A chronic dysfunctional stress response can cause stroke by stimulating platelet activation, migraine, and hypertension.

A hypothesis is presented on the mechanism of acute intracranial occlusion. The hypothesis is that a chronic dysfunctional response to stress can include migraine, hypertension and systemic platelet activation (a hypercoagulable state). Stress is defined as the perception of excessive threats or demands. Migraine, hypertension, and platelet activation constitute a physiological triad that exists as a distinct entity and can undergo sudden provoked or unprovoked worsening, causing acute stroke. The hypertension and headache may not be apparent in every stroke, much as headache is absent in acephalgic migraine. In support of this idea, a literature review is undertaken which leads to the conclusion that the labile rise in blood pressure and headache often seen with acute stroke are unlikely to be caused by the stroke. Systemic platelet activation has been documented in both migraine and stroke and is the missing piece of the puzzle. Migraine (or non-specific headache) and hypertension are markers of co-existing platelet activation, the hypercoagulable state which causes stroke. Migraine, and, putatively, hypertension and platelet activation, are driven by overactive pacemaker cells in the dorsal raphe nucleus of the midbrain, the nucleus which mediates one arm of the physiologic response to stress. A therapeutic prediction is made that drugs such as ethosuximide, which block the low voltage-activated T-type calcium channel, which is one of the ion channels implicated in the generation of pacemaker currents in the dorsal raphe nucleus, would be useful in stroke prevention.