Hypersensitivity of Intrinsically Photosensitive Retinal Ganglion Cells in Migraine Induces Cortical Spreading Depression.

Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks.

Features of Patients Aged 80 Years or Older with Embolic Stroke of Undetermined Source.

BACKGROUND: Embolic stroke of undetermined source has not been thoroughly investigated in older patients. In this study, we investigated the features of this condition in patients greater than or equal to 80 years of age. METHODS: All patients with acute ischemic stroke in our hospital underwent diffusion-weighted imaging, magnetic resonance angiography, T2-weighted imaging, and fluid-attenuated inversion recovery sequence imaging. Embolic stroke of undetermined source was defined as a radiologically confirmed nonlacunar brain infarct on diffusion-weighted imaging without (1) extracranial or intracranial atherosclerosis causing greater than or equal to 50% luminal stenosis in arteries supplying the ischemic area, (2) major-risk cardioembolic source, and (3) any other specific cause of stroke. We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the embolic stroke of undetermined source diagnostic criteria and investigated patients' baseline and diagnostic findings. RESULTS: We divided 122 consecutive embolic stroke of undetermined source patients (median age: 73 years; 49 men, 73 women) into 2 groups by age at admission. Patients aged greater than or equal to 80 years had higher D-dimer and brain natriuretic peptide levels, more frequent premature atrial complexes/day in 24-hour Holter electrocardiography, and thicker maximum intima media thickness on ultrasound compared with patients aged less than 80 years (P < .05, U test). CONCLUSIONS: Our results suggest that high admission D-dimer and brain natriuretic peptide levels are associated with age of onset in patients with embolic stroke of undetermined source. Patients aged greater than or equal to 80 years tended to have more frequent premature atrial complexes and thicker maximum intima media thickness compared with patients aged less than 80 years.