Migraine preventive treatments include both oral therapies, such as beta-blockers, antiseizure medications and anti-depressive drugs, and more recently developed parenteral therapies, that is, onabotulinumtoxin-A and monoclonal antibodies against the calcitonin-gene-related peptide (CGRP mAbs). The latter are targeted against the CGRP pharmacological system, which has been known as a primary key factor involved in the pathophysiology of migraine. CGRP acts as a neuropeptide released by the trigeminal

Background Although white matter hyperintensities (WMH) volumetric assessment is now customary in research studies, inconsistent WMH measures among homogenous populations may prevent the clinical usability of this biomarker. Purpose To determine whether a point estimate and reference standard for WMH volume in the healthy aging population could be determined. Study Type Systematic review and meta‐analysis. Population In all, 9716 adult subjects from 38 studies reporting WMH volume were retrieved following a systematic search on EMBASE. Field Strength/Sequence 1.0T, 1.5T, or 3.0T/fluid‐attenuated inversion recovery (FLAIR) and/or proton density/T2‐weighted fast spin echo sequences or gradient echo T1‐weighted sequences. Assessment After a literature search, sample size, demographics, magnetic field strength, MRI sequences, level of automation in WMH assessment, study population, and WMH volume were extracted. Statistical Tests The pooled WMH volume with 95% confidence interval (CI) was calculated using the random‐effect model. The I2 statistic was calculated as a measure of heterogeneity across studies. Meta‐regression analysis of WMH volume on age was performed. Results Of the 38 studies analyzed, 17 reported WMH volume as the mean and standard deviation (SD) and were included in the meta‐analysis. Mean and SD of age was 66.11 ± 10.92 years (percentage of men 50.45% ± 21.48%). Heterogeneity was very high (I2 = 99%). The pooled WMH volume was 4.70 cm3 (95% CI: 3.88–5.53 cm3). At meta‐regression analysis, WMH volume was positively associated with subjects' age (β = 0.358 cm3 per year, P < 0.05, R2 = 0.27). Data Conclusion The lack of standardization in the definition of WMH together with the high technical variability in assessment may explain a large component of the observed heterogeneity. Currently, volumes of WMH in healthy subjects are not comparable between studies and an estimate and reference interval could not be determined. Level of Evidence 1 Technical Efficacy Stage 1

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BackgroundCalcitonin gene-related peptide (CGRP) plays a pivotal role in migraine physiology, not only regarding migraine pain but also associated symptoms such as photophobia. The aim of the present study was to assess monoclonal antibodies targeting CGRP efficacy not only in terms of headache and migraine frequency and disability but also in reducing ictal photophobia.Material and methodsThis is a retrospective observational study, conducted at the Headache Center–ASST Spedali Civili Brescia. All patients in monthly treatment with galcanezumab with at least a 6-month follow-up in September 2022 with reported severe photophobia during migraine attacks were included. Data regarding headache frequency, analgesics consumption, and migraine disability were collected quarterly. Moreover, patients were asked the following information regarding photophobia: (1) whether they noticed an improvement in photophobia during migraine attacks since galcanezumab introduction; (2) the degree of photophobia improvement (low, moderate, and high); and (3) timing photophobia improvement.ResultsForty-seven patients were enrolled in the present study as they met the inclusion criteria. Seventeen patients had a diagnosis of high-frequency episodic migraine and 30 of chronic migraine. From baseline to T3 and T6, a significant improvement in terms of headache days (19.2 ± 7.6 vs. 8.6 ± 6.8 vs. 7.7 ± 5.7; p &lt; 0.0001), migraine days (10.4 ± 6.7 vs. 2.9 ± 4.3 vs. 3.6 ± 2.8; p &lt; 0.0001), analgesics consumption (25.1 ± 28.2 vs. 7.6 ± 7.5 vs. 7.6 ± 8.1; p &lt; 0.0001), MIDAS score (82.1 ± 48.4 vs. 21.6 ± 17.6 vs. 18.1 ± 20.5; p &lt; 0.0001), and HIT-6 score (66.2 ± 6.2 vs. 57.2 ± 8.6 vs. 56.6 ± 7.6; p &lt; 0.0001) was found. Thirty-two patients (68.1%) reported a significant improvement in ictal photophobia, with over half of the patients reporting it within the first month of treatment. Photophobia improvement was more frequent in patients with episodic migraine (p = 0.02) and triptans responders (p = 0.03).ConclusionsThe present study confirms previous reports regarding galcanezumab efficacy beyond migraine frequency. In particular, over 60% of patients, in our cohort, documented a significant improvement also in reducing ictal photophobia. This improvement was, in most patients, moderate to high, and within the first 6 months of treatment, regardless of the clinical response on migraine frequency.

The aim of the present study was to assess erenumab efficacy in migraine disability and intensity throughout the first treatment cycle, discontinuation, and the first 6 months of re-treatment in patients with high-frequency episodic migraine. The study design was retrospective and observational. Inclusion criteria were the following: diagnosis of high-frequency episodic migraine and ongoing treatment with erenumab 140 mg currently at their second treatment cycle. Data regarding migraine frequency, disability (MIDAS score), and severity of attacks (NRS score) were collected quarterly. Twenty-five patients were enrolled. At the end of the first treatment cycle, compared to baseline, a significant improvement of MIDAS scores was found (13.5 ± 11.1 vs. 72.5 ± 32.1; <i>p</i> = 0.005), with a subsequent worsening during treatment suspension (30.1 ± 26.9; <i>p</i> = 0.03). Pain intensity remained unmodified during the first treatment cycle (NRS score baseline: 7.6 ± 0.9 vs. 12 months: 7.5 ± 0.7; <i>p</i> = 0.13). During re-treatment, MIDAS scores documented a new significant improvement, reaching the same level at 6 months of re-treatment as at the end of the first cycle (30.1 ± 26.9 vs. 12.9 ± 5.4; <i>p</i> = 0.03). A significant improvement, compared to baseline, was observed for pain intensity during re-treatment (6.8 ± 2.2 vs. 5.6 ± 0.9 at RT3 vs. 5.2 ± 1.4 at RT6; <i>p</i> = 0.05). In conclusion, during re-treatment with erenumab 140 mg, migraine pain intensity and disability documented a significant and progressive improvement. Our data confirm the long-term efficacy, although in a very limited case series, of monoclonal antibodies targeting CGRP beyond headache frequency reduction.