Cerebral Vasomotor Reactivity in the acute phase and after 6 months in non-disabling stroke/TIA: a prospective cohort study.

BACKGROUND AND AIM: Cerebral Vasomotor Reactivity (VMR) is a property of cerebral hemodynamics that protects from cerebrovascular disease. We aimed to explore the VMR longitudinal changes in patients with acute non-disabling stroke/Transient Ischemic Attack (TIA) to understand its implication in stroke ethiopatogenesis. METHODS: VMR by Transcranial Doppler Breath Holding test was performed at 48-72 h from stroke onset (T1) and after 6 months (T2) on MCA of the non-affected hemisphere and PCA of the affected hemisphere. RESULTS: We consecutively enrolled 124 patients with a median age of 66.0 (IQR 54.75-74.25) years with a median NIHSS 2 (IQR 1-3). Both MCA (1.38 %/s SD 0.58) and PCA (1.35 %/s SD 0.75) BHI at T1 did not differ among different stroke subtypes (p=0.067 and p=0.350; N=124). MCA and PCA BHI decreased from T1 to T2 (respectively 1.39 %/s SD 0.56 vs 1.18%/s SD 0.44 and 1.30 %/s SD 0.69 vs 1.20 %/s SD 0.51; N=109) regardless of ethiopatogenesis (respectively p<0.0001 and p=0.111). CONCLUSION: the VMR is higher in acute phase than at 6 months in patients with non-disabling stroke/TIA, regardless of etiopathogenesis. The higher VMR in acute phase could be sustained by an increased Cerebral Blood Flow due to collateral circulation activation supporting the ischemic zone.

Rapid response to galcanezumab and predictive factors in chronic migraine patients: A 3-month observational, longitudinal, cohort, multicenter, Italian real-life study.

BACKGROUND AND PURPOSE: A rapid response to preventive therapy is of pivotal importance in severely disabled patients with chronic migraine (CM) and diverse preventive treatment failures. This prospective, observational, multicenter real-life study aimed at investigating the effectiveness of galcanezumab in the first 3 months of treatment of CM patients at 14 Italian headache centers. METHODS: All consecutive adult patients with CM diagnosis with the clinical indication for galcanezumab were considered. We collected patients' baseline characteristics, monthly headache days, monthly painkiller intake, migraine clinical characteristics, and disability scale scores during a 1-month run-in period (baseline) and the first 3 months of therapy. Possible predictive factors of treatment were considered. RESULTS: A total of 156 patients (82.4% female, aged 47.3 ± 12.3 years) were enrolled. The 65 (41.7%) patients with a consecutive ≥50% response rate (RR) in the 3 months of therapy presented a lower body mass index (p = 0.004) and more frequently presented unilateral migraine pain (p = 0.002) and good response to triptans (p = 0.003). Persistent conversion from CM to episodic migraine was observed in 55.8% (87/156) of patients. They more frequently presented a good response to triptans (p = 0.003) and unilateral pain (p = 0.046). At baseline, 131 of 156 (83.9%) patients presented medication overuse (MO). Of these, 61.8% (81/131) no longer displayed MO consistently during the 3 months. These patients were more frequently responders to triptans (p = 0.002) and less frequently suffered from gastrointestinal comorbidity (p = 0.007). CONCLUSIONS: Unilateral pain, good response to triptans, and normal weight may be associated with a persistent positive response in the first 3 months of therapy with galcanezumab in CM patients.

Erenumab does not alter cerebral hemodynamics and endothelial function in migraine without aura.

OBJECTIVE: To assess whether erenumab influences cerebral vasomotor reactivity and flow-mediated dilation in migraine patients. METHODS: Consecutive migraineurs prescribed erenumab at our Headache Centre and age and sex-matching controls were invited to participate in this observational longitudinal study. Patients were evaluated for cerebral vasomotor reactivity to hypercapnia (breath-holding index) in middle and posterior cerebral arteries and for brachial corrected flow mediated dilation at baseline (T0), after 2 weeks from the first erenumab injection (T2) and after 2 weeks from the fourth Erenumab injection (T18). Patients displaying a reduction of at least 50% in monthly migraine days after completing the fourth month of therapy were classified as responders. RESULTS: Sixty patients and 25 controls agreed to participate. Middle and posterior cerebral artery mean flow velocities, breath-holding index and flow-mediated dilation did not differ at T0 and from T0 to T2 in patients and controls. In patients, we neither observed a variation of the explored variables from T0 to T18 nor an interaction between evaluation times (T0-T2 or T0-T18) and chronic condition at T0, responder state or erenumab fourth dose. CONCLUSIONS: Our findings demonstrate that erenumab preserves cerebral vasomotor reactivity and flow-mediated dilation in migraineurs without aura.

Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study.

BACKGROUND: Monoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients. METHODS: This observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1-3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO). RESULTS: We enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman's analysis of rank, p < .001). In the F-UP1-3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (- 47.7% [25th, - 79.5; 75th,-17.0]) than in CM patients (- 25.5% [25th, - 47.1; 75th, - 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01). CONCLUSION: Migraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.

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 .

Right-to-Left Shunt and the Clinical Features of Migraine with Aura: Earlier but Not More.

BACKGROUND: The causal relationship between patent foramen ovale (PFO) and migraine with aura (MA) is controversial. We aimed at exploring whether attack clinical features relate to the presence of right-to-left shunt (RLS) in MA patients. METHODS: We retrospectively examined a cohort of consecutive patients diagnosed with MA in our headache center and undergoing transcranial doppler (TCD) for RLS detection. We collected from our clinical electronic dossiers, clinical features of MA attacks (type, frequency, duration of aura phenomenon, trigger factors, onset age), family history for MA, thrombophilia genotypes, and the response to preventive treatments. RLS was stratified for severity according to the results of the TCD examination. RESULTS: We found 111 patients. Binary logistic regression analysis showed that among features of MA attacks, only onset age was associated with the presence of RLS (p < 0.0001). Patients with RLS presented the first MA attack at a younger age (p < 0.0001). The greater RLS severity, the younger was onset age (p < 0.00001) and the presence of atrial septal aneurysms (ASA) was associated with a further decrease in onset age (ρ = -539, p < 0.00001). Family history for MA was associated with the presence of RLS (chi-square p = 0.022). Response to preventive treatments was not influenced by the type of treatment (antiplatelet compared with no antiplatelet drugs), comorbidity with migraine without aura, RLS presence, or by their double interactions (Logistic regression, consistently p > 0.05). CONCLUSION: Our findings support the hypothesis that although PFO does not influence MA attack frequency, it is not merely a bystander in MA physiopathology, as RLS, its severity, and the presence of ASA possibly make a difference in the disease history.

Carotid Artery Plaque Progression: Proposal of a New Predictive Score and Role of Carotid Intima-Media Thickness.

BACKGROUND: We aimed to investigate if the carotid intima-media thickness (IMT) at baseline and the HAD2S score, composed of the sum of single risk factors (hypertension, age ≥ 75 years, diabetes, dyslipidemia, smoking), were predictive of plaque progression. METHODS: We performed a retrospective analysis on real-life prospectively collected data from patients with any detectable carotid plaque at follow up. The plaque score, calculated at baseline (T0) and at a median follow up of 36.6 months (IQR 39.6-34.3) (T3), was defined as 0: no plaque or stenosis < 30%; 1: stenosis in the range 30-49%; 2: in the range 50-69%; 3: in the range 70-99% and 4: occlusion. Carotid IMT was measured at T0 and T3; HAD2S score was calculated at baseline. RESULTS: We included 340 patients with a mean age of 69.9 (9.1) years and 25.3% subjects had plaque progression. Individuals with progression had a median HAD2S score of 3 (1) while those without progression had 2 (1). Patients with progression had a mean baseline IMT of 0.86 (0.17) while those without progression had 0.77 (0.18) (p < 0.0001). A correlation between progression and baseline IMT was found (p = 0.002). CONCLUSION: Baseline IMT could be considered a predictor of progression. Patients with progression had an HAD2S score higher than those without evolution.

Shorter visual aura characterizes young and middle-aged stroke patients with migraine with aura.

OBJECTIVE: To identify the clinical profile and aura characteristics of patients with Migraine with Aura (MwA) having acute cerebral ischemia, we compared stroke phenotype and risk factors in stroke patients with (S+MwA+) or without (S+MwA-) MwA and aura features in MwA patients with (S+MwA+) or without (S-MwA+) stroke. METHODS: In this retrospective multicenter case-control study, we reviewed stroke phenotypes and vascular risk factors in S+MwA+ and S+MwA- patients younger than 60 years and risk factors and aura type, duration, onset age, and the frequency in the previous year in S+MwA+ patients and S-MwA+ subjects matched for age and disease history, investigated for patent foramen ovale (PFO). RESULTS: 539 stroke (7.7% S+MwA+) and 94 S-MwA + patients were enrolled. S+MwA+ patients were younger (p =.0.004) and more frequently presented PFO [OR 4.89 (95% CI 2.12-11.27)], septal interatrial aneurism [OR 2.69 (95% CI 1.15-6.27)] and cryptogenic ischemic stroke (CIS) [OR 6.80 (95% CI 3.26-14.18)] than S+MwA- subjects. Significant atherosclerosis was not detected in S+MwA+ patients. Compared to S-MwA+, S+MwA+ patients were characterized by visual [OR 3.82 (95% CI 1.36-10.66)] and shorter-lasting (20.0 min IQr 13.1 vs 30.0 min IQr 25.0; p < 0.001) aura, and PFO [OR 1.26 (95% CI 1.03-1.54)]. Regression analysis evidenced that only shorter aura duration associated with stroke (p = 0.001). High-risk PFO was equally represented in S+MwA-, S+MwA+, S-MwA+ groups. CONCLUSIONS: Shorter visual aura and CIS characterize MwA patients with stroke. Although more prevalent, PFO can not be considered the main responsible for the increased stroke risk in MwA patients but as a part of a complex multifactorial condition.