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This article describes a case of Foreign accent syndrome (FAS) in an Italian woman who developed a Canadian-like foreign accent without brain damage (functional FAS). The patient underwent an in-depth neuroimaging and (neuro)psychological evaluation. Language networks in the frontotemporal-parietal areas were typically activated bilaterally through fMRI and MEG assessments based on task-based data. Resting-state fMRI showed preserved connectivity between language areas. An obsessive-compulsive personality profile and mild anxiety were found, suggesting psychological and psychiatric factors may be relevant. Accordingly with our findings, multimodal imaging is beneficial to understand FAS neurological and functional etiologies.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization’s new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022–2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a ‘neurological revolution’ across four key pillars — surveillance, prevention, acute care and rehabilitation — termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

Background and purpose: Brain health is essential for health, well-being, productivity and creativity across the entire life. Its definition goes beyond the absence of disease embracing all cognitive, emotional, behavioural and social functions which are necessary to cope with life situations. Methods: The European Academy of Neurology (EAN) Brain Health Strategy responds to the high and increasing burden of neurological disorders. It aims to develop a non-disease-, non-age-centred holistic and positive approach (‘one brain, one life, one approach’) to prevent neurological disorders (e.g., Alzheimer's disease and other dementias, stroke, epilepsy, headache/migraine, Parkinson's disease, multiple sclerosis, sleep disorders, brain cancer) but also to preserve brain health and promote recovery after brain damage. Results: The pillars of the EAN Brain Health Strategy are (1) to contribute to a global and international brain health approach (together with national and subspecialty societies, other medical societies, the World Health Organization, the World Federation of Neurology, patients' organizations, industry and other stakeholders); (2) to support the 47 European national neurological societies, healthcare and policymakers in the implementation of integrated and people-centred campaigns; (3) to foster research (e.g., on prevention of neurological disorders, determinants and assessments of brain health); (4) to promote education of students, neurologists, general practitioners, other medical specialists and health professionals, patients, caregivers and the general public; (5) to raise public awareness of neurological disorders and brain health. Conclusions: By adopting this ‘one brain, one life, one approach’ strategy in cooperation with partner societies, international organizations and policymakers, a significant number of neurological disorders may be prevented whilst the overall well-being of individuals is enhanced by maintaining brain health through the life course.

Background: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. Methods: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. Results: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. Conclusions: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Glioma is the most common primary brain cancer in adults. Long-term and progression-free survivals are dependent on the type and grade of glioma, as well as on the extent of resection and postoperative treatments. In Italy, it is unclear how long follow-up care should last and whether the primary care sector is either willing or able to take this on. The aim is to determine pathways of follow-up care and evaluate the professional attitude of doctors to prescribe to patient visits and exams after surgery. A retrospective study was performed on patients with glioma II and III who underwent surgery at tertiary care Neurological Institute Besta of Milan (FINCB) from 2012 to 2020. Data were collected through electronic medical records and inserted in an ad hoc developed database. Three pathways have been identified: a common preliminary pathway (from the pre-operative visit to surgery) for all patients undergoing surgery for gliomas II and III and two follow-up pathways (with or without second surgery). FINCB has developed care pathways that are sometimes personalized according to the doctor’s expertise and attitude to prescribe new examinations. Given the lack of guidelines on this issue, we can cautiously conclude that it is necessary to identify whether, in addition to standard care, personalized supportive care intervention and pathway plan can significantly improve patients’ outcome.

Migraine is a complex condition in which genetic predisposition interacts with other biological and environmental factors determining its course. A hyperresponsive brain cortex, peripheral and central alterations in pain processing, and comorbidities play a role from an individual biological standpoint. Besides, dysfunctional psychological mechanisms, social and lifestyle factors may intervene and impact on the clinical phenotype of the disease, promote its transformation from episodic into chronic migraine and may increase migraine-related disability.Thus, given the multifactorial origin of the condition, the application of a biopsychosocial approach in the management of migraine could favor therapeutic success. While in chronic pain conditions the biopsychosocial approach is already a mainstay of treatment, in migraine the biomedical approach is still dominant. It is instead advisable to carefully consider the individual with migraine as a whole, in order to plan a tailored treatment. In this review, we first reported an analytical and critical discussion of the biological, psychological, and social factors involved in migraine. Then, we addressed the management implications of the application of a biopsychosocial model discussing how the integration between non-pharmacological management and conventional biomedical treatment may provide advantages to migraine care.

Objectives The management of chronic migraine (CM) with Medication Overuse Headache (MOH) consists of withdrawal therapy, education on medications’ use and prescription of prophylaxis. Little attention has been given to patients who fail in achieving a successful short‐term outcome after withdrawal: we aim to describe predictors of failure. Methods Patients with CM and MOH were enrolled at the Neurological Institute C. Besta of Milano, and included if they completed the three months follow‐up. Withdrawal failure was defined as the situation in which patients either did not revert from chronic to episodic migraine (EM), were still overusing acute medications, or both did not revert to EM and kept overusing acute medications. Predictors of failure were addressed with a logistic regression, and for all variables, the longitudinal course in the two groups was described. Results In 39, out of 137 patients, withdrawal was unsuccessful: the predictors included day‐hospital‐based withdrawal (OR: 2.37; 95% CI: 1.06–5.29), emergency room (ER) access before withdrawal (OR: 2.81; 95% CI: 1.13–6.94) and baseline headache frequency >69 days/three months (OR: 2.97; 95% CI: 1.32–6.65). Patients who failed withdrawal did not improve on medications intake, use of prophylactic and non‐pharmacological treatments, symptoms of anxiety and depression. Conclusions Patients who were treated in day‐hospital, those who recently attended ER for headache, and those with more than 69 headache/3 months, as well as to those with relevant symptoms of anxiety and depression who did not improve should be closely monitored to reduce likelihood of non‐improvement after structured withdrawal.

Background The COVID-19 pandemic leads to disruptions of health services worldwide. To evaluate the particular impact on neurological services a rapid review was conducted. Methods Studies reporting the provision of neurological services during the pandemic and/or adopted mitigation strategies were included in this review. PubMed and World Health Organization’s (WHO) COVID-19 database were searched. Data extraction followed categories used by WHO COVID-19 pulse surveys and operational guidelines on maintaining essential health services during COVID-19. Findings The search yielded 1101 articles, of which 369 fulfilled eligibility criteria, describing data from 210,419 participants, being adults (81%), children (11.4%) or both (7.3%). Included articles reported data from 105 countries and territories covering all WHO regions and World Bank income levels (low income: 1.9%, lower middle: 24.7%, upper middle: 29.5% and high income; 44.8%). Cross-sectoral services for neurological disorders were most frequently disrupted (62.9%), followed by emergency/acute care (47.1%). The degree of disruption was at least moderate for 75% of studies. Travel restrictions due to lockdowns (81.7%) and regulatory closure of services (65.4%) were the most commonly reported causes of disruption. Authors most frequently described telemedicine (82.1%) and novel dispensing approaches for medicines (51.8%) as mitigation strategies. Evidence for the effectiveness of these measures is largely missing. Interpretation The COVID-19 pandemic affects all aspects of neurological care. Given the worldwide prevalence of neurological disorders and the potential long-term neurological consequences of COVID-19, service disruptions are devastating. Different strategies such as telemedicine might mitigate the negative effects of the pandemic, but their efficacy and acceptability remain to be seen.

Background: The standardization of outcome measures is needed for comparing studies and using common measures in clinical practice. We aimed to identify cognitive and patient-reported outcomes and timing of assessment for glioma, meningioma, and vascular surgery. Method: A consensus study was conducted. Participants selected cognitive and patient-reported measures among a list of instruments identified through a literature search. Results: Seventeen cognitive tests for the glioma and meningioma’s evaluation, 8 for the vascular diseases, and one questionnaire on quality of life and one on emotional distress were identified. The timing of outcome assessment selected was before surgery, at discharge, and after 3 and 12 months for glioma; before surgery and after 3 months for meningioma; before surgery, at discharge, and after 6 months for vascular diseases. Conclusion: The identification of common outcome measures is the first step toward a shared data collection improving the quality and comparability of future studies.

Objective:This study aims to generate country-specific norms for two episodic memory tasks and a verbal fluency test among middle-aged and older adults using nationally representative data from nine low-, middle-, and high-income countries.Method:Data from nine countries in Africa, Asia, Europe, and Latin America were analyzed (n = 42,116; aged 50 years or older). Episodic memory was assessed with the word list memory (three trials of immediate recall) and word list recall (delayed recall). Verbal fluency was measured through the animal naming task. Multiple linear regression models with country-specific adjustments for gender, age, education, and residential area were carried out.Results:Both age and education showed high influence on test performance (i.e. lower cognitive performance with increasing age and decreasing years of education, respectively), while the effect of sex and residential area on cognitive function was neither homogeneous across countries nor across cognitive tasks.Conclusions:Our study provided sex-, age-, education-, and residential area-specific regression-based norms that were obtained from one of the largest normative study worldwide on verbal recall and fluency tests to date. Findings derived from this study will be especially useful for clinicians and researchers based at countries where cognitive norms are limited.

Brain fog has been described up to 1 year after SARS-CoV-2 infection, notwithstanding the underlying mechanisms are still poorly investigated. In this study, we aimed to evaluate the prevalence of cognitive complaints at 1-year follow-up and to identify the factors related to persistent brain fog in COVID-19 patients.Out of 246 COVID patients, hospitalized from March 1st to May 31st, a sample of 137 patients accepted to be evaluated at 1 year from discharge, through a full clinical, neurological, and psychological examination, including the Montreal Cognitive Assessment (MoCA), impact of event scale-revised (IES-R), Zung self-rating depression scale (SDS), Zung self-rating anxiety scale (SAS), and fatigue severity scale (FSS). Subjects with prior cognitive impairment and/or psychiatric disorders were excluded.Patients with cognitive disorders exhibited lower MoCA score (22.9 ± 4.3 vs. 26.3 ± 3.1, p = 0.002) and higher IES-R score (33.7 ± 18.5 vs. 26.4 ± 16.3, p = 0.050), SDS score (40.9 ± 6.5 vs. 35.5 ± 8.6, p = 0.004), and fatigue severity scale score (33.6 ± 16.1 vs. 23.7 ± 12.5, p = 0.001), compared to patients without cognitive complaints. Logistic regression showed a significant correlation between brain fog and the self-rating depression scale values (p = 0.020), adjusted for age (p = 0.445), sex (p = 0.178), premorbid Cumulative Illness Rating Scale (CIRS) (p = 0.288), COVID-19 severity (BCRSS) (p = 0.964), education level (p = 0.784) and MoCA score (p = 0.909).Our study showed depression as the strongest predictor of persistent brain fog, adjusting for demographic and clinical variables. Wider longitudinal studies are warranted to better explain cognitive difficulties after COVID-19.

Background The COVID-19 pandemic outbreak has dramatically disrupted healthcare systems. Two rapid WHO pulse surveys studied disruptions in mental health services, but did not particularly focus on neurology. Here, a global survey was conducted and addresses the impact of the pandemic on neurology services. Methods A cross-sectional study was carried out in which 34 international neurological associations were asked to distribute the survey to national associations. The responses represented the national situation, in November–December 2020, with regard to the main disrupted neurological services, reasons and the mitigation strategies implemented as well as the disruption on training of residents and on neurological research. A comparison with the situation in February–April 2020, first pandemic wave, was also requested. Findings 54 completed surveys came from 43 countries covering all the 6 WHO regions. Overall, neurological services disruption was reported as mild by 26%, moderate by 30%, complete by 13% of associations. The most affected services were cross-sectoral neurological services (57%) and neurorehabilitation (56%). The second wave of the pandemic, however, was associated with the improvement of service provision for diagnostics services (44%) and for neurorehabilitation (41%). Governmental directives were the major cause of services’ disruption (56%). Mitigation strategies were mostly established through telemedicine (48%). Almost half of respondents reported a significant impact on neurological research (48%) and educational activities (60%). Most associations (67%) were not involved in decision making for neurological patients’ issues by their national government. Interpretation The COVID-19 pandemic affects neurological services and raises the universal need for the development of neurological health care at the policy, systems and services levels. A global national plan on mitigation strategies for disruption of neurological services during pandemic situations should be established and neurological scientific and patients associations should get involved in decision making. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10641-3.

Background Several people affected by COVID-19 experienced neurological manifestations, altered sleep quality, mood disorders, and disability following hospitalization for a long time. Objective To explore the impact of different neurological symptoms on sleep quality, mood, and disability in a consecutive series of patients previously hospitalized for COVID-19 disease. Methods We evaluated 83 patients with COVID-19 around 3 months after hospital discharge. They were divided into 3 groups according to their neurological involvement (i.e., mild, unspecific, or no neurological involvement). Socio-demographic, clinical data, disability level, emotional distress, and sleep quality were collected and compared between the three groups. Results We found that higher disability, depressive symptoms, and lower sleep quality in patients with mild neurological involvement compared to patients with unspecific and no neurological involvement. Differences between groups were also found for clinical variables related to COVID-19 severity. Conclusion After 3 months from hospital discharge, patients with more severe COVID-19 and mild neurological involvement experienced more psychosocial alterations than patients with unspecific or no neurological involvement. Both COVID-19 and neurological manifestations’ severity should be considered in the clinical settings to plain tailored interventions for patients recovering from COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-022-05907-1.

Chronic migraine (CM) diagnosis is nowadays based on the threshold of 15 headache days/month for three consecutive months, of which at least eight have migraine headache features. In recent years, proposals for reducing the threshold to 8 days/month have been proposed. The sole frequency parameter, however, is partial considering the variability in frequency, pain severity, associated symptoms, such as nausea, osmophobia, and photophobia, and presence of aura, but also the variable response to treatment and the association with several comorbidities. Therefore, in our opinion, a multiparameter perspective has to be taken into account that considers the underlying pathophysiology, in particular the presence of tension-type-like pain, cutaneous allodynia, and reduced pain threshold. A paradigm change in the definition of chronic migraine moves far beyond the mere 8 vs. 15 days/month, but has ethical and practical implications for treatment: should patients be treated with the most effective prophylactic drugs, i.e., monoclonal antibodies (MABs), if they enter into a new definition of CM? How should clinicians deal with treatment escalation towards MABs? What is the role of associated conditions, response to treatments, lifestyle issues, and psychological factors? And, finally, which endpoint should we use to define effectiveness? Is improvement in headache frequency enough, or should we move towards disability, quality of life, or workplace productivity?

Background Health economic evaluations support health-care decision-making by providing information on the costs and consequences of health interventions. No universally accepted methodology exists for modelling effectiveness and cost-effectiveness of interventions designed to close treatment gaps for headache disorders in countries of Europe (or elsewhere). Our aim here, within the European Brain Council’s Value-of-Treatment project, was to develop headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. Methods We developed three headache-type-specific decision-analytical models using the WHO-CHOICE framework and adapted these for three European Region country settings (Luxembourg, Russia and Spain), diverse in geographical location, population size, income level and health-care systems and for which we had population-based data. Each model compared current (suboptimal) care vs target care (delivered in accordance with the structured headache services model). Epidemiological and economic data were drawn from studies conducted by the Global Campaign against Headache; data on efficacy of treatments were taken from published randomized controlled trials; assumptions on uptake of treatments, and those made for Healthy Life Year (HLY) calculations and target-care benefits, were agreed with experts. We made annual and 5-year cost estimates from health-care provider (main analyses) and societal (secondary analyses) perspectives (2020 figures, euros). Results The analytical models were successfully developed and applied to each country setting. Headache-related costs (including use of health-care resources and lost productivity) and health outcomes (HLYs) were mapped across populations. The same calculations were repeated for each alternative (current vs target care). Analyses of the differences in costs and health outcomes between alternatives and the incremental cost-effectiveness ratios are presented elsewhere. Conclusions This study presents the first headache-type-specific analytical models to evaluate effectiveness and cost-effectiveness of implementing structured headache services in countries in the European Region. The models are robust, and can assist policy makers in allocating health budgets between interventions to maximize the health of populations.

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

Background: Neurological conditions are highly prevalent and disabling, in particular in the elderly. The Italian population has witnessed sharp ageing and we can thus expect a rising trend in the incidence, prevalence and disability of these conditions. Methods: We relied on the Global Burden of Disease 2019 study to extract Italian data on incidence, prevalence and years lived with a disability (YLDs) referred to a broad set of neurological disorders including, brain and nervous system cancers, stroke, encephalitis, meningitis, tetanus, traumatic brain injury, and spinal cord injury. We assessed changes between 1990 and 2019 in counts and age-standardized rates. Results: The most prevalent conditions were tension-type headache, migraine, and dementias, whereas the most disabling were migraine, dementias and traumatic brain injury. YLDs associated with neurological conditions increased by 22.5%, but decreased by 2.3% in age-standardized rates. The overall increase in prevalence and YLDs counts was stronger for non-communicable diseases with onset in old age compared to young to adult-age onset ones. The same trends were in the opposite direction when age-standardized rates were taken into account. Conclusions: The increase in YLDs associated with neurological conditions is mostly due to population ageing and growth: nevertheless, lived disability and, as a consequence, impact on health systems has increased. Actions are needed to improve outcome and mitigate disability associated with neurological conditions, spanning among diagnosis, treatment, care pathways and workplace interventions.

BackgroundThere have been several calls for estimations of costs and consequences of headache interventions to inform European public-health policies. In a previous paper, in the absence of universally accepted methodology, we developed headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. Here we apply this methodology and present the findings.MethodsData sources were published evidence and expert opinions, including those from an earlier economic evaluation framework using the WHO-CHOICE model. We used three headache-type-specific analytical models, for migraine, tension-type-headache (TTH) and medication-overuse-headache (MOH). We considered three European Region case studies, from Luxembourg, Russia and Spain to include a range of health-care systems, comparing current (suboptimal) care versus target care (structured services implemented, with provider-training and consumer-education). We made annual and 5-year cost estimates from health-care provider and societal perspectives (2020 figures, euros). We expressed effectiveness as healthy life years (HLYs) gained, and cost-effectiveness as incremental cost-effectiveness-ratios (ICERs; cost to be invested/HLY gained). We applied WHO thresholds for cost-effectiveness.ResultsThe models demonstrated increased effectiveness, and cost-effectiveness (migraine) or cost saving (TTH, MOH) from the provider perspective over one and 5 years and consistently across the health-care systems and settings. From the societal perspective, we found structured headache services would be economically successful, not only delivering increased effectiveness but also cost saving across headache types and over time. The predicted magnitude of cost saving correlated positively with country wage levels. Lost productivity had a major impact on these estimates, but sensitivity analyses showed the intervention remained cost-effective across all models when we assumed that remedying disability would recover only 20% of lost productivity.ConclusionsThis is the first study to propose a health-care solution for headache, in the form of structured headache services, and evaluate it economically in multiple settings. Despite numerous challenges, we demonstrated that economic evaluation of headache services, in terms of outcomes and costs, is feasible as well as necessary. Furthermore, it is strongly supportive of the proposed intervention, while its framework is general enough to be easily adapted and implemented across Europe.

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

This corrects the article DOI: 10.3389/fneur.2020.526465

Background Clinical investigations have argued for long-term neurological manifestations in both hospitalised and non-hospitalised COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity. Methods From a sample of 208 consecutive non-neurological patients hospitalised for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardised clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses. Results At 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%) and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older age, premorbid comorbidities and severity of COVID-19 were independent predictors of neurological manifestations in logistic regression analyses. Conclusions Premorbid vulnerability and severity of SARS-CoV-2 infection impact on prevalence and severity of long-term neurological manifestations.

ObjectiveAim of this study was to analyse the impact of COVID-19 on clinical and laboratory findings and outcome of neurological patients consecutively admitted to the emergency department (ED) of a tertiary hub center.MethodsAll adult patients consecutively admitted to the ED for neurological manifestations from February 20th through April 30th 2020 at Spedali Civili of Brescia entered the study. Demographic, clinical, and laboratory data were extracted from medical records and compared between patients with and without COVID-19.ResultsOut of 505 consecutively patients evaluated at ED with neurological symptoms, 147 (29.1%) tested positive for SARS-CoV-2. These patients displayed at triage higher values of CRP, AST, ALT, and fibrinogen but not lymphopenia (pConclusionsCOVID-19 impacts on clinical presentation of neurological disorders, with higher frequency of stroke, encephalitis and delirium, and was strongly associated with increased hospitalisation, mortality and disability.

The impact of language impairment on the clinical assessment of patients suffering from disorders of consciousness (DOC) is unknown or underestimated and may mask the presence of conscious behavior. In a group of DOC patients (n = 11; time post-injury range: 5–252 months), we investigated the main neural functional and structural underpinnings of linguistic processing, and their relationship with the behavioral measures of the auditory function using the Coma Recovery Scale-Revised (CRS-R). We assessed the integrity of the brainstem auditory pathways, of the left superior temporal gyrus and arcuate fasciculus, the neural activity elicited by passive listening of an auditory language task, and the mean hemispheric glucose metabolism. Our results support the hypothesis of a relationship between the level of preservation of the investigated structures/functions and the CRS-R auditory subscale scores. Moreover, our findings indicate that patients in minimally conscious state minus (MCS−): (1) when presenting the auditory startle (at the CRS-R auditory subscale) might be aphasic in the receptive domain, being severely impaired in the core language structures/functions; (2) when presenting the localization to sound might retain language processing, being almost intact or intact in the core language structures/functions. Despite the small group of investigated patients, our findings provide a grounding of the clinical measures of the CRS-R auditory subscale in the integrity of the underlying auditory structures/functions. Future studies are needed to confirm our results that might have important consequences for the clinical practice.

Background: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people, and with increasing trends in general populations. Different risk factors for pain have been identified, but generally from studies with limited samples and a limited number of candidate predictors. The aim of this study is to evaluate the predictors of pain from a large set of variables and respondents. Methods: We used part of the harmonized dataset of ATHLOS project, selecting studies and waves with a longitudinal course, and in which pain was absent at baseline and with no missing at follow-up. Predictors were selected based on missing distribution and univariable association with pain, and were selected from the following domains: Socio-demographic and economic characteristics, Lifestyle and health behaviours, Health status and functional limitations, Diseases, Physical measures, Cognition, personality and other psychological measures, and Social environment. Hierarchical logistic regression models were then applied to identify significant predictors. Results: A total of 13,545 subjects were included of whom 5348 (39.5%) developed pain between baseline and the average 5.2 years' follow-up. Baseline risk factors for pain were female gender (OR 1.34), engaging in vigorous exercise (OR 2.51), being obese (OR 1.36) and suffering from the loss of a close person (OR 1.88) whereas follow-up risk factors were low energy levels/fatigue (1.93), difficulties with walking (1.69), self-rated health referred as poor (OR 2.20) or average to moderate (OR 1.57) and presence of sleep problems (1.80). Conclusions: Our results showed that 39.5% of respondents developed pain over a five-year follow-up period, that there are proximal and distal risk factors for pain, and that part of them are directly modifiable. Actions aimed at improving sleep, reducing weight among obese people and treating fatigue would positively impact on pain onset, and avoiding vigorous exercise should be advised to people aged 60 or over, in particular if female or obese., The ATHLOS project (Ageing Trajectories of Health: Longitudinal Opportunities and Synergies) has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 635316

While the epidemics of Coronavirus disease 2019 (COVID-19) continues to spread globally, more and more evidence is collected about the presence of neurological manifestations and symptoms associated with it. A systematic review has been performed of papers published until 5 April 2020. 29 papers related to neurological manifestations associated with COVID-19 were examined. The results show presence of central and peripheral nervous system manifestations related to coronavirus. Neurological manifestations or NeuroCOVID are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of CNS symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. Further clinical, epidemiological, and basic science research is urgently needed in order to understand and address neurological sequalae of COVID-19. Concomitant risk factors or determinants (e.g. demographic factors, comorbidities, or available biomarkers) that may predispose a person with COVID-19 to neurological manifestations also need to be identified. The review shows that although more and more papers are reporting neurological manifestations associated with COVID19, however many items remain unclear and this uncertainty calls for a global action that requires close coordination and open-data sharing between hospitals, academic institutions and the fast establishment of harmonised research priorities and research consortia to face the NeuroCOVID19 complications.

Caregivers of patients diagnosed with disorders of consciousness (DoCs) play a pivotal role in the care pathway of these patients. Due to the high costs of care, among other symptoms and disorders previously described in the literature, they can manifest also mood and stress-related disorders which greatly impact their life and increase their burden. It is noteworthy to identify which factors are better related to the manifestation of mood and stress-related disorders to care for the caregivers in time. However, no studies have explored which factors are related to the manifestation of these disorders within this population yet. We explored with different questionnaires whether patient-, caregiver-, and caregiving environment-related factors are associated with mood and stress-related disorders on 114 caregivers of patients with DoCs. Our results showed that female caregivers manifested higher levels of both depression and prolonged grief disorder; furthermore, the presence of economic problems increased the levels of depression. Moreover, different levels of caregivers’ depression, anxiety, anger expression, and prolonged grief disorder were closely linked to the degree of behavioural responsiveness of the patients. Our results highlighted the need to consider also caregivers’ mood and stress-related disorders when defining the care pathway of patients with DoCs; indeed, caregivers constitute the main environment of DoC patients and they need tailored interventions aimed at reducing their burden due to caregiving.

The purpose of the present study was to review the existing data on preoperative nonmedical factors that are predictive of outcome in brain tumor surgery. Our hypothesis was that also the individual characteristics (e.g., emotional state, cognitive status, social relationships) could influence the postoperative course in addition to clinical factors usually investigated in brain tumor surgery. PubMed, Embase, and Scopus were searched from 2008 to 2018 using terms relating to brain tumors, craniotomy, and predictors. All types of outcome were considered: clinical, cognitive, and psychological. Out of 6.288 records identified, 16 articles were selected for analysis and a qualitative synthesis of the prognostic factors was performed. The following nonmedical factors were found to be predictive of surgical outcomes: socio-demographic (age, marital status, type of insurance, gender, socio-economic status, type of hospital), cognitive (preoperative language and cognitive deficits, performance at TMT-B test), and psychological (preoperative depressive symptoms, personality traits, autonomy for daily activities, altered mental status). This review showed that nonmedical predictors of outcome exist in brain tumor surgery. Consequently, individual characteristics (e.g., emotional state, cognitive status, social relationships) can influence the postoperative course in addition to clinical factors.

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020;88:423-427.

Background The definition of chronic migraine has long been debated. Recently, it was suggested to define subjects with at least 8/migraine days as chronic migraine; that is, incorporating so-called high frequency episodic migraine (eight or more migraine days but less than 15 headache days per month). Methods We addressed the possible problems that might arise based on this proposal accounting for clinical, pathophysiological, impact and public health aspects. Results and conclusions Defining chronic migraine on the basis of headache frequency alone does not account for clinical and pathophysiological aspects, as well as for the impact of chronic migraine in terms of disability and quality of life. Moreover, it is potentially harmful for patients in terms of allocation of resources. These issues are discussed in the present manuscript, and we support the idea of defining high frequency episodic migraine as an independent entity as a viable path to follow.

Background: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates. Methods: We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content "self-reported pain experienced at the time of the interview", with a dichotomous (yes or no) modality. Results: Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50. Conclusions: Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates., The ATHLOS project (Ageing Trajectories of Health: Longitudinal Opportunities and Synergies) has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 635316.

ObjectiveTo report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19).MethodsIn this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period.ResultsOne hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0–83.8 years vs 70.1 years, IQR 52.9–78.6 years, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7–1.1 vs 0.5, IQR 0.4–0.6, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, p = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0–6.0 vs 2.0, IQR 1.0–3.0, p < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, p < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21–16.5, p = 0.025), lower platelet count (OR 0.98, 95% CI 0.97–0.99, p = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00–1.03, p = 0.009) on admission.ConclusionsPatients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.

Background It is common clinical experience that, after structured withdrawal, some patients with chronic migraine and medication overuse headache (CM with MOH) are more prone than others to relapse and to be in need of further structured treatments. Our aim was to explore similarities and differences between frequent relapsers (FRs) and non-frequent relapsers (NFRs) by considering their point of view, perceptions, and perspective of their subjective experience with relapse into CM with MOH. Methods Patients were consecutively recruited on occasion of a structured withdrawal treatment and were interviewed individually about their headache experience and their perspectives on relapse into CM with MOH. We considered FR those patients requiring 2 or more structured withdrawals for MOH within 3 years. A narrative approach with no preconceived coding schemes was employed. To facilitate coding, categorization and organization of data the software QRS NVivo 11.0 was used: themes were defined as common to FR and NFR, or peculiar (by frequency or content) to one of the 2 groups. Results Sixteen patients (13 women; mean age of 53) were interviewed: 7 were classified as FRs. A total of 22 themes emerged from 552 single quotations (the 10 most relevant covered 82% of the entire body of quotations). Four themes were commonly reported by both FR and NFR patients, and 6 were peculiar to one group only. Common aspects included issues connected to the dilemma between disclosing, concealing and the feelings of isolation around MOH, the idea of being addicted to medication, presence of anxiety, and the attempt to use non-pharmacological therapies as an alternative to medication. Peculiar aspects included causal attribution (FRs attributed headache to uncontrollable factors); future expectations at the time point of withdrawal (FRs were generally resigned); high-performance functioning (FRs believed they are "forced" to reach high levels of performance as a consequence of others' inability); coping strategies (FRs tended to "passively accept" problems and showed avoidance-related behaviors). Moreover, FRs were less frequently aware of their problems and described more frequently depressive symptoms. Conclusions Our results highlight that some differences between FR and NFR patients with CM and MOH exist. Frequent relapsers among patients with CM and MOH reported some important peculiarities of the lived experience of having chronic migraine; clinicians should recognize these psychosocial aspects such as social relationships, future expectations, the experience of illness, medication management, and how the withdrawal experience is regarded, as they may be associated with frequent relapse into MOH.

The Brief Post-Coma Scale (BPCS) is an easy diagnostic tool for individuals with disorders of consciousness (DoC), in a reduced version from a previously Post-Coma Scale, that could distinguish patients in the minimally conscious state (MCS) from those in unresponsive wakefulness syndrome (UWS), formerly defined as vegetative state (VS). Aim of the study was to assess the diagnostic validity of the BPCS in comparison with the Coma Recovery Scale-Revised (CRS-R), in its Italian validated version, the Disability Rating Scale (DRS), the Level of Cognitive Functioning (LCF), and the Glasgow Outcome Scale (GOS). In an Italian multicenter study on 545 patients with DoC, 36 post-acute rehabilitation wards, 32 long-term care centers, and 2 family associations participated to data collection. Statistically significant correlations were found between the BPCS and the other clinical scales: R = 0.586 (p

BACKGROUND Behavioral treatments in the management of primary headache disorders in adults and children are increasingly being recognized as effective; however, the level and durability of their effectiveness is still a matter of debate. This review aims to provide more updated information on the effects of behavioral therapies in adults and adolescents with primary headache disorders, with a special focus on new and emerging behavioral treatments. METHODS We searched SCOPUS for peer-reviewed papers that reported randomized controlled trial or observational studies addressing behavioral treatment for headache disorders published in the period January 2010 to October 2017. RESULTS A total of 22 publications, in which 2110 participants were recruited, were included in the review. Most of the studies referred to cognitive behavioral therapies, and a reduction of headache frequency higher than 35% was generally reported irrespective of the approach. In addition, valuable impact disability and quality of life was observed, as well as improvements in depression, anxiety, self-efficacy, and intake of medications. CONCLUSIONS Behavioral approaches are effective and less prone to produce side or harmful effects, which makes them a valid option particularly for women who are pregnant or nursing, people with other chronic conditions requiring pharmacological treatments putting them at risk for drug-drug interactions, and children.

This study aims to assess surgical outcome in brain tumor surgery using patient reported outcome measures (PROMs) and to compare their results with traditional clinical outcome measurements. Neuro-oncological patients undergoing surgical removal for the lesion were enrolled; MOCA test, PROMs (EUROHIS-QoL, PGWB-S, WHODAS-12), and the clinical scale Karnofsky Performance Status (KPS) were administered to evaluate respectively cognitive status, quality of life, well-being, disability, and functional status before surgery and at 3-month follow-up. Wilcoxon test was performed to evaluate the longitudinal change of test scores, the smallest detectable difference to classify the change of patients in PROMs, the Cohen kappa to investigate the concordance between KPS and PROMs in classifying the patients’ change, and Mann-Whitney U test to compare patients with complications and no complications. A total of 101 patients were enrolled (54 woman, mean age 50.2 ± 14.1, range 20–85): psychological well-being improved at follow-up; 95 patients (94.1%) were improved/unchanged and 6 (5.9%) were worsened according to PROMs; functional status measured with KPS had a slight agreement with quality of life and disability and no agreement with psychological well-being questionnaires; patients with complications had a greater worsening in KPS. According to PROMs measuring QoL, disability, and psychological well-being, most of the patients were improved/unchanged after surgery. Since PROMs and KPS detect different aspects of the patients’ health status, PROMs should be integrated in surgical outcome evaluation. Furthermore, their association with complications and with other clinical and subjective variables that could influence patient’s perception of health status should be investigated.

Objective We assessed sleep patterns in 85 patients with chronic disorders of consciousness (DOC) in order to reveal any relationship with the degree of the impairment. Methods Nocturnal polysomnography (PSG) was scored in patients classified as being in an unresponsive wakefulness syndrome/vegetative state (UWS/VS; n = 49) or a minimally conscious state (MCS; n = 36) in accordance with the rules of the American Academy of Sleep Medicine. The PSG data in the two diagnostic groups were compared, and the PSG parameters associated with the degree of impairment were analysed. Results In 19/49 UWS/VS patients, signal attenuation was the only EEG pattern detectable in sleep. Non-REM 2 (NREM2) and slow-wave sleep (SWS) (but not REM) stages were more frequent in the MCS patients. The presence of SWS was the most appropriate factor for classifying patients as UWS/VS or MCS, and the duration of SWS was the main factor that significantly correlated with revised Coma Recovery Scale scores. Conclusion The presence of NREM sleep (namely SWS) reflects better preservation of the circuitry and structures needed to sustain this stage of sleep in DOC patients. Significance PSG is a simple and effective technique, and sleep patterns may reflect the degree of impairment in chronic DOC patients.

The epidemiological data of Indian patients with disorders of consciousness (DOC), specifically vegetative state and minimally conscious state, have not been investigated. The present study sought to explore the current state of the art in India for patients with DOC promoting a pilot survey. An ad hoc questionnaire was sent to a total of 400 Indian professionals who are affiliated to various centers; 59 professionals completed the questionnaire and 52 of them declared that their centers hospitalized patients with DOC in the last year for rehabilitation/medical treatments. The majority of the professionals were from Maharashtra region. The main preliminary findings showed that the prevalence rates of traumatic and nontraumatic etiologies were equally distributed, that the rate of use of the coma recovery scale-revised was low, and that the rehospitalization was always or frequently possible in neurological and rehabilitation units. The extrapolated estimated rate of patients with DOC hospitalized in the centers involved in 2017 was equal to 4 per million of population in Maharashtra region. More than 50% of the professionals declared that there were neither sufficient nor adequate services for caregivers' support. Even if the present pilot survey has some limitations, the present article offers the first preliminary data on patients with DOC in Indian country.

Background and aims: Objective: Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. No data about clinical, imaging and biomarkers presentations as well as long-term outcomes are available for SARS-CoV-2 encephalitis in comparison with infectious and autoimmune encephalitis. Methods: The ENCOVID European registry included patients with probable or definite diagnosis of encephalitis with and without SARS-CoV-2 infection admitted for hospitalization in the European recruiting centers between February 1st 2020 and March 30th, 2021. Each patient underwent a standardized assessment including full infectious screening, CSF, EEG, MRI data. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded. Results: Results – Out of 155 cases screened, forty-five cases of encephalitis positive for SARS-CoV-2 infection and 63 without COVID-19 with full available data were included. SARS-CoV-2 encephalitis exhibited common presentation with aphasia and dysarthria compared to non-COVID- encephalitis and exhibited higher prevalence of patients with normal MRI but mild hyperproteinorracchia/pleocytosis. Most SARS-CoV-2 cases appeared during the onset of COVID-19 and exhibited different response to treatment and long-term outcomes compared to non COVID encephalitis. Conclusions: Conclusions –The registry identified a wide spectrum of encephalitis associated with COVID19 infection, with clinical characteristics and course different from classical infectious and autoimmune encephalitis. Biomarkers studies are warranted in order to evaluate the specific inflammatory pathways associated with SARS-Cov-2 encephalitis.