Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or... Show moreMigraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 x 10(-9), odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 x 10(-11) (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 x 10(-5), permuted threshold for genome-wide significance 7.7 x 10(-5)). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine. Show less
We present a previously unreported early 18th-century description of cluster headache by the English antiquary Abraham de la Pryme (1671-1704) initially attributed to hydrophobia (rabies). We will... Show moreWe present a previously unreported early 18th-century description of cluster headache by the English antiquary Abraham de la Pryme (1671-1704) initially attributed to hydrophobia (rabies). We will also give a short overview of other descriptions of cluster and cluster-like headache in historical literature. Show less
Introduction: The increased risk of cerebro- and cardiovascular disease in migraineurs may be the consequence of a systemic condition affecting whole body vasculature. At cerebrovascular level,... Show moreIntroduction: The increased risk of cerebro- and cardiovascular disease in migraineurs may be the consequence of a systemic condition affecting whole body vasculature. At cerebrovascular level, this may be reflected by interictal global or regional cerebral perfusion abnormalities. Whether focal perfusion changes occur during interictal migraine has not been convincingly demonstrated.Methods: We measured brain perfusion with dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in 29 interictal female migraineurs (12 migraine with aura (MA), 17 migraine without aura (MO)), and 16 female controls. Perfusion maps were compared between these groups with a voxelwise (p < 0.001, uncorrected, minimum cluster size 20 voxels) and a region-of-interest approach.Results: In whole brain voxelwise analyses interictal hyperperfusion was observed in the left medial frontal gyrus in migraineurs and in the inferior and middle temporal gyrus in MO patients, in comparison with controls. Hypoperfusion was seen in the postcentral gyrus and in the inferior temporal gyrus in MA patients and in the inferior frontal gyrus in MO patients. Additional focal sites of hyperperfusion were noted in subgroups based on attack frequency and disease history. Region-of-interest analyses of the pons, hypothalamus, occipital lobe, and cerebellum did not show interictal perfusion differences between migraineurs and controls.Conclusions: We conclude that interictal migraine is characterized by discrete areas of hyper- and hypoperfusion unspecific for migraine pathophysiology and not explaining the increased vulnerability of particular brain regions for cerebrovascular damage. Show less
Arkink, E.B.; Terwindt, G.M.; Craen, A.J.M. de; Konishi, J.; Grond, J. van der; Buchem, M.A. van; ... ; PROSPER Study Grp 2015
ObjectiveWe used magnetization transfer imaging to assess white matter tissue integrity in migraine, to explore whether white matter microstructure was more diffusely affected beyond visible white... Show moreObjectiveWe used magnetization transfer imaging to assess white matter tissue integrity in migraine, to explore whether white matter microstructure was more diffusely affected beyond visible white matter hyperintensities (WMHs), and to explore whether focal invisible microstructural changes precede visible focal WMHs in migraineurs.MethodsWe included 137 migraineurs (79 with aura, 58 without aura) and 74 controls from the Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis (CAMERA) study, a longitudinal population-based study on structural brain lesions in migraine patients, who were scanned at baseline and at a 9-year follow-up. To assess microstructural brain tissue integrity, baseline magnetization transfer ratio (MTR) values were calculated for whole brain white matter. Baseline MTR values were determined for areas of normal-appearing white matter (NAWM) that had progressed into MRI-detectable WMHs at follow-up and compared to MTR values of contralateral NAWM.ResultsMTR values for whole brain white matter did not differ between migraineurs and controls. In migraineurs, but not in controls, NAWM that later progressed to WMHs at follow-up had lower mean MTR (mean [SD] 0.354 [0.009] vs 0.356 [0.008], p = 0.047) at baseline as compared to contralateral white matter.ConclusionsWe did not find evidence for widespread microstructural white matter changes in migraineurs compared to controls. However, our findings suggest that a gradual or stepwise process might be responsible for evolution of focal invisible microstructural changes into focal migraine-related visible WMHs. Show less
AimTo provide a comprehensive overview of cardiovascular disease (CVD) risk prediction models for women and models that include female-specific predictors.MethodsWe performed a systematic review of... Show moreAimTo provide a comprehensive overview of cardiovascular disease (CVD) risk prediction models for women and models that include female-specific predictors.MethodsWe performed a systematic review of CVD risk prediction models for women in the general population by updating a previous review. We searched Medline and Embase up to July 2017 and included studies in which; (a) a new model was developed, (b) an existing model was validated, or (c) a predictor was added to an existing model.ResultsA total of 285 prediction models for women have been developed, of these 160 (56%) were female-specific models, in which a separate model was developed solely in women and 125 (44%) were sex-predictor models. Out of the 160 female-specific models, 2 (1.3%) included one or more female-specific predictors (mostly reproductive risk factors). A total of 591 validations of sex-predictor or female-specific models were identified in 206 papers. Of these, 333 (56%) validations concerned nine models (five versions of Framingham, SCORE, Pooled Cohort Equations and QRISK). The median and pooled C statistics were comparable for sex-predictor and female-specific models. In 260 articles the added value of new predictors to an existing model was described, however in only 3 of these female-specific that no competing interests exist. predictors (reproductive risk factors) were added.ConclusionsThere is an abundance of models for women in the general population. Female-specific and sex-predictor models have similar predictors and performance. Female-specific predictors are rarely included. Further research is needed to assess the added value of female-specific predictors to CVD models for women and provide physicians with a well-performing prediction model for women. Show less
Balkaya, M.; Seidel, J.L.; Sadeghian, H.; Qin, T.; Chung, D.Y.; Eikermann-Haerter, K.; ... ; Ayata, C. 2019
