Management of medication overuse headache.

Medication overuse headache (MOH) is a secondary headache characterized by frequent use of acute or symptomatic migraine medications at a sufficient frequency to transform patients from episodic to chronic migraine. MOH represents a significant medical problem, with a serious burden on patients' lives and on society as a whole. MOH patients often have additional comorbidities, and the clinical challenge of helping patients reduce acute medication use and revert to episodic headache can be marked. Treatment includes education and prevention; withdrawal programs; pharmacological prophylaxis; multidisciplinary therapies with behavioral and noninvasive neuromodulation options; and scheduled, frequent follow-up to prevent relapses. The advent of anti-CGRP therapy monoclonal antibodies may provide an alternative to more extensive programs for less complex patients. This review also provides guidance for which patients may benefit most from coordinated integrated programs.

Drug Survival of Upadacitinib and Predicting Factors of Discontinuation in Adult Patients Affected by Moderate-to-Severe Atopic Dermatitis: An Italian Multicenter Analysis.

Background: Limited real-world data are available on upadacitinib drug survival in patients with atopic dermatitis (AD). Objectives: To investigate upadacitinib drug survival, and the reasons and predictors of drug discontinuation in AD patients. Methods: All consecutive patients aged 18-75 years, affected by moderate-to-severe AD, and treated with upadacitinib for more than 1 month at dermatological clinics were included during November 2020-August 2023. Upadacitinib survival was investigated through Kaplan-Meier survival analysis and the predictors through multivariable logistic regression analysis. Results: Overall, 325 adult AD patients (mean (SD) age, 38.6(15.6) years) had a 1-year and 1.5-year upadacitinib drug survival of 91.5% and 80.2%, respectively. The main reasons for drug discontinuation (25/325, 7.7%) were adverse events (4.9%), including cutaneous or infectious diseases (1.5%), such as acne and herpes zoster; blood test changes (1.2%), including hypercholesterolemia, creatine phosphokinase or liver enzyme elevation, and lymphopenia; urinary or respiratory infections (0.9%); deep venous thrombosis (0.3%); malignancies (0.3%); loss of consciousness (0.3%); and arthralgias (0.3%); followed by ineffectiveness (0.6%). No specific characteristic was significantly associated with an increased risk of upadacitinib discontinuation. Conclusions: Our findings show that upadacitinib was effective in moderate-to-severe AD after more than 1 year of continuous treatment but point to the need for clinical and laboratory monitoring of patients.

Societal and personal impact of migraine.

Migraine is one of the main causes of years lived with disability (YLDs) worldwide, as showed in the Global Burden of Diseases Study. Its influence on patients' life is relevant and pervasive, with a specific impact on social, family, and work functioning, considering that migraine mainly affects adults under the age of 50. Several studies demonstrated that relations inside the family as well as in every social context are negatively influenced by migraine. According to the results of studies and surveys from different countries, patients' daily activities are often limited during migraine attacks, particularly in terms of performance in social and domestic activities and in terms of reduced productivity in work and school duties. Also an interictal burden is present. Migraineurs are conditioned by the fear of the next attack, often suffer from comorbid conditions such as anxiety and depression, and are subject to different forms of stigma. Consequently, migraine implies relevant costs for the individuals and for society, with higher figures for indirect costs (related to reduced participation and to limited productivity) than indirect costs (related to drugs, medical visits, examinations, and hospitalization).

Efficacy of mindfulness added to treatment as usual in patients with chronic migraine and medication overuse headache: a phase-III single-blind randomized-controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. METHODS: In this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7-10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson's Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models. RESULTS: Out of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p < 0.0001), and showed superior improvement in headache frequency, QoL and disability, headache impact, loss of productive time, medication intake, and in total, indirect and direct healthcare costs. CONCLUSIONS: A mindfulness-based treatment composed of six-week session and 7-10 min daily self-practice added on to TaU is superior to TaU alone for the treatment of patients with CM and MOH. TRIAL REGISTRATION: MIND-CM was registered on clinicaltrials.gov (NCT03671681) on14/09/2018.

Triazine Herbicide and NPK Fertilizer Exposure: Accumulation of Heavy Metals and Rare Earth Elements, Effects on Cuticle Melanization, and Immunocompetence in the Model Species Tenebrio molitor.

The increasing use of agrochemicals, including fertilizers and herbicides, has led to worrying metal contamination of soils and waters and raises serious questions about the effects of their transfer to different levels of the trophic web. Accumulation and biomagnification of essential (K, Na, Mg, Zn, Ca), nonessential (Sr, Hg, Rb, Ba, Se, Cd, Cr, Pb, As), and rare earth elements (REEs) were investigated in newly emerged adults of Tenebrio molitor exposed to field-admitted concentrations of a metribuzin-based herbicide and an NPK blend fertilizer. Chemical analyses were performed using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) supported by unsupervised pattern recognition techniques. Physiological parameters such as cuticle melanization, cellular (circulating hemocytes), and humoral (phenoloxidase enzyme activity) immune responses and mass loss were tested as exposure markers in both sexes. The results showed that NPK fertilizer application is the main cause of REE accumulation in beetles over time, besides toxic elements (Sr, Hg, Cr, Rb, Ba, Ni, Al, V, U) also present in the herbicide-treated beetles. The biomagnification of Cu and Zn suggested a high potential for food web transfer in agroecosystems. Gender differences in element concentrations suggested that males and females differ in element uptake and excretion. Differences in phenotypic traits show that exposure affects metabolic pathways involving sequestration and detoxification during the transition phase from immature-to-mature beetles, triggering a redistribution of resources between sexual maturation and immune responses. Our findings highlight the importance of setting limits for metals and REEs in herbicides and fertilizers to avoid adverse effects on species that provide ecosystem services and contribute to soil health in agroecosystems.

Long-term efficacy and safety of secukinumab in real life: a 240 weeks multicenter study from Southern Italy.

BACKGROUND: Long-term real-life data on secukinumab use in psoriasis are limited. OBJECTIVES: Determine the long-term effectiveness of secukinumab in moderate-to-severe psoriasis in real-life. METHODS: Multicenter retrospective study analyzing data from adult patients treated with secukinumab for at least 192 weeks and up to 240 weeks in Southern Italy, between 2016 and 2021. Clinical data, including concurrent comorbidities and prior treatments were collected. Effectiveness was assessed by Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), Dermatology Life Quality Index (DLQI) scores at the initiation of secukinumab and at weeks 4, 12, 24, 48, 96, 144, 192, and 240. RESULTS: Two hundred and seventy-five patients (174 males), mean age 50.80 ± 14.78 years, were included; 29.8% had an uncommon localization, 24.4% psoriatic arthritis, 71.6% comorbidities. PASI, BSA, and DLQI improved significantly from week 4 and continued to improve over time. Between weeks 24 and 240, PASI score was mild (≤10) in 97-100% of patients, 83-93% had mild affected BSA (BSA ≤ 3), and 62-90% reported no effect of psoriasis on their quality of life (DLQI 0-1). Only 2.6% of patients reported adverse events and no patient discontinued the treatment during the study period. CONCLUSIONS: Secukinumab effectiveness in the long-term treatment of psoriasis is confirmed in real-world.

Seven-year monitoring of mercury in wet precipitation and atmosphere at the Amsterdam Island GMOS station.

Mercury (Hg) fate and transport research requires more effort to obtain a deep knowledge of its biogeochemical cycle, particularly in the Southern Hemisphere and Tropics that are still missing of distributed monitoring sites. Continuous monitoring of atmospheric Hg concentrations and trend worldwide is relevant for the effectiveness evaluation of the Minamata Convention on Mercury (MCM) actions. In this context, Gaseous Elemental Mercury (GEM) and total mercury (THg) in precipitations were monitored from 2013 to 2019 at the Amsterdam Island Observatory (AMS - 37°48'S, 77°34'E) to provide insights into the Hg pathway in the remote southern Indian Ocean, also considering ancillary dataset of Rn-222, CO2, CO, and CH4. GEM average concentration was 1.06 ± 0.07 ng m-3, with a slight increase during the austral winter due to both higher wind speed over the surface ocean and contributions from southern Africa. In wet depositions, THg average concentration was 2.39 ± 1.17 ng L-1, whereas the annual flux averaged 2.04 ± 0.80 µg m-2 year-1. In general, both GEM and Volume-Weighted Mean Concentration (VWMC) of THg did not show an increasing/decreasing trend over the seven-year period, suggesting a substantial lack of evolution about emission of Hg reaching AMS. Air masses Cluster Analysis and Potential Source Contribution Function showed that oceanic evasion was the main Hg contributor at AMS, while further contributions were attributable to long-range transport events from southern Africa, particularly when the occurrence of El Niño increased the frequency of wildfires.

A Preliminary Analysis on the Feasibility and Short-Term Efficacy of a Phase-III RCT on Mindfulness Added to Treatment as Usual for Patients with Chronic Migraine and Medication Overuse Headache.

This preliminary analysis of a single-blind phase-III RCT aims to compare the feasibility and short-term efficacy of mindfulness as an add-on to treatment as usual (TaU) in the management of patients with chronic migraine (CM) and medication overuse headache (MOH). Patients were randomized to either TaU (structured withdrawal of overused drugs, patient education and pharmacological prophylaxis) or TaU + MIND, wherein patients additionally received six 90 min weekly group sessions of mindfulness-based therapy. Repeated measures analyses were used to test whether patients in the two arms showed different course with regard to headache frequency and medication intake over a three-month period. Drop-out rates were not different between the two groups: 6/89 (6.7%) and 9/88 (10.2%) among those in TaU and TaU + MIND, respectively. A significant effect of time for all variables was shown, together with a significant effect of time by group, favoring TaU + MIND condition for headache frequency (p = 0.025) and NSAID intake (p = 0.007), controlling for age and CM duration. In total, 45/83 (54.2%) and 69/79 (75.9%) of the patients allocated to TaU and TaU + MIND, respectively, achieved 50% or more headache-day reduction (chi-squared 8.38, p = 0.004). Our preliminary analysis indicates that adding six mindfulness-based sessions to TaU was feasible and showed short-term efficacy in the treatment of patients with CM and MOH.

Addressing the cost of chronic and episodic migraine and its main drivers: a short-term longitudinal analysis from a third-level Italian center.

BACKGROUND: Chronic migraine (CM) is one of the most disabling neurological diseases, often associated to medication overuse headache (MOH). These patients make high use of pharmacological and non-pharmacological treatments, and experience high work-related indirect costs. The aim of this study was to address and compare the main driver of cost associated to CM-MOH and EM, and to evaluate the effect of improvement in migraine profile on disease cost. METHODS: We selected patients with baseline CM-MOH who reverted to an episodic pattern by 3 months after structured withdrawal. Paired sample t-test was used to explore the variation in headache frequency and its costs. Regression models were run to address the impact of single cost categories on total migraine cost. RESULTS: A total of 261 patients were included. Significant reductions in headache frequency and its costs were observed, with the exception of medical prophylaxis cost. The cost of migraine from chronic to episodic pattern is reduced by 533€ per month and 80% of this reduction is accountable to reduced indirect costs, i.e., loss of productive time. CONCLUSIONS: The results of our study open to future considerations on future approaches to the treatment of CM-MOH in which new migraine-specific treatments, i.e., monoclonal antibodies, should be combined with other pharmacological and non-pharmacological ones.

Recent applications and novel strategies for mercury determination in environmental samples using microextraction-based approaches: A review.

The growing need to monitor Hg levels in the environment to control its emissions and evaluate the effectiveness of reduction policies is driving the scientific community to focus efforts on creating analytical methods that are simpler, lower cost, more performing, and environmentally sustainable. In this context, an important contribution is provided by microextraction techniques, which have long proven to be simple, reliable, and to ensure an environmentally responsible sample preparation. This manuscript reviews the recent progress in the determination of environmental Hg using microextraction techniques. The considered studies involve all environmental compartments (i.e., air, water, soil, and biota) and have been discussed by grouping them according to the employed technique while pointing out the main advances achieved and the most important limitations. The ultimate goal is to provide an up-to-date overview of the analytical potential of microextraction techniques that can be exploited in various investigation fields and to highlight the most important knowledge gaps that should be addressed in the coming years, such as in-situ sampling, the use of natural materials, and the value of metrological support to obtain data SI-traceable and comparable.

Activating ATF6 in spinal muscular atrophy promotes SMN expression and motor neuron survival through the IRE1α-XBP1 pathway.

AIM: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by survival of motor neuron (SMN) deficiency that induces motor neuron (MN) degeneration and severe muscular atrophy. Gene therapies that increase SMN have proven their efficacy but not for all patients. Here, we explored the unfolded protein response (UPR) status in SMA pathology and explored whether UPR modulation could be beneficial for SMA patients. METHODS: We analysed the expression and activation of key UPR proteins by RT-qPCR and by western blots in SMA patient iPSC-derived MNs and one SMA cell line in which SMN expression was re-established (rescue). We complemented this approach by using myoblast and fibroblast SMA patient cells and SMA mouse models of varying severities. Finally, we tested in vitro and in vivo the effect of IRE1α/XBP1 pathway restoration on SMN expression and subsequent neuroprotection. RESULTS: We report that the IRE1α/XBP1 branch of the unfolded protein response is disrupted in SMA, with a depletion of XBP1s irrespective of IRE1α activation pattern. The overexpression of XBP1s in SMA fibroblasts proved to transcriptionally enhance SMN expression. Importantly, rebalancing XBP1s expression in severe SMA-like mice, induced SMN expression and spinal MN protection. CONCLUSIONS: We have identified XBP1s depletion as a contributing factor in SMA pathogenesis, and the modulation of this transcription factor proves to be a plausible therapeutic avenue in the context of pharmacological interventions for patients.

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.

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.

Long-term (48 weeks) effectiveness, safety, and tolerability of erenumab in the prevention of high-frequency episodic and chronic migraine in a real world: Results of the EARLY 2 study.

OBJECTIVE: To evaluate the long-term effectiveness, safety, and tolerability of erenumab in a real-world migraine population, looking for putative predictors of responsiveness. BACKGROUND: Erenumab proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long-term extension studies of double-blind, placebo-controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures. METHODS: A 48-week, multicenter, longitudinal cohort real-life study was conducted at 15 headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high-frequency episodic migraine (HFEM) or CM aged 18-65 years. Each patient was treated with erenumab 70 mg, administered monthly. The dose was switched to 140 mg in nonresponders and in responders who had become nonresponders for at least 4 weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45-48 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a ≥50%, ≥75%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test-6 scores (HIT-6) during the same time interval. RESULTS: A total of 242 patients with migraine received at least one dose of erenumab 70 mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for ≥48 weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with ≥3 migraine-preventive medication classes. From baseline to Weeks 45-48, erenumab treatment reduced MMD by 4.3 ± 5.3 (mean ± SD) in patients with HFEM, and MHD by 12.8 ± 8.9 (mean ± SD) in subjects with CM. VAS and HIT-6 scores were decreased by 1.8 ± 1.9 (mean ± SD) and 12.3 ± 11 (mean ± SD) in HFEM, and by 3.0 ± 2.2 (mean ± SD) and 13.1 ± 11.2 (mean ± SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range [IQR] 10.0-13.0) to 5 (IQR 2.0-8.0) in HFEM and from 20.0 (IQR 15.0-30.0) to 6.0 (IQR 3.8-10.0) in CM. The ≥50% responders were 56.1% (32/57) in HFEM and 75.6% (124/164) in CM; ≥75% responders were 31.6% (18/57) and 44.5% (73/164); and 100% responders were 8.8% (5/57) and 1.2% (2/164), respectively. At Week 48, 83.6% (137/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52-19.41; p = 0.009) in HFEM. In patients with CM, ≥50% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03-8.7; p = 0.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05-1.20; p = 0.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15-0.87; p = 0.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64-0.92; p = 0.004). CONCLUSIONS: Long-term (48-week) erenumab treatment provides sustained effectiveness, safety, and tolerability in real-life patients with HFEM or CM with ≥3 prior preventive treatment failures. The dose of 140 mg was required in most patients along the study and should be taken into consideration as the starting dose. Allodynia (in HFEM), male sex, and baseline migraine frequency (in CM) might represent positive responsiveness predictors. Conversely, psychiatric comorbidities and multiple prior preventive treatment failures could be negative predictors in patients with CM.

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

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.

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

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.

Safety profile of biologic drugs for psoriasis in clinical practice: An Italian prospective pharmacovigilance study.

Psoriasis is an inflammatory and chronic skin disorder associated with physical and psychological burden impairing patients' quality of life. In the last decade, biologic drugs have widely changed treatment of moderate-severe psoriasis and their number is increasing overtime. To early identify expected/unexpected adverse events (AEs) with biologic treatments, pharmacovigilance programs are needed. We designed a post-marketing active pharmacovigilance program to monitor and analyse AEs and/or serious adverse events (SAEs) reports. All consecutive patients treated with one biologic drug during a two-years period and satisfying inclusion criteria have been enrolled in five Dermatology tertiary units. Demographic and clinical features of patients, type of treatment used, therapy discontinuation, failures, switch/swap to another biologic, and possible onset of AEs were collected. Overall, 512 patients with a diagnosis of psoriasis (286; 55.9%) or arthropathic psoriasis (226; 44.1%) have been enrolled. Eighty-two (16%) patients with AEs and 5 (1%) with SAEs have been identified. Further, 59 (11.5%) had a primary/secondary failure (mainly on infliximab and etanercept). The adverse events and SAEs were reported with golimumab (4/12), adalimumab (32/167), infliximab (9/48), etanercept (31/175) and ustekinumab (11/73), no adverse events have occurred with secukinumab (0/37). Infliximab and etanercept were significantly associated with primary/secondary failures, whereas no differences have been highlighted for AEs insurgence. On the other hand, ustekinumab seems to be associated with a low rate of AEs (p = 0.01) and no adverse events or failures have been reported with secukinumab (p = 0.04 and 0.03, respectively). Our study, even though limited by a small sample size and a brief follow-up period, provide useful data on widely used biologic drugs and their tolerability, discontinuation rate and the incurrence of severe adverse events. Further studies are necessary to include the recently approved biologic drugs and to increase the sample size for more detailed analysis.

Headache in spontaneous intracranial hypotension: an overview with indications for differential diagnosis in the clinical practice.

Headache is the most common symptom of spontaneous intracranial hypotension (SIH). The present review focuses on data regarding headache features reported in the most relevant published articles and summarizes the main SIH headache features, namely, orthostatic headache, headache triggered by Valsalva maneuver, pattern of onset of headache, and location and quality of headache. Published data indicate that the clinical suspect of this disorder may be challenging, due to its protean presentation. Among the main implications for clinical practice, we suggest to suspect SIH in all patients with a new onset headache, as different forms of primary and secondary headache should be considered in the differential diagnosis of SIH, particularly cervicogenic headache, new daily persistent headache, and headaches precipitated by Valsalva maneuver. The clinical interview must include specific questions on the possible orthostatic feature of headache, although its absence should not make clinicians to reject the SIH hypothesis as headache cannot be orthostatic in each patient and in all periods of the natural history of the disease. Other disorders with orthostatic symptoms, such as in postural tachycardia syndrome (POTS) and persistent postural-perceptual dizziness (PPPD), should be considered in the differential diagnosis. Awareness that SIH can present with acute, sudden onset requires that clinicians working in the emergency settings should consider SIH in the range of diagnoses of thunderclap headache.

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

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.