Vestibular migraine vs. migraine only: integrated transcriptome-clinical profiling reveals shared inflammation and divergent metabolic pathways for targeted therapy.

backgroundVestibular migraine (VM) is often considered a subtype of migraine, but the pathogenesis of both has not been fully elucidated. The aim of this study is to integrate clinical data systems through transcriptome sequencing to explore the similarities and differences between the two in terms of pathogenesis and clinical manifestations and predict therapeutic drugs.

methodsThis study included 9 cases of VM, 6 cases of migraine only (MO), and 14 healthy controls (HC). Detailed records were kept of each participants basic information and clinical characteristics related to their onset of illness, with statistical analysis conducted using R. Additionally, peripheral blood mononuclear cells (PBMCs) from each participant were collected for high-throughput RNA sequencing. Next, DEseq2 packages were used to identify differentially expressed genes (DEGs) between MO/HC, VM/HC, and VM/MO. Pearson correlation was used to calculate co-expressed genes between MO/HC and VM/HC, and gene sets were functional annotation and pathway enrichment analysis. Furthermore, hub genes were screened using protein interaction and Cytoscapes Degree algorithm, and further evaluation was conducted using transcriptome data. Finally, common therapeutic drugs were predicted using DGIdb, Drugbank, and ClinicalTricals.

resultsCompared to HC, both VM and MO patients exhibited higher incidences of anxiety, depression, and sleep disorders, with overlapping triggers and symptoms. However, VM patients demonstrated higher headache frequency, longer attack duration, and a higher prevalence of abnormal vestibular function tests. Transcriptomic analysis revealed significant activation of neutrophil activation and cholesterol metabolism pathways in MO, while Interleukin-17 (IL-17) signaling, calcium signaling, and estrogen-related pathways were prominent in VM. Co-expression analysis identified IL-17 signaling as a key pathway, more activated in VM than MO, potentially explaining VM's higher attack frequency and delayed onset (average 9 years after migraine diagnosis). C-X-C motif chemokine ligand 8 (CXCL8) was validated as a common biomarker for both conditions. Drug prediction identified 55 potential therapeutic agents, including nonsteroidal antiinflammatory drugs (NSAIDs), vitamin A, and verapamil.

conclusionVM and MO share overlapping clinical and pathogenic features, particularly inflammation and metabolic dysregulation. CXCL8 serves as a shared biomarker, and NSAIDs, vitamin A, and verapamil may offer therapeutic benefits. The heightened inflammatory activation in VM suggests it could represent an advanced stage of MO, emphasizing the importance of early intervention in migraine progression.