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While the majority of brain metastases arise from lung cancer, breast cancer, or melanoma, new treatments and improved prognoses have altered the profile of primary cancers that metastasize to the brain. We sought to determine the proportion of brain metastases from less common primary sites and conduct trend analyses. We reviewed the charts of 3585 patients with brain metastases seen at our institution from 2008 to 2018. We determined the primary site for each of these patients, and the Mann-Kendall test was used to evaluate temporal trends in the yearly proportion of brain metastases originating from each primary cancer. The five most common primary sites were lung (43.0%), breast (19.9%), melanoma (8.2%), renal (5.0%), and colorectal (3.8%). The proportion of yearly brain metastases originating from breast cancer (p = 0.029) and melanoma (p = 0.013) decreased by 23.8% and 46.7%, respectively, from 2008 (0.21 breast, 0.15 melanoma) to 2018 (0.16 breast, 0.08 melanoma), while no change was found in the proportion of brain metastases from lung, renal, and colorectal cancers. Brain metastases arising from rare primary sites, defined as those comprising at most 2% of all brain metastases, increased by 34.4% (p = 0.005). Limited sample size prohibited trend analysis of other individual primary sites. We report a decrease over 11 years in the proportion of brain metastases originating from breast cancer and melanoma at our institution, and an increase in brain metastases from rare primary sites. Further work with larger, multi-center databases will enable additional evaluation of brain metastases from rare primary sites., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Migraine headache is a common condition with an estimated lifetime prevalence of greater than 20%. While it is a well-established risk factor for cardiovascular disease and ischemic stroke, its association with subarachnoid hemorrhage is largely unexplored. We sought to compare the incidence of aneurysmal subarachnoid hemorrhage in a cohort of migraine patients with a cohort of patients with tension headache. A cohort comparison study utilizing the MarketScan insurance claims database compared patients diagnosed with migraine who were undergoing treatment with abortive or prophylactic pharmacotherapy (treatment cohort) and patients diagnosed with tension headache who had never been diagnosed with a migraine and who were naïve to migraine pharmacotherapy (control cohort). Patients with major pre-existing risk factors for aSAH were excluded from the study, and minor risk factors such as smoking status and hypertension were accounted for using coarsened exact matching (CEM) and subsequent cox proportional-hazards (CPH) regression. More than 679,000 patients (~125,000 treatment and ~ 550,000 control) with an average follow-up of more than three years were analyzed for aneurysmal subarachnoid hemorrhage. CPH regression on matched data showed that treated migraine patients had a significantly lower hazard of aneurysmal subarachnoid hemorrhage compared with tension headache patients (HR = 0.40, 95% CI: 0.19 - 0.86, p = 0.02). This large cohort comparison study, analyzing more than 679,000 patients, demonstrated that migraine patients undergoing pharmacologic treatment had a lower hazard of aneurysmal subarachnoid hemorrhage than patients diagnosed with tension headaches. Future work specifically focusing on migraine medications may identify the mechanisms underlying this association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)