Publications by authors named "Alberto Raggi"

191 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

The Pre-Lumbar puncture Intracranial Hypertension Scale (PLIHS): A practical scale to identify subjects with normal cerebrospinal fluid pressure in the management of idiopathic intracranial hypertension.

J Neurol Sci 2021 Oct 27;429:118058. Epub 2021 Aug 27.

Fondazione IRCCS Istituto Neurologico Carlo Besta, Neuroalgology Unit, Milano, Italy. Electronic address:

Background: Idiopathic Intracranial Hypertension (IIH) diagnosis requires lumbar puncture to measure cerebrospinal fluid (CSF) pressure. The Pre-Lumbar puncture Intracranial Hypertension Scale (PLIHS) is aimed to detect cases that will show raised or normal CSF opening pressure.

Methods: Retrospective analysis of records of patients who underwent lumbar puncture for suspect IIH. The target was CSF opening pressure ≥ 250 mmH2O, whereas a set of known neurological, neuro-ophthalmological and neuro-radiological parameters, plus obesity, were used as predictors in a logistic regression model. The PLIHS was based on significant predictors and a cut-off was validated using chi-squared test around CSF opening pressure ≥ 250 and < 200 mmH2O.

Results: Records of 162 patients were included: CSF opening pressure was <200 mmH2O in 40 and ≥ 250 mmH2O in 95 patients; 85 fulfilled IIH diagnosis. PLIHS is based on Frisén grade 2 or higher papilledema, tinnitus, empty sella, perioptic subarachnoid space distension, and obesity. Score range is 0-7: correlation with CSF opening pressure is 0.508 (p < .001), and PLIHS score is different between subjects not diagnosed with IIH, and those diagnosed with IIH both with and without papilledema (p < .001). PLIHS score ≤ 2 identifies cerebrospinal fluid pressure < 200 mmH2O; PLIHS score ≥ 3 identifies CSF opening pressure ≥ 250 mmH2O, IIH diagnosis, visual acuity ≤0.7, and optic nerve atrophy.

Conclusions: The PLIHS, can be used to identify patients who will particularly need LP, thus helping with the organization of the diagnostic work-up by optimising healthcare resources and potentially limit the likelihood to incur in LP-related adverse events.
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http://dx.doi.org/10.1016/j.jns.2021.118058DOI Listing
October 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

Comorbidities of primary headache disorders: a literature review with meta-analysis.

J Headache Pain 2021 Jul 14;22(1):71. Epub 2021 Jul 14.

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

Background: Primary headache disorders are common and burdensome conditions. They are associated to several comorbidities, such as cardiovascular or psychiatric ones, which, in turn, contribute to the global burden of headache. The aim of this study is to provide a comprehensive description of the pooled prevalence of comorbidities of primary headache disorders using a meta-analytical approach based on studies published between 2000 and 2020.

Methods: Scopus was searched for primary research (clinical and population studies) in which medical comorbidities were described in adults with primary headache disorders. Comorbidities were extracted using a taxonomy derived from the Global Burden of Disease (GBD) study. We compared prevalence of comorbidities among headache sufferers against general population using GBD-2019 estimates, and compared comorbidities' proportions in clinical vs. population studies, and by age and gender.

Results: A total of 139 studies reporting information on 4.19 million subjects with primary headaches were included: in total 2.75 million comorbidities were reported (median per subject 0.64, interquartile range 0.32-1.07). The most frequently addressed comorbidities were: depressive disorders, addressed in 51 studies (pooled proportion 23 %, 95 % CI 20-26 %); hypertension, addressed in 48 studies (pooled proportion 24 %, 95 % CI 22-26 %); anxiety disorders addressed in 40 studies (pooled proportion 25 %, 95 % CI 22-28 %). For conditions such as anxiety, depression and back pain, prevalence among headache sufferers was higher than in GBD-2109 estimates. Associations with average age and female prevalence within studies showed that hypertension was more frequent in studies with higher age and less females, whereas fibromyalgia, restless leg syndrome, and depressive disorders were more frequent in studies with younger age and more female.

Conclusions: Some of the most relevant comorbidities of primary headache disorders - back pain, anxiety and depression, diabetes, ischemic heart disease and stroke - are among the most burdensome conditions, together with headache themselves, according to the GBD study. A joint treatment of headaches and of these comorbidities may positively impact on headache sufferers' health status and contribute to reduce the impact of a group of highly burdensome diseases.
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http://dx.doi.org/10.1186/s10194-021-01281-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278743PMC
July 2021

Acceptance and commitment therapy for high frequency episodic migraine without aura: Findings from a randomized pilot investigation.

Headache 2021 06 11;61(6):895-905. Epub 2021 Jun 11.

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

Objective: We compared the incremental effects of adding acceptance and commitment therapy (ACT) to pharmacological treatment as usual (TAU) in a sample of patients with high frequency episodic migraine without aura (HFEM), assessing impact on a spectrum of measures across multiple domains.

Background: Patients with HFEM are at risk of developing chronic migraine and medication overuse headache. ACT has been shown to be effective for the treatment of various chronic pain conditions, but little attention has been given to its therapeutic value in the management of recurring headaches.

Methods: In this single-blind (masking for outcome assessor), open-label, randomized clinical trial, 35 patients with HFEM, with a monthly headache frequency ranging from 9 to 14 days, were recruited at the headache center of C. Besta Neurological Institute and randomized to either TAU (patient education and pharmacological prophylaxis; n = 17) or TAU + ACT (n = 18). Patients assigned to the combined treatment arm additionally received six 90-min weekly group sessions of ACT therapy and two supplementary "booster" sessions. All patients were on a stable course of prophylactic medication in the 3 months prior to initiating either treatment. Monthly headache frequency served as the primary outcome measure, with all other data collected being considered as secondary measures (medication intake, disability, headache impact, anxiety and depression, catastrophizing, allodynia, cognitive inflexibility, pain acceptance, mindful attention and awareness).

Results: A total of 35 patients were enrolled: 17 randomized to TAU, of whom three dropped out, and 18 to TAU + ACT (no dropouts in this group). Headache frequency and medication intake decreased in both groups over 12 months, with patients in the TAU + ACT group showing statistically significant reduction earlier, that is, by month 3. Headache frequency was reduced by 3.3 days (95% CI: 1.4 to 5.2) among those randomized to ACT + TAU, whereas it increased by 0.7 days (95% CI: -2.7 to 1.3) among those randomized to TAU only (p = 0.007, partial η  = 0.21), the difference being 4 days (95% CI: 1.2 to 6.8). Medication intake was reduced by 4.1 intakes (95% CI: 2.0 to 6.3) among those randomized to ACT + TAU and by 0.4 intakes (95% CI: -1.8 to 2.5) among those randomized to TAU only (p = 0.016; partial η  = 0.17), the difference being 3.8 intakes (95% CI: 0.7 to 6.8). At 6 and 12 months, the variations were not different between the two groups for headache frequency and medication intake. The opposite was found for measures of headache impact and pain acceptance, where the differences over time favored patients allocated to TAU. Both groups improved with regard to measures of disability, anxiety and depression, catastrophizing, and cognitive inflexibility, whereas measures of allodynia and pain acceptance were stable over time.

Conclusions: Our preliminary findings indicate that supplementing TAU with ACT can enhance the main clinical outcomes, namely headache frequency and medication intake of patients with HFEM.
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http://dx.doi.org/10.1111/head.14139DOI Listing
June 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

Auditory mismatch negativity in bipolar disorder: a focused review.

Rev Neurosci 2021 Apr 9. Epub 2021 Apr 9.

Department of Neurology IC, Oasi Research Institute-IRCCS, Via Conte Ruggero 73, 94018Troina, Italy.

The auditory mismatch negativity, a component of the event-related potential elicited by an unexpected stimulus in a sequence of acoustic stimuli, provides an objective measure of the accuracy of the echoic information processing of the human brain . Auditory mismatch negativity is also a useful probe of cortical glutamatergic -methyl-d-aspartate receptor activity and disturbance. Notably, auditory mismatch negativity is consistently impaired in schizophrenia. Because of the wide spectrum extending from bipolar affective illness and schizoaffective psychosis to typical schizophrenia, we examined the literature on auditory mismatch negativity in bipolar disorder with the aim to find any neurophysiological dysfunction concerning pre-attentive information processing shared by these clinical conditions. This focused review includes 26 original articles published in peer-reviewed journals and indexed in the National Institutes of Health National Library of Medicine (PubMed) search system. Overall, evidence is consistent with the finding that auditory mismatch negativity is impaired in bipolar disorder with psychotic features, even though to a lesser extent than in schizophrenia. It must be acknowledged that, in a few twin and family studies, mismatch negativity abnormalities were not specifically associated with bipolar disorder. In conclusion, auditory mismatch negativity research supports the involvement of the N-methyl-d-aspartate system in the pathophysiology of bipolar disorder, as previously assessed for schizophrenia, thus creating an intriguing between these two mental illnesses and stimulating the development of novel therapeutic agents. With additional replication and validation, auditory mismatch negativity may be further considered as a correlate of a common psychopathology of schizophrenia and bipolar spectrum illnesses.
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http://dx.doi.org/10.1515/revneuro-2021-0010DOI Listing
April 2021

Telephone-Based Reality Orientation Therapy for Patients With Dementia: A Pilot Study During the COVID-19 Outbreak.

Am J Occup Ther 2021 Mar-Apr;75(2):7502205130p1-7502205130p9

Raffaele Ferri, MD, is Scientific Director, Oasi Research Institute-IRCCS, Troina, Italy.

Importance: When in-person rehabilitation is not feasible, interventions delivered in remote telephone-based sessions may be an option.

Objective: To determine whether telephone-based reality orientation therapy (T-ROT) can improve cognition, mood, and neuropsychiatric symptoms among patients with major neurocognitive disorders (NCDs) who are forced to isolate and also whether T-ROT can relieve the burden of distress among their caregivers.

Design: Nonrandomized interventional comparison study.

Setting: Individual telephone calls between practitioners and patients and their caregivers.

Participants: Twenty-seven patients (14 in the experimental group, 13 in the control group) with a major NCD and their primary caregivers.

Intervention: Ten T-ROT sessions and a pretest-posttest neuropsychological evaluation over 4 wk.

Outcomes And Measures: Outcomes measured included cognitive and behavioral symptoms of patients with major NCDs and correlations between changes in patient clinical condition and caregiver stress. Primary outcome measures were two measures of depressive symptoms, the Neuropsychiatric Inventory Questionnaire and the Telephone Mini-Mental State Examination, administered at baseline and program discharge.

Results: T-ROT significantly outperformed nontreatment on all measures of depression, behavior, cognition, and caregiver burden.

Conclusions And Relevance: T-ROT combined with emotional support appears to be an effective intervention for monitoring and managing the behavioral symptoms of patients with major NCDs who are forced to isolate.

What This Article Adds: Occupational therapy practitioners can use T-ROT or similar procedures not only during a pandemic but also when it is not possible to treat patients in person at a hospital or at home. Telephone-based treatment may also represent a good practice to be integrated into traditional rehabilitation programs.
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http://dx.doi.org/10.5014/ajot.2021.046672DOI 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

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

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

Mindfulness as an add-on treatment for patients with chronic migraine and medication overuse: a preliminary analysis.

Neurol Sci 2020 12;41(Suppl 2):469-471

Headache and Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.

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http://dx.doi.org/10.1007/s10072-020-04662-5DOI Listing
December 2020

Alcohol Drinking and Health in Ageing: A Global Scale Analysis of Older Individual Data through the Harmonised Dataset of ATHLOS.

Nutrients 2020 Jun 11;12(6). Epub 2020 Jun 11.

Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 70 Eleftheriou Venizelou Ave, Attica, 176 61 Athens, Greece.

We investigated the relation between alcohol drinking and healthy ageing by means of a validated health status metric, using individual data from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project. For the purposes of this study, the ATHLOS harmonised dataset, which includes information from individuals aged 65+ in 38 countries, was analysed ( = 135,440). Alcohol drinking was reflected by means of three harmonised variables: alcohol drinking frequency, current and past alcohol drinker. A set of 41 self-reported health items and measured tests were used to generate a specific health metric. In the harmonised dataset, the prevalence of current drinking was 47.5% while of past drinking was 26.5%. In the pooled sample, current alcohol drinking was positively associated with better health status among older adults ((b-coef (95% CI): 1.32(0.45 to 2.19)) and past alcohol drinking was inversely related (b-coef (95% CI): -0.83 (-1.51 to -0.16)) with health status. Often alcohol consumption appeared to be beneficial only for females in all super-regions except Africa, both age group categories (65-80 years old and 80+), both age group categories, as well as among all the financial status categories (all < 0.05). Regional analysis pictured diverse patterns in the association for current and past alcohol drinkers. Our results report the need for specific alcohol intake recommendations among older adults that will help them maintain a better health status throughout the ageing process.
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http://dx.doi.org/10.3390/nu12061746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353331PMC
June 2020

Characterization of novel progranulin gene variants in Italian patients with neurodegenerative diseases.

Neurobiol Aging 2021 01 13;97:145.e7-145.e15. Epub 2020 May 13.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. Electronic address:

Loss-of-function mutations in the gene encoding for the protein progranulin (PGRN), GRN, are one of the major genetic abnormalities involved in frontotemporal lobar degeneration. However, genetic variations, mainly missense, in GRN have also been linked to other neurodegenerative diseases. We found 12 different pathogenic/likely pathogenic variants in 21 patients identified in a cohort of Italian patients affected by various neurodegenerative disorders. We detected the p.Thr272SerfsTer10 as the most frequent, followed by the c.1179+3A>G variant. We characterized the clinical phenotype of 12 patients from 3 pedigrees carrying the c.1179+3A>G variant, demonstrated the pathogenicity of this mutation, and detected other rarer variants causing haploinsufficiency (p.Met1?, c.709-2A>T, p.Gly79AspfsTer39). Finally, by applying bioinformatics, neuropathological, and biochemical studies, we characterized 6 missense/synonymous variants (p.Asp94His, p.Gly117Asp, p.Ala266Pro, p.Val279Val, p.Arg298His, p.Ala505Gly), including 4 previously unreported. The designation of variants is crucial for genetic counseling and the enrollment of patients in clinical studies.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.05.004DOI Listing
January 2021

Pain rates in general population for the period 1991-2015 and 10-years prediction: results from a multi-continent age-period-cohort analysis.

J Headache Pain 2020 May 13;21(1):52. Epub 2020 May 13.

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

Background: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates.

Methods: We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content "self-reported pain experienced at the time of the interview", with a dichotomous (yes or no) modality.

Results: Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50.

Conclusions: Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates.
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http://dx.doi.org/10.1186/s10194-020-01108-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218619PMC
May 2020

Pearls and pitfalls in brain functional analysis by event-related potentials: a narrative review by the Italian Psychophysiology and Cognitive Neuroscience Society on methodological limits and clinical reliability-part I.

Neurol Sci 2020 Oct 9;41(10):2711-2735. Epub 2020 May 9.

Neurology Ward Unit, Bambino Gesù Hospital, Rome, Italy.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.
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http://dx.doi.org/10.1007/s10072-020-04420-7DOI Listing
October 2020

Information Processing in Migraine: A Review of Studies on P300.

Appl Psychophysiol Biofeedback 2020 09;45(3):131-144

Unit of Neurology I.C., Oasi Research Institute - IRCCS, Troina, Italy.

Subjective cognitive dysfunction is common among migraineurs. The aim of this review is to evaluate the usefulness of psychophysiology by means of the P300 component of the event-related potential in the understanding of subtle and sub-clinical changes in cognition that may occur during and between migraine episodes. Some P300 studies suggest a potential impairment of information processing, as reflected by only few findings of interictal decreased amplitude and prolonged latency, ictal augmented amplitude and prolonged latency, changes in cognitive habituation, and limited capacity to relocate attention away from painful stimuli. P300 may represent a valuable aid for clinicians to identify patients at risk of chronicization and cognitive weakening due to neurovascular complications; in this perspective a research agenda may be planned involving larger numbers of patients undergoing psychophysiological studies.
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http://dx.doi.org/10.1007/s10484-020-09469-wDOI Listing
September 2020

Outcome prediction in brain tumor surgery: a literature review on the influence of nonmedical factors.

Neurosurg Rev 2021 Apr 7;44(2):807-819. Epub 2020 May 7.

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

The purpose of the present study was to review the existing data on preoperative nonmedical factors that are predictive of outcome in brain tumor surgery. Our hypothesis was that also the individual characteristics (e.g., emotional state, cognitive status, social relationships) could influence the postoperative course in addition to clinical factors usually investigated in brain tumor surgery. PubMed, Embase, and Scopus were searched from 2008 to 2018 using terms relating to brain tumors, craniotomy, and predictors. All types of outcome were considered: clinical, cognitive, and psychological. Out of 6.288 records identified, 16 articles were selected for analysis and a qualitative synthesis of the prognostic factors was performed. The following nonmedical factors were found to be predictive of surgical outcomes: socio-demographic (age, marital status, type of insurance, gender, socio-economic status, type of hospital), cognitive (preoperative language and cognitive deficits, performance at TMT-B test), and psychological (preoperative depressive symptoms, personality traits, autonomy for daily activities, altered mental status). This review showed that nonmedical predictors of outcome exist in brain tumor surgery. Consequently, individual characteristics (e.g., emotional state, cognitive status, social relationships) can influence the postoperative course in addition to clinical factors.
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http://dx.doi.org/10.1007/s10143-020-01289-0DOI Listing
April 2021

Predictors of pain in general ageing populations: results from a multi-country analysis based on ATHLOS harmonized database.

J Headache Pain 2020 May 6;21(1):45. Epub 2020 May 6.

National Research Council, Neuroscience Institute, Padova, Italy.

Background: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people, and with increasing trends in general populations. Different risk factors for pain have been identified, but generally from studies with limited samples and a limited number of candidate predictors. The aim of this study is to evaluate the predictors of pain from a large set of variables and respondents.

Methods: We used part of the harmonized dataset of ATHLOS project, selecting studies and waves with a longitudinal course, and in which pain was absent at baseline and with no missing at follow-up. Predictors were selected based on missing distribution and univariable association with pain, and were selected from the following domains: Socio-demographic and economic characteristics, Lifestyle and health behaviours, Health status and functional limitations, Diseases, Physical measures, Cognition, personality and other psychological measures, and Social environment. Hierarchical logistic regression models were then applied to identify significant predictors.

Results: A total of 13,545 subjects were included of whom 5348 (39.5%) developed pain between baseline and the average 5.2 years' follow-up. Baseline risk factors for pain were female gender (OR 1.34), engaging in vigorous exercise (OR 2.51), being obese (OR 1.36) and suffering from the loss of a close person (OR 1.88) whereas follow-up risk factors were low energy levels/fatigue (1.93), difficulties with walking (1.69), self-rated health referred as poor (OR 2.20) or average to moderate (OR 1.57) and presence of sleep problems (1.80).

Conclusions: Our results showed that 39.5% of respondents developed pain over a five-year follow-up period, that there are proximal and distal risk factors for pain, and that part of them are directly modifiable. Actions aimed at improving sleep, reducing weight among obese people and treating fatigue would positively impact on pain onset, and avoiding vigorous exercise should be advised to people aged 60 or over, in particular if female or obese.
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http://dx.doi.org/10.1186/s10194-020-01116-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201730PMC
May 2020

First case of an gene mutation causing frontotemporal dementia preceded by adult onset psychiatric symptoms.

Amyotroph Lateral Scler Frontotemporal Degener 2020 08 14;21(5-6):467-469. Epub 2020 Apr 14.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy.

Recently, mutations in genes related to frontotemporal dementia and/or amyotrophic lateral sclerosis have been described as the cause of late onset psychosis. Here, we report a 68-year-old patient, carrier of a mutation in the gene encoding ubiquilin-2 (), who presented adult onset psychotic manifestations followed by a dysexecutive syndrome compatible with the diagnosis of behavioral variant of frontotemporal dementia. Therefore, we suggest that variants in should be sought in patients with this clinical condition preceded by psychiatric disorders.
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http://dx.doi.org/10.1080/21678421.2020.1752251DOI Listing
August 2020

Disability, Quality of Life, and Socioeconomic Burden of Cluster Headache: A Critical Review of Current Evidence and Future Perspectives.

Headache 2020 04 28;60(4):809-818. Epub 2020 Feb 28.

Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.

Objective: To summarize the available evidence on disability, quality of life (QoL), and economic burden on societies of cluster headache (CH), and to present which tools have been used to measure these domains with indications for future research.

Background: CH is a rare and severe primary headache. The focus of research on this disorder has historically been on understanding its complex pathophysiological mechanisms, whereas personal and global healthcare impact, disability, and QoL received little attention.

Methods: We reviewed the available literature published up to 2019, identifying primary research addressing QoL, disability, impact, or impairment in daily life due to episodic CH (ECH) or chronic CH (CCH), and its societal impact.

Results: CH produces a significant impact on sufferers QoL, disability, and work-related aspects, with a stronger impact on CCH than ECH. The CH-related disability appears to be greater than is seen in subjects with other primary headache disorders.

Conclusions: Information about patient-reported outcomes is rarely collected in patients with CH. An effort to improve the amount of information on the lived experience of patients with CH is needed and CH-specific disability and QoL measures require development.
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http://dx.doi.org/10.1111/head.13784DOI Listing
April 2020

Employment in Myasthenia Gravis: A Systematic Literature Review and Meta-Analysis.

Neuroepidemiology 2020 25;54(4):304-312. Epub 2020 Feb 25.

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

Introduction: Myasthenia gravis (MG) is an autoimmune disease whose period of typical onset is around 20-40 years (i.e., early onset), thus in the peak of working age, or around 60-80 years (i.e., late onset). However, the information on work-related issues and employment status are sparse and not systematically reported. Therefore, we performed a systematic literature review with meta-analysis to address the employment status of MG patients.

Methods: We searched for papers reporting employment status on participants with MG published between January 2000 and May 2019. Information on employment was extracted. Random-effects models were used to produce meta-analytic estimates for the proportion of employed patients.

Results: In total, 1,045 records were retrieved, of which 19 fitted the inclusion criteria. In total, 3,600 participants (average age 47.5, range 35-60) were included in the studies and 1,579 of them were employed. The proportion of employed patients varied from 28 to 82%, with an extreme heterogeneity between studies. Overall, the pooled proportion of workers was 50% (95% CI 41-60%). Subgroup analyses suggested a possible, although not significant, higher proportion of workers among women, younger participants, those with a higher level of education, shorter MG duration, and less frequently thymectomized, whereas a lower proportion was observed among those with generalized, bulbar, and respiratory symptoms.

Conclusions: The results of our meta-analysis show that the percentage of employment is considerably low if we take into account that the mean age of MG patients involved in the included studies was around 48 years, thus in peak of working life. Therefore, it is important to understand what kind of influence MG exerts on work dynamics.
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http://dx.doi.org/10.1159/000506310DOI Listing
August 2021

Keeping People with Dementia or Mild Cognitive Impairment in Employment: A Literature Review on Its Determinants.

Int J Environ Res Public Health 2020 01 29;17(3). Epub 2020 Jan 29.

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

Approximately 10-20% of people with early onset dementias (EOD) or mild cognitive impairment (MCI) are aged under 65 and, due to extended working life and increasing prevalence of dementias, they more and more frequently will be present in the active workforce. This review aimed to synthesize the available information about the ability of people with EOD or MCI to retain their participation in the labor workforce. : We searched SCOPUS and EMBASE for peer-reviewed papers that reported studies assessing work ability in employees with EOD or MCI that were published in the period of January 2010 to August 2019. : We selected four publications, in which 1012 participants with EOD or MCI were enrolled (41.2% males). Cognitive difficulties rather than motor dysfunction were found to reduce patients' ability to work. Two main themes emerged: management of dementia in the workplace and the impact of symptoms on working status. : EOD and MCI impact on workforce participation by determining problems in executive functions. Although this review was based on a small sample of studies, it can be shown that support in the workplace may act as a facilitator to enhance workforce participation, and occupational health professionals can help patients with EOD or MCI continue working as much as possible.
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http://dx.doi.org/10.3390/ijerph17030842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037722PMC
January 2020

Peri-operative prognostic factors for primary skull base chordomas: results from a single-center cohort.

Acta Neurochir (Wien) 2021 03 16;163(3):689-697. Epub 2020 Jan 16.

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

Background: Skull base chordomas (SBC) are rare malignant tumors and few factors have been found to be reliable markers for clinical decision making and survival prognostication. The aim of the present work was to identify specific prognostic factors potentially useful for the management of SBC patients.

Methods: A retrospective review of all the patients diagnosed and treated for SBC at the Fondazione IRCCS Istituto Neurologico "Carlo Besta" between January 1992 and December 2017 has been performed. Survival analysis was performed and a logistic regression model was used. Statistically significant predictors were rated based on their log odds in order to preliminarily build a personalized grading scale-the Peri-Operative Chordoma Scale (POCS).

Results: Fifty-nine primary chordoma patients were included. The average follow-up from the first treatment was 82.6 months (95% CI, 65.5-99.7). POCS was built over PFS and MR contrast enhancement (intense vs mild/no, value 4), preoperative motor deficit (yes vs no, value 3), and the development of any postoperative complications (yes vs no, value 2). POCS ranges between 0 and 9, with higher scores being associated with reduced likelihood of survival and progression-free state.

Conclusions: Our results show that preoperative clinical symptoms (motor deficits), surgical features (extent of tumor resection and surgeon's experience), development of postoperative complications, and KPS decline represent significant prognostic factors. The degree of MR contrast enhancement significantly correlated to both OS and PFS. We also preliminarily developed the POCS as a prognostic grading scale which may help neurosurgeons in the personalized management of patients undergoing potential adjuvant therapies.
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http://dx.doi.org/10.1007/s00701-020-04219-7DOI Listing
March 2021

HEADWORK Questionnaire: Why Do We Need a New Tool to Assess Work-Related Disability in Patients With Migraine?

Headache 2020 02 13;60(2):497-504. Epub 2020 Jan 13.

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

Objective: This article reviews current headache disability measures and clinical need, as well as presenting the rationale for a new measure addressing work-related disability in migraine patients and the steps devoted to this aim.

Background: Episodic and chronic migraine (EM and CM) constitute an enormous economic burden to societies, and the vast majority of this burden is attributable to indirect costs, ie those associated with productivity loss. A measure of work-related disability is therefore needed to quantify the impact of EM and CM on patients' ability to carry out work tasks.

Methods: We briefly present the advantages and disadvantages of the disability measures that have been most commonly used for this purpose and the rationale for developing a new measure.

Results: The entire process of development of HEADWORK, a questionnaire designed to assess work-related disability, is presented together with short-term sensitivity to change.

Conclusions: Current headache disability measures need improvement. HEADWORK is a valid, reliable, and sensitive questionnaire to address the amount and severity of work-related difficulties and of the factors contributing to such difficulties. HEADWORK is suitable for daily clinical practice, epidemiological research and for clinical trials, and potentially to define work-related disability weights for the calculation of migraine indirect costs.
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http://dx.doi.org/10.1111/head.13735DOI Listing
February 2020
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