Explore the vast range of titles available.

Backgrounderenumab was safe and effective in clinical trials for the prevention of migraine. However, real-life data are still lacking. Here we report the clinical experience from an Italian real-world setting using erenumab in patients with chronic migraine experiencing previous unsuccessful preventive treatments.MethodsSeventy patients with chronic migraine and failure to ≥4 migraine preventive medication classes initially received monthly erenumab 70 mg s.c. Patients without a clinically meaningful improvement, considered as a > 30% reduction in headache days per month, after ≥3 months of therapy switched to monthly erenumab 140 mg. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity and migraine-related disability and impact, and validated questionnaires to explore depression/anxiety, sleep, and quality of life (QoL). Finally, the Pain Catastrophizing Scale, Allodynia Symptom Checklist-12 and MIGraine attacks-Subjective COGnitive impairments scale (MIG-SCOG) were administered.Results70% of patients were “responders” after the third administration of erenumab 70 mg, whereas 30% switched to erenumab 140 mg; 29% (6 pts) responded after the sixth administration. The headache-day frequency was reduced from 21.1 ± 0.7 to 11.4 ± 0.9 days after the third administration (p < 0.001) and to 8.9 ± 0.7 days after the sixth administration (p < 0.001). 53% and 70% of patients, respectively, showed a reduction of ≥50% of headache days/month after the third and the sixth administrations.Also improved were headache pain severity, migraine-related disability, and impact on daily living, QoL, pain catastrophizing and allodynia (all p < 0.001), quality of sleep, symptoms of depression or anxiety (p < 0.05) but not MIG-SCOG. There were no new adverse event signals.ConclusionThese real-world data support monthly erenumab 70 or 140 mg s.c. as a safe and effective preventive treatment to reduce headache frequency and severity in chronic migraine patients experiencing previous unsuccessful preventive treatments.

BackgroundDespite the growing body of advanced studies investigating the neuronal correlates of pain processing in patients with migraine without aura (MwoA), only few similar studies have been conducted in patients with migraine with aura (MwA). Therefore, we aimed to explore the functional brain response to trigeminal noxious heat stimulation in patients with MwA.MethodsSeventeen patients with MwA and 15 age- and sex-matched healthy controls (HC) underwent whole-brain blood oxygen level–dependent (BOLD) fMRI during trigeminal noxious heat stimulation. To examine the specificity of any observed differences between patients with MwA and HC, the functional response of neural pathways to trigeminal noxious heat stimulation in patients with MwA was compared with 18 patients with MwoA. Secondary analyses investigated the correlations between BOLD signal changes and clinical parameters of migraine severity.ResultsWe observed a robust cortical and subcortical pattern of BOLD response to trigeminal noxious heat stimulation across all participants. Patients with MwA showed a significantly increased activity in higher cortical areas known to be part of a distributed network involved in advanced visual processing, including lingual gyrus, inferior parietal lobule, inferior frontal gyrus and medial frontal gyrus. Moreover, a significantly greater cerebellar activation was observed in patients with MwA when compared with both patients with MwA and HC. Interestingly, no correlations were found between migraine severity parameters and magnitude of BOLD response in patients with MwA.ConclusionOur findings, characterized by abnormal visual pathway response to trigeminal noxious heat stimulation, support the role of a functional integration between visual and trigeminal pain networks in the pathophysiological mechanisms underlying migraine with aura. Moreover, they expand the concept of “neurolimbic-pain network” as a model of MwoA including both limbic dysfunction and cortical dys-excitability. Indeed, we suggest a model of “neurolimbic-visual-pain network” in MwA patients, characterized by dysfunctional correlations between pain-modulating circuits not only with the cortical limbic areas but with advanced visual areas as well. Furthermore, the abnormal cerebellar response to trigeminal noxious heat stimulation may suggest a dysfunctional cerebellar inhibitory control on thalamic sensory gating, impinging on the advanced visual processing cortical areas in patients with MwA.

Onabotulinumtoxin-A (onabotA) is a neurotoxin widely used for several indications, including chronic migraine (CM) preventive treatment, due to its well-demonstrated efficacy, tolerability, and safety. However, onabotA safety during pregnancy and breastfeeding remains unclear, as these populations are typically excluded from clinical trials. The action of onabotA starts locally at the injection sites, modulating the pain pathway with minimal systemic absorption, which theoretically minimizes risks to the fetus or breastfeeding infant. Preclinical studies demonstrate that onabotA does not distribute systemically in significant amounts after administration, although adverse fetal outcomes in rats and rabbits were reported when injected at high doses. Limited human data suggest that onabotA exposure during pregnancy may not be associated with major malformations or significant adverse outcomes for the fetus, especially when used at therapeutic doses for migraine prevention during the first trimester or earlier. Data on breastfeeding are even scarcer but indicate a low likelihood of drug transfer into breast milk. This narrative review highlights the available evidence on the use of onabotA in pregnancy and breastfeeding women, including real-word evidence, with a focus on the use for CM.

BackgroundMonoclonal antibodies acting on the calcitonin gene-related peptide (CGRP) or its receptor have changed migraine preventive treatment. Those treatments have led to reconsidering the outcomes of migraine prevention. Available data mostly considered benefits in terms of relative efficacy (percent or absolute decrease in monthly migraine days [MMDs] or headache days compared with baseline). However, not enough attention has been paid to residual MMDs and/or migraine-related disability in treated patients. In the present study, we aimed at comparing the relative and absolute efficacy of erenumab.MethodsESTEEMen was a collaborative project among 16 European headache centers which already performed real-life data collections on patients treated with erenumab for at least 12 weeks. For the present study, we performed a subgroup analysis on patients with complete data on MMDs at baseline and at weeks 9-12 of treatment. Starting from efficacy thresholds proposed by previous literature, we classified patients into 0-29%, 30-49%, 50-74%, and ≥75% responders according to MMD decrease from baseline to weeks 9-12 of treatment. For each response category, we reported the median MMDs and Headache Impact test-6 (HIT-6) scores at baseline and at weeks 9-12. We categorized the number of residual MMDs at weeks 9-12 as follows: 0-3, 4-7, 8-14, ≥15. We classified HIT-6 score into four categories: ≤49, 50-55, 56-59, and ≥60. To keep in line with the original scope of the ESTEEMen study, calculations were performed in men and women.ResultsOut of 1215 patients, at weeks 9-12, 381 (31.4%) had a 0-29% response, 186 (15.3%) a 30-49% response, 396 (32.6%) a 50-74% response, and 252 (20.7%) a ≥75% response; 246 patients (20.2%) had 0-3 residual MMDs, 443 (36.5%) had 4-7 MMDs, 299 (24.6%) had 8-14 MMDs, and 227 (18.7%) had ≥15 MMDs. Among patients with 50-74% response, 246 (62.1%) had 4-7 and 94 (23.7%) 8-14 residual MMDs, while among patients with ≥75% response 187 (74.2%) had 0-3 and 65 (25.8%) had 4-7 residual MMDs.ConclusionsThe present study shows that even patients with good relative response to erenumab may have a clinically non-negligible residual migraine burden. Relative measures of efficacy cannot be enough to thoroughly consider the efficacy of migraine prevention.

BackgroundIn the past decades a plethora of studies has been conducted to explore resting-state functional connectivity (RS-FC) of the brain networks in migraine with conflicting results probably due to the variability and susceptibility of signal fluctuations across the course of RS-FC scan. On the other hand, the structural substrates enabling the functional communications among the brain connectome, characterized by higher stability and reproducibility, have not been widely investigated in migraine by means of graph analysis approach. We hypothesize a rearrangement of the brain connectome with an increase of both strength and density of connections between cortical areas specifically involved in pain perception, processing and modulation in migraine patients. Moreover, such connectome rearrangement, inducing an imbalance between the competing parameters of network efficiency and segregation, may underpin a mismatch between energy resources and demand representing the neuronal correlate of the energetically dysfunctional migraine brain.MethodsWe investigated, using diffusion-weighted MRI imaging tractography-based graph analysis, the graph-topological indices of the brain “connectome”, a set of grey matter regions (nodes) structurally connected by white matter paths (edges) in 94 patients with migraine without aura compared to 91 healthy controls.ResultsWe observed in migraine patients compared to healthy controls: i) higher local and global network efficiency (p < 0.001) and ii) higher local and global clustering coefficient (p < 0.001). Moreover, we found changes in the hubs topology in migraine patients with: i) posterior cingulate cortex and inferior parietal lobule (encompassing the so-called neurolimbic-pain network) assuming the hub role and ii) fronto-orbital cortex, involved in emotional aspects, and visual areas, involved in migraine pathophysiology, losing the hub role. Finally, we found higher connection (edges) probability between cortical nodes involved in pain perception and modulation as well as in cognitive and affective attribution of pain experiences, in migraine patients when compared to healthy controls (p < 0.001). No correlations were found between imaging and clinical parameters of disease severity.ConclusionThe imbalance between the need of investing resources to promote network efficiency and the need of minimizing the metabolic cost of wiring probably represents the mechanism underlying migraine patients’ susceptibility to triggers. Such changes in connectome topography suggest an intriguing pathophysiological model of migraine as brain “connectopathy”.

BackgroundClinical trials have demonstrated galcanezumab as safe and effective in migraine prevention. However, real-life data are still lacking and overlook the impact of galcanezumab on those different migraine facets strongly contributing to migraine burden. Herein we report the clinical experience from an Italian real-world setting using galcanezumab in patients with migraine experiencing previous unsuccessful preventive treatments.MethodsForty-three patients with migraine and failure of at least 3 migraine preventive medication classes received monthly galcanezumab 120 mg s.c. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity. Furthermore, validated questionnaires were administered to explore migraine-related disability, impact, and quality of life as well as symptoms of depression or anxiety, pain catastrophizing, sleep quality and the ictal cutaneous allodynia.ResultsAfter the third and the sixth administration of monthly galcanezumab 120 mg s.c., headache attacks frequency reduced from 20.56 to 7.44 and 6.37 headache days per month, respectively. Moreover, a significant improvement in headache pain intensity (from 8.95 to 6.84 and 6.21) and duration (from 9.03 to 3.75 and 2.38) as well as in scores assessing migraine related disability and impact, depressive and anxious symptoms, and pain catastrophizing was observed. Furthermore, we demonstrated a significant reduction in the values of “whole pain burden”, a composite score derived from the product of the average of headache frequency, intensity, and duration in the last three months.ConclusionReal-world data support monthly galcanezumab 120 mg s.c. as a safe and effective preventive treatment in reducing headache frequency, intensity, and duration as well as comorbid depressive or anxious symptoms, pain catastrophizing and quality of life in both episodic and chronic migraine patients with previous unsuccessful preventive treatments. Furthermore, we demonstrated that monthly galcanezumab 120 mg s.c. is able to induce a significant improvement in the scores of “whole pain burden”. The latter is a reliable and easy-to-handle tool to be employed in clinical setting to evaluate the effectiveness of preventive drugs (in this case, galcanezumab) or when the decision of continuing the treatment with anti-CGRP mAbs is mandatory.

Over the last months, due to coronavirus disease (COVID-19) pandemic, containment measures have led to important social restriction. Healthcare systems have faced a complete rearrangement of resources and spaces, with the creation of wards devoted to COVID-19 patients. In this context, patients affected by chronic neurological diseases, such as amyotrophic lateral sclerosis (ALS), are at risk to be lost at follow-up, leading to a higher risk of morbidity and mortality. Telemedicine may allow meet the needs of these patients. In this commentary, we briefly discuss the digital tools to remotely monitor and manage ALS patients. Focusing on detecting disease progression and preventing life-threatening conditions, we propose a toolset able to improve ALS management during this unprecedented situation.

BackgroundCognitive deficits related to frontotemporal dysfunction are common in Amyotrophic Lateral Sclerosis (ALS). Visuospatial deficits, related to posterior cerebral regions, are often underestimated in ALS, though they play a crucial role in attending daily living activities. Our pilot study aims at assessing visuospatial abilities using a domain-specific tool in ALS patients compared to healthy controls (HC).MethodsTwenty-three patients with early ALS and 23 age- and education-matched HC underwent the Battery for Visuospatial Abilities (BVA), including 4 visuo-perceptual and 4 visuo-representational subtests.ResultsWhen compared to HC, ALS scored worse in 2 visuo-perceptual subtests (i.e., Line Length Judgment and Line Orientation Judgment) and 1 visuo-representational tasks (i.e., Hidden Figure Identification, HFI) (p < 0.01). No correlations arose between ALS clinical features and BVA performance. More than 80% of the ALS cohort obtained abnormal scores in the HFI subtest.ConclusionsOur findings revealed that patients with ALS scored worse (compared to HC) on selective tests tapping “perceptual” and “representational” visuospatial abilities, since the early stages of disease. In clinical practice, our findings highlight the need for multi-domain neuropsychological assessment, for monitoring disease courses and properly organizing care management of patients with ALS.

Background: Lasmiditan, an oral 5-HT1F receptor agonist, has been recently approved for acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, scarce data is available regarding effectiveness and tolerability in the real-world setting. Objectives: To evaluate lasmiditan effectiveness and tolerability in the real-world setting in 16 Italian headache centers. Design: LasmiDitan as Acute migRaine Treatment (DART) study is a prospective, multicentric, observational study. Methods: We enrolled 58 participants with migraine (84.5% females, age 49.0 (45.2–52.9) years, 24.1% with chronic migraine) reporting 9.4 (7.4–11.3) monthly migraine days. Participants were instructed to treat their migraine attacks with oral lasmiditan 50 or 100 mg. Using an ad hoc electronic diary, participants prospectively collected migraine attack features at baseline and every 30 min after lasmiditan administration, up to 2 h post-dose. The primary outcome was 2-h pain freedom for the first-treated attack after lasmiditan intake. We also collected the occurrence of treatment-emergent adverse events (AE) after administration. Results: Overall, participants treated 100 attacks, of which 58 first-treated attacks. Regarding first-treated attacks, 44.8% of subjects rated migraine intensity as severe at lasmiditan intake. Pain freedom 2-h post-dosing was reported in 32.8% (19/58) of individuals and was associated with baseline pain intensity, being higher in subjects treating a mild/moderate attack (p = 0.044). Conversely, it was not influenced by timing of intake (p = 0.375), dosage (p = 0.727), or previous triptan failure (p = 0.351). Regarding all-treated attacks, pain freedom 2-h post-dosing was 37.0% (37/100). At least one AE was reported by 53.4% of participants (31/58), predominantly asthenia, dizziness, somnolence, anxiety or agitation, and paresthesia. Tolerability was rated as good-to-excellent by 51.8% of subjects. Conclusion: Our study supports clinical effectiveness of oral lasmiditan 50 and 100 mg for the treatment of acute migraine attacks. Lasmiditan effectiveness was not associated with the previous triptan failure and may therefore represent a valuable therapeutic option in subjects who did not benefit from, or have contraindications to, triptans. Trail registration: The study was preregistered on clinicaltrial.gov, NCT05903040 (https://clinicaltrials.gov/study/NCT05903040?cond=migraine&intr=lasmiditan&rank=5).

IntroductionAdvanced neuroimaging techniques have extensively contributed to elucidate the complex mechanisms underpinning the pathophysiology of migraine, a neurovascular disorder characterized by episodes of headache associated with a constellation of non-pain symptoms. The present manuscript, summarizing the most recent progresses of the arterial spin labelling (ASL) MRI techniques and the most significant findings from ASL studies conducted in migraine, is aimed to clarify how ASL investigations are contributing to the evolving insight on migraine pathophysiology and their putative role in migraine clinical setting. ASL techniques, allowing to quantitatively demonstrate changes in cerebral blood flow (CBF) both during the attacks and in the course of interictal period, could represent the melting point between advanced neuroimaging investigations, conducted with pure scientific purposes, and conventional neuroimaging approaches, employed in the diagnostic decision-making processes.Main bodyConverging ASL evidences have demonstrated that abnormal CBF, exceeding the boundaries of a single vascular territory, with biphasic trend dominated by an initial hypoperfusion (during the aura phenomenon but also in the first part of the headache phase) followed by hyperperfusion, characterizes migraine with aura attack and can represent a valuable clinical tool in the differential diagnosis from acute ischemic strokes and epileptic seizures.Studies conducted during migraine without aura attacks are converging to highlight the involvement of dorsolateral pons and hypothalamus in migraine pathophysiology, albeit not able to disentangle their role as “migraine generators” from mere attack epiphenomenon. Furthermore, ASL findings tend to support the presence of perfusion abnormalities in brain regions known to be involved in aura ignition and propagation as well as in areas involved in multisensory processing, in both patients with migraine with aura and migraine without aura.ConclusionAlthough ASL studies have dramatically clarified quality and timing of perfusion abnormalities during migraine with aura attacks, the same cannot be said for perfusion changes during migraine attacks without aura and interictal periods. Future studies with more rigorous methodological approaches in terms of study protocol, ASL technique and sample selection and size are mandatory to exploit the possibility of better understanding migraine pathophysiology and identifying neuroimaging biomarkers of each migraine phase in different migraine phenotypes.