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.

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 Impact of Relapses on Pain and Quality of Life in Patients with Multiple Sclerosis Treated with Corticosteroids.

BACKGROUND: We assessed the prevalence and risks associated with pain during and after a multiple sclerosis (MS) relapse, and the impact of pain on quality of life (QoL), in MS patients. METHODS: 117 patients suffering an acute MS relapse were evaluated with clinician- and patient-reported outcomes, including the expanded disability status scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), and MS Walking scale-12 (MSWS-12). Relapse-related pain was assessed via the short-form 36 (SF-36) questionnaire upon first visit (relapse onset) and at 6 weeks after treatment with intravenous methylprednisolone (follow-up visit). RESULTS: Pain was present in 80% of patients at relapse onset. Patients with pain were more impaired physically (higher mean scores on MSIS-29phys and MSWS-12 and lower mean scores on SF-36 role physical, physical, and vitality scales) at relapse and six weeks after. In total, 74% of patients with MS relapse reported a poorer QoL due to pain. A lower psychological well-being was correlated with greater pain (MSIS29psy score). An increased number of prior relapses was a predictor of more pain at relapse onset. CONCLUSIONS: Pain was common at the time of MS relapse and improved, but was still significant, six weeks after treatment with corticosteroids. Further studies are required to better understand relapse-related pain.

Efficacy of Pregabalin and Duloxetine in Patients with Painful Diabetic Peripheral Neuropathy (PDPN): A Multi-Centre Phase IV Clinical Trial-BLOSSOM.

INTRODUCTION: Our trial (ClinicalTrials.gov Identifier: NCT04246619) evaluates the efficacy of two generic medications, pregabalin and duloxetine, for treating pain in PDPN patients. METHODS: The patients were randomised either into the pregabalin (99) or the duloxetine (102) arm. Pain was evaluated using the DN-4 questionnaire, and visual analogue scales (VASs, 0-100 mm) were used to measure the average pain intensity (API), worst pain intensity (WPI) in the last 24 h and current pain intensity (CPI). RESULTS: The proportion of patients with a clinically significant improvement in the API at Week 12 was 88.3% [CI 81.7%, 94.8%] in the pregabalin arm and 86.9% [CI 76.7%, 97.1%] in the duloxetine arm. After 12 weeks, the CPI, API, and WPI decreased by -35.3 [-40.5, -30.0], -37.0 [-41.4, -32.6], and -41.6 [-46.6, -36.5] in the pregabalin arm, and by -35.0 [-39.2, -30.7], -36.9 [-41.5, -32.3], and -40.0 [-44.8, -35.2] in the duloxetine arm (all in mm, all p < 0.001). CONCLUSION: Our results demonstrate that pregabalin and duloxetine are effective medications for treating pain in PDPN in more than 86% of all randomised patients.

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.

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.

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.

Traumatic Brain Injury during the SARS-CoV-2 Pandemics in Slovenia: A Single Center Study.

(1) Background: The SARS-CoV-2 pandemic had a significant impact on the management of traumatic brain injury (TBI). We aimed to compare the clinical characteristics and outcomes of TBI patients before and during the SARS-CoV-2 pandemic.; (2) Methods: We analyzed depicted data from existing medical records on sex, age, mechanism of injury, clinical performance at admission and discharge, neuroimaging, laboratory values at admission, mortality, duration of hospitalization, and referrals after discharge from the traumatology department for all adult patients during the SARS-CoV-2 pandemic and a year before. Variables were compared using the Chi-square or t-test between both groups.; (3) Results: Most patients had mild (n = 477), followed by moderate (11) and severe (11) TBI. Mild TBI was less frequent during the SARS-CoV-2 period (n = 174 vs. n = 303). The incidence of high falls increased during the SARS-CoV-2 period (14.5% vs. 24.7%; p < 0.05) in the group with mild TBI. Patients had similar mean Glasgow Coma Scales (GCS), Glasgow Outcome Scales-Extended (GOSE), and glucose levels at admission before and during the pandemic. Serum ethanol levels were significantly lower during the SARS-CoV-2 period (1.3 ± 0.7 mmol/L vs. 0.7 ± 1.2 mmol/L; p < 0.001). At discharge, the mean GCS was significantly lower (14.7 ± 1.8 vs. 14.1 ± 0.5; p < 0.05) for patients treated during the SARS-CoV-2 period than before the SARS-CoV-2 period. There were no differences in GOSE; (4) Conclusions: our results demonstrated a significant impact of SARS-CoV-2 pandemic on the frequency, mechanism, and consequences of TBI, and may help improve care for our patients.

A multicenter study of genetic testing for Parkinson's disease in the clinical setting.

Parkinson's disease (PD) guidelines lack clear criteria for genetic evaluation. We assessed the yield and rationale of genetic testing for PD in a routine clinical setting on a multicenter cohort of 149 early-onset and familial patients by exome sequencing and semi-quantitative multiplex ligation-dependent probe amplification of evidence-based PD-associated gene panel. We show that genetic testing for PD should be considered for both early-onset and familial patients alike, and a clinical yield of about 10% in the Caucasian population can be expected.

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.

Brain Dynamics Underlying Preserved Cycling Ability in Patients With Parkinson's Disease and Freezing of Gait.

Parkinson's disease (PD) is generally associated with abnormally increased beta band oscillations in the cortico-basal ganglia loop during walking. PD patients with freezing of gait (FOG) exhibit a more distinct, prolonged narrow band of beta oscillations that are locked to the initiation of movement at ∼18 Hz. Upon initiation of cycling movements, this oscillation has been reported to be weaker and rather brief in duration. Due to the suppression of the overall beta band power during cycling and its continuous nature of the movement, cycling is considered to be less demanding for cortical networks compared to walking, including reduced need for sensorimotor processing, and thus unimpaired continuous cycling motion. Furthermore, cycling has been considered one of the most efficient non-pharmacological therapies with an influence on the subthalamic nucleus (STN) beta rhythms implicative of the deep brain stimulation effects. In the current review, we provide an overview of the currently available studies and discuss the underlying mechanism of preserved cycling ability in relation to the FOG in PD patients. The mechanisms are presented in detail using a graphical scheme comparing cortical oscillations during walking and cycling in PD.

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.

Cognitive Impairment in People with Epilepsy.

People with epilepsy frequently have cognitive impairment. The majority of cognitive problems is influenced by a variety of interlinked factors, including the early onset of epilepsy and the frequency, intensity and duration of seizures, along with the anti-epileptic drug treatment. With a systematic review, we investigate significant factors about the cognitive impairment in epilepsy. Most cognitive problems in adult people with epilepsy include memory, attention and executive function deficits. However, which cognitive area is mainly affected highly depends on the location of epileptic activity. Moreover, modifications in signalling pathways and neuronal networks have an essential role in both the pathophysiology of epilepsy and in the mechanism responsible for cognitive impairment. Additionally, studies have shown that the use of polytherapy in the treatment of epilepsy with anti-epileptic drugs (AEDs) heightens the risk for cognitive impairment. It can be challenging to distinguish the contribution of each factor, because they are often closely intertwined.

Validation of Slovenian version of ADAS-Cog for patients with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia where the most prominent cognitive impairment is memory loss. Screening tests are valuable tools for detecting cognitive impairment. One such test is the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) which consists of 11 tasks. The main goal of our study was to validate the Slovenian version of the ADAS-Cog for detecting mild cognitive impairment (MCI) and AD patients. METHODS: Our sample included 128 participants: 61 healthy controls, 32 people with MCI, and 35 with AD. All participants were evaluated with the Slovenian translation of ADAS-Cog. RESULTS: The optimal cut-off for the ADAS-Cog for MCI was 10/11 points. The sensitivity was 88%, specificity 85% and likelihood ratio 6. The optimal cut-off for AD was 11/12 points. Sensitivity was 100%, specificity 95% and likelihood ratio 20. CONCLUSION: The obtained cut-off values are comparable to the results from similar validation studies. We can conclude that the ADAS-Cog is a reliable and valid tool for identifying people with MCI and AD from among healthy controls in the Slovenian population.

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.