Small spheno-ethmoidal meningoencephalocele versus ethmoidal mucocele in spontaneous intracranial hypotension.

Background: Meningoencephalocele is defined as an abnormal sac of brain tissue and meninges extending beyond natural skull margins, often leading to cerebrospinal fluid (CSF) leakage. When this condition arises in the spheno-ethmoidal region, the diagnosis becomes more challenging as it can be mistaken for other nasal pathologies, such as mucocele. Research question: We show in this case report a non-congenital sphenoethmoidal meningoencephalocele causing rhinoliquoral fistula and spontaneous intracranial hypotension. Results: this 65-year-old woman presented with sporadic rhinoliquorrhoea associated with orthostatic headache, nausea and dizziness. Brain MRI revealed a small lesion of an ethmoidal sinus, which was successfully treated with endoscopic endonasal surgery. Histology confirmed the presence of meningoencephalic tissue positive for S100 protein on immunohistochemistry. Conclusions: When dealing with lesions of the paranasal sinuses in contact with the anterior skull base, rhinoliquorrhoea presence suggests meningoencephalocele. In dubious cases, a proper workup, including a thorough clinical history and neurological examination, specific imaging, and a direct search of CSF-like markers, is essential to support the differential diagnosis. In such cases, a transnasal endoscopic surgical approach is recommended to obtain a final histological diagnosis and to perform eventual dural plastic surgery.

Triptans utilization in Italian population: A real-life study in community pharmacies.

The term Headache Disorders (HD) refers to a number of nervous system pathologies characterised by recurrent headaches. Despite the serious impact HD have on the health system, society, and the economy, these are an underestimated, underdiagnosed, and, hence, undertreated phenomenon. Triptans are the first-line therapy for the acute treatment of moderate to severe migraine but their utilization is still inadequate, perhaps also because in Italy no triptan can be bought without a medical prescription. In this article, the data from a 2016-2017 study has been further analysed with the aim of evaluating any associations between the use of triptans and the other series of variables identified in the questionnaire. This further analysis has been connected to the role that community pharmacies could play on this issue. The questionnaire was administered to 4,424 pharmacy users by 610 purposely trained pharmacists working in 514 pharmacies. The survey was carried out in 19 of the 20 Italian regions. The data shows that only 25% of patients suffering from HDs are prescribed triptans. Older patients, those with definite migraines, and those with a chronic disorder resort more frequently to this class of pharmaceuticals, as do those patients in care at a specialist headache centre. The multivariable analysis also confirmed these results. Our study, which performed a direct detection, in real life, on patients requesting pharmacological treatment for a migraine headache, therefore confirmed the need to investigate the reasons behind the low use and prescription of triptans in the Italian population. Moreover, any future studies should take advantage of community pharmacies, plan actions that would allow a series of evaluations over time of the requirements of migraineurs, and establish a process to put these patients under the care of the pharmacy to ensure adherence to therapy.

Overview on effectiveness of erenumab, fremanezumab, and galcanezumab in reducing medication overuse headache in chronic migraine patients.

BACKGROUND: Migraine is a disabling primary headache disorder with socioeconomic burden. Medication overuse headache (MOH) is caused by chronic overuse of symptomatic drugs often observed in migraine patients. The approved for migraine prevention CGRP antagonists erenumab, fremanezumab, and galcanezumab are effective in migraine prophylaxis but there are only few data regarding efficacy on MOH. AIM OF THE STUDY: To assess efficacy of erenumab, galcanezumab, and fremanezumab in reducing headache in patients with chronic migraine complicated by medication overuse headache. METHODS: Patients fitting International Classification of Headache Disorders 3rd Edition criteria for chronic migraine and MOH were enrolled and treated with CGRP antagonists without performing drug withdrawal. Efficacy was assessed by improvement of Migraine Impact and Disability Assessment Scale (MIDAS) and reduction of monthly use of symptomatic medications. Patients reporting a ≥ 50% reduction of monthly headache days and ≥ 50% reduction of analgesic and/or triptan use compared with a 3-month baseline period were defined as responders. RESULTS: Three hundred three patients, 252 females and 51 males, were enrolled. Patients were treated for at least 6 months up to 1 year. Two hundred forty-two out of 303 (80%) showed both a ≥ 50% reduction of monthly headache days and analgesics intake at 3-month follow-up visit compared to the 3-month baseline period; 239 on 303 (78.8%) continued to have ≥ 50% improvement in both at 6-month follow-up visit. CONCLUSION: Monoclonal antibodies inhibiting CGRP are effective in reducing monthly headache days in migraine patients with MOH.

Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis.

BACKGROUND AND AIM: The pathogenesis of the pain that occurs in episodic migraine attack is due to the activation of the trigeminal system's first neuron receptors located on vessel wall. The release from the endothelium of nitric oxide, a product of arginine metabolism, causes vasodilation and stretching of the vascular trigeminal system and promotes pain. It is unknown whether this same metabolic event is involved in the pain accompanying chronic migraine. To understand the possible role of arginine in the pathogenesis of chronic migraine patients, we evaluated the metabolism of arginine in plasma of chronic migraine and control subjects. METHODS: We evaluated the metabolism of arginine in a group of patients affected by chronic migraine. Quantification of arginine, ornithine, citrulline, monomethyl arginine (NMMA), dimethylarginines (ADMA, SDMA), and tyramine was performed by ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometer. RESULTS: Chronic migraine patients showed low plasma levels of arginine, significantly elevated levels of ornithine, ADMA, and NMMA whereas the levels of citrulline and SDMA were in the range of controls. CONCLUSIONS: The elevated levels of ADMA and NMMA, inhibitors of nitric oxide synthase, suggest that the metabolism of arginine may be inhibited with a possible reduction of NO release in the circulation of chronic patients. This suggests that the origin of pain may not be related to the vasodilation of trigeminal vascular system that occurs in episodic migraine patients.

Primaries non-migraine headaches treatment: a review.

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.

Prevention, education and counselling: the worldwide role of the community pharmacist as an epidemiological sentinel of headaches.

Headache disorders are the third among the worldwide causes of disability, measured in years of life lost to disability. Given the pharmacies' importance in general in headache patient and, in particular in migraine patient management, various studies have been carried out in recent years dealing with this issue. Indeed, in 2014, our research group first analysed publications on a number of studies conducted worldwide. As five years have passed since our first analysis of the literature and having carried out a number of specific studies in Italy since 2014, we wish to analyse once again the studies carried out globally on this topic to evaluate how the situation has evolved in the meantime. The key words used for the bibliographic search were "community pharmacy" and "headache"; we considered articles published between 2014 and 2018. The selected studies regarded Sweden USA, Belgium, Ireland, Jordan and Ethiopia. From the analysis of the international research papers, it is evident that, despite the time that has passed since the previous analyses and the general agreement that pharmacists find themselves in an ideal position to offer adequate levels of counselling to headache patients, the knowledge of pharmacists is not yet sufficient. Clearly, there is a strong need to develop training programmes specifically focused on this subject. Regarding Italy, a national study, commenced in 2016, was designed as a cross-sectional survey employing face-to-face interviews between pharmacist and patient using a questionnaire drawn up by experts in compliance with best practice from scientific literature. Six hundred ten pharmacists followed a specific training course; 4425 questionnaires were correctly completed. The use of pharmacies as epidemiological sentinels, given their capillarity and daily contact with the local population in Italy, enabled us to obtain an epidemiological snapshot closer to the real-life situation compared to specialist headache centres. Over the course of this study, data on headaches were gathered in Italian pharmacies with the highest levels of numerosity in the world.

Headache attributed to IIH: clinical evolution in IHS criteria through the years.

Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure without a detectable cause. The most common symptom of IIH is a headache, which occurs in almost all cases at the time of diagnosis with various headache phenotypes. In clinical practice, diagnosis of headache attributed to IIH is given referring to the International Headache Society (IHS) criteria of the International Classification of Headache Disorders. In the present publication, we consider how the IHS diagnostic criteria for headache attributed to intracranial idiopathic hypertension have evolved through the years.

When does the brain choose pain?

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.

Self-medication for migraine: A nationwide cross-sectional study in Italy.

Headache disorders are considered the second leading cause of years lived with disability worldwide, and 90% of people have a headache episode at least once a year, thus representing a relevant public health priority. As the pharmacist is often the first and only point of reference for people complaining of headache, we carried out a survey in a nationwide sample of Italian pharmacies, in order to describe the distribution of migraine or non-migraine type headaches and medicines overuse among people entering pharmacies seeking for self-medication; and to evaluate the association, in particular of migraine, with socio-demographic and clinical characteristics, and with the pathway of care followed by the patients. A 14-item questionnaire, including socio-demographic and clinical factors, was administered by trained pharmacists to subjects who entered a pharmacy requesting self-medication for a headache attack. The ID Migraine™ Screener was used to classify headache sufferers in four classes. From June 2016 to January 2017, 4424 people have been interviewed. The prevalence of definite migraines was 40%, significantly higher among women and less educated people. About half of all headache sufferers and a third of migraineurs do not consider their condition as a disease and are not cared by any doctor. Among people seeking self-medication in pharmacies for acute headache attacks, the rate of definite or probable migraine is high, and a large percentage of them is not correctly diagnosed and treated. The pharmacy can be a valuable observatory for the study of headaches, and the first important step to improve the quality of care delivered to these patients.

Transcutaneous supraorbital neurostimulation for the prevention of chronic migraine: a prospective, open-label preliminary trial.

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.

Community pharmacies as epidemiological sentinels of headache: first experience in Italy.

Migraine is a disabling neurovascular syndrome which affects 12-15% of the global population and it represents the third cause in years lived with disability in both males and females aged 15-49 years. Among migraineurs, the symptomatic drug abuse may be a risk factor in the development of medication overuse headache (MOH). Detecting cases of MOH is not straightforward; community pharmacists may, therefore, be in a strategic position to identify individuals who self-medicate, particularly with respect to prevent the development of MOH. In 2014, our group published the results of a survey conducted in Piedmont, Italy, on the patterns of use and dispensing of drugs in patients requesting assistance from pharmacists for relief of a migraine attack. We decided, now, to expand the scope of the model to a national level. The study is based on cross-sectional face-to-face interviews using questionnaires, presented in this paper, consisting of a first part regarding the socio-economic situation and a second part which aimed to classify the disease and any excessive use of drugs. Of the 610 pharmacists trained with an online course, 446 gathered a total of 4425 correctly compiled questionnaires. The participation of community pharmacies has highlighted various criticalities especially of an organisational nature; however, it also revealed the power of this method as a means of gathering epidemiological data with a capillarity which few other methods can match. The objective was also to identify each territory's requirements and facilitate the decision-making process in terms of understanding what patients/citizens actually require.

Usefulness of nutraceuticals in migraine prophylaxis.

Several studies have supported the efficacy of complementary and alternative medicine approaches (physical, behavioral and nutraceutical therapies) in the treatment of headache disorders. Nutraceutical treatment consists of taking vitamins, supplements (magnesium, riboflavin, coenzyme Q10, and alpha lipoic acid) and herbal preparations (feverfew and butterbur), and its usage is frequently determined by dissatisfaction with conventional medical therapies. There is a growing body of research on nutraceutical use for migraine prophylaxis. This brief overview provides information about the potential efficacy and side effects of various nutraceutical products summarizing randomized controlled trials of some of the most commonly used non-pharmacological treatments for the prophylaxis and treatment of migraine, including magnesium, coenzyme Q10, riboflavin (vitamin B2), petasites, and feverfew.

Chiari malformation-related headache: outcome after surgical treatment.

The outcome of headache in a series of 135 operated CM1 is presented. Favorable results were obtained in 85% of atypical and 93% typical headache with the support of a multidisciplinary approach that restricted the indications for surgery.