Pathogenesis and Preventive Pharmacotherapy of Migraine Aura: A Critical Review of Cortical Spreading Depolarization Mechanisms, Drug Repurposing Evidence, and the Emerging Therapeutic Pipeline
Abstract
Objective: : To synthesise the pathobiology of cortical spreading depolarization (CSD) and critically appraise current and emerging pharmacological strategies specifically targeting migraine aura prevention.
Background:: Migraine with aura affects 25–30% of patients, and the aura phenomenon remains a substantial unmet preventive need. Calcitonin gene-related peptide (CGRP) monoclonal antibodies do not readily cross the blood–brain barrier and frequently fail to suppress CSD, the neurophysiological substrate of aura.
Methods:: A literature search of PubMed, Embase, and the Cochrane Library (inception through January 2026) identified studies on CSD pathophysiology, preclinical CSD suppression, and clinical efficacy of candidate agents. Evidence quality was assessed with GRADE; risk of bias with Cochrane RoB 2 (RCTs) and ROBINS-I (observational); narrative synthesis followed SWiM. De novo quantitative estimations (post-hoc power analyses, sample-size projections, worst-case sensitivity analyses) were used as methodological tools, not as original empirical data.
Results:: CSD pathogenesis is organised into four phases: pre-CSD vulnerability, initiation, glial propagation, and neuro-inflammatory transduction. Lamotrigine and memantine target initiation and have the most advanced clinical evidence; both lack aura-specific RCTs. A 2024 network meta-analysis ranked memantine favourably (50% responder rate OR 5.58, 95% CI 2.41–12.92) but no contributing trial stratified by aura. An a…
Read the paper
Related studies
- Calcium Ions in the Physiology and Pathology of the Central Nervous System
- AI-powered in silico twins: redefining precision medicine through simulation, personalization, and predictive healthcare
- In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene
- In Silico drug repurposing pipeline using deep learning and structure based approaches in epilepsy
- Targeting serotonin receptors with phytochemicals – an in-silico study
- In silico exploration of anti-prostate cancer compounds from differential expressed genes
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.