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.

European Academy of Neurology guidelines on the treatment of cluster headache.

BACKGROUND AND PURPOSE: Cluster headache is a relatively rare, disabling primary headache disorder with a major impact on patients' quality of life. This work presents evidence-based recommendations for the treatment of cluster headache derived from a systematic review of the literature and consensus among a panel of experts. METHODS: The databases PubMed (Medline), Science Citation Index, and Cochrane Library were screened for studies on the efficacy of interventions (last access July 2022). The findings in these studies were evaluated according to the recommendations of the European Academy of Neurology, and the level of evidence was established using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RECOMMENDATIONS: For the acute treatment of cluster headache attacks, there is a strong recommendation for oxygen (100%) with a flow of at least 12 L/min over 15 min and 6 mg subcutaneous sumatriptan. Prophylaxis of cluster headache attacks with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy and tolerability) is recommended. Corticosteroids are efficacious in cluster headache. To reach an effect, the use of at least 100 mg prednisone (or equivalent corticosteroid) given orally or at up to 500 mg iv per day over 5 days is recommended. Lithium, topiramate, and galcanezumab (only for episodic cluster headache) are recommended as alternative treatments. Noninvasive vagus nerve stimulation is efficacious in episodic but not chronic cluster headache. Greater occipital nerve block is recommended, but electrical stimulation of the greater occipital nerve is not recommended due to the side effect profile.

Comparison study between erenumab, fremanezumab, and galcanezumab in the preventive treatment of high frequency episodic migraine and chronic migraine.

The treatment of migraine now includes the possibility of using the anti CGRP monoclonal antibodies erenumab, fremanezumab and galcanezumab. Registration studies and real life studies have shown excellent efficacy and extraordinary tolerability of these treatments. Little is known about the possible differences between the three treatments and this observational study was conducted with a view to comparing the efficacy, safety and impact that anti-CGRP monclonal antibodies have on additional parameters such as disability in social, family and work activities.

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.

Cluster headache in relation to different age groups.

Cluster headache (CH) has always been considered a type of primary headache affecting predominantly male subjects in early and medium adulthood. However, recent studies carried out in large case series of patients with CH show that not infrequently it may set in also after age 50; by contrast, onset before adolescence is very rare. Additionally, when onset occurs before age 14 or from the sixth decade of life onward, male predominance decreases to the point that in chronic forms CH predominantly affects the female sex. This particular pattern of the gender ratio in relation to onset in different age groups suggests that hormonal factors may actually play a role in the genesis of CH. In particular, future studies should be aimed at investigating the possible protective role of estrogen.

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.

Headache as a presenting symptom of glioma: A cross-sectional study.

Objective The objective of this study was to analyse the prevalence and the clinical features of headache as a presenting symptom of glioma. Methods We interviewed 527 consecutive adult patients with histologically confirmed glioma, admitted to the Regina Elena National Cancer Institute between 2010 and 2015. We defined four headache phenotypes: Tension-type-like headache (TTH), migraine-like headache, worsening of a pre-existing headache (WPH) and classic brain tumour headache (BTH). Logistic regression analysis was carried out to investigate potential risk factors for headache at presentation of glioma. Results 12.5% (n = 66) of patients with glioma indicated headache as a presenting symptom of their disease. Of these, 31 patients (47%) had TTH, while BTH and WPH were reported by 28 (42%) and seven (11%) patients, respectively. We did not find any case of migraine-like headache. Infratentorial ( p = 0.038) and right-sided tumours ( p = 0.013) were more frequently associated with the presence of headache at onset. Patients with TTH were older than patients with BTH and WPH ( p = 0.035). BTH was less frequently associated with other neurological signs ( p < 0.0001). The multivariate logistic regression analysis showed the localization of the brain tumour in the left hemisphere to be a protective factor for the development of headache. Conclusions Our study includes a very large series of patients with glioma, providing a description of headache phenotype at first presentation of disease and investigating possible factors that may influence the clinical features of headache.

A case-report of migraine "sine headache".

Background and objectives We describe a case of a female patient whose otherwise "typical" migraine attacks turned into episodes with a full spectrum of associated symptoms but without headache. Case report We evaluated a 53-year-old woman with a long history of migraine without aura. In concomitance with premenopausal menstrual dysregulation, she reported episodes of nausea and vomiting, associated with photophobia, phonophobia and osmophobia, but without headache; these episodes were responsive to oral triptans. Alternative diagnoses were excluded through extensive examinations. Discussion To date, no reports have been published in the literature on otherwise typical migraine attacks that are not accompanied by headache, nor did our case seem comparable to cases of abdominal migraine and cyclic vomiting syndrome. Conclusion Pathophysiologically, we hypothesize that functional dysregulation of the hypothalamus-brainstem connectivity may generate migraine attacks with a full spectrum of associated symptoms but without pain.

Childhood-Onset Cluster Headache: Observations From a Personal Case-Series and Review of the Literature.

BACKGROUND/OBJECTIVES: Puberty seems to be a turning point in cluster headache (CH) onset. To verify its influence on CH phenotype, we focused on cases with onset ≤13 years. A review of the literature follows. METHOD: We considered CH cases with age-of-onset ≤13 years evaluated at our center between 1975 and 2015; these cases were matched by sex to two consecutive patients with age-of-onset as close as possible (±2 years) to the median age-of-onset of the overall CH population. RESULTS: Of the overall 808 cases (585 men and 223 women, M:F ratio = 2.6), 38 patients (20 men and 18 women, M:F ratio = 1.1) had pediatric onset (PO). The diagnostic delay was significantly higher among cases with PO (21.2 ± 12.4 years, P < .0001). In this group, females had more frequently a chronic course and a familiarity for CH. Men with PO had some significant distinctive features, including higher frequency and longer duration of headache attacks, and higher proportion of various cranial autonomic and migraine-like symptoms. CONCLUSIONS: We confirmed that CH with childhood onset does not show a male predominance, which was actually inverted for chronic cases. Furthermore, males with PO seem to have a specific clinical phenotype.

Neurobiology of chronicization.

In the past few years, research on chronicization of headache has focussed primarily on migraine, even though there are other types of primary headache that over time can turn into chronic forms. Only a minority of migraine sufferers will develop a chronic condition, with attacks that are likely to vary in their clinical features. As a result, in chronic migraine the specific diagnostic criteria for this headache type do not always exhibit the typical features of migraine. Among the factors that play a major role in favouring chronicization are a high frequency of migraine attacks since the beginning, overuse of symptomatic medication and onset of depression or arterial hypertension. Several neurophysiology, biochemistry and functional neuroimaging studies suggest that chronic migraine may be associated with structural, functional and metabolic changes in the brain, especially involving the brainstem.

Pediatric migraine with aura in an Italian case series.

The aim of the present study was to describe the characteristics of migraine with aura (MwA) in a case series of patients with headache onset before 12 years of age. We considered all consecutive patients referred to the Parma Headache Centre between 1975 and 2015 affected by MwA, diagnosed by our team of trained neurologists; the cases were subsequently reviewed applying the ICHD3-beta criteria. We then identified those cases with headache age-of-onset <12 years (i.e., "pediatric" cases), which were compared to all remaining cases. We identified 283 cases with pediatric onset (87 males and 196 females). The male-to-female ratio was 1:2.3 in both "pediatric" and "non-pediatric" cases. The time lag between MwA onset and our first evaluation was significantly higher among the pediatric cases (18.7 ± 13.3 vs 10.4 ± 10.4 years). In both groups of patients, visual aura was the most common type of aura, followed by sensory and speech disturbances; however, these two latter aura symptoms were significantly more common among pediatric cases. In this group of patients, aura without headache was significantly less frequent (1.8 vs 5.3%); furthermore, headache had migraine characteristics in a higher proportion of cases (90.1 vs 82.6%). A family history of MwA was significantly more frequent among cases with pediatric onset (31.1 vs 16.9%). Males but not females with pediatric MwA had more frequently a comorbid migraine without aura (27.6 vs 16.8%). Among cases with pediatric onset, we did not find any significant differences between males and females. In conclusion, in our very large case series of MwA, patients with headache onset before 12 years of age seem to have a specific clinical phenotype, without significant gender differences.

The PACE study: lifetime and past-year prevalence of headache in Parma's adult general population.

Headache is a widespread disorder and therefore it has a strong impact on quality of life. In the present work we focused on lifetime and past-year prevalence of headache in general and by gender, in a population-based sample in Parma. A total of 904 subjects representative of Parma's adult general population were interviewed face-to-face by a physician from the Parma Headache Centre, using a validated questionnaire. The lifetime prevalence of headache was 69.1%, i.e. 75.8% in women and 60.6% in men; the crude past-year prevalence of headache was 42.8%, i.e. 52.0% in women and 31.1% in men. Both lifetime and past-year prevalence rates were significantly higher in females than in males (odds ratio, respectively, 2.0 and 2.4). In our study, past-year prevalence decreased after age 50 in both genders. Most people suffer from one headache subtype. In over 80% of cases, headache starts before age 40 and therefore people were not very likely to develop headache after 50 years. The past-year and lifetime prevalence rate of headache in general that we found in our study falls within the lower range of values for headache prevalence in European countries. Further researches need to be set in the Italian epidemiological background.

Cluster Headache With Accompanying Migraine-Like Features: A Possible Clinical Phenotype.

BACKGROUND: There are limited literature data on migraine-like accompanying features (MLF) in patients with cluster headache (CH). These symptoms are frequently reported by patients and may delay CH diagnosis. OBJECTIVE: The aim of the present study was to investigate the occurrence of migraine-like symptoms in an Italian case series of CH patients and to determine whether these features influence the clinical phenotype of CH. METHODS: A cross-sectional study was performed in all consecutive patients referred to the Parma Headache Centre between 1975 and 2013 affected by CH; the cases were subsequently reviewed applying the ICHD3-beta criteria. Our initial study sample consisted of 785 subjects, 569 men (72.5%) and 216 women (27.5%). We then identified those patients who reported at least one of the migraine accompanying symptoms (ie, nausea or vomiting or photophobia and phonophobia). RESULTS: We found 362 patients (46%) with MLF, 250 men (43.9% of the initial male sample) and 112 women (51.9% of the initial female sample), and 423 patients (54%) without MLF, 319 men (56.1% of the initial male sample) and 104 women (48.1% of the initial female sample). Multiple logistic regression analysis highlighted some demographic and clinical features that significantly characterized patients with MLF after adjusting for confounding: they were more frequently female (OR 1.78, CI 1.11-2.80), with a relatively younger age of onset (OR 1.82, CI 1.06-2.91) than expected, attacks were longer in duration (OR 1.85, CI 1.04-2.46) and accompanied by a more frequent ptosis (OR 1.67, CI 1.04-2.34), sweating (OR 1.63, CI 1.02-2.21), and miosis (OR 1.54, CI 1.12-1.93); osmophobia was also more frequently reported (OR 1.76, CI 1.28-2.46). CONCLUSION: Our study confirms the high proportion of CH patients with MLF, which is reported in literature. The presence of MLF seems to relate to some peculiar demographic and clinical characteristics of CH sufferers. Whether these features influence the response to therapy remains to be determined.

The use of onabotulinum toxin A (Botox(®)) in the treatment of chronic migraine at the Parma Headache Centre: a prospective observational study.

Chronic migraine is a debilitating headache, whose treatment is often complicated by the concomitant overuse of symptomatic medication and by the poor efficacy of standard prophylactic treatments. The PREEMPT studies have demonstrated the efficacy and tolerability of onabotulinum toxin A (Botox(®)) in the treatment of this headache type. Data about its use in clinical practice are still scarce. Our study evaluated all subjects with chronic migraine who were treated with onabotulinum toxin A between February 2014 and November 2015 at the Parma Headache Centre. Botox was injected according to the PREEMPT paradigm every 3 months. The data about variations in the number of headache days and in symptomatic medication intake before and after the Botox injections were collected from the patients' headache diaries. The study also evaluated tolerability to treatment, disability, and depressive symptoms. Of the 52 treated subjects, 14 received Botox treatment for at least 9 months and showed a significant decrease in the median number of headache days (from 19 to 14.5, p = 0.011) and in the median number of days of symptomatic medications intake and symptomatic drugs. Overall, the treatment was well tolerated. The average MIDAS and BDI-II scores after 9 months were reduced, though not significantly. The treatment with Botox proved effective and well tolerated in our clinical practice. Further studies on larger patient samples will help shed light on the persistence of the drug's effect at long term and identify the predictive factors of response to treatment.

Age of onset of episodic and chronic cluster headache - a review of a large case series from a single headache centre.

BACKGROUND: In the largest case series of cluster headache (CH) published in the literature, age of onset varies between 29.6 and 31.6 years. Differences in onset age based on gender and subtype diagnosis are reported, while there are only few data on patients with childhood and elderly onset. We therefore deemed it useful to review our own large case series of CH patients. METHODS: The age of onset of cluster headache was investigated in a consecutive case series of 808 patients (585 men and 223 women), including 686 (503 men and 183 women) with episodic cluster headache (ECH), 103 (66 men and 37 women) with chronic cluster headache (CCH), and 19 with an indeterminate form of CH (16 men and three women). RESULTS: The mean age of onset was 30.2 ± 13.8 years (30.1 ± 13.0 in men and 30.4 ± 15.7 in women). The women with primary CCH had a mean onset age of 42.8 ± 21.7 years, while the women with secondary CCH did not differ much from those with ECH. Distribution of the study subjects by decades of onset age showed a peak in the third decade both in men and in women, but when only CCH patients were considered it displayed a more marked bimodal pattern in women (with peaks in the second and the sixth decade) than men (with peaks in the third and the fifth decade). The clear male predominance in cases with onset in the central age groups became attenuated in the extreme age groups. In patients with onset between ≤ 15 years and ≥ 50 years, the traditional male-to-female ratio was actually inverted in CCH. CONCLUSIONS: Based on these epidemiological findings, it would be important to investigate the possible role, causative or protective, played by hormonal factors in CH pathogenesis.

Familial cluster headache in an Italian case series.

To investigate the familial occurrence of cluster headache (CH) in a series of Italian patients, we focused on possible differences in the mean age of onset between familial and non-familial CH cases. We considered all consecutive patients referred to the Parma Headache Centre between 1975 and 2013 affected by CH; we subsequently reviewed these cases applying the ICHD3-beta criteria (785 probands, 569 men and 216 women). We identified those cases who reported at least a first-degree relative with a diagnosis of CH, which was confirmed by the clinical documentation they provided. Each one of the "familial cases" was matched by sex and age (±2 years) at the first visit to three consecutive CH patients who did not report any first-degree relative affected by CH. A positive family history of CH was found in 40 probands (5.1 %), 28 men (4.9 %), and 12 women (5.6 %). The male:female ratio was 2.3:1 among the 40 CH familial cases, while it was 2.7:1 among all the CH non-familial cases (745 patients). The mean age of onset was significantly (p < 0.01) lower in women with familial CH (28.5 years, SD 17.7 years, range 10-63 years) than in women with non-familial CH (46.7 years, SD 13.7 years, range 11-74 years); we did not find a significant age difference among men (the mean age of onset for the familial cases was 29.6 years, SD 13.6 years, range 6-63 years; while for the non-familial cases, it was 29.3 years, SD 13.2 years, range 13-59 years). Our study suggests that genetic factors may play a role in the female gender causing an earlier age of onset and a lower male-to-female sex ratio in familial cases.