Abstract
This clinical study evaluates over medium-to-long term the hypothesis that intermittent spontaneous ocular choroidal vasculature-related congestive and nociceptive corneoscleral envelope distention have a pathogenetic role in genesis of episodic lateralizing migraine headache attacks. No neuro-anatomic or -physiologic difference prevails between the three divisions of the trigeminal nerve, but migraine dominantly affect the ophthalmic division. Use of topical ophthalmic solution for managing acute headache attacks of migraine has given contradictory results in controlled trials. I report the distribution of weekend-migraine headache attacks on a single‐participant (N=1) level for 2 patients over a 3-year period (2017-2020) without misuse of any recreational drug other than caffeine on week-days. After a run-in basal period of 6-months recorded on their Smartphones app, with their informed consent, a trial was carried out with topical long-acting β-blocker timolol maleate 0.5% w/v ophthalmic solution once weekly on Saturday night just before sleeping with no other advice to promote nocturnal sleeping or early awakening the next morning; only alcohol binge was proscribed. No week-end attacks of lateralizing migraine headache were reported in the 2 patients over a period of 3- years, a long-term consistent response. The biologically-plausible and defensible mechanistic link between migraine, intraocular pressure, ocular choroidal vasculature, nociceptive corneoscleral envelope aberration, and the pharmacologic basis for therapeutic ocular hypotension for prophylaxis of migraine headache attacks is elucidated for the first time in migraine literature.
Highlights
Despite advanced technology and a vast literature, including neuroimaging, genetic studies, and artificial intelligence, pathophysiology of migraine remains obscure, and, its management both pharmacologic and non-pharmacologic remains devoid of defensible and robust therapeutic principles [1,2,3]
Migraine is prominently linked to stress, with the greatest susceptibility to headache attacks evidenced in the post-stress or let-down period [25,26,27]
Select medications with sedative side-effects, such as tricyclic antidepressants (TCA), including AMT, are common evidence-based agents used at tertiary-care headache centres to prevent migraine [40,41]
Summary
Despite advanced technology and a vast literature, including neuroimaging, genetic studies, and artificial intelligence, pathophysiology of migraine remains obscure, and, its management both pharmacologic and non-pharmacologic remains devoid of defensible and robust therapeutic principles [1,2,3]. Diagnosis of migraine was made in accord with the International Classification of Headache Disorders-3 [45] In both patients, Sunday mornings emerged as being the exclusive day of developing a lateralizing headache attack with definitive morbidity (>5/10 on the visual analogue scale invariably requiring proprietary analgesic consumption) following oversleeping over Saturday night. Sunday mornings emerged as being the exclusive day of developing a lateralizing headache attack with definitive morbidity (>5/10 on the visual analogue scale invariably requiring proprietary analgesic consumption) following oversleeping over Saturday night Both patients, after written informed consent, agreed to undertake once-weekly ipsilateral topical ocular therapy with TM 0.5% w/v before sleeping only over the weekend. Systemic hypotension (systolic BP
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