Migraine chronification as an allostatic disorder: a proof-of-concept study.

OBJECTIVE: The underpinning biologics of migraine chronification are not well understood. We aim to investigate the role of the cumulative burden of stress, namely the allostatic load, in migraine chronification. METHODS: This was a cross-sectional study. The allostatic load was measured with a composite multi-system score (BALI: Bologna Allostatic Load Index), evaluating 20 biomarkers representing four physiological systems: immune, metabolic, cardiovascular, and neuroendocrinological systems. BALI score was subdivided into high score and low score based on the distribution in controls. Migraine patients were included and subclassified into low-frequency episodic migraine group (low-EM group), high-frequency episodic migraine group (high-EM group), and chronic migraine group (CM group). RESULTS: The distribution of BALI high-score increased in parallel with headache attacks monthly frequency: 16% in low-EM group (n = 10), 24% in high-EM group (n = 12), and 40% in CM group (n = 21) (p = 0.017). In a multivariable analysis, the odds ratio of having a high-score BALI in CM patients (vs. low-EM patients) was 2.78 (95% CI 1.07-7.22; p = 0.036). Individual BALI biomarkers values which were significantly different among migraine subgroups included systolic blood pressure (p = 0.018), diastolic blood pressure (p < 0.001), and heart rate (p = 0.019). CONCLUSION: Our study substantiates this emerging concept of migraine chronification as an allostatic disorder.

Is physiotherapy in migraines known to sufferers? A cross-sectional study.

BACKGROUND: Migraine, a prevalent neurological condition, often impairs daily functioning and quality of life. While medications are the primary treatment, the potential of physiotherapy as an integrative approach remains underexplored. The aim of the study was to explore the awareness and experience of migraine patients regarding physiotherapy as a complementary treatment. METHODS: A comprehensive survey was conducted on 200 migraine patients. Data collected included demographics, diagnosis, Migraine Disability Assessment Score Questionnaire (MIDAS) scores, and perceptions and experiences related to physiotherapy. RESULTS: The average age of participants was 47.7 ± 13.2 years, with a predominance of females, 149 out of 200 (74.5%). The mean MIDAS score was 36.7 ± 45.3, indicating a significant impact on daily life. While 39 out of 200 (19.5%) had undergone physiotherapy for their headache, 161 out of 200 (80.5%) had not. Of those who had, 22 out of 39 (56.4%) reported benefits, including reduced attack intensity and frequency. Interestingly, 145 out of 161 (90.1%) expressed interest in physiotherapy, with many expecting it to reduce attack intensity, 57 out of 200 (28.5%) and frequency, 77 out of 200 (38.5%). CONCLUSIONS: The study highlights the substantial burden of migraines and the potential of physiotherapy as an adjunctive treatment. Increasing awareness and accessibility to physiotherapy could offer migraine patients a more holistic treatment approach; however, randomized controlled trials are mandatory in order to confirm its efficacy.

Gender-related stress factors and emotional perception in migraine: a structured online questionnaire in migraine patients and controls.

BACKGROUND: While migraine is markedly prevalent in women, gender-related phenotype differences were rarely assessed. For this reason, we investigated, through a multicenter observational cross-sectional study, based on an online questionnaire, gender-related differences in stress factors, emotions, and pain perception in migraine patients and controls and their impact on migraine severity. METHODS: The study was designed as an online questionnaire. The link was emailed to healthy subjects (C) and migraine patients (MIG) (age 18-75, education ≥ 13 years) recruited during the first visit in 8 Italian Headache Centers adhering to Italian Society for Headache Study (SISC). The questionnaire included personal/social/work information, the Perceived Stress Scale, the Romance Quality Scale, the Emotion Regulation Questionnaire, the Beck Anxiety Inventory, the Body Perception Questionnaire, the pain perception, and a self-assessment of migraine severity in the last 3 months. RESULTS: 202 MIG and 202 C completed the survey. Independently from gender, migraine was characterized by higher pain sensitivity and more severe partner relationships. The female gender, in MIG, exhibited higher anxiety scores, body awareness, and reduced emotional suppression. Body awareness and emotional suppression were discriminating factors between genders in control and migraine groups without relevant influence on disease features. Perceived perception of migraine severity was similar between genders. CONCLUSION: Gender-related emotional and stress factors did not contribute to delineate a distinct phenotype in migraine men and women. The possible impact of emotional and stress factors characterizing genders could be considered for a single case-tailored therapeutic approach.

The evolutionary meaning of migraine.

INTRODUCTION: Migraine's astonishing prevalence and preserved genetic background contrast with the definition of a disease and the biological meaning of experiencing recurrent, severe headache attacks is still puzzling. METHODS: To provide a comprehensive explanation of the migraine evolutionary meaning, we review (i) the putative role of the autonomic nervous system in migraine attacks, (ii) the inter-ictal autonomic, functional, and metabolic signature of migraine patients, (iii) the bio-behavioral perspective of pain, and (iv) the allostatic perception of migraine chronification. RESULTS: Migraineurs have inter-ictal cortical hyperexcitability and metabolic dysfunction that predisposes to brain energetic imbalance. Multiple precipitating factors may lead to brain energy consumption over the migraine attack generation threshold. In response, the brain engenders adaptive, evolutionary conserved, autonomic-behavior responses through the antidromic activation of the trigeminovascular system. The sickness behavior and severe pain experienced during migraine attacks result in avoiding mental and physical activity, allowing brain energy restoration. Chronic exposure to stressors may result in an allostatic overload, leading to maladaptive chronic activation of these responses. In this bio-behavioral perspective, the chronification of migraine should be envisioned as a pathological process, whereas the migraine itself should not. CONCLUSION: Migraine has an evolutionary (Darwinian) meaning.

Prevalence, natural history and dynamic nature of chronic headache and medication overuse headache in Italy: The SPARTACUS study.

BACKGROUND: Chronic headaches and medication overuse headache are common and burdening conditions. No studies have evaluated the prevalence of chronic headache and medication overuse headache in an unselected Italian population. METHODS: We performed a three-year cross-sectional and longitudinal population-based study to investigate prevalence, natural history, and prognostic factors of chronic headache. We delivered a self-administered questionnaire to 25,163 subjects. Chronic headache patients were interviewed by General Practitioners. After three years, medication overuse headache patients were invited to undergo a neurological evaluation at our Center. RESULTS: 16,577 individuals completed the questionnaire; 6878 (41,5%) were episodic headache sufferers and 636 (3.8%) were chronic headache subjects. 239 (1.4%) patients were acute medication over-users. All medication overuse headache patients had migraine or headache with migrainous features. At the three-year follow-up of 98 patients, we observed conversion to episodic headaches in 53 (54.1%) patients. 27 (50.9%) patients remitted spontaneously. CONCLUSIONS: We present the first prevalence data on chronic headache and medication overuse headache in an unselected Italian population and a high rate of spontaneous remission. These data support the interpretation of medication overuse headache as a specific migraine-related disorder that may reflect chronic migraine's dynamic nature, the need for more specific medication overuse headache diagnostic criteria, and highlight the priority of targeted public health policies.

Vessel-wall MRI in primary headaches: The role of neurogenic inflammation.

OBJECTIVE: The purpose of this study was to investigate if vessel-wall magnetic resonance imaging (VW-MRI) could differentiate among primary headaches disorders, such as migraine and cluster headache (CH), and detect the presence of neurogenic inflammation. BACKGROUND: The pathophysiology of primary headaches disorders is complex and not completely clarified. The activation of nociceptive trigeminal afferents through the release of vasoactive neuropeptides, termed "neurogenic inflammation," has been hypothesized. VW-MRI can identify vessel wall changes, reflecting the inflammatory remodeling of the vessel walls despite different etiologies. METHODS: In this case series, we enrolled seven patients with migraine and eight patients with CH. They underwent a VW-MRI study before and after the intravenous administration of contrast medium, during and outside a migraine attack or cluster period. Two expert neuroradiologists analyzed the magnetic resonance imaging (MRI) studies to identify the presence of vessel wall enhancement or other vascular abnormalities. RESULTS: Fourteen out of 15 patients had no enhancement. One out of 15, with migraine, showed a focal parietal enhancement in the intracranial portion of a vertebral artery, unmodified during and outside the attack, thus attributable to atherosclerosis. No contrast enhancement attributable to neurogenic inflammation was observed in VW-MRI, both during and outside the attack/cluster in all patients. Moreover, MRI angiography registered slight diffuse vasoconstriction in one of seven patients with migraine during the attack and in one of eight patients with cluster headache during the cluster period; both patients had taken triptans as symptomatic therapy for pain. CONCLUSIONS: These preliminary results suggest that VW-MRI studies are negative in patients with primary headache disorders even during migraine attacks or cluster periods. The VW-MRI studies did not detect signs of neurogenic inflammation in the intracranial intradural vessels of patients with migraine or CH.

Self-administered subcutaneous diclofenac sodium in acute migraine attack: A randomized, double-blind, placebo-controlled dose-finding pilot study.

BACKGROUND: A novel formulation of diclofenac, complexed with hydroxypropyl-ß-cyclodextrin (HPßCD) as a solubility enhancer, in a prefilled syringe for self-administered subcutaneous injection may overcome the limitations of acute migraine treatments administered by oral, rectal, intramuscular, or intravenous routes. METHODS: This multicentre, phase 2, double-blind, randomized, placebo-controlled, dose-finding pilot study evaluated the efficacy, safety and tolerability of three different doses (25/50/75 mg/1 mL) of subcutaneous diclofenac sodium in the treatment of an acute migraine attack in 122 subjects. The primary efficacy endpoint was the percentage of patients pain-free at 2 hours after the study drug injection. RESULTS: A significantly higher percentage of patients in the 50 mg diclofenac group 14 (46.7%) were pain-free at 2 hours when compared with placebo: 9 (29.0%) (p = 0.01). The 50 mg dose proved superior to placebo also in the majority of the secondary endpoints. The overall global impression favoured diclofenac vs placebo. There were no adverse events leading to study withdrawal. The majority of treatment-emergent adverse events were mild. CONCLUSIONS: The 50 mg dose of this novel formulation of diclofenac represents a valuable self-administered option for the acute treatment of migraine attacks.Trial registration: EudraCT Registration No. 2017-004828-29.

Detoxification vs non-detoxification before starting an anti-CGRP monoclonal antibody in medication overuse headache.

BACKGROUND: Medication overuse headache significantly contributes to the chronification process and treatment refractoriness of migraine. Currently, abrupt discontinuation of the overused medication still represents the best management strategy for these patients, challenging public health system resources. METHODS: In this prospective study, chronic migraine and medication overuse headache sufferers with at least 28 days of analgesic consumption per month were included. Assessment of efficacy outcomes at three months were compared among patients who underwent in-hospital abrupt discontinuation of overused acute medication (YES-DETOX group) and patients who did not (NO-DETOX group) before starting an anti-CGRP monoclonal antibody. RESULTS: Of 401 patients who received either erenumab or galcanezumab, 28% (n = 111) satisfied inclusion criteria (YES-DETOX n = 28; NO-DETOX n = 83). After three months of treatment, 59% (n = 65; 47/83 YES-DETOX; 18/28 NO-DETOX) patients reverted from medication overuse headache and 51% (n = 57; 42/83 YES-DETOX; 15/28 NO-DEOTX) achieved ≥50% reduction in monthly headache days; yet no statistical differences were observed between the two groups (p = 0.4788 and p = 0.8393, respectively). Monthly consumption of pain medication was the only baseline prognostic factor in multivariate analysis in the overall cohort (p = 0.016). CONCLUSION: Our results support the emerging evidence that anti-CGRP monoclonal antibodies may be effective in medication overuse headache patients irrespective of detoxification, yet further studies are needed to draw definitive conclusions.

Real-life assessment of erenumab in refractory chronic migraine with medication overuse headache.

OBJECTIVE: To determine whether erenumab is effective and safe in refractory chronic migraine with medication overuse headache. METHODS: In this prospective, multicentric, real-life study, chronic migraine with medication overuse headache patients who received erenumab were recruited. Study inclusion was limited to patients who previously failed onabotulinumtoxinA in addition to at least three other pharmacological commonly used migraine preventive medication classes. RESULTS: Of 396 patients who received erenumab, 38% (n = 149) met inclusion criteria. After 3 months, 51% (n = 76) and 20% (n = 30) patients achieved ≥ 50% and ≥ 75% reduction in monthly headache days, respectively. Monthly pain medications intake decreased from 46.1 ± 35.3 to 16.8 ± 13.9 (p < 0.001), while monthly headache days decreased from 25.4 ± 5.4 to 14.1 ± 8.6 (p < 0.001). Increasing efficacy of erenumab over the study period was observed. Allodynia was a negative predictive factor of erenumab response (odds ratio = 0.47; p = 0.03). Clinical conversion to episodic migraine with no medication overuse was observed in 64% (n = 96) patients. No serious adverse events were observed. CONCLUSIONS: Erenumab reduced significantly migraine frequency and pain medication intake in refractory chronic migraine with MOH patients.

Great occipital nerve long-acting steroid injections in cluster headache therapy: an observational prospective study.

BACKGROUND: Injections targeting the occipital nerve are used to reduce headache attacks and abort cluster bouts in cluster headache patients. There is no widely accepted agreement over the optimal technique of injection, type and doses of steroids and/or anesthetics to use, as well as injection regimens. The aim of this study was to verify the effectiveness and safety of greater occipital nerve long-acting steroid injections in the management of episodic and chronic cluster headache. METHODS: We conducted a prospective observational cohort study on episodic (ECH) and chronic cluster headache patients (CCH). ECH were included in the study at the beginning of a cluster period. Three injections with 60 mg methylprednisolone were performed on alternate days. We registered the frequency and intensity of attacks three days before and 3, 7 and 30 days after the treatment, the latency of cluster relapse, adverse events, scores evaluating anxiety (Zung scale), depression (Beck's Depression Scale) and quality of life (Disability Assessment Schedule II, 12-Item Self-Administered Version). Primary outcome was the interruption of the cluster after the three injections. Responders conducted a follow-up period of 12 months. RESULTS: We enrolled 60 patients, 47 with ECH and 13 with CCH. We observed a complete response in 47.8% (22/46) of episodic and 33.3% (4/12) of chronic patients. Moreover, a partial response (reduction of at least 50% of attacks) was obtained in further 10.8% (5/46) of episodic and in 33.3% (4/12) of chronic patients at 1 month. Median pain-free period was of 3 months for CCH responders. Only mild adverse events were reported in 38.3% (23/58) cases. CONCLUSIONS: We suggest three greater occipital nerve injections of 60 mg methylprednisolone on alternate days as useful therapy in episodic and chronic cluster headache. This leads to a long pain-free period in chronic forms. Adverse effects are mild and support its use as first choice. TRIAL REGISTRATION: The study was inserted in AIFA observational studies register.

Do catastrophizing and autonomic-reduced flexibility mediate pain outcomes in chronic headache?

OBJECTIVES: Maladaptive cognitive strategies and reduced autonomic flexibility have been reported in chronic pain conditions. No study to date addressed the effects of maladaptive coping and reduced autonomic flexibility, as indexed by heart rate variability (HRV), in chronic headaches. The present study aimed to assess the mediating role of pain catastrophizing and HRV on pain outcomes in patients with chronic headache. METHODS: Thirty-two chronic headache patients and 28 healthy controls were recruited. Self-reported pain severity, pain interference on daily activity, and pain catastrophizing were assessed through the Multidimensional Pain Inventory and the Pain-Related Self Statements Scale. HRV was recorded at rest. Correlations and mediation analysis between self-report, HRV, and pain outcomes were run. RESULTS: Patients with chronic headache reported significantly higher pain severity (p < .001; d = - 1.98), pain interference on daily activity (p < .001; d = - 1.81), and pain catastrophizing (p < .001; d = - 0.96) compared to controls. They also presented significantly lower HRV (p < .05; d = 0.57). Both pain catastrophizing and HRV were associated with pain interference on daily activity. However, from mediation analysis, pain catastrophizing only emerged as the mediator for pain severity (p < .001; b = 0.30) and pain interference (p < .001; b = 0.14). CONCLUSION: Present results showed that chronic headache patients are characterized by high catastrophizing and lower physiological adaptability. Pain catastrophizing emerged as the only mediator of pain outcomes, suggesting that cognitive factors might have a major influence on the severity of pain and its interference on daily activities. Further studies are needed to evaluate these autonomic-cognitive interactions in chronic pain.

Applications of Ketogenic Diets in Patients with Headache: Clinical Recommendations.

Headaches are among the most prevalent and disabling neurologic disorders and there are several unmet needs as current pharmacological options are inadequate in treating patients with chronic headache, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. Among these, the largest body of evidence supports the use of the ketogenic diet (KD). Exactly 100 years ago, KD was first used to treat drug-resistant epilepsy, but subsequent applications of this diet also involved other neurological disorders. Evidence of KD effectiveness in migraine emerged in 1928, but in the last several year's different groups of researchers and clinicians began utilizing this therapeutic option to treat patients with drug-resistant migraine, cluster headache, and/or headache comorbid with metabolic syndrome. Here we describe the existing evidence supporting the potential benefits of KDs in the management of headaches, explore the potential mechanisms of action involved in the efficacy in-depth, and synthesize results of working meetings of an Italian panel of experts on this topic. The aim of the working group was to create a clinical recommendation on indications and optimal clinical practice to treat patients with headaches using KDs. The results we present here are designed to advance the knowledge and application of KDs in the treatment of headaches.

Chronic Migraine and Medication Overuse Headache Worsening After OnabotulinumtoxinA Withdrawn Due to the Severe Acute Respiratory Syndrome-Coronavirus-2 Pandemic.

Introduction: OnabotulinumtoxinA (BT-A) is a preventive treatment for chronic migraine (CM), which needs to be administered regularly by a trained clinician every 3 months. The spread of the severe acute respiratory syndrome coronavirus-2 pandemic has forced many patients to momentarily stop the scheduled BT-A injections. The goal of this study was to explore whether those patients experienced a worsening of their CM and, if any, the clinical predictors of migraine worsening after BT-A withdrawal. Methods: This was a retrospective, multicenter study. Patients' clinical data were obtained from their clinical documentation stored at each center. In particular, the following variables were collected: the mean number of headache days in the last month (NHD), the average number of painkillers taken in the last month (AC), the average number of days in which patients took, at least, one painkiller in the last month (NDM), the average intensity of migraine using the numeric rating scale (NRS) score in the last month, and the average score obtained at the six-item Headache Impact Test. The variables mentioned earlier were compared before and after BT-A withdrawal. Results: After BT-A suspension, there was a significant increase in the NHD (P = 0.0313, Kruskal-Wallis rank test), AC (P = 0.0421, Kruskal-Wallis rank test), NDM (P = 0.0394, paired t-test), NRS score (P = 0.0069, Kruskal-Wallis rank test), and six-item Headache Impact Test score (P = 0.0372, Kruskal-Wallis rank test). Patients who were not assuming other preventive treatments other than BT-A displayed similar results. Patients who experienced a >30% worsening in NHD after BT-A was withdrawn displayed a longer CM history (P = 0.001, Kruskal-Wallis rank test), a longer MOH duration (P = 0.0017, Kruskal-Wallis rank test), a higher AC value at the baseline (P = 0.0149, Kruskal-Wallis rank test), a higher NDM (P = 0.0024, t-test), and a higher average value of the NRS score (P = 0.0073, Kruskal-Wallis rank test). Conclusion: BT-A withdrawn during severe acute respiratory syndrome coronavirus-2 pandemic was associated with a general worsening in patients suffering from CM, hence the need to continue BT-A injection to avoid patients' worsening.

Insights into real-world treatment of cluster headache through a large Italian database: prevalence, prescription patterns, and costs.

Objective: This study aimed at estimating the treated cluster headache (CH) prevalence and describing prescription patterns and direct costs paid by the Italian National-Health-System.Methods: Through the ReS database (healthcare administrative data collection of a large sample of the Italian population), adults in treatment for CH (acute therapy with sumatriptan/subcutaneous or oxygen, associated with preventive therapy with verapamil or lithium) were selected. A cross-sectional analysis described the prevalence of CH-treated subjects repeated annually in 2013-2017. A longitudinal analysis of patients selected in 2013-2015 and followed for 2 years provided the prescription patterns.Results: The annual prevalence of CH-treated patients increased from 6.4×100,000 adults in 2013 to 6.7 in 2017. In 2013-2015, 570 patients (80.7% M; mean age 46) treated for CH were found. In 50.4%, the identifying CH treatment was sumatriptan/subcutaneous+verapamil. During follow-up, >1/3 changed the preventive drug and interruption was the most frequent modification, although acute treatments were still prescribed. The mean annual cost/patient ranged from €2,956 to €2,267; pharmaceuticals expenditure represented the 56.4% and 57.3%, respectively.Conclusions: This study showed an important unmet need among CH patients, carrying a high economic burden that should be considered in the evaluation of the impact of incoming therapies (e.g. Calcitonin-Gene-Related-Peptide antibodies).

Galcanezumab for the prevention of high frequency episodic and chronic migraine in real life in Italy: a multicenter prospective cohort study (the GARLIT study).

BACKGROUND: The clinical benefit of galcanezumab, demonstrated in randomized clinical trials (RCTs), remains to be quantified in real life. This study aimed at evaluating the effectiveness, safety and tolerability of galcanezumab in the prevention of high-frequency episodic migraine (HFEM) and chronic migraine (CM) in a real-life setting. METHODS: This multicenter prospective observational cohort study was conducted between November 2019 and January 2021 at 13 Italian headache centers. Consecutive adult HFEM and CM patients clinically eligible were enrolled and treated with galcanezumab subcutaneous injection 120 mg monthly with the first loading dose of 240 mg. The primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients after 6 months of therapy (V6). Secondary endpoints were the Numerical Rating Scale (NRS), monthly painkiller intake (MPI), HIT-6 and MIDAS scores changes, ≥50% responder rates (RR), the conversion rate from CM to episodic migraine (EM) and Medication Overuse (MO) discontinuation. RESULTS: One hundred sixty-three patients (80.5% female, 47.1 ± 11.7 years, 79.8% CM) were included. At V6, MMDs reduced by 8 days in HFEM and MHDs by 13 days in CM patients (both p < .001). NRS, MPI, HIT-6 and MIDAS scores significantly decreased (p < .001). Ten patients (6.1%) dropped out for inefficacy and classified as non-responders. Patients with ≥50%RRs, i.e. responders, were 76.5% in the HFEM and 63.5% in the CM group at V6. Among CM patients, the V6 responders presented a lower body mass index (p = .018) and had failed a lower number of preventive treatments (p = .013) than non-responders. At V6, 77.2% of CM patients converted to EM, and 82.0% ceased MO. Adverse events, none serious, were reported in up to 10.3% of patients during evaluation times. CONCLUSIONS: Galcanezumab in real life was safe, well tolerated and seemed more effective than in RCTs. Normal weight and a low number of failed preventives were positively associated with galcanezumab effectiveness in CM patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04803513 .

Vessel-wall MRI in thunderclap headache: A useful tool to answer the riddle?

BACKGROUND: Finding an intracranial aneurysm (IA) during a thunderclap headache (TCH) attack, represents a problem because it is necessary to distinguish whether the aneurysm is responsible for the headache as a warning leak or as an incidental finding. High-Resolution Vessel-Wall (HRVW) MRI sequences have been proposed to assess the stability of the wall, as it permits to detect the presence of aneurysmal wall enhancement (AWE). In fact, AWE has been confirmed due to inflammation, recognizable preceding rupture.Case 1: A 37-year-old woman with a migraine more intense than her usual. A CTA revealed a 10 mm AComA aneurysm without subarachnoid hemorrhage (SAH) and HRVW-MRI excluded AWE. The patient's headache improved, and therefore, the aneurysm was considered an incidental finding, and the headache diagnosed as TCH attack. Subsequently, the aneurysm was surgically clipped, and typical migraine relapsed was reported at follow-up (FU).Case 2: A 67-year-old woman with no history of headaches underwent CTA for an abrupt onset of headache. A 7 mm right carotid-ophthalmic aneurysm with no sign of SAH was discovered. HRVW-MRI demonstrated AWE and thus, a TCH attack for a warning leak of an unstable wall was suspected. Endovascular coiling was immediately performed and at FU any further headache attack was reported. CONCLUSIONS: HRVW-MRI is useful in case of finding aneurysm as the cause of headaches, particularly the TCH attack. In fact, HRVW-MRI could assess the stability of the aneurysms wall, allowing different patient management and eventually the aneurysmal treatment.

Locking down the CGRP pathway during the COVID-19 pandemic lockdown: the PandeMig study.

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.