Publications by authors named "Matilde Leonardi"

270 Publications

Long-term neurological manifestations of COVID-19: prevalence and predictive factors.

Neurol Sci 2021 Sep 15. Epub 2021 Sep 15.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy.

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.
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http://dx.doi.org/10.1007/s10072-021-05586-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439956PMC
September 2021

Incidence, prevalence and disability associated with neurological disorders in Italy between 1990 and 2019: an analysis based on the Global Burden of Disease Study 2019.

J Neurol 2021 Sep 8. Epub 2021 Sep 8.

Neurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.

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.
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http://dx.doi.org/10.1007/s00415-021-10774-5DOI Listing
September 2021

Structured headache services as the solution to the ill-health burden of headache. 2. Modelling effectiveness and cost-effectiveness of implementation in Europe: methodology.

J Headache Pain 2021 Aug 23;22(1):99. Epub 2021 Aug 23.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.

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.
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http://dx.doi.org/10.1186/s10194-021-01310-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383423PMC
August 2021

Structured headache services as the solution to the ill-health burden of headache. 3. Modelling effectiveness and cost-effectiveness of implementation in Europe: findings and conclusions.

J Headache Pain 2021 Aug 11;22(1):90. Epub 2021 Aug 11.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.

Background: There 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.

Methods: Data 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.

Results: The 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.

Conclusions: This 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.
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http://dx.doi.org/10.1186/s10194-021-01305-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359596PMC
August 2021

Structured Q1 headache services as the solution to the ill-health burden of headache: 1. Rationale and description.

J Headache Pain 2021 Jul 21;22(1):78. Epub 2021 Jul 21.

Department of Neurology, Ghent University Hospital, Ghent, Belgium.

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.
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http://dx.doi.org/10.1186/s10194-021-01265-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293530PMC
July 2021

Pathways of follow-up care in an Italian center: retrospective study on patients with gliomas II and III.

Neurol Sci 2021 Jul 8. Epub 2021 Jul 8.

UOC Neurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133, Milan, Italy.

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1007/s10072-021-05415-8DOI Listing
July 2021

Global survey on disruption and mitigation of neurological services during COVID-19: the perspective of global international neurological patients and scientific associations.

J Neurol 2021 Jun 11. Epub 2021 Jun 11.

Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.

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.
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http://dx.doi.org/10.1007/s00415-021-10641-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195244PMC
June 2021

Brain Tumor Resection in Elderly Patients: Potential Factors of Postoperative Worsening in a Predictive Outcome Model.

Cancers (Basel) 2021 May 12;13(10). Epub 2021 May 12.

Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.

The decision of whether to operate on elderly patients with brain tumors is complex, and influenced by pathology-related and patient-specific factors. This retrospective cohort study, based on a prospectively collected surgical database, aims at identifying possible factors predicting clinical worsening after elective neuro-oncological surgery in elderly patients. Therefore, all patients ≥65 years old who underwent BT resection at a tertiary referral center between 01/2018 and 12/2019 were included. Age, smoking, previous radiotherapy, hypertension, preoperative functional status, complications occurrence, surgical complexity and the presence of comorbidities were prospectively collected and analyzed at discharge and the 3-month follow-up. The series included 143 patients (mean 71 years, range 65-86). Sixty-five patients (46%) had at least one neurosurgical complication, whereas 48/65 (74%) complications did not require invasive treatment. Forty-two patients (29.4%) worsened at discharge; these patients had a greater number of complications compared to patients with unchanged/improved performance status. A persistent worsening at three months of follow-up was noted in 20.3% of patients; again, this subgroup presented more complications than patients who remained equal or improved. Therefore, postoperative complications and surgical complexity seem to influence significantly the early outcome in elderly patients undergoing brain tumor surgery. In contrast, postoperative complications alone are the only factor with an impact on the 3-month follow-up.
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http://dx.doi.org/10.3390/cancers13102320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151018PMC
May 2021

Withdrawal failure in patients with chronic migraine and medication overuse headache.

Acta Neurol Scand 2021 Oct 25;144(4):408-417. Epub 2021 May 25.

Fondazione IRRCS Istituto Neurologico C. Besta, UO Neurologia Salute Pubblica e Disabilità, Milano, Italy.

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.
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http://dx.doi.org/10.1111/ane.13475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453823PMC
October 2021

Disruptions of neurological services, its causes and mitigation strategies during COVID-19: a global review.

J Neurol 2021 Nov 22;268(11):3947-3960. Epub 2021 May 22.

Neurology, Public Health, Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

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.
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http://dx.doi.org/10.1007/s00415-021-10588-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140556PMC
November 2021

Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy.

Neurol Sci 2021 Jul 30;42(7):2637-2644. Epub 2021 Apr 30.

Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced.

Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children.

Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March-September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high.

Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.
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http://dx.doi.org/10.1007/s10072-021-05252-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086222PMC
July 2021

Theoretical Models of Consciousness: A Scoping Review.

Brain Sci 2021 Apr 24;11(5). Epub 2021 Apr 24.

Neurology, Public Health, Disability Unit-Scientific Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.

The amount of knowledge on human consciousness has created a multitude of viewpoints and it is difficult to compare and synthesize all the recent scientific perspectives. Indeed, there are many definitions of consciousness and multiple approaches to study the neural correlates of consciousness (NCC). Therefore, the main aim of this article is to collect data on the various theories of consciousness published between 2007-2017 and to synthesize them to provide a general overview of this topic. To describe each theory, we developed a thematic grid called the dimensional model, which qualitatively and quantitatively analyzes how each article, related to one specific theory, debates/analyzes a specific issue. Among the 1130 articles assessed, 85 full texts were included in the prefinal step. Finally, this scoping review analyzed 68 articles that described 29 theories of consciousness. We found heterogeneous perspectives in the theories analyzed. Those with the highest grade of variability are as follows: subjectivity, NCC, and the consciousness/cognitive function. Among sub-cortical structures, thalamus, basal ganglia, and the hippocampus were the most indicated, whereas the cingulate, prefrontal, and temporal areas were the most reported for cortical ones also including the thalamo-cortical system. Moreover, we found several definitions of consciousness and 21 new sub-classifications.
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http://dx.doi.org/10.3390/brainsci11050535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146510PMC
April 2021

Analyzing the Loss and the Recovery of Consciousness: Functional Connectivity Patterns and Changes in Heart Rate Variability During Propofol-Induced Anesthesia.

Front Syst Neurosci 2021 6;15:652080. Epub 2021 Apr 6.

Neurology, Public Health, Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

The analysis of the central and the autonomic nervous systems (CNS, ANS) activities during general anesthesia (GA) provides fundamental information for the study of neural processes that support alterations of the consciousness level. In the present pilot study, we analyzed EEG signals and the heart rate (HR) variability (HRV) in a sample of 11 patients undergoing spinal surgery to investigate their CNS and ANS activities during GA obtained with propofol administration. Data were analyzed during different stages of GA: baseline, the first period of anesthetic induction, the period before the loss of consciousness, the first period after propofol discontinuation, and the period before the recovery of consciousness (ROC). In EEG spectral analysis, we found a decrease in posterior alpha and beta power in all cortical areas observed, except the occipital ones, and an increase in delta power, mainly during the induction phase. In EEG connectivity analysis, we found a significant increase of local efficiency index in alpha and delta bands between baseline and loss of consciousness as well as between baseline and ROC in delta band only and a significant reduction of the characteristic path length in alpha band between the baseline and ROC. Moreover, connectivity results showed that in the alpha band there was mainly a progressive increase in the number and in the strength of incoming connections in the frontal region, while in the beta band the parietal region showed mainly a significant increase in the number and in the strength of outcoming connections values. The HRV analysis showed that the induction of anesthesia with propofol was associated with a progressive decrease in complexity and a consequent increase in the regularity indexes and that the anesthetic procedure determined bradycardia which was accompanied by an increase in cardiac sympathetic modulation and a decrease in cardiac parasympathetic modulation during the induction. Overall, the results of this pilot study showed as propofol-induced anesthesia caused modifications on EEG signal, leading to a "rebalance" between long and short-range cortical connections, and had a direct effect on the cardiac system. Our data suggest interesting perspectives for the interactions between the central and autonomic nervous systems for the modulation of the consciousness level.
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http://dx.doi.org/10.3389/fnsys.2021.652080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055941PMC
April 2021

Characteristics of Patients Returning to Work After Brain Tumor Surgery.

Front Hum Neurosci 2020 3;14:609080. Epub 2021 Feb 3.

Neurology, Public Health and Disability Unit, Fondazione IRCSS Istituto Neurologico Carlo Besta, Milan, Italy.

To investigate the differences between patients returning to work and those who did not after brain tumor surgery. Patients were evaluated before surgery and after 3 months. The Montreal Cognitive Assessment test, Trail-Making Test (parts A and B), 15-word Rey-Osterrieth Word List (immediate and delayed recall), F-A-S tests, and Karnosfky Performance Status were used to assess cognitive status, attention, executive functions, memory, word fluency, and functional status. Patient-reported outcome measures (PROMs) used to evaluate emotional distress and disability were the Hospital Anxiety and Depression Scale and World Health Organization Disability Assessment Schedule. Clinical and work-related variables, PROMs, and cognitive tests were compared using chi-squared, -test or Mann-Whitney test. Sixty patients were included. Patients returning to work were 61.3 and 31.0% among people with meningioma and glioma, respectively. They reported lower postoperative disability and lesser home-to-work travel time. Patients with meningioma also showed better preoperative and postoperative attention and executive functions, better postoperative functional and cognitive status, and lower frequency of treatments. These variables should be considered in a clinical context to plan interventions for people who need support during return to work and in future research to investigate preoperative and postoperative predictive factors of going back to work.
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http://dx.doi.org/10.3389/fnhum.2020.609080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886680PMC
February 2021

A WHO resolution on epilepsy and other neurological disorders.

Lancet Neurol 2021 03;20(3):171-172

Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russia; Russian National Research Medical University, Moscow, Russia.

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http://dx.doi.org/10.1016/S1474-4422(21)00026-0DOI Listing
March 2021

Non-Pharmacological Approaches to Headaches: Non-Invasive Neuromodulation, Nutraceuticals, and Behavioral Approaches.

Int J Environ Res Public Health 2021 02 5;18(4). Epub 2021 Feb 5.

UOC Neurologia, Salute Pubblica e Disabilità, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.

Significant side effects or drug interactions can make pharmacological management of headache disorders very difficult. Non-conventional and non-pharmacological treatments are becoming increasingly used to overcome these issues. In particular, non-invasive neuromodulation, nutraceuticals, and behavioral approaches are well tolerated and indicated for specific patient categories such as adolescents and pregnant women. This paper aims to present the main approaches reported in the literature in the management of headache disorders. We therefore reviewed the available literature published between 2010 and 2020 and performed a narrative presentation for each of the three categories (non-invasive neuromodulation, nutraceuticals, and behavioral therapies). Regarding non-invasive neuromodulation, we selected transcranial magnetic stimulation, supraorbital nerve stimulation, transcranial direct current stimulation, non-invasive vagal nerve stimulation, and caloric vestibular stimulation. For nutraceuticals, we selected Feverfew, Butterbur, Riboflavin, Magnesium, and Coenzyme Q10. Finally, for behavioral approaches, we selected biofeedback, cognitive behavioral therapy, relaxation techniques, mindfulness-based therapy, and acceptance and commitment therapy. These approaches are increasingly seen as a valid treatment option in headache management, especially for patients with medication overuse or contraindications to drug treatment. However, further investigations are needed to consider the effectiveness of these approaches also with respect to the long-term effects.
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http://dx.doi.org/10.3390/ijerph18041503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914516PMC
February 2021

Visual fixation in disorders of consciousness: Development of predictive models to support differential diagnosis.

Physiol Behav 2021 03 4;230:113310. Epub 2021 Jan 4.

Neurology, Public Health, Disability Unit - Coma Research Centre; Scientific Directorate, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, 20133, Italy. Electronic address:

The visual fixation represents a doubtful behavioral sign to discriminate Vegetative from Minimally Conscious State (MCS). To disentangle its meaning, we fitted univariate and multivariable logistic regression models matching different neurophysiological and neuroimaging data of 54 patients with Disorders of Consciousness to select the best model predicting which visual performance (visual blink or pursuit) was shown by patients and the best predictors set. The best models found highlighted the importance of the structural MRI and the visual evoked potentials data in predicting visual pursuit. Then, a qualitative pilot test was made on four patients showing visual fixation revealing that the obtained models correctly predict whether the patients' visual performance could support/correlate to a cognitively mediated behavior. The present pilot models could help clinicians to evaluate if the visual fixation response can support the MCS diagnosis.
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http://dx.doi.org/10.1016/j.physbeh.2021.113310DOI Listing
March 2021

Preservation of Language Processing and Auditory Performance in Patients With Disorders of Consciousness: A Multimodal Assessment.

Front Neurol 2020 21;11:526465. Epub 2020 Dec 21.

Neuroradiology Department, Fondazione IRCCS Neurologico Carlo Besta, Milan, Italy.

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 ( = 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 (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 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.
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http://dx.doi.org/10.3389/fneur.2020.526465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779550PMC
December 2020

Global Burden of Headache Disorders in Children and Adolescents 2007-2017.

Int J Environ Res Public Health 2020 12 31;18(1). Epub 2020 Dec 31.

UOC Neurologia, Salute Pubblica, Disabilità, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.

Headache disorders are prevalent and disabling conditions impacting on people of all ages, including children and adolescents with substantial impact on their school activities and leisure time. Our study aims to report specific information on headaches in children and adolescents based on the Global Burden of Disease (GBD) study, that provides estimates for incidence, prevalence, fatal and non-fatal outcomes. We relied on 2007 and 2017 GBD estimates for prevalence and Years Lived with Disability (YLDs) at the global level and in WHO regions. The results show that, migraine and tension-type headache (TTH) together account for 37.5% of all-cause prevalence and for 7% of all-cause YLDs. Over the past decade, prevalence rates showed a mild increase of TTH in all ages and of migraine alone for adolescents. The YLDs increased among females of all ages with some regional differences that might be connected to the unequal availability of effective acute and prophylactic treatments across world regions. GBD data support the need to promote public health policies and strategies including diagnosis, pharmacological and non-pharmacological treatments that are expected to help reduce the disability and burden associated to migraine and TTH among children and adolescents.
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http://dx.doi.org/10.3390/ijerph18010250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795582PMC
December 2020

Mapping Assessments Instruments for Headache Disorders against the ICF Biopsychosocial Model of Health and Disability.

Int J Environ Res Public Health 2020 12 31;18(1). Epub 2020 Dec 31.

UOC Neurologia, Salute Pubblica, Disabilità, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.

Headache disorders have a strong impact on sufferers' lives. However, the "content" of assessment instruments addressing concepts, such as disability and quality of life (QoL), has not comprehensively been addressed. We searched SCOPUS for research papers in which outcome measures were used in adult populations of patients with migraine, tension-type headache (TTH), and cluster headache (CH). The content of single instruments was then mapped against the International Classification of Functioning, Disability, and Health. A total of 150 papers and 26 instruments were included: 15 addressed disability or impact, two addressed work-related difficulties, and nine addressed QoL. Few instruments were commonly used across the conditions and covered domains of functioning were impact on daily life activities, homework, school, and work-related tasks, leisure time, informal and family relations, pain, emotional difficulties, energy level, and impulse control. Most of the research is based on instruments that were developed for migraine, which is critical for CH, and the impact of headache disorders on work-related activities is poorly acknowledged. Further research is needed to expand the scope of headaches impact on daily life activities, and on environmental factors relevant to headache disorders to raise knowledge on the less represented areas, e.g., TTH impact.
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http://dx.doi.org/10.3390/ijerph18010246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795912PMC
December 2020

Older Adults' Risk Perception during the COVID-19 Pandemic in Lombardy Region of Italy: A Cross-sectional Survey.

J Gerontol Soc Work 2021 Sep 3;64(6):585-598. Epub 2021 Jan 3.

UOC Neurology, Public Health, Disability, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

During COVID-19 pandemic, older adults are the segment of the population at higher health risk. Given the important role the risk perception has in influencing both the behaviors and psychological well-being, it appears useful exploring this factor in this segment of the population. Despite different studies already described the factors influencing the risk perception, few focused on older adults. For this reason, we investigated risk perception in 514 people over 60 years during the lockdown. We administered a structured interview collecting socio-demographic information, sources of information used, actions undertaken to avoid contagion, and risk perception. Risk perception related to COVID-19 was significantly lower than the perceived risk associated with other threats, and it was correlated to the number of sources of information used but not to the actions undertaken. Furthermore, we found higher risk perception in who knew infected persons, and a negative correlation between the risk perception and age, with the over 75 perceiving a lower risk of getting infected compared to the younger participants. Our results should be taken as informative for future studies. Indeed, further studies on the older adults and the risk perception during emergencies are needed to better orient both communication and supporting strategies.
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http://dx.doi.org/10.1080/01634372.2020.1870606DOI Listing
September 2021

Development of a common scale for measuring healthy ageing across the world: results from the ATHLOS consortium.

Int J Epidemiol 2021 07;50(3):880-892

Wittgenstein Centre for Demography and Global Human Capital, International Institute for Applied Systems Analysis, Laxenburg, Austria.

Background: Research efforts to measure the concept of healthy ageing have been diverse and limited to specific populations. This diversity limits the potential to compare healthy ageing across countries and/or populations. In this study, we developed a novel measurement scale of healthy ageing using worldwide cohorts.

Methods: In the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) project, data from 16 international cohorts were harmonized. Using ATHLOS data, an item response theory (IRT) model was used to develop a scale with 41 items related to health and functioning. Measurement heterogeneity due to intra-dataset specificities was detected, applying differential item functioning via a logistic regression framework. The model accounted for specificities in model parameters by introducing cohort-specific parameters that rescaled scores to the main scale, using an equating procedure. Final scores were estimated for all individuals and converted to T-scores with a mean of 50 and a standard deviation of 10.

Results: A common scale was created for 343 915 individuals above 18 years of age from 16 studies. The scale showed solid evidence of concurrent validity regarding various sociodemographic, life and health factors, and convergent validity with healthy life expectancy (r = 0.81) and gross domestic product (r = 0.58). Survival curves showed that the scale could also be predictive of mortality.

Conclusions: The ATHLOS scale, due to its reliability and global representativeness, has the potential to contribute to worldwide research on healthy ageing.
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http://dx.doi.org/10.1093/ije/dyaa236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271194PMC
July 2021

Employment and Work Ability of Persons With Brain Tumors: A Systematic Review.

Front Hum Neurosci 2020 29;14:571191. Epub 2020 Oct 29.

Unità Operativa Complessa Neurologia, Salute Pubblica, Disabilità, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan, Italy.

Brain tumors (BT) are between the eight most common cancers among persons aged 40 years, with an average survival time of 10 years for patients affected by non-malignant brain tumor. Some patients continue to work, reporting difficulties in work-related activities, or even job loss. The purpose of the present study was to review the existing information about the ability people with BT to return to work and to identify factors associated with job loss. We performed a systematic review on SCOPUS and EMBASE for peer-reviewed papers that reported studies assessing work ability in patients with BT that were published in the period from January 2010 to January 2020. Out of 800 identified records, 7 articles were selected for analysis, in which 1,507 participants with BT were enrolled overall. Three main themes emerged: the impact of neuropsychological functioning on work productivity, the change of employment status for long-term survivors and issues related to return to work processes. Based on the results of selected studies, it can be concluded that the impact of BT on workforce participation is determined by depressive symptoms and cognitive deficits, as well as by high short-term mortality but also on environmental barriers. Vocational Rehabilitation programs should be implemented to help patients wishing to return to or maintain their current work, as much as possible.
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http://dx.doi.org/10.3389/fnhum.2020.571191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658191PMC
October 2020

Disability assessment in an Italian cohort of patients with obesity using an International Classification of Functioning, Disability and Health (ICF)-derived questionnaire.

Eur J Phys Rehabil Med 2021 Aug 9;57(4):630-638. Epub 2020 Nov 9.

Neurology, Public Health, Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Background: Obesity is a clinical condition that contributes to the development of related disability in different areas (physical, psychological and social). Multidisciplinary treatment calls for specific instruments able to evaluate all related functional problems. We have developed a tool (an ICF-based assessment instrument, the ICF-OB schedule) to evaluate obesity-related disability, composed of an inventory of 71-items from the WHO International Classification of Functioning, Disability and Health (ICF).

Aim: The aim of the present study was to validate this new tool for the definition of obesity-related disability. We also sought to examine the relationship between obesity disability, an index of multimorbidity (Cumulative Illness Rating Scale [CIRS]) and a well-validated score of perceived obesity-related disability (Italian Obesity Society Test for Obesity-Related Disability [TSD-OC]).

Design: Process validation of the ICF-OB schedule.

Setting: Baseline conditions of out- and in-patients.

Population: A large cohort of obese patients recruited from 9 multidisciplinary centers belonging to the Italian Obesity Society (SIO) network, which provide specialized obesity care.

Methods: A total of 353 patients (F: 70%, age: 50.2±12.7yrs, BMI: 41.4±8.3kg/m) were enrolled between January 2017 and June 2018. The ICF-OB was used to define patients' functioning and disability profiles in order to set and appraise rehabilitation goals.

Results: We described the distribution of body functions (BF), body structures (BS) and activities and participations (A&P) categories and the agreement rates were significant for the majority of these. The ICF-OB was more often significantly associated, and with stronger coefficients, with patients' comorbidities as described by the CIRS rather than with Body Mass Index (BMI). The TSD-OC also presented a strong association with A&P indexes.

Conclusions: The complexity of clinical condition, that generates disability in obesity might be well identified with the use of this new instrument that appear significant related to the perceived disability for each patients and also with their multimorbidity.

Clinical Rehabilitation Impact: The ICF-OB shows great promise as a tool for goal setting in the rehabilitation of obese patients.
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http://dx.doi.org/10.23736/S1973-9087.20.06512-0DOI Listing
August 2021

Clinical Presentation and Outcomes of Severe Acute Respiratory Syndrome Coronavirus 2-Related Encephalitis: The ENCOVID Multicenter Study.

J Infect Dis 2021 01;223(1):28-37

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

Background: Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of encephalitis in coronavirus disease 2019 (COVID-19) disease, but very few data have focused on clinical presentations, clinical course, response to treatment, and outcomes.

Methods: The SARS-CoV-2 related encephalopaties (ENCOVID) multicenter study included patients with encephalitis with full infectious screening, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) data and confirmed SARS-CoV-2 infection recruited from 13 centers in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment, and outcomes were recorded.

Results: Twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction resulted negative. Based on MRI, cases were classified as acute demyelinating encephalomyelitis (ADEM; n = 3), limbic encephalitis (LE; n = 2), encephalitis with normal imaging (n = 13), and encephalitis with MRI alterations (n = 7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (P = .001) and were associated with previous, more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to those with other encephalitis.

Conclusions: SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes.
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http://dx.doi.org/10.1093/infdis/jiaa609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543535PMC
January 2021

EEG Power spectra and subcortical pathology in chronic disorders of consciousness.

Psychol Med 2020 Sep 23:1-10. Epub 2020 Sep 23.

Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.

Background: Despite a growing understanding of disorders of consciousness following severe brain injury, the association between long-term impairment of consciousness, spontaneous brain oscillations, and underlying subcortical damage, and the ability of such information to aid patient diagnosis, remains incomplete.

Methods: Cross-sectional observational sample of 116 patients with a disorder of consciousness secondary to brain injury, collected prospectively at a tertiary center between 2011 and 2013. Multimodal analyses relating clinical measures of impairment, electroencephalographic measures of spontaneous brain activity, and magnetic resonance imaging data of subcortical atrophy were conducted in 2018.

Results: In the final analyzed sample of 61 patients, systematic associations were found between electroencephalographic power spectra and subcortical damage. Specifically, the ratio of beta-to-delta relative power was negatively associated with greater atrophy in regions of the bilateral thalamus and globus pallidus (both left > right) previously shown to be preferentially atrophied in chronic disorders of consciousness. Power spectrum total density was also negatively associated with widespread atrophy in regions of the left globus pallidus, right caudate, and in the brainstem. Furthermore, we showed that the combination of demographics, encephalographic, and imaging data in an analytic framework can be employed to aid behavioral diagnosis.

Conclusions: These results ground, for the first time, electroencephalographic presentation detected with routine clinical techniques in the underlying brain pathology of disorders of consciousness and demonstrate how multimodal combination of clinical, electroencephalographic, and imaging data can be employed in potentially mitigating the high rates of misdiagnosis typical of this patient cohort.
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http://dx.doi.org/10.1017/S003329172000330XDOI Listing
September 2020

Avoiding the Banality of Evil in Times of COVID-19: Thinking Differently with a Biopsychosocial Perspective for Future Health and Social Policies Development.

SN Compr Clin Med 2020 Sep 1:1-3. Epub 2020 Sep 1.

CanChild - Centre for Childhood Disability Research, McMaster University, Hamilton, Ontario Canada.

The COVID-19 pandemic provides the opportunity to re-think health policies and health systems approaches by the adoption of a biopsychosocial perspective, thus acting on environmental factors so as to increase facilitators and diminish barriers. Specifically, vulnerable people should not face discrimination because of their vulnerability in the allocation of care or life-sustaining treatments. Adoption of biopsychosocial model helps to identify key elements where to act to diminish effects of the pandemics. The pandemic showed us that barriers in health care organization affect mostly those that are vulnerable and can suffer discrimination not because of severity of diseases but just because of their vulnerability, be this age or disability and this can be avoided by biopsychosocial planning in health and social policies. It is possible to avoid the banality of evil, intended as lack of thinking on what we do when we do, by using the emergence of the emergency of COVID-19 as a Trojan horse to achieve some of the sustainable development goals such as universal health coverage and equity in access, thus acting on environmental factors is the key for global health improvement.
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http://dx.doi.org/10.1007/s42399-020-00486-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462656PMC
September 2020
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