Evaluating the Effectiveness, Tolerability, and Safety of Eptinezumab in High-Frequency and Chronic Migraine in Real World: EMBRACE-The First Italian Multicenter, Prospective, Real-Life Study.

We conducted a multicenter, prospective study (EMBRACE) evaluating the real-life effectiveness, safety, and tolerability of eptinezumab (100 mg/300 mg)-a monoclonal antibody targeting the calcitonin-gene-related peptide (anti-CGRP mAb)-in high-frequency episodic migraine (HFEM) or chronic migraine (CM). The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at weeks 9-12 compared to baseline. The secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates. The safety analysis involved 44 subjects; the effectiveness analysis included 26 individuals. Eptinezumab was well-tolerated. In CM patients, eptinezumab significantly reduced MHD (-16.1 ± 9.9, p < 0.001), MAI, NRS, HIT-6, MIDAS, and MIBS-4. In HFEM patients, it significantly reduced NRS, HIT-6, MIDAS, and MIBS-4, though reductions in MMD (-3.3 ± 4.5) and MAI were not statistically significant. Overall, ≥50% and ≥75% response rates were 61.5% and 30.8%, respectively (60% and 30% in non-responders to subcutaneous anti-CGRP mAbs). The clinical change was rated as much or very much improved by 61.0% of the patients. Eptinezumab demonstrated high effectiveness, safety, and tolerability in real-life among hard-to-treat migraine patients with multiple treatment failures, including anti-CGRP mAbs.

Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.

INTRODUCTION: Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities. METHODS: A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks 45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates. RESULTS: Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48 weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period. PRIMARY ENDPOINT: fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM - 6.0; CM -16.5), NRS (HFEM - 3.4; CM - 3.4), HIT-6 (HFEM - 16.9; CM - 17.9) and MIDAS score (HFEM - 50.4; CM - 76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason. CONCLUSION: This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs.

Impact of multiple treatment cycles with anti-CGRP monoclonal antibodies on migraine course: focus on discontinuation periods. Insights from the multicenter, prospective, I-GRAINE study.

OBJECTIVES: While a single 12-month treatment cycle (TrC) with anti-CGRP mAbs is not disease-modifying for most patients, there is limited understanding of the effects of multiple TrCs on migraine course. We evaluated whether a second TrC might modify the migraine course by comparing the occurrence of migraine relapse after discontinuation of the second TrC to that following the cessation of the first TrC. METHODS: In a real-life, multicenter, prospective study we considered all consecutive patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and treated with any anti-CGRP mAbs for ≥ 2 consecutive 12-month TrCs who were responders at week 12. The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at the first month of treatment discontinuation after the second TrC (D2) compared to the first TrC (D1). Secondary endpoints included variations in monthly analgesic medications (MAM), Numeric Rating Scale (NRS), and Headache Impact Test (HIT-6) scores, ≥ 50%, ≥ 75%, and 100% response rates, and relapse from episodic migraine to CM and from no-medication overuse (MO) to MO at D2 vs. D1. RESULTS: One-hundred-seventy-eight patients completed two 12-month TrCs with anti-CGRP mAbs. At D2, patients experienced a significant reduction in MMD (- 0.6, p = 0.028), MHD (- 2.6, p < 0.001), monthly analgesic medications (- 2.0, p < 0.001), and HIT-6 score (- 2.2, p < 0.001) compared to D1, indicating improved effectiveness. The ≥ 50% response rate at weeks 45-48 during the first TrC was 95.5%, while at weeks 45-48 of the second TrC was 99.4%. Corresponding rates at D1 was 20.2% whereas at D2 was 51.6% (p < 0.0001). No statistical difference emerged in ≥ 75% and 100% responders. The relapse rate from episodic migraine to CM at D2 was lower than at D1 (12.3% vs 30.4%; p = 0.0002) Fewer patients experienced relapse from no-MO to MO at D2 compared to D1 (29.5% vs 68.7%; p = 0.00001). DISCUSSION: A second TrC with anti-CGRP mAbs demonstrated clinical improvements compared to the first one, as indicated by a milder migraine relapse at D2 compared to D1. Multiple TrCs with anti-CGRP mAbs could progressively modify migraine evolution by reducing CGRP-dependent neuroinflammatory nociceptive inputs to the brain.

Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study.

OBJECTIVE: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders). METHODS: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks. RESULTS: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain-either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)-a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020). CONCLUSION: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2-3 months of treatment.

Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: the multicenter, prospective, real-life FRIEND2 study.

BACKGROUND: To verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM: ≥ 15 days/month), and multiple preventive treatment failures. METHODS: This is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21-24 compared to baseline. Secondary endpoints encompassed changes in monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS, HIT-6 and MIDAS scores at the same time interval. Changes in MMDs/MHDs, monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS and HIT-6 scores at week 4 were also monitored. RESULTS: Four hundred ten patients who had received ≥ 1 dose of fremanezumab were considered for safety analysis while 148 patients treated for ≥ 24 weeks were included in the efficacy analysis. At weeks 21-24, fremanezumab significantly (p < 0.001) reduced MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM compared to baseline. The proportions of ≥ 50%, ≥ 75% and 100% responders at weeks 21-24were 75.0%, 30.8%, 9.6% (HFEM), and 72.9, 44.8 and 1% (CM). A significant (p < 0.001) decrease in MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM was already present at week 4. The proportions of ≥ 50%, ≥ 75%, and 100% responders at week 4 were 67.6%, 32.4%, 11.8% (HFEM) and 67.3%, 40%, 1.8% (CM). CM remitted to episodic migraine and medication overuse to no-medication overuse in 83.3 and 75% of patients at week 24, and in 80 and 72.4% at week 4. Adverse events were rare (2.4%), mild and transient. No patient discontinued treatment for any reason. CONCLUSIONS: Fremanezumab is characterized by an early and sustained efficacy in HFEM and CM patients with multiple preventive treatment failures in real-life, revealing an optimal safety and tolerability profile.

Predictors of response to anti-CGRP monoclonal antibodies: a 24-week, multicenter, prospective study on 864 migraine patients.

BACKGROUND AND OBJECTIVES: The identification of predictors of response to antiCGRP mAbs could favor tailored therapies and personalized treatment plans. This study is aimed at investigating predictors of ≥ 50%, ≥ 75% and 100% response at 24 weeks in patients with high-frequency episodic (HFEM: 8-14 days/month) or chronic migraine (CM). METHODS: This is a large, multicenter, cohort, real-life study. We considered all consecutive adult patients affected by HFEM or CM who were prescribed antiCGRP mAbs for ≥ 24 weeks in 20 headache centers. Patients were interviewed face-to-face using a shared semi-structured questionnaire carefully exploring socio-demographic and clinical characteristics. Patients received subcutaneous erenumab (70 mg or140 mg, monthly), galcanezumab (120 mg monthly, following a 240 mg loading dose), or fremanezumab (225 mg, monthly or 675 mg, quarterly) according to drug market availability, physician's choice, or patient's preference. The primary endpoint of the study was the assessment of ≥ 50% response predictors at 24 weeks. Secondary endpoints included ≥ 75% and 100% response predictors at 24 weeks. RESULTS: Eight hundred sixty-four migraine patients had been treated with antiCGRP mAbs for ≥ 24 weeks (erenumab: 639 pts; galcanezumab: 173 pts; fremanezumab: 55 pts). The ≥50% response (primary endpoint) in HFEM was positively associated with unilateral pain (UP) + unilateral cranial autonomic symptoms (UAs) (OR:4.23, 95%CI:1.57-11.4; p = 0.004), while in CM was positively associated with UAs (OR:1.49, 95%CI:1.05-2.11; p = 0.026), UP + UAs (OR:1.90, 95%CI:1.15-3.16; p = 0.012), UP + allodynia (OR:1.71, 95%CI:1.04-2.83; p = 0.034), and negatively associated with obesity (OR:0.21, 95%CI:0.07-0.64; p = 0.006). The 75% response (secondary endpoint) was positively associated with UP + UAs in HFEM (OR:3.44, 95%CI:1.42-8.31; p = 0.006) and with UP + UAs (OR:1.78, 95%CI:1.14-2.80; p = 0.012) and UP + allodynia (OR:1.92, 95%CI:1.22-3.06; p = 0.005) in CM. No predictor of 100% response emerged in patients with HFEM or CM. CONCLUSIONS: A critical evaluation of headache characteristics indicating peripheral or central sensitization may help in predicting responsiveness to antiCGRP mAbs in HFEM and CM. A more precise pain profiling may represent a steppingstone for a mechanism-based approach and personalized treatment of migraine with compounds targeting specific molecular mechanisms.

Trends of recanalization therapies and state of art for ischemic stroke treatment in Campania region, Italy.

BACKGROUND: According to the last Italian report by the Ministry of Health in 2018, the estimated number of acute ischemic strokes (AIS) in Campania is 10,000/year, with an expected number of 1390 intravenous thrombolysis (IVT) and 694 mechanical thrombectomies (MT). In 2017, only 1.5% of expected patients received IVT and 0.2% MT. This study analyzed the trend of IVT and MT in 2019-2020 and depicted the state of art of Stroke Care in Campania. METHODS: From the regional health task force, we obtained the hospital discharge forms from all private and public hospitals in Campania; we selected patients with a principal diagnosis of AIS and measured the rate of patients admitted to neurology units and the rate of IVT, MT, and IVT + MT for both 2019 and 2020. RESULTS: In 2019, we observed 4817 admissions for AIS; 2858/4817 (59.3%) patients were admitted to neurology units. Out of 4817 patients, 192 received IVT, 165 MT, and 131 IVT + MT (488 treated patients; 10.1%). In 2020, we observed 4129 admissions for AIS; 2502/4129 (62.7%) patients were admitted to neurology units. Out of 4129 patients, 198 received IVT, 250 MT, and 180 IVT + MT (628 treated patients; 15.2%). These results showed that despite a reduction of AIS admissions in 2020, the relative and absolute rate of recanalization treatments increased. However, the number of patients who were not admitted to neurology units nor received acute treatments remained dramatically high. CONCLUSION: Despite the development of acute treatments, the Campania Stroke Network still needs significative efforts to improve.

Neuropsychological correlates of theory of mind in chronic migraine.

OBJECTIVE: Theory of mind (ToM), the ability to understand other minds-that is, their beliefs, intentions (cognitive ToM), or emotions (affective ToM)-and its neuropsychological mechanisms in migraine have been poorly investigated. The aim of the study was to explore the deficit of cognitive and affective ToM and its possible associations with cognitive functioning in patients with chronic migraine (CM). METHOD: Forty participants with CM and 40 age-, education-, and sex-matched healthy controls (HC) underwent clinical assessment, cognitive (the ToM Pictures Sequencing Task and the Advanced Test of ToM) and affective ToM (the Reading the Mind in the Eyes Task and the Emotion Attribution Task) tasks, and a comprehensive neuropsychological battery. RESULTS: Patients with CM significantly reported a lower performance on tasks assessing ToM compared to HC, with an impairment demonstrated for cognitive ToM. Moreover, patients with CM achieved significantly lower scores on tests assessing cognitive flexibility, planning, abstract reasoning, and long-term memory with respect to HC. ToM abilities were significantly related to migraine severity, executive, and memory functions in CM patients. CONCLUSIONS: The findings demonstrated that patients with CM present difficulties in inferring others' mental states, which would be related to clinical and cognitive functioning. The clinical importance of these findings, implications for clinical practice, and future research are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Relationship between apathy and cognitive dysfunctions in multiple sclerosis: A 4-year prospective longitudinal study.

BACKGROUND: Cognitive dysfunctions are highly prevalent in multiple sclerosis (MS) and negatively impact occupational and social functioning. OBJECTIVE: In the present longitudinal study, we aimed at modeling cognitive changes and at assessing whether apathy could be a predictor of cognitive decline in MS. METHODS: We assessed 67 people with MS at two-time points (baseline, T0; 4-year follow-up, T1), by means of several clinical, behavioural, and cognitive measures. We used a delta approach to measure cognitive decline during the follow-up period. We applied a mixed factorial design and a linear regression model to explore factors associated with cognitive changes over time. RESULTS: A higher level of apathy at baseline predicted the progressive cognitive decline at follow-up, whereas a higher level of depression did not. Among demographic and clinical characteristics, only low education level was significantly associated with cognitive decline over time. Interestingly, participants with persistent apathy (diagnosis of apathy at T0 and T1, A+A+) and those who developed apathy (A-A+) showed poorer inhibitory control and a larger decline in executive functioning during the 4-year follow-up than participants who had never received the diagnosis of apathy (A-A-). CONCLUSION: Apathy represents an early marker of cognitive decline in MS. These findings have important clinical and prognostic implications.

Conversion from chronic to episodic migraine in patients treated with galcanezumab in real life in Italy: the 12-month observational, longitudinal, cohort multicenter GARLIT experience.

OBJECTIVE: To investigate in real-life the conversion from chronic migraine (CM) to episodic migraine (EM), specifically to EM with High-Frequency (HFEM: 8-14 monthly migraine days, MMDs), Medium-Frequency (MFEM, 4-7 MMDs), and Low-Frequency EM (LFEM, 0-3 MMDs), and its persistence during 1 year of treatment with galcanezumab. METHODS: Consecutive CM patients treated with galcanezumab completing 1 year of observation were enrolled. We collected data on MMDs, pain intensity (Numeric Rating Scale, NRS score), and monthly acute medication intake (MAMI) from baseline (V1) to the 12-month visit (V12). RESULTS: Of the 155 enrolled patients, 116 (around 75%) reverted to EM at every visit and 81 (52.3%) for the entire 1-year treatment. Patients with older onset age (p = 0.010) and fewer baseline MMDs (p = 0.005) reverted more frequently to EM. At V12, 83 participants (53.5%) presented MFEM or LFEM. Patients reverted to MFEM or LFEM for 7 months (25th 1, 75th 11). The medication overuse discontinuation rate at V12 was 82.8% and occurred for 11 months (25th 8, 75th 12). From baseline to V12, the MAMI decreased by 17 symptomatic drugs (p < 0.000001) while the NRS score reduced by almost 2 points (p < 0.000001). A consistent transition to EM for the entire treatment year was observed in 81 (52.3%) patients. DISCUSSION: The 1-year GARLIT experience suggests that more than half of CM patients treated with galcanezumab persistently reverted to EM in real life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04803513.

Fremanezumab in the prevention of high-frequency episodic and chronic migraine: a 12-week, multicenter, real-life, cohort study (the FRIEND study).

BACKGROUND: Fremanezumab has demonstrated to be effective, safe, and tolerated in the prevention of episodic or chronic migraine (CM) in randomized, placebo-controlled trials (RCTs). Real-life studies are needed to explore drug effects in unselected patients in routine circumstances and to provide higher generalizability results. This study explores the effectiveness, safety, and tolerability of fremanezumab in a real-life population of individuals affected by high-frequency episodic (HFEM: 8-14 days/month) or CM. METHODS: This is a 12-week multicenter, prospective, cohort, real-life study. We considered all consecutive patients affected by HFEM or CM visited at 9 Italian headache centers from 28/07/2020 to 11/11/2020. Eligible patients were given subcutaneous fremanezumab at the doses of 225 mg monthly or 675 mg quarterly, according to their preference. Primary study endpoints were the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients at weeks 9-12 compared to baseline. Secondary endpoints encompassed variation in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), HIT-6 and MIDAS scores, and ≥ 50%, ≥ 75% and 100% responder rates at the same time intervals. RESULTS: Sixty-seventh number migraine patients had received ≥ 1 subcutaneous fremanezumab dose and were considered for safety analysis, while 53 patients completed 12 weeks of treatment and were included also in the effectiveness analysis. Fremanezumab was effective in both HFEM and CM, inducing at week 12 a significant reduction in MMDs (-4.6, p < 0.05), MHDs (-9.4, p < 0.001), MAI (-5.7, p < 0.05; -11.1, p < 0.001), NRS (-3.1, p < 0.001; -2.5, p < 0.001), and MIDAS scores (-58.3, p < 0.05; -43.7; p < 0.001). HIT-6 was significantly reduced only in HFEM patients (-18.1, p < 0.001). Remission from CM to episodic migraine and from MO to no-MO occurred in 75% and 67.7% of the patients. The ≥ 50%, ≥ 75% and 100% responder rates at week 12 were 76.5%, 29.4% and 9.9% in HFEM and 58.3%, 25% and 0% in CM. Younger age emerged as a positive response predictor (OR = 0.91; 95% CI 0.85-0.98, p = 0.013). Treatment-emergent adverse events were uncommon (5.7%) and mild. No patient discontinued fremanezumab for any reason. CONCLUSIONS: Fremanezumab seems more effective in real-life than in RCTs. Younger age emerges as a potential response predictor.

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.

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 .

Perfusion-weighted MRI in cerebral amyloid angiopathy-related transient focal neurological episodes.

INTRODUCTION: Sporadic cerebral amyloid angiopathy (CAA) is a common age-related cerebral small vessel disease characterized by progressive ß-amyloid deposition in the walls of small cortical arteries, arterioles, and capillaries in the cerebral cortex and overlying leptomeninges. CAA-related transient focal neurological episodes (CAA-TFNEs) represent a challenging clinical feature interesting from a pathophysiological point of view. CASE REPORT: Here we present two cases of CAA-TFNEs in which we performed functional imaging with perfusion-weighted imaging MR and brain 18 F-FDG PET. In both cases, we found a topographic relationship between the involved cortical areas and the clinical expression of CAA-TFNEs. Cortical superficial siderosis in the first case and a convexity subarachnoid hemorrhage in the second case were found in the contralateral rolandic area corresponding to the clinical symptoms. The same areas showed a reduction of rCBV and rCBF on perfusion-weighted MR and were also associated in one case with hypometabolism on 18 F-FDG PET. DISCUSSION: These new findings strengthen the hypothesis that CAA involves the superficial leptomeningeal arteries but also the short penetrating arterioles reaching different depths in the cortex generating hypoperfusion and altered vascular reactivity and consequently reduced neuronal activity. CONCLUSION: Understanding CAA-TFNEs is pivotal because they carry a very high risk of subsequent lobar intracerebral hemorrhage but are frequently misdiagnosed as TIAs and treated with antithrombotics enhancing the bleeding risk associated with CAA.

The Impact of Covid-19 Lockdown on Stroke Admissions and Treatments in Campania.

OBJECTIVES: The enforcement of complete lockdown with home confinement has been necessary to limit SARS-CoV-2 contagions in Italy, one the most affected countries worldwide. Simultaneously, in several Emergency Departments, a reduction in cardio- and cerebrovascular presentations was noticed. This study analyses the impact of Covid-19 pandemic and lockdown measures on the incidence of stroke, in Campania, the most densely-populated region in Italy. MATERIALS AND METHODS: We retrospectively analyzed data regarding acute stroke patients presenting at 5 Campania stroke hubs, before and after the issue of lockdown in Italy on March 9th, 2020. RESULTS: Compared to the pre-lockdown, we observed a significant reduction in the number of acute reperfusion treatments in stroke (P for interact 0.001); however the global number of patients presenting with acute stroke did not significantly differ. The time to reach medical attention was significantly longer in the lockdown phase (230 versus 154 min, P 0.016). For patients who underwent acute reperfusion treatment we also observed significantly longer time-to-imaging (30 versus 40 min, P 0.0005) and a trend to longer time-to-needle (75 versus 90 min P 0.23), but not time-to-groin. CONCLUSIONS: This study showed the reduction in acute reperfusion treatments for acute ischemic stroke and the slowdown of stroke pathways, during the lockdown phase of Covid-19 pandemic, in Campania, the third-most-populous and the most-densely populated Italian Region. In the next future, the risk for high-grade disability and death, due to delayed or even avoided hospital presentation due to fear of contagion, may be high.

Impulse control disorders in chronic migraine with medication overuse after onabotulinumtoxinA: A single-center prospective cohort study.

Chronic migraine (CM) with medication overuse headache (MOH) is one of the most common and disabling chronic headache disorders associated with both frequencies of use of medication and behavioral alterations, including psychopathology and psychological drug dependence. Several previous studies on large patient samples have demonstrated the efficacy of Onabotulinum toxin A (OnabotA) on physical symptomatology treatment of headache, but effects on behavioral alterations remain still debate. Our study investigated the effects of OnabotA on psychiatric comorbidities and on quality of life of patients with CM and MOH that failed on traditional therapies. OnabotA was injected, according to the PREEMPT paradigm, 40 patients with CM and MOH and data on headache-related impairment, before and after the OnabotA injections were collected from the patient's headache diaries. Data on depressive, anxiety symptomatology and impulse control disorders also were collected by means of self-report scales and a semi-structured interview. After six months, patients with CM and MOH showed a significant decrease in monthly headache attacks (from 19.3 ± 5.9 to 11.8 ± 8.5, p = 0.003), monthly headache days (from 23 ± 8.9 to 11.1 ± 6.2, p = 0.001), numbers of analgesics used per month (from 18.2 ± 6.3 to 8.5 ± 4.7, p < 0.0001). The anxiety symptomatology (p ≤ 0.003) and impulse control disorders (from 30% to 10%), but not depressive symptomatology (p = 0.81), were significantly reduced from throughout the study. The treatment with OnabotA proved beneficial effects on anxiety symptomatology and on impulse control disorders in our clinical practice with CM and MOH and further studies should shed light in larger patient samples on long-term behavioural effects.