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The “Ponte delle Grazie” is a three spans bridge, with a total length of 72 meters, built between 1948 and 1952 in Faenza, Italy. The reinforced concrete main beams of the deck have undergone a strong deterioration over the years. In detail atmospheric agents and chemical aggressions caused a strong deterioration of the concrete, up to the point of making the structure not accessible and at risk of collapse. In fact, the five main beams were heavily damaged, as well as the concrete bearings were strongly compromised. So, an urgent intervention was necessary to save the structure of this historic bridge. A delicate restoration has allowed to remove the deteriorated concrete and to restore the resistant sections with new materials compatible with the old remaining structures. In particular, a specific rehabilitation procedure was studied using fiber-reinforced cement mortar with low elastic modulus, that is shrinkage compensated, in combination with composite materials reinforcements. Without modifying the structural behavior of the bridge, the deteriorated concrete was restored and reinforced, in a sustainable way, in order to make the structure safe and usable again. After the restoration and reinforcement the bridge capacity satisfy a reduced live load useful for urban traffic. After the restoration and reinforcement the bridge capacity satisfy a reduced live load useful for urban traffic. Even if the structure has returned to be suitable for vehicular traffic, it has been necessary to set up a real-time monitoring system, which monitors the live load and the behavior of the bridge. In detail it is used a system of geophones, that are able to detect the displacement of structures by integrating in time their response. They can provide continuous health monitoring of the bridge by transmitting the data to a remote server.

Introduction: Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) without established etiology. Venous sinus stenosis contributes to IIH; however, it is still uncertain whether the stenosis is a primary cause of IIH or a secondary result in response to elevated ICP. Transverse sinus stenosis is frequently identified in patients with IIH and it is suggestive of raised ICP. Here, we report a case of IIH caused by intrinsic superior sagittal sinus stenosis (SSS)., Case Presentation: A 43-year-old man suffered from IIH with headache, papilledema, and visual impairment. Angiography demonstrated isolated SSS stenosis with a pressure gradient of 30 mmHg. SSS stenosis was resistant to revascularization by stenting alone and intrastent balloon angioplasty was then performed to overcome such resistance. The rigidity of the vein wall suggests that the vein is not collapsed and the stenosis is intrinsic, secondary to idiopathic anatomical local changes. Post-procedure headache disappeared and visual acuity improved., Conclusion: An isolated SSS stenosis could lead to intracranial hypertension and this condition should be taken into account in the diagnostic workup of IIH. By now, SSS stenosis is not mentioned in any current consensus guidelines or paper on the diagnostic workflow of intracranial hypertension., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Migraine is a highly underestimated and burdensome disease. Real-world studies evidence that migraine is more frequent and severe in women than men. However, to this day, no diagnostic-therapeutic pathways exist to satisfy the specific needs of female patients., Methods: In this study, migraine experts, specialists in women's health, patient, and decision makers, analyzed the diagnostic and therapeutic options for women with migraine across various ages and health conditions within the Italian healthcare system. A Delphi approach was used to formulate statements and achieve a consensus., Results: Gaps in clinical practice were identified, and strategies to accommodate women's needs were proposed. The experts agreed that a socio-behavioral intervention should be planned before any pharmacological treatment in pediatric/adolescent female patients and that the assessment of migraine with aura is considered crucial for adult women requiring contraceptive therapy. Acupuncture emerged as an effective treatment for pregnant and breastfeeding women, and hormone-replacement therapy selection in menopausal patients requires careful consideration to mitigate safety risks. The experts highlighted the absence of literature and guidelines for the management of migraine in women undergoing assisted reproductive procedures or oncological treatment. In light of these observations, the experts advocated the establishment of multidisciplinary collaborations between neurologists/headache specialists and other healthcare professionals, including general practitioners, pediatricians, gynecologists, and oncologists. Comprehensive migraine education for all healthcare professionals potentially involved in managing the disease, including pharmacists, was emphasized. Efforts to increase migraine awareness among women should be prioritized., Conclusion: The insights gained from this Italian consensus study should serve to develop an improved, female-specific pathway to diagnose and treat migraine., Competing Interests: SC received grants for scientific advisory board, speaker panels, travel grants by Abbvie, Allergan, Angelini, Eli-Lilly, Lundbeck, Novartis, Pfizer, Teva; was investigator for trials with Amgen, Biohaven, Eli-Lilly, Lundbeck, Novartis, Pfizer, Teva. Piero B reports personal compensation for consulting, serving on a scientific advisory board, speaker panels, travel grants, research support, collaborated for clinical trials, or other activities with Abbvie, Alder, Allergan, Amgen, Angelini, Assosalute, Bayer, Biohaven, ElectroCore, Eli-Lilly, Fondazione Ricerca e Salute, GSK, Lundbeck, Lusofarmaco, 1MED, MSD, New Penta, Noema Pharma, Novartis, Pfizer, Stx-Med, Teva, Visufarma, Zambon and serves as President with Italian Association of Headache Sufferers. CF received grants for scientific advisory board, speaker panels, travel grants by Abbvie, Eli-Lilly, Lundbeck, Novartis, Pfizer, Teva; was investigator for trials with Abbvie, Amgen, Biohaven, Janssen, Pfizer, Teva. FF received grants for scientific advisory board, speaker panels, travel grants by Cristalfarma, Eli-Lilly, Lundbeck, Pfizer, Piam, Teva; he was investigator for trials with Teva. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cevoli, Barbanti, Finocchi, Benedan, Mariani, Orthmann, Bauleo, Brusa, Cianci, Marozio, Masseroni, Sangermani, Frediani and Allais.)

Objective: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders)., Methods: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks., Results: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain-either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)-a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020)., Conclusion: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2-3 months of treatment., (© 2024. The Author(s).)

Background: To verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM: ≥ 15 days/month), and multiple preventive treatment failures., Methods: This is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21-24 compared to baseline. Secondary endpoints encompassed changes in monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS, HIT-6 and MIDAS scores at the same time interval. Changes in MMDs/MHDs, monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS and HIT-6 scores at week 4 were also monitored., Results: Four hundred ten patients who had received ≥ 1 dose of fremanezumab were considered for safety analysis while 148 patients treated for ≥ 24 weeks were included in the efficacy analysis. At weeks 21-24, fremanezumab significantly (p < 0.001) reduced MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM compared to baseline. The proportions of ≥ 50%, ≥ 75% and 100% responders at weeks 21-24were 75.0%, 30.8%, 9.6% (HFEM), and 72.9, 44.8 and 1% (CM). A significant (p < 0.001) decrease in MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM was already present at week 4. The proportions of ≥ 50%, ≥ 75%, and 100% responders at week 4 were 67.6%, 32.4%, 11.8% (HFEM) and 67.3%, 40%, 1.8% (CM). CM remitted to episodic migraine and medication overuse to no-medication overuse in 83.3 and 75% of patients at week 24, and in 80 and 72.4% at week 4. Adverse events were rare (2.4%), mild and transient. No patient discontinued treatment for any reason., Conclusions: Fremanezumab is characterized by an early and sustained efficacy in HFEM and CM patients with multiple preventive treatment failures in real-life, revealing an optimal safety and tolerability profile., (© 2023. The Author(s).)

Background and Objectives: The identification of predictors of response to antiCGRP mAbs could favor tailored therapies and personalized treatment plans. This study is aimed at investigating predictors of ≥ 50%, ≥ 75% and 100% response at 24 weeks in patients with high-frequency episodic (HFEM: 8-14 days/month) or chronic migraine (CM)., Methods: This is a large, multicenter, cohort, real-life study. We considered all consecutive adult patients affected by HFEM or CM who were prescribed antiCGRP mAbs for ≥ 24 weeks in 20 headache centers. Patients were interviewed face-to-face using a shared semi-structured questionnaire carefully exploring socio-demographic and clinical characteristics. Patients received subcutaneous erenumab (70 mg or140 mg, monthly), galcanezumab (120 mg monthly, following a 240 mg loading dose), or fremanezumab (225 mg, monthly or 675 mg, quarterly) according to drug market availability, physician's choice, or patient's preference. The primary endpoint of the study was the assessment of ≥ 50% response predictors at 24 weeks. Secondary endpoints included ≥ 75% and 100% response predictors at 24 weeks., Results: Eight hundred sixty-four migraine patients had been treated with antiCGRP mAbs for ≥ 24 weeks (erenumab: 639 pts; galcanezumab: 173 pts; fremanezumab: 55 pts). The ≥50% response (primary endpoint) in HFEM was positively associated with unilateral pain (UP) + unilateral cranial autonomic symptoms (UAs) (OR:4.23, 95%CI:1.57-11.4; p = 0.004), while in CM was positively associated with UAs (OR:1.49, 95%CI:1.05-2.11; p = 0.026), UP + UAs (OR:1.90, 95%CI:1.15-3.16; p = 0.012), UP + allodynia (OR:1.71, 95%CI:1.04-2.83; p = 0.034), and negatively associated with obesity (OR:0.21, 95%CI:0.07-0.64; p = 0.006). The 75% response (secondary endpoint) was positively associated with UP + UAs in HFEM (OR:3.44, 95%CI:1.42-8.31; p = 0.006) and with UP + UAs (OR:1.78, 95%CI:1.14-2.80; p = 0.012) and UP + allodynia (OR:1.92, 95%CI:1.22-3.06; p = 0.005) in CM. No predictor of 100% response emerged in patients with HFEM or CM., Conclusions: A critical evaluation of headache characteristics indicating peripheral or central sensitization may help in predicting responsiveness to antiCGRP mAbs in HFEM and CM. A more precise pain profiling may represent a steppingstone for a mechanism-based approach and personalized treatment of migraine with compounds targeting specific molecular mechanisms., (© 2022. The Author(s).)

Background: A novel formulation of diclofenac, complexed with hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer, in a prefilled syringe for self-administered subcutaneous injection may overcome the limitations of acute migraine treatments administered by oral, rectal, intramuscular, or intravenous routes., Methods: This multicentre, phase 2, double-blind, randomized, placebo-controlled, dose-finding pilot study evaluated the efficacy, safety and tolerability of three different doses (25/50/75 mg/1 mL) of subcutaneous diclofenac sodium in the treatment of an acute migraine attack in 122 subjects. The primary efficacy endpoint was the percentage of patients pain-free at 2 hours after the study drug injection., Results: A significantly higher percentage of patients in the 50 mg diclofenac group 14 (46.7%) were pain-free at 2 hours when compared with placebo: 9 (29.0%) ( p  = 0.01). The 50 mg dose proved superior to placebo also in the majority of the secondary endpoints. The overall global impression favoured diclofenac vs placebo. There were no adverse events leading to study withdrawal. The majority of treatment-emergent adverse events were mild., Conclusions: The 50 mg dose of this novel formulation of diclofenac represents a valuable self-administered option for the acute treatment of migraine attacks. Trial registration: EudraCT Registration No. 2017-004828-29.

Background: Although migraine is widespread and disabling, stigmatisation and poor awareness of the condition still represent barriers to effective care; furthermore, research on migraine individual and social impact must be enhanced to unveil neglected issues, such as caregiving burden. The project investigated the migraine illness experience through Narrative Medicine (NM) to understand daily life, needs and personal resources of migraneurs, their caregivers and clinicians, and to provide insights for clinical practice., Methods: The project involved 13 Italian headache centres and targeted migraneurs, their caregivers and migraine specialists at these centres. Written narratives, composed by a sociodemographic survey and illness plot or parallel chart, were collected through the project's webpage. Illness plots and parallel charts employed open words to encourage participants' expression. Narratives were analysed through Nvivo software, interpretive coding and NM classifications., Results: One hundred and seven narratives were collected from patients and 26 from caregivers, as well as 45 parallel charts from clinicians. The analysis revealed migraine perception in social, domestic and work life within the care pathway evolution and a bond between chaos narratives and day loss due to migraine; furthermore, narratives suggested the extent of the caregiving burden and a risk of underestimation of migraine burden in patients' and caregivers' life., Conclusion: The project represents the first investigation on migraine illness experience through NM simultaneously considering migraneurs', caregivers' and clinicians' perspectives. Comparing narratives and parallel charts allowed to obtain suggestions for clinical practice, while NM emerged as able to foster the pursuing of migraine knowledge and awareness., (© 2021. The Author(s).)

Headaches are among the most prevalent and disabling neurologic disorders and there are several unmet needs as current pharmacological options are inadequate in treating patients with chronic headache, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. Among these, the largest body of evidence supports the use of the ketogenic diet (KD). Exactly 100 years ago, KD was first used to treat drug-resistant epilepsy, but subsequent applications of this diet also involved other neurological disorders. Evidence of KD effectiveness in migraine emerged in 1928, but in the last several year's different groups of researchers and clinicians began utilizing this therapeutic option to treat patients with drug-resistant migraine, cluster headache, and/or headache comorbid with metabolic syndrome. Here we describe the existing evidence supporting the potential benefits of KDs in the management of headaches, explore the potential mechanisms of action involved in the efficacy in-depth, and synthesize results of working meetings of an Italian panel of experts on this topic. The aim of the working group was to create a clinical recommendation on indications and optimal clinical practice to treat patients with headaches using KDs. The results we present here are designed to advance the knowledge and application of KDs in the treatment of headaches.

Objective: To assess the effectiveness, safety, and tolerability of erenumab in a real-life migraine population, while trying to identify responsiveness predictors., Background: Erenumab is a fully human Ig-2 monoclonal antibody blocking the calcitonin gene-related peptide receptor, indicated for migraine prophylaxis. Phase II and III trials demonstrated that erenumab is effective, safe, and well tolerated in the prevention of episodic and chronic migraine (CM), showing an early onset of action., Methods: This is a multicenter, prospective, cohort, and real-life study. We considered for enrolment all consecutive patients aged 18-65 affected by high-frequency episodic migraine (HFEM) or CM, with or without medication overuse, visited at nine Italian Headache Centers from December 20, 2018 to September 30, 2019. Each patient was treated with erenumab 70 mg, administered subcutaneously every 4 weeks. Treatment duration was planned to last from 6 to 12 months, depending on the patient's response. The primary endpoint was the change in monthly migraine days (MMDs) at weeks 9-12 compared to baseline. Secondary endpoints included changes in monthly analgesics intake, ≥50%, ≥75%, and 100% responder rates and any variation in the Visual Analog Scale (VAS) and Headache Impact Test scores (HIT)., Results: In total, 372 migraine patients were treated with at least one dose of erenumab 70 mg. At weeks 9-12, erenumab decreased MMDs by 4.5 ± 4.1 days (mean ± SD) in patients with HFEM and by 9.3 ± 9.1 (mean ± SD) days in those with CM compared to baseline. At weeks 9-12 VAS score was reduced by 1.9 ± 1.9 (mean ± SD), HIT score by 10.7 ± 8.8 (mean ± SD), and median monthly analgesics intake passed from 12.0 (interquartile range [IQR] 10.0-14.0) to 5.0 (IQR 3.0-7.0) in HFEM. In CM patients, VAS was reduced by 1.7 ± 2.0 (mean ± SD), HIT by 9.7 ± 10.4 (mean ± SD), and median monthly analgesics intake passed from 20.0 (IQR 15.0-30.0) to 8.0 (IQR 5.0-15.0). At week 12, ≥50% responders were 60/101 (59.4%) for HFEM and 146/263 (55.5%) for CM, ≥75% responders were 17/101 (16.8%) and 59/263 (22.4%) and 100% responders 1/101 (1.0%) and 3/263 (1.1%), respectively. Erenumab responsiveness in HFEM was positively associated with unilateral pain localization (OR: 3.03, 95% CI: 1.24-7.40; p = 0.015), whereas in CM responsiveness was positively associated with and baseline migraine frequency (OR: 1.06, 95% CI:1.02-1.11; p = 0.031), dopaminergic symptoms (OR: 2.01, 95% CI: 1.14-3.52; p = 0.015), and negatively associated with psychiatric comorbidities (OR: 0.43, 95% CI: 0.20-0.93; p = 0.003)., Conclusions: Erenumab 70 mg is effective, safe, and well tolerated in real life. Easily obtainable clinical features might be of help in predicting patient's responsiveness., (© 2020 American Headache Society.)

In the "headache world," great attention has always been paid to migraine patients, especially for the research and development of new therapies. For the other forms of primary headaches, especially those of Chapters 2 and 3 of the classification, there are however therapies that, even if not specific, can give significant results. Tension-type headache recognizes in NSAIDs the most effective drugs to treat acute attack, while prevention is based on the use of tricyclic antidepressants and muscle relaxants. For TACs, the discussion is more complex: first of all, there are two forms of primary headache that respond absolutely to indomethacin. For these, the main problem is how to manage the possible side effects arising from prolonged treatments and possibly what to use as an alternative. For cluster headaches and short-lasting unilateral neuralgiform headache attacks, we have drugs with good efficacy as regards medical therapy, such as verapamil or lamotrigine, but in recent years, neuromodulation techniques, both surgical and non-invasive, have also been affirming themselves, which represent a more possibility for forms of headache that are often very disabling and resistant to common analgesics.

Objectives: Understanding migraine management using data from a sample of patients representative of the Italian general adult population. Methods: Retrospective analysis on IQVIA Italian Longitudinal Patient Database. Two cohorts were created. (a) The triptan user cohort included patients with triptan prescriptions between November 2015 and October 2016. Migraine days were estimated counting triptan and indometacin/caffeine/prochlorperazine (ICP) pills prescribed during the 6 months following first triptan prescription. Patients were categorized as having episodic (EM) or chronic (CM) migraine based on the number of migraine days following International Classification of Headache Disorders criteria. (b) The migraine preventive treatment (MPT) user cohort included patients with MPT prescriptions during the period June 2016-May 2017. MPTs considered included beta-blockers, calcium-channel blockers, antiepileptics, antidepressants and antiserotoninergics. Migraine days experienced by MPTs users were estimated counting triptan and ICP pills prescribed during the 6 months following the most recent MPT prescription, while the number of MPT switches was estimated based on MPT prescriptions during the previous two years. Results: There were 9461 patients with triptan prescriptions to treat migraine acute attacks, which accounted yearly for 0.8% of general adult population. CM patients accounted for 3% of triptan users. There were 2004 patients prescribed with MPTs, which accounted for 0.16% of general adult population. Overall, among MPT users, 291 (15%) were still experiencing at least four migraine days/month, with this proportion increasing with the increase in the number of MPT switches. Conclusions: Results from this study suggest an unmet need in the management of migraine: too many patients did not receive MPTs, with this potentially due to several reasons requiring further investigations. Furthermore, even among patients receiving MPTs, disease control level with now available drugs seems to be sub-optimal.

Background: Chronic migraine is a disabling condition that is currently underdiagnosed and undertreated. In this narrative review, we discuss the future of chronic migraine management in relation to recent progress in evidence-based pharmacological treatment., Findings: Patients with chronic migraine require prophylactic therapy to reduce the frequency of migraine attacks, but the only currently available evidence-based prophylactic treatment options for chronic migraine are topiramate and onabotulinumtoxinA. Improved prophylactic therapy is needed to reduce the high burden of chronic migraine in Italy. Monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway of migraine pathogenesis have been specifically developed for the prophylactic treatment of chronic migraine. These anti-CGRP/R monoclonal antibodies have demonstrated good efficacy and excellent tolerability in phase II and III clinical trials, and offer new hope to patients who are currently not taking any prophylactic therapy or not benefitting from their current treatment., Conclusions: Treatment of chronic migraine is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualised treatments for this condition. Establishing a culture of prevention is essential for reducing the personal, social and economic burden of chronic migraine.

Why does the brain choose pain? Why does an organ that is able to mask pain, even when intense as in fractures or in fighting wounds, decide to let pain pass and begin conscious, such as that of migraine, when there is no noxa patogena and there is no threat to the integrity of the organism, failing in the main function of pain, that of protection? In this brief review, we retrace the journey that led to the identification of the first complex mechanism of regulation of painful input, the spinal gate control system, through the identification of the predominantly thalamocortical supraspinal centers of the neuromatrix, up to the recognition of a pain matrix extremely articulate and sophisticated that integrates elementary sensations with much more complex functions, related to memory, affectivity, emotion, autonomic self-regulation, and homeostasis systems and so on. Why does the protection system lose its fundamental function in migraine in a behavioral harakiri that periodically damages only itself? This is the challenge facing those dealing with primary headaches in the next future: why migraine? The great strides made in the last decades that have led to the understanding of complex pathogenetic mechanisms risk remaining orphans if we fail to identify the primum movens at the base of one of the most common pathologies in the human race.

Background: The degree to which work-related difficulties are recognized in headache research is poor and often carried out with inadequate information such as "reduced ability to work as usual", which do not capture at all the variety of difficulties and the factors that impact over them. The aim of this paper is to present the validation of the HEADWORK questionnaire, which addresses the amount and severity of difficulties in work-related tasks and the factors that impact over them., Methods: We developed a set of items based on a previous literature review and patients' focus groups and tested it on a wide set of patients with episodic and chronic migraine attending eight different Italian headache centers. HEADWORK factor structure was assessed with exploratory and confirmatory factor analysis; internal consistency and construct validity were addressed as well., Results: The validation sample (N = 373) was mostly composed of patients with episodic migraine without aura (64.3%) and of females (81%). Factor analysis retrieved two different scales: "Work-related difficulties", composed of eleven items which explain 67.1% of the total variance, and "Factors contributing to work difficulties", composed of six items which explain 52.1% of the total variance. Both HEADWORK subscales have good measurement properties, with higher scores being associated to higher disability, lower quality of life, lower productivity, higher headache frequency and pain intensity., Conclusions: HEADWORK is a 17-item, two-scale questionnaire addressing the impact of migraine on work-related difficulties in terms of difficulties in general or specific skills, and the factors contributing to these difficulties, defined as negative impact on work tasks. It can be used to address disability weights for the purpose of calculating the burden of migraine, and to assess the balance between therapeutic and side effects of medication on productivity.

A 56-year-old man with behavioural disorders and facial-brachio-crural right hemiparesis presented with a brain lesion studied with computed tomography, magnetic resonance imaging and brain biopsy, leading to the diagnosis of cerebral vasculitis. Hepatitis C virus (HCV) infection in a phase of activity, without cryoglobulins, was also detected. Brain biopsy, laboratory analysis and response to a specific therapy supported the diagnosis of central nervous system vasculitis that was HCV related.

Timely treatment is essential in acute ischemic stroke as the chances of recovery diminish over time, so efforts are necessary to streamline in-hospital pathways and reduce delays. Here, we analyse the interventions to reduce door-to-needle time in stroke patients suitable for intravenous thrombolysis at the Emergency Department of San Carlo Borromeo Hospital, Milan, Italy. All stroke patients consecutively treated with intravenous thrombolysis at our centre from January 1, 2013 to December 31, 2015 were included in this analysis. The main interventions adopted were (1) continuous education of personnel, (2) reconsideration of blood tests and identify the ones really affecting treatment decision, (3) approval of a new high-urgency Stroke Code activated as soon as the triage nurse comes to know of a potential thrombolysis candidate. Median door-to-needle time progressively decreased from 103 min (iqr 78-120) in 2013, to 92 min (iqr 72-112) in 2014, and to 37 min (iqr 27-58) with the new Stroke Code (p < 0.001) in 2015. Simultaneously, median onset-to-treatment time decreased from 177 min (iqr 142-188) in 2013, to 155 min (iqr 141-198) in 2014, and to 114 min (iqr 86-160) with the new Stroke Code (p < 0.001 and p 0.005, respectively). We did not observe any significant difference in bleeding risks or deaths, whereas the likelihood of favourable outcome (mRS 0-2) increased. Streamlining in-hospital pathways with progressive interventions significantly decreases door-to-needle time and onset-to-treatment time and may contribute to improve stroke outcomes.

Since chronic migraine is difficult to treat and often associated with medication overuse, non-invasive neurostimulation approaches are worth investigating. Transcutaneous supraorbital neurostimulation using the Cefaly ® device is promising as a non-invasive preventive treatment for episodic migraine, but no data are available for chronic migraine. Our aim was to perform a preliminary evaluation of the efficacy of the Cefaly ® device for the prophylaxis of chronic migraine with or without medication overuse. Primary endpoints were 50% reduction in monthly migraine days and 50% reduction in monthly medication use over 4 months. In an open-label study, twenty-three consecutive headache center patients with chronic migraine, diagnosed according to International Headache Society criteria, were recruited prospectively. After informed consent, patients were trained to use Cefaly ® and instructed to use it for 20 min daily over 4 months. All patients received active neurostimulation. Thirty-five percent of the patients enrolled in the study achieved the study endpoints. Over half the patients had a greater than 50% reduction in acute medication consumption.

A few clinic-based magnetic resonance imaging studies report an increased risk of signal abnormalities in migraineurs brain's white matter, especially in migraine with aura subjects. A vascular genesis has been hypnotized and migraine with aura was considered an independent risk factor for stroke. Available data of magnetic resonance imaging alterations are often nonspecific and sometimes controversial. The aim of our study is to investigate migraine with aura patients with standardized brain magnetic resonance imaging to detect and to quantify the presence of white matter lesions and to analyze their relation with clinical data. We report preliminary data about first 90 subjects. We did not recognize any clinical aspect in close relationship with these alterations. The only clinical feature that seems to play a role in the presence of alterations is the age, and only in migraineurs women.

Several studies report the presence of white matter lesions on brain magnetic resonance imaging in patients with migraine. The aim of our study was to detect the entity of white matter T2-hyperintensities in 90 high selected patients affected by migraine with aura, compared to a group of 90 healthy controls. We found no significant difference of incidence of white matter alterations comparing these two groups.

HaNDL (transient headache and neurological deficits with cerebrospinal fluid lymphocytosis) syndrome is an infrequent condition included at group 7 "headache attributed to non-vascular intracranial disorder" in the recent International Classification of Headache Disorders (ICHD-3), code 7.3.5. The description states "migraine-like headache episodes (typically 1-12) accompanied by neurological deficits including hemiparaesthesia, hemiparesis and/or dysphasia, but positive visual symptoms only uncommonly, lasting several hours. There is lymphocytic pleocytosis. The disorder resolves spontaneously within 3 months". In this description confusional state is not considered as a main symptom, even if in the literature this aspect is frequently reported. Here, we report the cases of two young boys presenting with confusional state as the main complaint. The possible pathogenesis of the different clinical presentation is discussed.

The early use of triptan in combination with a nonsteroidal anti-inflammatory drug after headache onset may improve the efficacy of acute migraine treatment. In this retrospective analysis of a randomized, double-blind, parallel group study, we assessed the efficacy of early or late intake of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex 25 and FroDex 37.5) vs. frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks. In this double-blind, randomized parallel group study 314 subjects with acute migraine with or without aura were randomly assigned to Frova, FroDex 25, or FroDex 37.5. Pain free (PF) at 2-h (primary endpoint), PF at 4-h and pain relief (PR) at 2 and 4-h, speed of onset at 60, 90, 120 and 240-min, and sustained pain free (SPF) at 24-h were compared across study groups according to early (≤1-h; n = 220) or late (>1-h; n = 59) intake. PF rates at 2 and 4-h were significantly larger with FroDex 37.5 vs. Frova (early intake, n = 71 FroDex 37.5 and n = 75 Frova: 49 vs. 32 % and 68 vs. 52 %, p < 0.05; late intake, n = 20 Frodex 37.5, and n = 18 Frova: 55 vs. 17 %, p < 0.05 and 85 vs. 28 %, p < 0.01). Also with FroDex 25, in the early intake group (n = 74) PF episodes were significantly higher than Frova. PR at 2 and 4-h was significantly better under FroDex 37.5 than Frova (95 % vs. 50 %, p < 0.001, 100 % vs. 72 %, p < 0.05) in the late intake group (n = 21). SPF episodes at 24-h after early dosing were 25 % (Frova), 45 % (FroDex 25) and 41 % (FroDex 37.5, p < 0.05 combinations vs. monotherapy), whereas they were not significantly different with late intake. All treatments were equally well tolerated. FroDex was similarly effective regardless of intake timing from headache onset.

Background: Drugs for migraine attacks include triptans and NSAIDs; their combination could provide greater symptom relief., Methods: A total of 314 subjects with history of migraine, with or without aura, were randomized to frovatriptan 2.5 mg alone (Frova), frovatriptan 2.5 mg + dexketoprofen 25 mg (FroDex25) or frovatriptan 2.5 mg + dexketoprofen 37.5 mg (FroDex37.5) and treated at least one migraine attack. This was a multicenter, randomized, double-blind, parallel-group study. The primary end point was the proportion of pain free (PF) at two hours. Secondary end points were PF at one and four hours, pain relief (PR) at one, two, four hours, sustained PF (SPF) at 24 and 48 hours, recurrence at 48 hours, resolution of nausea, photophobia and phonophobia at two and four hours, the use of rescue medication and the judgment of the treatment., Results: The results were assessed in the full analysis set (FAS) population, which included all subjects randomized and treated for whom at least one post-dose intensity of headache was recorded. The proportions of subjects PF at two hours (primary end point) were 29% (27/93) with Frova compared with 51% (48/95 FroDex25 and 46/91 FroDex37.5) with each combination therapies ( P < 0.05). Proportions of SPF at 24 hours were 24% (22/93) for Frova, 43% (41/95) for FroDex25 ( P < 0.001) and 42% (38/91) for FroDex37.5 ( P < 0.05). SPF at 48 hours was 23% (21/93) with Frova, 36% (34/95) with FroDex25 and 33% (30/91) with FroDex37.5 ( P = NS). Recurrence was similar for Frova (22%, 6/27), FroDex25 (29%, 14/48) and FroDex37.5 (28%, 13/46) ( P = NS), meaning a lack of improvement with the combination therapy. Statistical adjustment for multiple comparisons was not performed. No statistically significant differences were reported in the occurrence of total and drug-related adverse events. FroDex25 and FroDex37.5 showed a similar efficacy both for primary and secondary end points. There did not seem to be a dose response curve for the addition of dexketoprofen., Conclusion: FroDex improved initial efficacy at two hours compared to Frova whilst maintaining efficacy at 48 hours in this study. Tolerability profiles were comparable. Intrinsic pharmacokinetic properties of the two single drugs contribute to this improved efficacy profile.

Early triptan use after headache onset may help improve the efficacy of acute migraine treatment. This may be particularly the case when triptan therapy is combined with a nonsteroidal anti-inflammatory drug (NSAID). The objective of this is to assess whether the combination of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex25 and FroDex37.5) is superior to frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks in patients who took the drug within 30 min from the onset of pain (early use) or after (late use). A total of 314 subjects with a history of migraine with or without aura were randomized into a double-blind, multicenter, parallel group, pilot study to Frova, FroDex25 or FroDex37.5 and were required to treat at least one migraine attack. In the present post hoc analysis, traditional migraine endpoints were compared across study drugs for subgroups of the 279 patients of the full analysis set according to early (n = 172) or late (n = 107) drug use. The proportion of patients pain free at 2 h in the early drug use subgroup was 33 % with Frova, 50 % with FroDex25 and 51 % with FroDex37.5 mg (p = NS combinations vs. monotherapy), while in the late drug use subgroup was 22, 51 and 50 % (p < 0.05 FroDex25 and FroDex37.5 vs. Frova), respectively. Pain-free episodes at 4 h were 54 % for early and 34 % for late use of Frova, 71 and 57 % with FroDex25 and 74 and 68 % with FroDex37.5 (p < 0.05 for early and p < 0.01 for late use vs. Frova). The proportion of sustained pain free at 24 h was 26 % under Frova, 43 % under FroDex25 mg and 40 % under FroDex37.5 mg (p = NS FroDex25 or 37.5 vs. Frova) in the early drug intake subgroup, while it was 19 % under Frova, 43 % under FroDex25 mg and 45 % under FroDex37.5 mg (p < 0.05 FroDex25 and FroDex37.5 vs. Frova) in the late drug intake subgroup. Risk of relapse at 48 h was similar (p = NS) among study drug groups (Frova: 25 %, FroDex25: 21 %, and FroDex37.5: 37 %) for the early as well as for the late drug use subgroup (14, 42 and 32 %). FroDex was found to be more effective than Frova taken either early or late. The intrinsic pharmacokinetic properties of the two single drug components made FroDex combination particularly effective within the 2-48-h window from the onset of the acute migraine attack. The efficacy does not seem to be influenced by the time of drug use relative to the onset of headache.

Several dietary and lifestyle habits can be associated with headaches or with their progression to chronic forms in adults. We report the results of the first population study performed in Italy on a sample of preadolescent and adolescent students to assess the possible association between headache and specific habits and lifestyle factors. Preliminary data from 800 questionnaires showed that 365 subjects had headaches, which were of moderate-severe intensity, associated with anorexia, and caused absence from school in more than 50 % of students. The main finding was the evidence of a clear association between headache and irregular intake of meals (especially irregular breakfast) and sleep disturbance with significant differences when subjects with and without headache were compared. If confirmed, these results are likely to influence clinical practice as well to address educational programs in preadolescents and adolescents.

Although migraine (MH) and tension type headache (TTH) are the most common and important causes of recurrent headache in adolescents, they are poorly understood and not recognized by parents and teachers, delaying the first physician evaluation for correct diagnosis and management. The purpose of this study is to assess the knowledge about headache impact among the students of a Communication Private High School in Rimini city, and to evaluate the main different types of headaches interfering with school and social day activities. A self-administered questionnaire interview was given to students of the last 2 years of high school; ten items assessed the headache experience during the prior 12 months, especially during school time: the features and diagnosis of headaches types (based on the 2004 IHS criteria), precipitating factors, disability measured using the migraine disability assessment (MIDAS); therapeutic intervention. Out of the 60 students, 84 % experienced recurrent headache during the last 12 months. 79 % were females, aged 17-20 years; a family history was present in 74 % of headache students, in the maternal line; 45 % of subjects were identified as having MH and 27 % TTH; 25 % had morning headache and 20 % in the afternoon; fatigue, emotional stress and lack of sleep were the main trigger factors for headache, respectively in 86, 50 and 50 % of students; 92 % of headache students could not follow the lessons, could not participate in exercises and physical activity because of the headache; none had consulted a medical doctor and the 90 % of all students had never read, listened or watched television about headache. This study remarks on the need to promote headache educational programs, starting from high school, to increase communication between teachers-family-physician and patient-adolescents, with the goal to have an early appropriate therapeutic intervention, improvement of the quality of life and to prevent long-term headache disease in the adult age.

Neurological complications frequently affect chronic kidney disease patients. They are important causes of morbidity and mortality. We present a review of neurological complications affecting hemodialysis patients, focusing on classical and new aspects. Neurological complications can be classified as central or peripheral, but they also include other conditions such as muscle and autonomic disorders. Neurological complications in hemodialysis patients are often underdiagnosed and undertreated. Dialysis treatment can modify the clinical pattern and the course of neurological complications, but it may also directly induce some specific, dialysis-related complications. A strict collaboration between nephrologists, neurologists and other specialists can potentially improve prevention and management of these disorders and improve quality of life for hemodialysis patients.

In the last years several studies have been performed on migraine; however, only few topics have changed the clinical practice. Among these, there are physiopathological insights (e.g., allodynia and gastric stasis) or therapeutical evidences (e.g., topiramate) that become very important in the management of migraine and could clarify the different response to the therapies. The aim of a training school on headache should be to link research to practice without transferring contradictory data. To teach is not only to support notions with simple data: we think that knowledge has to be used according to the condition of the patient and the situation in which the migraineurs live.

Migraine is a visceral pain. According to current theories, activation of trigeminocervical nerve endings releases calcitonin gene-related peptide and substance P, inducing vasodilation and plasma protein extravasation, leading to 'neurogenic' inflammation. Activation of the trigeminovascular system is followed by sensitisation of trigeminocervical fibres, maintaining a condition of hypersensitivity to non-noxious stimuli that support persistent pain during migraine attack. Other neurotransmitters (nitric oxide, bradykinins, 5-HT, etc.) play a role in regulating this complex mechanism. In this brief review, we consider the effect of drugs that, acting on the different transmitters involving in pain perception, can stop or inhibit these pathogenetic mechanisms.

The pathogenesis of migraine is obscure. A hyperexcitable brain state has been postulated. Cortical spreading depression (CSD) is the most suggestive argument for the brain hyperexcitability. It has been showed that valproate, topiramate, amitriptyline and propranolol inhibit CSD in rats, which suggests that most preventative treatments of migraine act by normalising neuronal firing and increasing a genetically lowered and environmentally modified threshold for neuronal discharge. It has also been suggested that some antimigraine prophylactic drugs (i.e., amitriptyline, candesartan and magnesium) may act by restoring central nociceptive dysmodulation.

Basilar-type migraine (BM) and hemiplegic migraine are clinically distinct subtypes of migraine with aura, however they do share clinical features and it is possible they may share genetic bases. In recent years, ATP1A2 and other gene mutations have been discovered in familial and sporadic hemiplegic migraine. More recently, an ATP1A2 mutation has been identified in an Italian family with BM. In this study we document the absence of ATP1A2 mutations in two Italian sisters with menstrual BM, suggesting that other genes are involved in the condition.

Efficacy of 5-day treatment with oral frovatriptan 2.5 mg/die for the prophylaxis of post-dural puncture headache (PDPH) was tested in 50 in-patients. A mild headache occurred in 7 (14%) patients for a total of 9 days (p < 0.01 vs. no-PDPH). Most episodes of PDPH occurred in the first days of treatment (only 1 patient had headache at dismissal): 5 patients had only 1 episode, while 2 had headache for 2 consecutive days. No other symptoms were recorded. Occurrence of PDPH in a subgroup of 6 (12%) patients previously submitted to a diagnostic lumbar puncture was also examined: 4 of them reported a PDPH on the previous lumbar puncture in absence of triptans. In only 1 of these 4 patients PDPH recurred under treatment with frovatriptan. In conclusion, our non-randomized open-label study suggests efficacy of oral frovatriptan for PDPH prevention. These results need to be confirmed in a randomized, controlled, double-blind study.