ArticleEuropean journal of neurology2026
The Relevance of Crystal Clear and Unclear Days to Evaluate Residual Interictal Burden in Patients With Migraine Treated With CGRP Monoclonal Antibodies.
Article in European journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAlthough treatment goals in migraine prevention have moved beyond the benchmark of a 50% reduction in monthly attacks, residual disease burden is still evaluated based on residual headache frequency. However, migraine-related symptoms can persist despite headache freedom, leading to so-called unclear days that may meaningfully contribute to interictal burden.
methodsIn this prospective, real-world study, patients with chronic or high-frequency episodic migraine treated with CGRP-monoclonal antibodies (CGRP-mAbs) were followed for six months. Interictal burden was assessed using the Migraine Interictal Burden Scale (MIBS-4) alongside the monthly unclear and crystal clear days. Patients achieving optimal (< 4 monthly attacks) or modest (4-6 monthly attacks) migraine control were stratified according to the presence of "residual interictal burden" (MIBS-4 ≥ 3).
resultsTwo hundred patients were included. CGRP-mAbs treatment was associated with a reduction in MIBS-4 scores and an increase in crystal clear days (p < 0.001). Despite optimal or modest migraine control, 45.1% of patients at month 3 and 27.2% at month 6 continued to exhibit a substantial "residual interictal burden". Patients with "residual interictal burden" showed significantly more unclear days and fewer crystal clear days compared with those without residual interictal migraine burden, while no differences were observed in residual headache days, concomitant preventive treatments, or cephalalgiophobia. DISCUSSION: Even when migraine attacks are adequately controlled, residual interictal burden may remain and seems to be predominantly associated with unclear days rather than with residual attacks. Assessing crystal clear and unclear days provides a complementary, patient-centered perspective on treatment response and interictal recovery in migraine.
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