To establish how headache intensity, prevalence, frequency, and precipitants differ by disability, gender, and MS subtypes, and if headache patterns are linked to early relapsing inflammatory or late progressive MS courses.

Headache is a common symptom among people with multiple sclerosis (MS), but its connection to disease process is incompletely characterized. New data indicate headache potentially serves as a marker for initial neuroinflammatory activity and cortical hyperexcitability, rather than progressive neurodegeneration. Describing headache across different disease stages potentially clarifies its connection between early inflammatory and progressive neurodegenerative processes.

We compared 294 MS patients’ headache frequency and intensity using a linked survey of headache, demographics, and Expanded Disability Status Scale (EDSS) at our center. Headache presence was self-reported by definition and intensity was determined using the Migraine Disability Assessment (MIDAS). Group comparisons were made by χ², t-tests, Mann–Whitney U, and Spearman correlation tests. Logistic modeling of predictors for sex, EDSS, and MS subtype was performed. Multiple comparisons were accounted for using false discovery rate correction.

Headaches were reported by 75% of participants and were more frequent in women (80.0%) than men (58.1%; χ² p=0.0007, surviving multiple-testing correction). Headache frequency declined with higher disability (mean EDSS 2.81 vs 3.40, p=0.039; OR 0.82 per point, p=0.0089) and was significantly lower in progressive compared with relapsing phenotypes (RRMS 79.1%, SPMS 53.6%, PPMS 46.7%; χ² p=0.00014; adjusted OR 0.29, p=0.006). Although less frequent in advanced disease, headache intensity correlated modestly with EDSS (ρ=0.175, p=0.012). 

Headache frequency in MS associates more with a relapsing–remitting pattern that is common in early, inflammatory stages and less frequent as the disease progresses and disability accrues. These results favor a paradigm of headache as reflective of cortical hyperexcitability and neuroinflammatory activity. Awareness of this relationship may improve understanding of disease biology, importance of symptomatic management, and timing of disease-modifying therapy.