Induced hypertension for the treatment of acute MCA occlusion beyond the thrombolysis window: case report

BACKGROUND: A minority of stroke patients is eligible for thrombolytic therapy. Small pilot case series have hinted that elevation of incident arterial blood pressure might be associated with a favorable prognosis either in acute or subacute stroke. However, these patients were not considered for thrombolytic therapy and were not followed – up systematically. We used pharmacologically induced hypertension in a stroke patient with middle cerebral artery (MCA) occlusion ineligible for thrombolysis that was followed-up by radiological, clinical and functional outcome assessment. CASE PRESENTATION: A patient with acute embolic MCA occlusion producing a large, ischemic penumbra confirmed by perfusion CT was treated by induced hypertension with phenylephrine started within 4 h of admission. Increase in the mean arterial pressure by 20% led to a reduction of neurological deficit by 3 points on the National Institute of Stroke Scale. MRI and CT scans performed during phenylephrine infusion showed the presence of limited subcortical and cortical infarct changes that were clearly less extensive than the perfusion deficit in the brain perfusion CT at baseline, found in the absence of MCA patency. No complications due to induced hypertension therapy occurred. Moderate functional improvement up to modified Rankin scale 2 at follow up took place. CONCLUSION: Induced hypertension in acute ischemic stroke seems clinically feasible and may be beneficial in selected normo- or hypotensive stroke patients not eligible for thrombolytic recanalization therapy

Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families

Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 × 10-109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 × 10-17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMigraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health (NIH) Finnish innovation fund Sitra Finska Lakaresallskapet Academy of Finland Sigrid Juselius Foundation Academy of Finland Appeared in source as:Academy of Finland Center of Excellence in Complex Disease Genetics Finnish Foundation for Cardiovascular Research Novo Nordisk Foundation Novocure Limited CANDY foundation (CEHEAD) South-Eastern Norway Regional Health Authorit

Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families

Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71–1.81, p = 1.7 × 10−109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25–1.38, p = 7.2 × 10−17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine. Gormley et al. use polygenic risk scores to show that common variation, captured by genome-wide association studies, in combination contributes to the aggregation of migraine in families. The results may have similar implications for other complex traits in general.</p

Correction: Common variant burden contributes to the familial aggregation of migraine in 1,589 families

(Neuron 98, 743–753.e1–e4; May 16, 2018) In the original publication of this paper, the middle initial of Michael D. Ferrari's name was inadvertently left out. This has since been corrected online. The authors apologize for the error.</p

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Abstract Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology