Publications by authors named "Ettore Beghi"

301 Publications

Trends in survival of ALS from a population-based registry.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Nov 24:1-9. Epub 2021 Nov 24.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.

To assess survival of ALS patients in general and in selected demographic and clinical subgroups comparing two periods (1998-2000 vs. 2008-2010). Newly diagnosed adults resident of Lombardy, Northern Italy from a population-based registry were included. Data were collected on age at diagnosis, sex, site of onset, diagnostic delay, and El-Escorial diagnostic category. Patients were followed until death or last observation. Survival was evaluated using Kaplan-Meier curves and Cox's proportional hazards models. In 2008-2010 (267 patients), median survival was 2.4 years and 1-year, 2-year, 3-year and 5-year survival rates were 79%, 56%, 41% and 24%. Longer survival was associated with male sex, younger age, spinal onset, and longer diagnostic delay. Multivariable analysis confirmed higher death in 65-69yr (HR 2.8; 95% CI 1.4-5.6), 70-74yr (HR 3.2; 95% CI 1.6-6.3) and 75 + yr (HR 6.9; 95% CI 3.5-13.8) categories, compared to ≤49yr, in females (HR 1.4; 95% CI 1.02-1.8), compared to males, and in patients diagnosed after 6-12 months (HR 1.9; 95% CI 1.4-2.7), compared with longer diagnostic delay. In 1998-2000 (235 patients), median survival was 2.2 years. The 1-year, 2-year, 3-year and 5-year survival rates were 77%, 53%, 38% and 20%. When adjusting for demographic and clinical variables, the HR for death in 2008-2010 versus 1998-2000 was 0.80 (95% CI 0.66-0.98). A significant increase of survival in 2008-2010 was found only in patients aged 50-59yr and 70-74yr at diagnosis. Survival of ALS has increased over time in the last decades, especially in middle aged and elderly patients. The benefits of comprehensive care in selected age groups might explain our findings.
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http://dx.doi.org/10.1080/21678421.2021.2004167DOI Listing
November 2021

Acute and post-acute neurological manifestations of COVID-19: present findings, critical appraisal, and future directions.

J Neurol 2021 Oct 21. Epub 2021 Oct 21.

Department of Neurology, Centre for Global Health, Technical University of Munich, Munich, Germany.

Acute and post-acute neurological symptoms, signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19). In this review, we aimed to summarize the current literature addressing neurological events following SARS-CoV-2 infection, discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID-19. The presence of neurological manifestations (symptoms, signs or diagnoses) both at the onset or during SARS-CoV-2 infection is associated with a more severe disease, as demonstrated by a longer hospital stay, higher in-hospital death rate or the continued presence of sequelae at discharge. Although biological mechanisms have been postulated for these findings, evidence-based data are still lacking to clearly define the incidence, range of characteristics and outcomes of these manifestations, particularly in non-hospitalized patients. In addition, data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19, with reference to geography, ethnicity, socio-cultural settings, and health care arrangements. As a consequence, at present a specific phenotype that would specify a post-COVID (or long-COVID) neurological syndrome has not yet been identified.
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http://dx.doi.org/10.1007/s00415-021-10848-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528941PMC
October 2021

Frequency of Neurologic Manifestations in COVID-19: A Systematic Review and Meta-analysis.

Neurology 2021 Oct 11. Epub 2021 Oct 11.

Rajendra Institute of Medical Sciences, Ranchi-834009, Jharkhand, India

Background And Objectives: One year since the onset of the COVID-19 pandemic, we aimed to summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality.

Methods: We searched PubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31 December 2019 to 15 December 2020 for studies enrolling consecutive COVID-19 patients presenting with neurological manifestations. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.

Results: Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence- 2%). In COVID-19 patients aged ≥60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91).

Discussion: Up to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.
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http://dx.doi.org/10.1212/WNL.0000000000012930DOI Listing
October 2021

Geographical clusters of amyotrophic lateral sclerosis and the Bradford Hill criteria.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Sep 25:1-15. Epub 2021 Sep 25.

Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy, and.

With the aim of shedding further light on the role of environmental factors in amyotrophic lateral sclerosis (ALS) etiology, we hereby conducted a historical narrative review to critically appraise the published reports on ALS geographical clusters using the modern interpretation of the Bradford Hill criteria for causation. Our research hypothesis was that the more criteria were met, the greater was the evidence supporting a causal association. We found that cluster studies that met the greatest number of Bradford's Hill criteria regarded the non-protein amino acid β-N-methylamino-L-alanine (L-BMAA) and exposure to metals and minerals, but the evidence for causation was at best moderate and was poor for other environmental factors. This defective picture might be attributed not only to the methodological approach adopted by published studies, but also to the inherent difficulties in the application of Bradford Hill criteria, due to the complexity of the disease phenotype and the underlying pathogenic mechanisms.
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http://dx.doi.org/10.1080/21678421.2021.1980891DOI Listing
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

Validity of 2 Fall Prevention Strategy Scales for People With Stroke, Parkinson's Disease, and Multiple Sclerosis.

J Geriatr Phys Ther 2021 Aug 13. Epub 2021 Aug 13.

IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy. IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Department of Physiopathology and Transplants, University of Milan, Milan, Italy.

Background And Purpose: Falls are a common and persistent concern among people with neurological disorders (PwND), as they frequently result in mobility deficits and may lead to loss of functional independence. This study investigated the ceiling and floor effects, internal consistency, and convergent validity of 2 patient-reported fall prevention strategy scales in PwND.

Methods: This is a prospective cohort study. Two-hundred and ninety-nine PwND (111 people with multiple sclerosis, 94 people with Parkinson's disease, and 94 people with stroke) were seen for rehabilitation and assessed. The number of retrospective and prospective falls, use of walking assistive devices, scores on the Fall Prevention Strategy Survey (FPSS), Falls Behavioural Scale (FaB), and balance and mobility scales (Berg Balance Scale, Dynamic Gait Index, Timed Up and Go, 10-m walking test, and Activities-specific Balance Confidence) were analyzed.

Results: Total score distributions showed negligible ceiling and floor effects for both the FPSS (ceiling: 0.3%, floor: 0.3%) and the FaB (ceiling: 0%, floor: 0%). The Cronbach α (CI) was of 0.87 (0.85-0.89) for the FPSS and 0.86 (0.84-0.88) for the FaB. In terms of convergent validity, the FPSS and FaB were moderately correlated (Spearman correlation coefficient = 0.65). Moreover, the correlations between the FPSS and FaB and balance and mobility scales ranged from 0.25 to 0.49 (P < .01). Both scales are slightly better able to distinguish between retrospective fallers/nonfallers [area under the curve, AUC (95% CI): FPSS: 0.61 (0.5-0.7); FaB: 0.60 (0.5-0.6)] compared with prospective fallers/nonfallers [AUC (95% CI): FPSS: 0.56 (0.4-0.6); FaB: 0.57 (0.4-0.6)]. Both scales accurately identified individuals who typically required the use of a walking assistive device for daily ambulation [AUC (95% CI): FPSS: 0.74 (0.7-0.8); FaB: 0.69 (0.6-0.7)]. Multiple regression analysis showed that previous falls, use of an assistive device, and balance confidence significantly predicted participants' prevention strategies (FPSS: R2 = 0.31, F(8,159) = 10.5, P < .01; FaB: R2 = 0.31, F(8,164) = 10.89, P < .01).

Conclusion: The FPSS and the FaB appear to be valid tools to assess fall prevention strategies in people with neurological disorders. Both scales provide the unique and added value in providing information on individual behavior for fall prevention.
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http://dx.doi.org/10.1519/JPT.0000000000000325DOI Listing
August 2021

ALS incidence and population aging in Northern Italy.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Aug 2:1-6. Epub 2021 Aug 2.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.

: Data on and increase of the incidence of amyotrophic lateral sclerosis (ALS) are conflicting and reflect the use of differing populations and designs. We investigated the incidence of ALS using data from a large population-based registry (SLALOM) in two three-year periods using the same diagnostic criteria and equal methods of case ascertainment. : The registry is based in Lombardy, a 10 million population area of Northern Italy. Using different sources of cases (hospital discharge and ambulatory records, regional claims and prescription records) from nine Lombardy provinces (population, 5,485,163), all patients with newly diagnosed ALS during the periods 1998-2000 and 2008-2010 were included. : A total of 235 and 440 newly diagnosed patients were traced during the two study periods. The corresponding incidence rates were, respectively, 1.61 and 2.72 per 100,000 person-years. Data varied with age, sex and province by a significant increase was found only in men aged 65 through 74 years. : Based on our findings, the increased incidence of ALS with time is real and can be largely interpreted as a reflection of the advancing age of the general population.
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http://dx.doi.org/10.1080/21678421.2021.1953076DOI Listing
August 2021

Comorbidities in patients with epilepsy: Frequency, mechanisms and effects on long-term outcome.

Epilepsia 2021 Oct 26;62(10):2395-2404. Epub 2021 Jul 26.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.

Objective: To assess frequency, types, and mechanisms of comorbidities in people with epilepsy and verify their association with disease features and outcome.

Methods: This cohort study was performed in 13 Italian epilepsy centers with nationwide distribution and accurate records. Eligible patients were children and adults diagnosed before December 31, 2005, and followed for a minimum of 10 years. Two pairs of raters independently reviewed patients' records and classified each comorbidity. In case of disagreement, a third reviewer made the final decision. Comorbidities were classified according to type (organ/system) and underlying mechanism (causal, shared risk factors, chance association). Comorbidity types and mechanisms were described in the entire sample and according to epilepsy prognostic patterns (sustained remission, relapsing-remitting course, no remission).

Results: Of 1006 included patients, 266 (26.4%) had at least one comorbidity. The most common were developmental/perinatal (7.5% of cases), psychiatric (6.2%), cardiovascular (5.3%), and endocrine/metabolic (3.8%). Among 408 reported comorbidities, the underlying mechanisms were, in decreasing order, chance association (42.2%), shared risk factors (31.1%), and causal (26.7%). Psychiatric diseases were present in 13.3% of patients with no remission, 5.9% of patients with relapsing-remitting course, and 4.8% of patients with sustained remission (p = .016). The corresponding numbers for endocrine/metabolic diseases were respectively, 9.6%, 3.4%, and 2.9% (p = .013); for respiratory diseases were 3.6%, .3%, and .3% (p = .001), and for urogenital diseases were 3.6%, .7%, and 1.6% (p = .048). The association of endocrine/metabolic, psychiatric, and respiratory comorbidities with epilepsy prognosis was confirmed by multivariable analysis adjusted for the main demographic and clinical variables, with patients with these comorbidities showing a lower probability of achieving remission.

Significance: Comorbidities in epilepsy are not uncommon and reflect differing underlying mechanisms. Psychiatric, endocrine/metabolic, and respiratory disorders are associated with a worse long-term epileptological outcome.
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http://dx.doi.org/10.1111/epi.17022DOI Listing
October 2021

Predictive factors of Status Epilepticus and its recurrence in patients with adult-onset seizures: A multicenter, long follow-up cohort study.

Seizure 2021 Oct 18;91:397-401. Epub 2021 Jul 18.

Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, National Council of Research, Institute of Clinical Physiology, Reggio Calabria, Italy.

Purpose: Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures.

Methods: We retrospectively analyzed data of 1115 patients with seizure onset>18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 2:1 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model.

Results: Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p<0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p<0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p<0.001).

Conclusions: In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.
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http://dx.doi.org/10.1016/j.seizure.2021.07.009DOI Listing
October 2021

European Academy of Neurology and European Federation of Neurorehabilitation Societies guideline on pharmacological support in early motor rehabilitation after acute ischaemic stroke.

Eur J Neurol 2021 09 21;28(9):2831-2845. Epub 2021 Jun 21.

RoNeuro Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania.

Background And Purpose: Early pharmacological support for post-stroke neurorehabilitation has seen an abundance of mixed results from clinical trials, leaving practitioners at a loss regarding the best options to improve patient outcomes. The objective of this evidence-based guideline is to support clinical decision-making of healthcare professionals involved in the recovery of stroke survivors.

Methods: This guideline was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. PubMed, Cochrane Library and Embase were searched (from database inception to June 2018, inclusive) to identify studies on pharmacological interventions for stroke rehabilitation initiated in the first 7 days (inclusive) after stroke, which were delivered together with neurorehabilitation. A sensitivity analysis was conducted on identified interventions to address results from breaking studies (from end of search to February 2020).

Results: Upon manually screening 17,969 unique database entries (of 57,001 original query results), interventions underwent meta-analysis. Cerebrolysin (30 ml/day, intravenous, minimum 10 days) and citalopram (20 mg/day, oral) are recommended for clinical use for early neurorehabilitation after acute ischaemic stroke. The remaining interventions identified by our systematic search are not recommended for clinical use: amphetamine (5, 10 mg/day, oral), citalopram (10 mg/day, oral), dextroamphetamine (10 mg/day, oral), Di-Huang-Yi-Zhi (2 × 18 g/day, oral), fluoxetine (20 mg/day, oral), lithium (2 × 300 mg/day, oral), MLC601(3 × 400 mg/day, oral), phosphodiesterase-5 inhibitor PF-03049423 (6 mg/day, oral). No recommendation 'for' or 'against' is provided for selegiline (5 mg/day, oral). Issues with safety and tolerability were identified for amphetamine, dextroamphetamine, fluoxetine and lithium.

Conclusions: This guideline provides information for clinicians regarding existing pharmacological support in interventions for neurorecovery after acute ischaemic stroke. Updates to this material will potentially elucidate existing conundrums, improve current recommendations, and hopefully expand therapeutic options for stroke survivors.
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http://dx.doi.org/10.1111/ene.14936DOI Listing
September 2021

Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19-A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium.

JAMA Netw Open 2021 05 3;4(5):e2112131. Epub 2021 May 3.

College of Nursing, The Ohio State University, Columbus.

Importance: The COVID-19 pandemic continues to affect millions of people globally, with increasing reports of neurological manifestations but limited data on their incidence and associations with outcome.

Objective: To determine the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19.

Design, Setting, And Participants: This cohort study included patients with clinically diagnosed or laboratory-confirmed COVID-19 at 28 centers, representing 13 countries and 4 continents. The study was performed by the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) from March 1 to September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) from March to October 2020. Three cohorts were included: (1) the GCS-NeuroCOVID all COVID-19 cohort (n = 3055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; (2) the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and (3) the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation.

Exposures: Clinically diagnosed or laboratory-confirmed COVID-19.

Main Outcomes And Measures: Neurological phenotypes were classified as self-reported symptoms or neurological signs and/or syndromes assessed by clinical evaluation. Composite incidence was reported for groups with at least 1 neurological manifestation. The main outcome measure was in-hospital mortality.

Results: Of the 3055 patients in the all COVID-19 cohort, 1742 (57%) were men, and the mean age was 59.9 years (95% CI, 59.3-60.6 years). Of the 475 patients in the COVID-19 neurological cohort, 262 (55%) were men, and the mean age was 62.6 years (95% CI, 61.1-64.1 years). Of the 214 patients in the ENERGY cohort, 133 (62%) were men, and the mean age was 67 years (95% CI, 52-78 years). A total of 3083 of 3743 patients (82%) across cohorts had any neurological manifestation (self-reported neurological symptoms and/or clinically captured neurological sign and/or syndrome). The most common self-reported symptoms included headache (1385 of 3732 patients [37%]) and anosmia or ageusia (977 of 3700 patients [26%]). The most prevalent neurological signs and/or syndromes were acute encephalopathy (1845 of 3740 patients [49%]), coma (649 of 3737 patients [17%]), and stroke (222 of 3737 patients [6%]), while meningitis and/or encephalitis were rare (19 of 3741 patients [0.5%]). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death (adjusted odds ratio [aOR], 5.99; 95% CI, 4.33-8.28) after adjusting for study site, age, sex, race, and ethnicity. Presence of preexisting neurological disorders (aOR, 2.23; 95% CI, 1.80-2.75) was associated with increased risk of developing neurological signs and/or syndromes with COVID-19.

Conclusions And Relevance: In this multicohort study, neurological manifestations were prevalent among patients hospitalized with COVID-19 and were associated with higher in-hospital mortality. Preexisting neurological disorders were associated with increased risk of developing neurological signs and/or syndromes in COVID-19.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.12131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114143PMC
May 2021

Immediate antiepileptic drug treatment, versus placebo, deferred, or no treatment for first unprovoked seizure.

Cochrane Database Syst Rev 2021 05 4;5:CD007144. Epub 2021 May 4.

Laboratorio di Malattie Neurologiche, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

Background: This is an updated version of the Cochrane review previously published in 2016. There is considerable disagreement about the risk of recurrence following a first unprovoked epileptic seizure. A decision about whether to start antiepileptic drug treatment following a first seizure should be informed by information on the size of any reduction in risk of future seizures, the impact on long-term seizure remission, and the risk of adverse effects.

Objectives: To review the probability of seizure recurrence, seizure remission, mortality, and adverse effects of antiepileptic drug (AED) treatment given immediately after the first seizure compared to controls (placebo, deferred treatment, or no treatment) in children and adults.

Search Methods: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to May 24, 2019) on 28 May 2019. There were no language restrictions. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised or quasi-randomised, controlled trials from Embase, ClinicalTrials.gov and the World Health Organisation International Clinical Trials Registry Platform (ICTRP).

Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs that could be blinded or unblinded. People of any age with a first unprovoked seizure of any type. Included studies compared participants receiving immediate antiepileptic treatment versus those receiving deferred treatment, those assigned to placebo, and those untreated.

Data Collection And Analysis: Two review authors independently assessed the studies identified by the search strategy for inclusion in the review and extracted data. The certainty of the evidence for the outcomes was classified in four categories according to the GRADE approach. Dichotomous outcomes were expressed as Risk Ratios (RR) with 95% confidence intervals (CI). Time-to-event outcomes were expressed as Hazard Ratios (HR) with 95% CI. Only one trial used a double-blind design, and the two largest studies were unblinded. Most of the recurrences were generalised tonic-clonic seizures, a major type of seizures that is easily recognised, which should reduce the risk of outcome reporting bias.

Main Results: After exclusion of irrelevant papers, six studies (eleven reports) were selected for inclusion. Individual participant data were available from the two largest studies for meta-analysis. Selection bias and attrition bias could not be excluded within the four smaller studies, but the two largest studies reported attrition rates and adequate methods of randomisation and allocation concealment. Only one small trial used a double-blind design and the other trials were unblinded; however, most of the recurrences were generalised tonic-clonic seizures, a type of seizure that is easily recognisable. Compared to controls, participants randomised to immediate treatment had a lower probability of relapse at one year (RR 0.49, 95% CI 0.42 to 0.58; 6 studies, 1634 participants; high-certainty evidence), at five years (RR 0.78; 95% CI 0.68 to 0.89; 2 studies, 1212 participants; high-certainty evidence) and a higher probability of an immediate five-year remission (RR 1.25; 95% CI 1.02 to 1.54; 2 studies, 1212 participants; high-certainty evidence). However, there was no difference between immediate treatment and control in terms of five-year remission at any time (RR 1.02, 95% CI 0.87 to 1.21; 2 studies, 1212 participants; high-certainty evidence). Antiepileptic drugs did not affect overall mortality after a first seizure (RR 1.16; 95% CI 0.69 to 1.95; 2 studies, 1212 participants; high-certainty evidence). Compared to deferred treatment, treatment of the first seizure was associated with a significantly higher risk of adverse events (RR 1.49, 95% CI 1.23 to 1.79; 2 studies, 1212 participants; moderate-certainty evidence). We assessed the certainty of the evidence as moderate to low for the association of higher risk of adverse events when treatment of the first seizure was compared to no treatment or placebo, (RR 14.50, 95% CI 1.93 to 108.76; 1 study; 118 participants) and (RR 4.91, 95% CI 1.10 to 21.93; 1 study, 228 participants) respectively.

Authors' Conclusions: Treatment of the first unprovoked seizure reduces the risk of a subsequent seizure but does not affect the proportion of patients in remission in the long term. Antiepileptic drugs are associated with adverse events, and there is no evidence that they reduce mortality. In light of this review, the decision to start antiepileptic drug treatment following a first unprovoked seizure should be individualised and based on patient preference, clinical, legal, and sociocultural factors.
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http://dx.doi.org/10.1002/14651858.CD007144.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094016PMC
May 2021

Invitation to participate in a prospective case-control study of sudden unexpected death in epilepsy.

Epilepsia 2021 05;62(5):1280-1281

School of Population Health, Grafton Campus, University of Auckland, Auckland, New Zealand.

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http://dx.doi.org/10.1111/epi.16898DOI Listing
May 2021

Approaches to understanding COVID-19 and its neurological associations.

Ann Neurol 2021 Apr 9. Epub 2021 Apr 9.

Department of Neurology, Center for Global Health, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

There is an accumulating volume of research into neurological manifestations of COVID-19. However, inconsistent study designs, inadequate controls, poorly-validated tests, and differing settings, interventions, and cultural norms weaken study quality, comparability, and thus the understanding of the spectrum, burden and pathophysiology of these complications. Therefore, a global COVID-19 Neuro Research Coalition, together with the WHO, has reviewed reports of COVID-19 neurological complications and harmonised clinical measures for future research. This will facilitate well-designed studies using precise, consistent case definitions of SARS-CoV2 infection and neurological complications, with standardised forms for pooled data analyses that non-specialists can use, including in low-income settings. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ana.26076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250622PMC
April 2021

Antiseizure medication in patients with Glioblastoma- a collaborative cohort study.

Seizure 2021 Apr 15;87:107-113. Epub 2021 Mar 15.

Center for Tumor-related Epilepsy, UOSD Neuroncology, Regina Elena National Cancer Institute IRCCS, Rome, Italy. Electronic address:

Purpose: We investigated, whether epileptic seizures (ES) as presenting symptom in adult patients with GBM are associated with better Overall Survival (OS) compared to ES presenting later during the course of GBM, and efficacy and safety of different antiseizure medications (ASMs).

Methods: Retrospective consecutive cohort study of adults with GBM: 50 from Norway and 50 from Italy. We compared the time to changing ASM treatments. OS was investigated with a Cox regression model adjusted for time dependency.

Results: Median follow-up was 17 months from GBM diagnosis. ES were the presenting symptom in 49 patients. All patients received ASM treatment. LEV was the first ASM in the majority of patients and the most effective at one year from the first prescription, (p = 0.004). Occurrence of adverse events (AEs) was similar between LEV and other ASMs (p = 0.47). Poorer OS correlated with older age at GBM diagnosis, country and ASM therapy. A negative impact of ASMs on OS was observed for LEV in a univariate and multivariate analysis, and for VPA (only in multivariate analysis), even when adjusted for O6-methylguanine-DNA-methyltransferase (MGMT) methylation status. Patients with ES as the onset symptom of GBM and patients who had first ES later had similar OS (p = 0.87).

Conclusion: ES as the GBM debut symptom did not lead to a longer OS. LEV was a more effective ASM compared to other treatments with no differences regarding AEs between LEV and other ASMs. Surprisingly, in our patients LEV and VPA were associated with worse OS than other ASMs. This result should be interpreted with caution due to the retrospective nature of this study along with the many variables which may affect the outcome in this population.
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http://dx.doi.org/10.1016/j.seizure.2021.03.012DOI Listing
April 2021

Discontinuation of antiseizure medications in seizure-free patients with long-term follow-up: Patients' profile, seizure recurrence, and risk factors.

Epilepsy Behav 2021 04 6;117:107871. Epub 2021 Mar 6.

Epilepsy Center, Department of Neurology, San Gerardo Hospital ASST Monza, University of Milano Bicocca, Monza, Italy.

Objective: To compare withdrawal of antiseizure medications (ASM) to continued treatment in newly diagnosed individuals achieving seizure freedom, and assess the risk of relapse and factors associated with relapse.

Methods: This is a multicenter retrospective cohort study with long-term follow-up. Patients with newly diagnosed epilepsy were identified from the medical records of 13 Italian epilepsy centers and followed up until the most recent visit or death. Seizure-free patients discontinuing treatment were compared to patients who maintained treatment for baseline characteristics. Treatment was stopped upon clinical judgment. The probability of relapse was calculated with the Kaplan-Meier method. Demographic, clinical, and instrumental variables associated with relapse were assessed with Cox proportional hazards models.

Results: One thousand and six patients aged 1 month to 72 years at diagnosis were enrolled and followed up for 17,892 person-years (median follow-up, 9.9 years). Three hundred and twenty patients (31.8%) underwent one or more treatment discontinuations. Factors associated with ASM withdrawal were younger age at remission and normal psychiatric examination. The probability of relapse after the first withdrawal was 16% at six months, 24% at 12 months, and 36%, 45%, and 53% at three, five, and ten years, respectively. The probability of remission after the first relapse was 59% at one month, 67%, 72, and 76% at three, six, and 12 months, respectively. Variables associated with relapse were age 14+ years, structural etiology, abnormal neuroimaging, ASM initiation after a single seizure, and symptomatic/cryptogenic epilepsy.

Conclusions: About one half of seizure-free patients stopping ASM relapse in 10 years. However, the possibility of remission after relapse is high, particularly in children and patients with idiopathic/cryptogenic epilepsy. Treatment deprescription might be encouraged at least in these patients.
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http://dx.doi.org/10.1016/j.yebeh.2021.107871DOI Listing
April 2021

Time-trend evolution and determinants of sex ratio in Amyotrophic Lateral Sclerosis: a dose-response meta-analysis.

J Neurol 2021 Aug 25;268(8):2973-2984. Epub 2021 Feb 25.

Unit of Biostatistics, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.

Background: A noticeable change of the male-to-female sex ratio (SR) has been observed in Amyotrophic Lateral Sclerosis (ALS) leading to an apparent regression of SR with time (SR close to 1:1).

Objective: To provide a global SR estimate and investigate its relation with respect to population age.

Methods: A systematic review and meta-analysis was conducted including only population-based studies with a high-quality methodology in European ancestral origin population. Male-to-female SR was estimated by three different measures: SR number, SR crude incidence and SR standardized incidence. Standard and dose-response meta-analyses were performed to assess the pooled SR measures (irrespective of population age) and the evolution of the SR measures with respect to population age, respectively. Potential sources of heterogeneity were investigated via meta-regression.

Results: Overall, 3254 articles were retrieved in the literature search. Thirty-nine studies stratified by time periods were included. The overall pooled male-to-female ratio was 1.28 (95% CI 1.23-1.32) for SR number, 1.33 (95% CI 1.29-1.38) for SR crude incidence and 1.35 (95% CI 1.31-1.40) for SR standardized incidence. The SR number with respect to population age reveals a progressive reduction of SR at increasing age, while the SR crude incidence in relation to age displays a U-shaped curve.

Conclusions: The number and the incidence of ALS cases were consistently higher in males than females. Dose-response meta-analysis showed that SR measures change with respect to population age. Further original research is needed to clarify if our findings are reproducible in other populations.
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http://dx.doi.org/10.1007/s00415-021-10464-2DOI Listing
August 2021

Appropriate use of generic and branded antiseizure medications in epilepsy: Updated recommendations from the Italian League Against Epilepsy (LICE).

Epilepsy Behav 2021 03 10;116:107804. Epub 2021 Feb 10.

Science of Health Department, School of Medicine, University of Catanzaro, Italy. Electronic address:

Generic drugs are increasingly used to treat many diseases including epilepsy. The growing importance of generic antiseizure medications (ASMs) has led the ASMs commission of the Italian League Against Epilepsy (LICE) to review current evidence in the literature about efficacy and safety of these products. Recommendations from other scientific organizations have also been considered to provide an update of the LICE position about their utilization (List of Recommendations). Compared with the previous literature review, randomized controlled trials assessing bioequivalence among branded drugs and generics are currently available. Although some contrasting results have been reported, brand-to-generic switching was effective and tolerable in real-life settings, with similar adverse event ratios. Based on these findings, LICE concluded that, conforming to the rigorous regulation of USA and EU markets, generic ASMs are not inferior to the respective branded, providing a cost advantage for patients starting or replacing monotherapy or add-on, and for those with incomplete seizure control. Branded-to-generic (and vice versa) switching is not recommended (although applicable) during seizure remission, as well as the generic-to-other generic switching. Other recommendations focus on the appropriateness of therapeutic drug monitoring (TDM) when switching is required, paying attention to avoiding the erroneous switch between modified and immediate-release formulations during dispensation. Finally, to support patients' compliance, they should be assured of generics' safety and efficacy and carefully informed with practical advice, particularly when the switching is associated with aspect modifications (e.g. color and shape changes) of the pill or the packaging.
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http://dx.doi.org/10.1016/j.yebeh.2021.107804DOI Listing
March 2021

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

Eur J Neurol 2021 11 5;28(11):3849-3855. Epub 2021 Feb 5.

Division of Neurology, CHU of Grenoble, Grenoble Institute of Neurosciences, Grenoble Alpes University, Grenoble, France.

Coronavirus disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID-19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID-19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long-term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID-19 Task Force intends to raise awareness of the potential impact of COVID-19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.
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http://dx.doi.org/10.1111/ene.14741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014664PMC
November 2021

Effects of lockdown on emergency room admissions for psychiatric evaluation: an observational study from the AUSL Romagna, Italy.

Int J Psychiatry Clin Pract 2021 Jun 21;25(2):135-139. Epub 2020 Dec 21.

Department of Biomedical Metabolic and Neural Sciences, University of Modena & Reggio Emilia, Modena, Italy.

Objectives: An observation of the admissions to the emergency room (ER) requiring psychiatric evaluation during the lockdown and investigation of the demographic and clinical variables.

Methods: Retrospective longitudinal observational study of ER accesses for psychiatric evaluation was performed, comparing two periods (9 March-3 May 2020 vs. 9 March-3 May 2019). Data (number of admissions, key baseline demographic and clinical variables) were extracted from the ER databases of referral centres in a well-defined geographic area of North-Eastern Italy (Cesena, Ravenna, Forlì, and Rimini).

Results: A 15% reduction of psychiatric referrals was observed, together with a 17% reduction in the total number of patients referring to the ER. This reduction was most evident in the first month of the lockdown period (almost 25% reduction of both referrals and patients). Female gender (OR: 1.52: 95%, CI: 1.12-2.06) and being a local resident (OR: 1.54: 95%CI: 1.02-2.34) were factors associated with the decrease.

Conclusions: Lockdown changed dramatically health priorities in the local population, including people with mental health. We speculate that our observations do not only refer to the confinement due to the lockdown regime but also to fear of contagion and adoption of different coping strategies, especially in women.Key-pointsDuring lockdown 15% reduction of psychiatric visits and >17% reduction in the number of psychiatric patients referring to the ER was observed.in the first four weeks of the lockdown almost 25% reduction of both visits and patients was observedFemale gender and being a local resident were factors associated with the decrease.
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http://dx.doi.org/10.1080/13651501.2020.1859120DOI Listing
June 2021

Stroke epidemiology and COVID-19 pandemic.

Curr Opin Neurol 2021 02;34(1):3-10

Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Purpose Of Review: The aim of this study was to describe the impact of the COVID-19 outbreak on the epidemiology, cause and clinical characteristics of incident stroke in different settings and populations.

Recent Findings: Several studies have shown that there are three main themes in the epidemiology of stroke during the COVID-19 pandemic: COVID-19 seems to be associated with stroke in a significant number of patients. This association has been reported in several clinical series, mainly from China. There is a consistent trend towards a decreased number of hospital admissions of stroke patients during the pandemic. There are no population-based data available on incident stroke in individuals with COVID-19.

Summary: In this review, we report on increased rates and severe prognosis of ischemic stroke among individuals with COVID-19, probably explained by hypercoagulability and inflammation, documented since the early phase of disease.We confirm the presence of falling rates of new ischemic stroke admissions in hospitals, probably due to social consequences of the pandemic: fear to be infected or not adequately treated in the hospital. This phenomenon is restricted to mild stroke and transient ischemic attacks.Short and long-term consequences of this trend of new strokes in the pandemic need to be evaluated.
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http://dx.doi.org/10.1097/WCO.0000000000000879DOI Listing
February 2021

The European Academy of Neurology COVID-19 registry (ENERGY): an international instrument for surveillance of neurological complications in patients with COVID-19.

Eur J Neurol 2021 Oct 3;28(10):3303-3323. Epub 2021 Jan 3.

Department of Neurology, Inselspital, University of Bern, Bern, Switzerland.

The COVID-19 pandemic is a global public health issue. Neurological complications have been reported in up to one-third of affected cases, but their distribution varies significantly in terms of prevalence, incidence and phenotypical characteristics. Variability can be mostly explained by the differing sources of cases (hospital vs. community-based), the accuracy of the diagnostic approach and the interpretation of the patients' complaints. Moreover, after recovering, patients can still experience neurological symptoms. To obtain a more precise picture of the neurological manifestations and outcome of the COVID-19 infection, an international registry (ENERGY) has been created by the European Academy of Neurology in collaboration with European national neurological societies and the Neurocritical Care Society and Research Network. ENERGY can be implemented as a stand-alone instrument for patients with suspected or confirmed COVID-19 and neurological findings or as an addendum to an existing registry not targeting neurological symptoms. Data are also collected to study the impact of neurological symptoms and neurological complications on outcomes. The variables included in the registry have been selected in the interests of most countries, to favour pooling with data from other sources and to facilitate data collection even in resource-poor countries. Included are adults with suspected or confirmed COVID-19 infection, ascertained through neurological consultation, and providing informed consent. Key demographic and clinical findings are collected at registration. Patients are followed up to 12 months in search of incident neurological manifestations. As of 19 August, 254 centres from 69 countries and four continents have made requests to join the study.
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http://dx.doi.org/10.1111/ene.14652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753513PMC
October 2021

Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study.

JAMA Neurol 2021 Feb;78(2):165-176

Department of Systems, Populations, and Leadership, University of Michigan, Ann Arbor.

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US.

Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017.

Design, Setting, And Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.

Exposures: Any of the 14 listed neurological diseases.

Main Outcome And Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated.

Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% [95% UI, -32.4% to -25.8%]); spinal cord injury prevalence (-38.5% [95% UI, -43.1% to -34.0%]); meningitis prevalence (-44.8% [95% UI, -47.3% to -42.3%]), deaths (-64.4% [95% UI, -67.7% to -50.3%]), and DALYs (-66.9% [95% UI, -70.1% to -55.9%]); and encephalitis DALYs (-25.8% [95% UI, -30.7% to -5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus.

Conclusions And Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.
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http://dx.doi.org/10.1001/jamaneurol.2020.4152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607495PMC
February 2021

Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study.

JAMA Neurol 2021 Feb;78(2):165-176

Department of Systems, Populations, and Leadership, University of Michigan, Ann Arbor.

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US.

Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017.

Design, Setting, And Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.

Exposures: Any of the 14 listed neurological diseases.

Main Outcome And Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated.

Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% [95% UI, -32.4% to -25.8%]); spinal cord injury prevalence (-38.5% [95% UI, -43.1% to -34.0%]); meningitis prevalence (-44.8% [95% UI, -47.3% to -42.3%]), deaths (-64.4% [95% UI, -67.7% to -50.3%]), and DALYs (-66.9% [95% UI, -70.1% to -55.9%]); and encephalitis DALYs (-25.8% [95% UI, -30.7% to -5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus.

Conclusions And Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.
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http://dx.doi.org/10.1001/jamaneurol.2020.4152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607495PMC
February 2021

The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017.

Lancet Public Health 2020 10;5(10):e551-e567

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; National Institute for Stroke and Applied Neurosciences, Auckland University of Technology, Auckland, New Zealand; Research Center of Neurology, Moscow, Russia.

Background: Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide.

Methods: The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were Alzheimer's disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, Parkinson's disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates.

Findings: In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5-23·9) in the EU and 41·1 million (36·7-45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09-1·14) in the EU and 1·97 million (1·95-2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3-17·1) of total DALYs and 19·5% (18·0-21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80-84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs.

Interpretation: Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries.

Funding: European Academy of Neurology.
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http://dx.doi.org/10.1016/S2468-2667(20)30190-0DOI Listing
October 2020

Frequency of diabetes and other comorbidities in chronic inflammatory demyelinating polyradiculoneuropathy and their impact on clinical presentation and response to therapy.

J Neurol Neurosurg Psychiatry 2020 10 31;91(10):1092-1099. Epub 2020 Aug 31.

Unit of Neurology, ASST 'Spedali Civili', University of Brescia, Brescia, Italy.

Objectives: To determine the prevalence of different comorbidities in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and their impact on outcome, treatment choice and response.

Methods: Using a structured questionnaire, we collected information on comorbidities from 393 patients with CIDP fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society criteria included in the Italian CIDP database.

Results: One or more comorbidities were reported by 294 patients (75%) and potentially influenced treatment choice in 192 (49%) leading to a less frequent use of corticosteroids. Response to treatment did not differ, however, from that in patients without comorbidities. Diabetes (14%), monoclonal gammopathy of undetermined significance (MGUS) (12%) and other immune disorders (16%) were significantly more frequent in patients with CIDP than expected in the general European population. Patients with diabetes had higher disability scores, worse quality of life and a less frequent treatment response compared with patients without diabetes. Patients with IgG-IgA or IgM MGUS had an older age at CIDP onset while patients with other immune disorders had a younger age at onset and were more frequently females. IgM MGUS was more frequent in patients with motor CIDP than in patients with typical CIDP.

Conclusions: Comorbidities are frequent in patients with CIDP and in almost 50% of them have an impact on treatment choice. Diabetes, MGUS and other immune diseases are more frequent in patients with CIDP than in the general population. Only diabetes seems, however, to have an impact on disease severity and treatment response possibly reflecting in some patients a coexisting diabetic neuropathy.
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http://dx.doi.org/10.1136/jnnp-2020-323615DOI Listing
October 2020

The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study.

Epilepsy Behav 2021 01 29;114(Pt A):107201. Epub 2020 Jul 29.

Laboratorio di Malattie Neurologiche, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. Electronic address:

Objective: The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease.

Methods: This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate.

Results: Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of specific information, like the risk of sudden unexpected death in epilepsy (SUDEP) or the existence of lay associations, which might be of special interest for selected categories of patients.

Significance: Differences between patients with epilepsy and their caring physicians in terms of needs and priorities and suboptimal communication call for the implementation of programs aimed at addressing the factors deemed most relevant by patients and caregivers for the management of the disease.
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http://dx.doi.org/10.1016/j.yebeh.2020.107201DOI Listing
January 2021
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