Effectiveness and safety of anti-CGRP monoclonal antibodies in hemiplegic migraine: an individual patient quantitative analysis

Hemiplegic migraine (HM) is a rare and disabling subtype of migraine with aura characterized by reversible motor weakness. Preventive treatment remains challenging, as patients with HM are systematically excluded from RCTs. Monoclonal antibodies targeting the calcitonin gene-related peptide pathway (anti-CGRP mAbs) have shown effectiveness in migraine with typical aura, but evidence in HM is limited. This systematic review and quantitative synthesis followed PRISMA guidelines. PubMed, Scopus, and Web of Science were searched for studies reporting patients with HM treated with anti-CGRP mAbs. Individual patient data were extracted, and pooled analyses were conducted for changes in monthly headache days (MHDs), days with aura, and Migraine Disability Assessment (MIDAS) score from baseline to three months. Risk of bias was assessed using the GRADE approach. Six studies (four case series and two case reports), including 13 patients, met the inclusion criteria. MHDs decreased from 18 (IQR 15–25) at baseline to 9 (IQR 3–20) at three months; however, the numerical decrease was not statistically significant (p = 0.077). Median monthly days with aura decreased from 3 (IQR 2–8) to 0.6 (IQR 0–2.3; p = 0.018), and the MIDAS score decreased from 88 (IQR 66–154) to 28 (IQR 5–74; p = 0.018). Ten patients (83%) achieved > 50% reduction in MHDs and aura frequency, and nine (75%) > 50% MIDAS reduction. No adverse events were reported. Although the overall evidence certainty is very low, anti-CGRP mAbs appear to reduce aura burden and migraine-related disability in HM with good tolerability, supporting the need for prospective multicenter studies and registries to confirm their effectiveness and safety in this rare, highly disabling condition.