anxiety symptoms (ß=0.34 [SE=0.13], p=0.011). PiB-PET SUVRs in the amygdala were associated only with depressive symptoms (ß=0.80 [SE=0.26], p=0.002). PiB-PET SUVRs in the striatum and thalamus were associated with depressive symptoms (striatum: ß=0.69 [SE=0.18], p<0.001; thalamus: ß=0.61 [SE=0.24], p=0.011) and anxiety symptoms (striatum: ß=0.56 [SE=0.18], p=0.002; thalamus: ß=0.65 [SE=0.24], p=0.008). In the mild cognitive impairment subsample, Aß deposition, regardless of neuroanatomic location, was associated with depressive symptoms but not anxiety symptoms. CONCLUSIONS: Elevated amyloid deposition in cortical and subcortical brain regions was associated with higher depressive and anxiety symptoms, although these findings did not significantly differ by cortical versus subcortical Aß deposition. This cross-sectional observation needs to be confirmed by a longitudinal study.

Clock Drawing Test: A Simple Scoring System for the Accurate Screening of Cognitive Impairment in Patients with Mild Cognitive Impairment and Dementia.

BACKGROUND/AIM: The Clock Drawing Test (CDT) is a valid alternative screening tool to the Mini-Mental State Examination (MMSE) and, crucially, it may be completed faster. The aim of our study was to standardize and simplify the CDT scoring system for screening in three common conditions: mild cognitive impairment (MCI), Alzheimer's disease (AD) and mixed dementia (MD). METHODS: We included 188 subjects (43 healthy volunteers, 49 patients with MCI, 54 patients with AD, and 42 patients with MD), who performed the MMSE and CDT. The CDT was evaluated using a modified 4-point scoring system. RESULTS: The healthy subjects had the highest median values for the MMSE and CDT, followed by patients with MCI, AD and MD. The optimal cut-off for all patients and each patient group separately was 3 out of 4 points. Sensitivity was 89% for AD, 93% for MD and 83% for all patients, while specificity was 91%. The MMSE produced similar results. In comparison to the MMSE, sensitivity for MCI was significantly higher using the CDT (20 vs. 69%, respectively). CONCLUSION: A simple, 4-point scoring system may be used as a screening method for fast and accurate detection of cognitive impairment in patients with MCI, AD and MD.

Separating the Idea from the Action: A sLORETA Study.

Simple imaginary movements activate similar cortical and subcortical areas to actual movements, chiefly in the sensory-motor network. However, only a few studies also examined the imagery of more skilful movements such as reaching. Ten volunteers performed reaching movements or imagined the same movements. EEG was simultaneously recorded and analysed with sLORETA, which compared the preparation for actual and imagined reaching with respect to their baseline and between tasks. Major differences between them were found at three time intervals after target presentation, always in favour of the actual reaching condition. The first one was from 160 to 220 msec in the frontal and parietal regions. The second difference was evident from 220 to 320 msec in the premotor cortex. The third difference was evident from 320 msec, mainly in the perirolandic region. Also, the anterior and posterior cingulate cortices were widely involved, in both tasks. We suggest the existence of two separate systems which may work together during actual reaching programming. The first one involves structures such as the premotor cortex, supplementary motor area and primary motor cortex, together with the parietal and occipital cortex. This system may integrate extrinsic target coordinates with proprioceptive information from the reaching arm and pre-stored programs in the associative motor cortex. It is activated strongly and involves more cortical areas in actual than imagined reaching. The second system, common to both tasks, involves anterior and posterior cingulate cortices, with the possible role of contributing awareness and focusing the various components of the process.

The diabetic brain and cognition.

The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders cannot be neglected. Therefore, early diagnosis of metabolic parameters including those relevant for T2DM is required. Moreover, it is possible that therapeutic options utilized today for diabetes treatment may also have an effect on the risk for dementia. T2DM/IRBS contribute to pathological processes in AD and VaD.

Assessment of the haptic robot as a new tool for the study of the neural control of reaching.

Current experimental methods for the study of reaching in the MRI environment do not exactly mimic actual reaching, due to constrains in movement which are imposed by the MRI machine itself. We tested a haptic robot (HR) as such a tool. Positive results would also be promising for combined use of fMRI and EEG to study reaching. Twenty right-handed subjects performed reaching tasks with their right hand with and without the HR. Reaction time, movement time (MT), accuracy, event-related potentials (ERPs) and event-related desynchronisation/synchronisation (ERD/ERS) were studied. Reaction times and accuracies did not differ significantly between the two tasks, while the MT was significantly longer in HR reaching (959 vs. 447 ms). We identified two positive and two negative ERP peaks across all leads in both tasks. The latencies of the P1 and N2 peaks were significantly longer in HR reaching, while there were no significant differences in the P3 and N4 latencies. ERD/ERS topographies were similar between tasks and similar to other reaching studies. Main difference was in ERS rebound which was observed only in actual reaching. Probable reason was significantly larger MT. We found that reaching with the HR engages similar neural structures as in actual reaching. Although there are some constrains, its use may be superior to other techniques used for reaching studies in the MRI environment, where freedom of movement is limited.

Cognitive impairment in people with epilepsy: Montreal Cognitive Assessment (MoCA) as a screening tool.

OBJECTIVES: Although cognitive impairment is common in people with epilepsy, it is often neglected in outpatient clinics. MoCA is a simple and reliable test, which was validated for the cognitive screening of Alzheimer's and vascular dementia. The aim of our study was to evaluate MoCA as a tool for a cognitive screening of people with epilepsy. METHODS: Our study included 50 people with epilepsy and 46 healthy individuals. All participants took the Slovenian version of the MoCA. Mean age, education and MoCA scores were compared between the two groups. RESULTS: There was no significant difference between people with epilepsy and the controls in age (47.6, SD 18.1 vs 50.9, SD 14.0 years) or education (12.8, SD 2.8 vs 13.4, SD 2.8 years). People with epilepsy had significantly lower total MoCA scores than did the controls (23.3, SD 4.5 vs 27.5, SD 1.9 points; p < 0.001). CONCLUSIONS: People with epilepsy achieved a lower score in several cognitive domains compared to the control group. MoCA can be used as an appropriate screening tool for cognitive impairment in people with epilepsy in the outpatient clinic. For a more accurate evaluation, neuropsychological assessments should be used.