BackgroundCluster headache (CH) is considered the most excruciating primary headache syndrome; although much less prevalent than migraine, it is not rare as it affects more than 1/1000 people. While its clinical presentation is considered stereotypic, atypical features are often encountered. Internationally, cluster headache is often misdiagnosed, undertreated and mistreated.MethodsWe prospectively studied 302 CH patients, all examined by the same headache specialist. The aim of our study was to describe the demographic and clinical characteristics of CH patients in Greece and draw attention to under-management, under-treatment and mis-treatment often encountered in clinical practice; our purpose is to improve recognition and successful treatment of cluster patients by Greek neurologists and other physicians.ResultsIn the present cohort, clinical characteristics of CH are similar to those described in other populations. Beyond the standard clinical characteristics, features like side shifts (12.6 %), location of maximal pain intensity outside the first trigeminal branch division (10.2 %), lack of autonomic features (7 %), presence of associated features of migraine and aggravation by physical activity (10 %) were encountered. Four out of five patients had consulted a physician prior to diagnosis. The median number of physicians seen prior to diagnosis was 3 and the median time to diagnosis was 5 years, though it improved for patients with recent onset. Chronic cluster headache, side shifts, pain location in the face or the back of the head and aggravation by physical activity were found, among others, to be statistically significantly related to delayed diagnosis or more physicians seen prior to diagnosis. Even properly diagnosed patients were often undertreated or mistreated.ConclusionsCluster headache, in a large cohort of Greek patients, has the same phenotypic characteristics as described internationally. Uncommon clinical features do exist and physicians should be aware of those, since they may eventuate in diagnostic problems. Most CH patients in Greece remain misdiagnosed or undiagnosed for rather lengthy periods of time, but time to diagnosis has improved recently. Even after diagnosis, treatment received was suboptimal.

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BackgroundSleep disorders and circadian dysregulation appear to be associated with primary headache disorders.ObjectiveThe aim of this study was to review the existing evidence for the deployment of melatonin in migraine prophylaxis. Initially, case‐control studies investigating nocturnal melatonin and 6‐sulphatoxymelatonin (aMT6s, melatonin metabolite discarded by the urine) levels in patients with migraine and healthy controls (HC) would be reviewed and meta‐analyzed. Second, results from randomized controlled trials (RCTs) and non‐randomized studies evaluating the use of melatonin in migraine would be synthesized.MethodsMEDLINE EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar, and OpenGrey were comprehensively searched. The quality of studies was assessed according to the Newcastle‐Ottawa Scale (case‐control studies) and the Risk‐of‐Bias Cochrane tool (RCTs). Random‐effects (RE) or fixed‐effects (FE) model was used based on heterogeneity among studies (homogeneity assumed when PQ > 0.1 and I2 < 30%). Publication bias was assessed by funnel plots.ResultsLiterature search provided 11 case‐control studies. Evidence was compatible with lower nocturnal serum [5 of 6 studies were synthesized due to deficient reporting of 1 abstract, migraine n = 197, HC n = 132, RE MD = −12.29 pg/ml, 95%CI = (−21.10, −3.49)] and urinary melatonin [3 studies, migraine n = 30, HC n = 29, RE MD = −0.12 nmol/nocturnal (12 hours) urinary collection, 95%CI = (−0.22, −0.03)], as well as urine aMT6s levels [1 study, migraine n = 146, HC n = 74, MD = −11.90 μg/nocturnal (12 hours) urine collection, 95%CI = (−19.23, −4.57)] in adult migraine patients compared to HC [1 study involving children did not reveal any difference regarding nocturnal urine aMT6s, n = 18 per group, MD = −6.00 μg/nocturnal (12 hours) urine collection, 95%CI = (−21.19, 9.19)]. Regarding the treatment‐prevention of migraine, 7 RCTs and 9 non‐randomized studies were retrieved. Data synthesis was not feasible for the comparison of melatonin and placebo due to the existing clinical and methodological heterogeneity of the 5 relevant RCTs. Overall, melatonin was more efficacious and equally safe with placebo in the prevention of migraine in adults (3 of 4 RCTs provided superior efficacy results for melatonin, 1 RCT revealed no difference regarding Headache Frequency ‐HF‐), while there are limited data for children (1 RCT revealed no difference against placebo regarding HF). Additionally, no difference was revealed between melatonin and amitriptyline (1 RCT), sodium valproate (1 RCT) or propranolol (1 non‐randomized study) with respect to their efficacy in adults with migraine, while melatonin was more effective than pizotifen (1 RCT). In children with migraine, amitriptyline is more efficacious regarding most assessed parameters (2 studies, n = 85 per group, HF: RE MD = 4.03, 95%CI = (2.64, 5.42), Headache Duration: RE MD = 0.72, 95%CI = (0.41, 1.03), Headache Severity: FE MD = 1.57, 95%CI = (1.13, 2.00), Response to Treatment: FE MD = 0.33, 95%CI = (0.16, 0.69), Headache Induced Disability Severity: RE MD = 6.07, 95%CI = (−11.87, 24.01 ), Analgesic Consumption – assessed in 1 study, n = 40 per group – MD = 1.11, 95%CI = (−0.10, 2.32)), although melatonin presents a superior safety profile than amitriptyline both in adults and in children.ConclusionsMelatonin may be of potential benefit in the treatment‐prevention of migraine in adults, but complementary evidence from high‐quality RCTs is required.

BackgroundWe aimed to explore patients’ preferences for headache treatments with a self-administered questionnaire including the Q-No questionnaire for nocebo.MethodsQuestionnaires from 514 outpatients naïve to neurostimulation and monoclonal antibodies were collected.ResultsPatients assessed that the efficacy of a treatment is more important than safety or route of administration. They preferred to use an external neurostimulation device for both acute (67.1%) and preventive treatment (62.8%). Most patients preferred to take a pill (86%) than any other drug given parenterally for symptomatic pharmaceutical treatment. For preventive pharmaceutical treatment, most patients preferred to take a pill once per day (52%) compared to an injection either subcutaneously or intravenously each month (9% and 4%), or three months (15% and 11%). 56.6% of all participants scored more than 15 in Q-No questionnaire indicating potential nocebo behaviors that contributed significantly in their choices.ConclusionThese patient preferences along with efficacy and safety data may help physicians better choose the right treatment for the right person.

BackgroundMigraine is included in the top-ten disabling diseases and conditions among the Western populations. Non-invasive neurostimulation, including the Cefaly® device, for the treatment of various types of pain is a relatively new field of interest. The aim of the present study was to explore the clinical experience with Cefaly® in a cohort of migraine patients previously refractory or intolerant to topiramate prophylaxis.MethodsA prospective, multi-center clinical study was performed in patients diagnosed with episodic or chronic migraine with a previous failure to topiramate treatment requiring prevention with Cefaly® according to the treating physician’s suggestion. A 1-month period of baseline observation was followed by a 3-month period of observation during the use of transcutaneous supraorbital nerve stimulation (t-SNS) with Cefaly® as the only preventive treatment.ResultsA small but statistically significant decline was shown over time in the number of days with headache (HA), the number of days with HA with intensity ≥5/10, and the number of days with use of acute medication after 3 months (p < 0.001 for all of the three changes). Twenty-three patients (65.7%) expressed their satisfaction and intent to continue treatment with Cefaly®. Compliance was higher among satisfied subjects compared to non-satisfied subjects. None of the explored factors were significantly associated with the reason for the failure of topiramate.ConclusionThree-months of preventive treatment for episodic or chronic migraine with t-SNS proved to be an effective, safe and well tolerated option for the treatment of patients with migraine who were intolerant or did not respond to topiramate.Trial registrationClinicalTrials NCT03125525. Registered 21 April 2017.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-017-0869-3) contains supplementary material, which is available to authorized users.

Migraine should be no longer considered a neurologic manifestation of systemic or organ-specific autoimmunity. Increased migraine prevalence in these patients found in previous studies could be due to methodological weaknesses.

BackgroundChronic migraine is a disabling condition, with limited treatment options. We conducted an open label, single arm, prospective clinical trial, to assess the efficacy and safety of onabotulinumtoxin-A in Greek patients with chronic migraine. Since recent evidence suggests that a meaningful clinical response may be delayed until after a third onabotulinumtoxin-A administration, we aimed at assessing outcomes at this time point.MethodsA total of 119 patients with CM, scheduled to be treated with Onabotulinumtoxin-A (Botox ®) every 3 months, according to the approved indication and standard clinical practice, were prospectively enrolled. Data documenting changes from baseline (T0—trimester before Onabotulinumtoxin-A first administration) to the period after its third administration (T3) in (i) mean number of monthly headache days (ii) migraine severity as expressed by the mean number of days with peak headache intensity of >4/10 in a 0–10 numerical scale, and (iii) mean number of days with use of any acute headache medication, were collected from patients’ headache diaries at each visit.ResultsOf the 119 patients, a total of 81 received 3 courses of onabotulinumtoxin-A and were included in the efficacy population. In those 81 patients, there was a significant decrease in mean headache days/month between T0 and T3 (21.3 ± 5.4 vs 7.7 ± 4.8; P < 0.001); a significant decrease in days with peak headache intensity of >4/10 (11.9 ± 5.5 vs 3.7 ± 3.3; P < 0.001) and finally, the change in days using acute headache medications per month between was also significant (16.2 ± 7.8 vs 5.2 ± 4.3; P < 0.001). Adverse events were few and of non- serious nature.ConclusionOur results strongly support the use of onabotulinumtoxin-A for the prophylaxis of CM, as this intervention proved effective, safe and well tolerated in our cohort of Greek patients.

The aim was to investigate the comorbidity of chronic refractory headache with obstructive sleep apnoea syndrome (OSAs). Seventy-two patients (51 women and 21 men) with chronic and refractory headaches, whose headache occurred during sleep or whose sleep was accompanied by snoring, were submitted to polysomnography. Patients diagnosed with OSAs (respiratory disturbance index > 10) began continuous positive airway pressure (C-PAP) treatment and were followed up for >or= 6 months. Twenty-one cases of OSAs were identified (29.2% of the total investigated, 13.7% of the women and 66.6% of the men). Headaches were classified into several headache disorders, medication overuse headache and cluster headache being the most prevalent (nine and six of the 21 cases, respectively). In one case (1.4% of the total sample, 4.7% of all the men), the criteria for hypnic headache were fulfilled. Multivariate regression analysis revealed that age, male gender and body mass index were associated with OSAs. C-PAP treatment improved both sleep apnoea and headache in only a third of the cases. Patients suffering from chronic refractory headache associated with sleep or snoring, in particular those who are also middle-aged, overweight men, should be considered for polysomnography. C-PAP treatment alone does not seem to improve headache, but further investigation is needed.