Headache after ischemic stroke: A systematic review and meta-analysis.

OBJECTIVE: Headache associated with ischemic stroke is poorly understood. To gain further insight, we systematically reviewed studies examining the prevalence and characteristics of new-onset poststroke headache. METHODS: Medline and PubMed databases were queried. A total of 1,812 articles were identified. Of these, 50 were included in this systematic review. Twenty were included in a meta-analysis and meta-regression. RESULTS: Headache occurred in 6%-44% of the ischemic stroke population. Most headaches had tension-type features, were moderate to severe, and became chronic in nature. Meta-analysis using an inverse-variance heterogeneity model revealed a pooled prevalence of 0.14 (95% confidence interval [CI] 0.07-0.23) with heterogeneity among studies. Metaregression revealed a significant association between prevalence and study location, the source population's national human development index (HDI), and study quality. We found higher prevalence in European (0.22, 95% CI 0.14-0.30) and North American (0.15, 95% CI 0.05-0.26) studies compared with Middle Eastern and Asian studies (0.08, 95% CI 0.01-0.18). However, within each region, populations from countries with higher HDI (p = 0.03) and studies with higher quality (p = 0.001) had lower prevalence. Calculated crude odds ratios (ORs) showed that posterior circulation stroke (pooled OR 1.92, 95% CI 1.4-2.64; n = 7 studies) and female sex (pooled OR 1.25, 95% CI 1.07-1.46; n = 11 studies) had greater odds of headache associated with ischemic stroke. CONCLUSIONS: Taken together, these data suggest that headache is common at the onset of or shortly following ischemic stroke and may contribute to poststroke morbidity. Better understanding of headache associated with ischemic stroke is needed to establish treatment guidelines and inform patient management.

Determinants of Optogenetic Cortical Spreading Depolarizations.

Cortical spreading depolarization (SD) is the electrophysiological event underlying migraine aura, and a critical contributor to secondary damage after brain injury. Experimental models of SD have been used for decades in migraine and brain injury research; however, they are highly invasive and often cause primary tissue injury, diminishing their translational value. Here we present a non-invasive method to trigger SDs using light-induced depolarization in transgenic mice expressing channelrhodopsin-2 in neurons (Thy1-ChR2-YFP). Focal illumination (470 nm, 1-10 mW) through intact skull using an optical fiber evokes power-dependent steady extracellular potential shifts and local elevations of extracellular [K+] that culminate in an SD when power exceeds a threshold. Using the model, we show that homozygous mice are significantly more susceptible to SD (i.e., lower light thresholds) than heterozygous ChR2 mice. Moreover, we show SD susceptibility differs significantly among cortical divisions (motor, whisker barrel, sensory, visual, in decreasing order of susceptibility), which correlates with relative channelrhodopsin-2 expression. Furthermore, the NMDA receptor antagonist MK-801 blocks the transition to SD without diminishing extracellular potential shifts. Altogether, our data show that the optogenetic SD model is highly suitable for examining physiological or pharmacological modulation of SD in acute and longitudinal studies.