Papilledema is not the point: intracranial pressure dysregulation as a common pathway in migraine and idiopathic intracranial hypertension
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ID: 320183
2026
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Abstract
Abstract Accumulating evidence challenges the traditional distinction between migraine and idiopathic intracranial hypertension (IIH). We tested whether impaired CSF volume/pressure regulation driven by dural venous sinus stenosis represents a shared substrate. Brain MRI and magnetic resonance venography scans from 161 consecutive patients - migraine without aura (MwoA, n=89), migraine with aura (MwA, n=36) and IIH (n=36) - were retrospectively analysed and compared with 37 prospectively recruited healthy controls. An Extended Combined Conduit Score – designed to quantify the degree and extent of venous-sinus narrowing, with higher values indicating greater outflow impairment, and also evaluating the superior sagittal sinus - quantified stenosis. Additional neuroradiological markers of raised intracranial pressure (empty sella, posterior globe flattening, optic nerve sheath diameter) were recorded. A receiver operating characteristic analysis defined the optimal stenosis degree threshold for distinguishing patients from controls, after which prevalence comparisons were performed. Median Extended Combined Conduit Score increased step wise from controls (2, interquartile range 1–3) to MwoA (3, 2–4), MwA (3, 3–4) and IIH (6, 5–6) (p < 0.001). Both migraine groups scored higher than controls (p <0.001) and lower than IIH (p <0.001). The area under the receiver operating characteristic curve was 0.786 (95% confidence interval 0.716–0.856); a cut off ≥ 3 provided 74.5% sensitivity and 73.0% specificity. Using this threshold, venous stenosis was more frequent in MwoA and MwA than in controls (each p <0.001) and highest in IIH (p <0.001 versus all); MwA exceeded MwoA (p =0.007) and was comparable to IIH (p =0.187). Bilateral stenosis occurred in 0% of controls, nearly 25% of patients with migraine (p <0.001 versus controls) and 77.8% of IIH patients (p <0.001). Empty sella was more common in MwoA (p =0.004) and MwA (p =0.025) than in controls, and markedly enriched in IIH (p <0.001 versus all). Other radiological markers were similarly more prevalent in IIH (all p<0.001) showing no additional significant between-group differences. Findings support a pathogenetic continuum linking MwoA, MwA and IIH, challenging the diagnostic primacy of papilledema, the rarity of IIH without it, and the perceived irrelevance of unilateral sinus narrowing. As already observed in IIH, an impaired intracranial volume/pressure regulation appears a necessary though not sufficient condition for migraine development; a “primary” predisposition to migraine, likely multifactorial and widely variable among individuals and in the same individual over time, is required for typical migraine pain to develop, also modulating its frequency. Future studies should assess whether targeting intracranial pressure, thus potentially preventing calcitonin gene-related peptide release, may complement or substitute calcitonin gene-related peptide based therapies in migraine patients.
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openalex_W7167608219
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| Authors | Simone Braca, Giuseppe Cardillo, Lorenzo Ugga, Serena Capasso, Antonio De Meo, Angelo Miele, Mattia Sansone, Guido Ferra, Angelo Ranieri, Cinzia Valeria Russo, Antonio Stornaiuolo, Gennaro Cretella, Caterina Giannini, Roberto De Simone |
| Journal | Brain communications |
| Year | 2026 |
| DOI |
10.1093/braincomms/fcag259
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| URL | |
| Keywords | Keywords not found |
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