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Objectives: The COVID-19 pandemic and the consequent lockdown came as a storm disrupting people’s everyday life. This study aimed at observing whether the COVID-19 related lockdown influenced migraine frequency and disability in migraine patients on therapy with monoclonal antibodies inhibiting the CGRP pathway. Methods: In this longitudinal observational cohort study, 147 consecutive patients receiving monthly administration of erenumab or galcanezumab were enrolled in four Italian headache centers. All patients filled a questionnaire concerning working and household settings, recent flu symptoms or COVID-19 diagnosis, and family loss due to COVID-19 infection. Monthly migraine days (MMDs), monthly painkiller intake (MPI), and HIT-6 disability relative to the first month of lockdown imposition (T-lock) and the month before (T-free) were also collected. Results: From T-free to T-lock, the cohort displayed a reduction in MMDs (from 10.5 ± 7.6 to 9.8 ± 7.6, p =.024) and HIT-6 scores (from 59.3 ± 8.3 men reduced MPI more frequently than women (p =.005). Conclusions: Our study observed that the lockdown impact to 57.8 ± 8.8, p=.009), while MPI resulted unchanged (from 11.6 ± 11.5 to 11.1 ± 11.7; p =.114). MMDs, MPI, and HIT-6 variations from T-free to T-lock did not differ according to work settings or household. Patients beyond the first 3 months of therapy presented less often a reduction in MMDs (p =.006) and on everyday life did not affect the migraine load in patients receiving monoclonal antibodies inhibiting the CGRP pathway. Patients in the first months of therapy experienced a greater improvement according to drug pharmacokinetics, while women more frequently needed rescue medications, possibly indicating presenteeism or cephalalgophobia.

Dopamine-beta-hydroxylase (DBH) enzyme activity is modulated at the genetic level by the presence of several polymorphisms. Among these, the 19-bp insertion/deletion (I/D) polymorphism (rs72393728/rs141116007) was investigated in several genetic association studies for its correlation with the susceptibility to develop episodic migraine, but conflicting results were achieved. In the present study we analyzed this genetic variant in a carefully characterized population of migraineurs encompassing both episodic and chronic migraine (with and without medication overuse) with the aim to perform a replication study and verify any possible correlation with migraine endophenotypes. Genotyping of the DBH 19-bp I/D polymorphism was performed on 400 migraine patients and 204 healthy individuals. The associations between genotypic frequencies and the clinical and sociodemographic features of migraineurs were then investigated. The DBH 19-bp I/D polymorphism did not correlate with migraine susceptibility or most clinical variables, with the exception of a statistically significant correlation within the subgroup of patients affected by chronic migraine were the individuals carrying the deleted (D) allele were significantly more prone to abuse in analgesics. As a result of this finding, the DBH 19-bp I/D polymorphism does not influence migraine susceptibility, but it might contribute to the development of medication overuse in patient with chronic migraine.

Background: Migraine is very common in women of childbearing age. Erenumab is a first-in-class anti-CGRP monoclonal antibody with a a favorable efficacy/tolerability profile. However, there are very limited data on its effects during pregnancy.Case presentation: We report a case of a 37-years-old woman affected by chronic migraine who became pregnant during erenumab treatment. At the time of her first visit at our Unit she was on prophylaxis with sodium valproate 600 mg/day reporting low efficacy (18 headache days/month) and tolerability (weight gain). She had already failed 5 prior preventative treatments. On the same day started erenumab 70 mg, tapering down valproate. Erenumab was rapidly effective, reducing migraine frequency (7 days/month) since the first administration. On the follow-up visit scheduled for the fifth erenumab administration, the patient informed us of her pregnancy, documented by appropriate serological test the day before. Erenumab was immediately stopped. The last erenumab administration was made on 04/07/2019, probably corresponding to the first two weeks of pregnancy. Serological fetal DNA test was normal. During the I pregnancy trimester the frequency of migraine increased up to 10 days/month, markedly improving and progressively disappearing during the II-III trimesters. Migraine attacks started again from the 34th week of pregnancy throughout delivery and breast feeding. No other adverse event or complication occurred during pregnancy. The baby, born by vaginal birth in healthy conditions, developed breastfeeding jaundice which progressively normalized over time.Conclusions: We document no complications, abnormalities, or adverse events in both the mother and the child, and a physiological normal course of pregnancy, delivery and breastfeeding in the first report of erenumab exposure during pregnancy in a migraine patient. More data from clinical studies and post-marketing surveillance are necessary to confirm our findings.

Recent clinical experiences and clinical trials have demonstrated the safety, tolerability, and efficacy of non-invasive vagus nerve stimulation (nVNS; gammaCore®) for the acute and prophylactic treatment of migraine. nVNS has a favorable adverse event profile, making it an attractive option for sensitive patient populations. We explored the safety, tolerability, and efficacy of nVNS as acute migraine treatment in adolescents. A group of adolescent patients suffering from migraine without aura were trained to use gammaCore to manage their migraine attacks. 46.8% of the treated migraine attacks (22/47) were considered successfully treated and did not require any rescue medication. No device-related adverse events were recorded. This preliminary study suggests that nVNS may represent a safe, well-tolerated, and effective for acute migraine treatment in adolescents.

Chronic migraine is a severely disabling headache evolving from episodic migraine as a result of different transforming factors and characterized by atypical pain modulation and peripheral and central sensitization. Discovered by serendipity, onabotulinum toxin A (BoNT-A) represents the only drug specifically approved for CM prophylaxis. According to the dominant opinion, BoNT-A acts peripherally, impairing the exocytosis of neuropeptide and neurotransmitter and the delivery of receptors and ion channels on the cell surface of peripheral trigeminal endings, thereby indirectly reducing central sensitization. However, it is not excluded that BoNT-A has also a central antinociceptive action, probably associated with an enhanced opioidergic and GABA-ergic transmission. This review discusses the rationale for use of BoNT-A in CM including its mechanisms of action and molecular targets and provides suggestions for a more tailored BoNT-A prophylaxis in patients with CM.

Tension-type headache (TTH) is the second most common human disease, accounting for intense disability, high costs and numerous workdays lost. Tension-type headache is less simple and easy-to-treat than commonly thought. Antidepressants, despite their poor tolerability, are still the first-choice drugs for preventing TTH. The most widely studied non-pharmacological approach to TTH, cognitive-behavioral techniques, effectively relieve pain only in selected patients. The most frequently used and recommended treatments for acute TTH, NSAIDs and paracetamol have scarce efficacy as documented by their low therapeutic gain over placebo in the 2-h pain-free response. Their effectiveness may be increased by a more proper use and by the adjunction of caffeine, antiemetics, myorelaxants or tranquillizers but the risk of medication-overuse headache must be considered. Hence, the need for more effective and tailored treatments in TTH remains.

Migraine pain is often preceded, accompanied and followed by dopaminergic symptoms (premonitory yawning and somnolence, accompanying nausea and vomiting, postdromal somnolence, euphoria and polyuria). After reviewing evidence from pharmacological, biochemical, genetic and animal experimental studies on the relationship between dopamine and migraine, and matching these data with patients' clinical features, we postulate that migraine attacks could be characterized by an ictal dopamine release in a subject with dopamine receptor hypersensitivity due to a chronic dopaminergic deficit synergistic to serotoninergic impairment. Our review suggests that when the attack begins, a low dopamine plasma concentration stimulates hypersensitive central presynaptic dopamine receptors thus causing prodromal symptoms such as yawning and somnolence. Increasing dopamine levels, though still insufficient to stop trigeminovascular activation, stimulate postsynaptic dopamine receptors thus inducing nausea, vomiting and hypotension. Finally, dopamine levels slowly return to baseline, giving rise to somnolence and fatigue, but, in some cases, continue to rise triggering postdromal symptoms such as euphoria and polyuria.

The development of Biobanks and recent advances in molecular biology have enhanced the possibility to accelerate translational research studies. The Interinstitutional Multidisciplinary BioBank (BioBIM) is organized in a large healthy donors collection and pathology-based biobanks with the aim to provide a service for development of interdisciplinary studies. A new pathology-based biobank has been organized to specifically collect biospecimen from patients affected by migraine, with the final goal to centralize data, collect blood, plasma, serum, DNA and RNA of patients with this disease. The BioBIM is fully equipped for the automation of sampling/processing, storage and tracking of biospecimens. Standard Operating Procedures have been developed for processing and storage phases as well as archive of clinical data. The availability of biospecimens and clinical data will constitute a resource for various research projects.

Migraine prevention hinges on a variety of non-specific drugs that mainly reduce neuronal hyperexcitability, the putative pathophysiological hallmark for migraine. The improved knowledge about migraine circuitry and neurobiology has prompted research to develop new specific migraine preventive medications targeted to innovative sites and mechanisms. Drugs designed to inhibit cortical spreading depression, for example tonabersat, might offer a useful option for the management of migraine with aura but not for migraine without aura. Inducible nitric-oxide synthase (iNOS) inhibition seems ineffective as a prophylactic strategy. Results are awaited from recent and ongoing phase II trials with glutamate receptor antagonists, third-generation antiepileptics, melatonin agonists, vitamin D3 and statins.

Progression of episodic migraine to chronic migraine may be related to comorbid medical conditions. In this study, we focused on the role played by arterial hypertension in migraine transformation. Several studies reveal that hypertension is associated with chronic migraine and may induce migraine chronification. Hypertension probably amplifies the effects of migraine on the vascular wall further enhancing the endothelial dysfunction in cerebral vasculature. Consequently, monitoring of blood pressure is recommended in migraineurs showing an otherwise unexplained increase in attack frequency. Studies are needed to verify if prophylactic treatment with drugs improving endothelial function (e.g. calcium channel blockers, beta blockers, calcium inhibitors, ACE inhibitors and sartans) may selectively ameliorate the course of migraine in these patients.