Quantitative electroencephalography in cerebral amyloid angiopathy.

OBJECTIVE: We investigated whether quantitative electroencephalography (qEEG) correlates with cognition and cortical superficial siderosis (cSS) in cerebral amyloid angiopathy. METHODS: We included patients with sporadic (sCAA) and hereditary Dutch-type CAA (D-CAA). Spectral measures and the phase lag index (PLI) were analyzed on qEEG. Cognition was assessed with the MoCA and cSS presence was scored on 3T-MRI. Linear regression analyses were performed to investigate these qEEG measures and cognition. Independent samples T-tests were used to analyze the qEEG measure differences between participants with and without cSS. RESULTS: We included 92 participants (44 D-CAA; 48 sCAA). A lower average peak frequency (ß[95 %CI] = 0.986[0.252-1.721]; P = 0.009) and a higher spectral ratio (ß[95 %CI] = -0.918[-1.761--0.075]; P = 0.033) on qEEG correlated with a lower MoCA score, irrespective of a history of symptomatic intracerebral hemorrhage (sICH). The PLI showed no correlation to the MoCA. qEEG slowing was not different in those with or without cSS. CONCLUSIONS: Spectral qEEG (but not PLI) reflects cognitive performance in patients with CAA with and without a history of sICH. We found no association between qEEG slowing and cSS. SIGNIFICANCE: qEEG could be a valuable biomarker, especially in challenging cognitive testing situations in CAA, and a potential predictive tool in future studies.

NFL and GFAP in (pre)symptomatic RVCL-S carriers: a monogenic cerebral small vessel disease.

BACKGROUND: Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as biomarkers for cerebral small vessel disease (SVD). We investigated their role in a hereditary SVD model, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). METHODS: NfL and GFAP levels of 17 pre-symptomatic, 22 symptomatic RVCL-S mutation carriers and 69 controls were measured using a Simoa assay. We assessed the association of serum and cerebrospinal fluid (CSF) levels of NfL and GFAP with RVCL-S symptomatology and neuropsychological functioning. RESULTS: Serum and CSF NfL levels were higher in symptomatic RVCL-S compared to controls ≥ 45 years (33.5 pg/mL vs. 9.2 pg/mL, p < 0.01; 8.5*102 pg/mL vs. 3.9*102 pg/mL, p < 0.01, respectively). Serum NfL levels were higher in symptomatic RVCL-S than pre-symptomatic carriers (33.5 pg/mL vs. 5.9 pg/mL, p = 0.02). Pre-symptomatic RVCL-S carriers had increased CSF NfL levels compared to controls < 45 years (5.2*102 pg/mL vs. 1.9*102 pg/mL, p < 0.01). No differences were found in GFAP levels across groups, but in RVCL-S carriers higher serum levels of both NfL and GFAP were linked to poorer global cognitive functioning (ß[95%CI] = - 2.86 [- 5.58 to - 0.13], p = 0.04 and ß[95%CI] = - 6.85 [- 11.54 to - 2.15], p = 0.01, respectively) and prolonged psychomotor test times (ß[95%CI] = 6.71 [0.78-12.65], p = 0.03 and ß[95%CI] = 13.84 [3.09-24.60], p = 0.01). DISCUSSION: Higher levels of serum NfL and GFAP are associated with worse cognitive functioning in RVCL-S carriers and may serve as marker for disease progression. CSF NfL levels may serve as early marker as pre-symptomatic RVCL-S patients already show differences compared to young controls.

Cerebrovascular reactivity to hypercapnia in patients with migraine: A dual-echo arterial spin labeling MRI study.

OBJECTIVE: This study aimed to compare cerebrovascular reactivity between patients with migraine and controls using state-of-the-art magnetic resonance imaging (MRI) techniques. BACKGROUND: Migraine is associated with an increased risk of cerebrovascular disease, but the underlying mechanisms are still not fully understood. Impaired cerebrovascular reactivity has been proposed as a link. Previous studies have evaluated cerebrovascular reactivity with different methodologies and results are conflicting. METHODS: In this single-center, observational, case-control study, we included 31 interictal patients with migraine without aura (aged 19-66 years, 17 females) and 31 controls (aged 22-64 years, 18 females) with no history of vascular disease. Global and regional cerebrovascular reactivities were assessed with a dual-echo arterial spin labeling (ASL) 3.0 T MRI scan of the brain which measured the change in cerebral blood flow (CBF) and BOLD (blood oxygen level dependent) signal to inhalation of 5% carbon dioxide. RESULTS: When comparing patients with migraine to controls, cerebrovascular reactivity values were similar between the groups, including mean gray matter CBF-based cerebrovascular reactivity (3.2 ± 0.9 vs 3.4 ± 1% ΔCBF/mmHg CO2 ; p = 0.527), mean gray matter BOLD-based cerebrovascular reactivity (0.18 ± 0.04 vs 0.18 ± 0.04% ΔBOLD/mmHg CO2 ; p = 0.587), and mean white matter BOLD-based cerebrovascular reactivity (0.08 ± 0.03 vs 0.08 ± 0.02% ΔBOLD/mmHg CO2 ; p = 0.621).There was no association of cerebrovascular reactivity with monthly migraine days or migraine disease duration (all analyses p > 0.05). CONCLUSION: Cerebrovascular reactivity to carbon dioxide seems to be preserved in patients with migraine without aura.

Sensitivity of the Boston criteria version 2.0 in Dutch-type hereditary cerebral amyloid angiopathy.

BACKGROUND AND AIM: The revised Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) add two radiological markers to the existing criteria: severe visible perivascular spaces in the centrum semiovale and white matter hyperintensities (WMHs) in a multispot pattern. This study aims to determine the sensitivity of the updated criteria in mutation carriers with Dutch-type hereditary CAA (D-CAA) in an early and later disease stage. METHODS: In this cross-sectional study, we included presymptomatic and symptomatic D-CAA mutation carriers from our prospective natural history study (AURORA) at the Leiden University Medical Center between 2018 and 2021. 3-Tesla scans were assessed for CAA-related magnetic resonance imaging (MRI) markers. We compared the sensitivity of the Boston criteria v2.0 to the previously used modified Boston criteria v1.5. RESULTS: We included 64 D-CAA mutation carriers (mean age 49 years, 55% women, 55% presymptomatic). At least one white matter (WM) feature was seen in 55/64 mutation carriers (86%: 74% presymptomatic, 100% symptomatic). Fifteen (23%) mutation carriers, all presymptomatic, showed only WM features and no hemorrhagic markers. The sensitivity for probable CAA was similar between the new and the previous criteria: 11/35 (31%) in presymptomatic mutation carriers and 29/29 (100%) in symptomatic mutation carriers. The sensitivity for possible CAA in presymptomatic mutation carriers increased from 0/35 (0%) to 15/35 (43%) with the new criteria. CONCLUSION: The Boston criteria v2.0 increase the sensitivity for detecting possible CAA in presymptomatic D-CAA mutation carriers and, therefore, improve the detection of the early phase of CAA.

Sex-specific metabolic profiling to explain the increased CVD risk in women with migraine: a narrative review.

BACKGROUND: Migraine is a disabling neurological disorder whose diagnosis is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the underlying neurobiological factors and sex-specific complications in migraine such as cardio- and cerebrovascular disease. Biomarker research can help to improve disease characterization and identify pathophysiological mechanism underlying these comorbidities. OBJECTIVE: In this narrative review we searched for sex-specific metabolomics research to identify markers that may explain the migraine-cardiovascular disease (CVD) relationship. DISCUSSION: Large-scale plasma metabolome analyses revealed alterations in migraine. Sex-specific findings showed a less CVD-protective HDL metabolism as well as the ApoA1 lipoprotein, especially for women with migraine. To explore other possible pathophysiological pathways, we expanded our review to include inflammatory markers, endothelial and vascular markers and sex hormones. Biological sex differences may affect the pathophysiology of migraine and its complications. CONCLUSIONS: There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis. Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine. Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account. By establishing the overlapping pathophysiological mechanism of migraine and CVD, and unraveling the associated effects these diseases exert on each other, better preventative measures can be identified.

Minocycline for sporadic and hereditary cerebral amyloid angiopathy (BATMAN): study protocol for a placebo-controlled randomized double-blind trial.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients. METHODS: The BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics. DISCUSSION: The results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov NCT05680389. Registered on January 11, 2023.

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S): An update on basic science and clinical perspectives.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, underrecognized, systemic small vessel disease caused by heterozygous C-terminal truncating TREX1 mutations. The disease is characterized by vascular retinopathy, focal neurological complaints, cognitive decline and a wide range of systemic manifestations, including Raynaud's phenomenon, anemia and liver and kidney disease. Eventually, RVCL-S leads to premature death. The underlying pathological finding in RVCL-S is a nonatherosclerotic, amyloid-negative angiopathy involving small arteries and capillaries. However, the exact mechanisms by which the truncated TREX1 protein causes angiopathy remains unknown. Timely recognition of this disease is important to slow down and treat complications of the disorder, but also to prevent unnecessary (invasive) diagnostic or therapeutic procedures. As we move forward, translational research combining basic science advances and clinical findings as well as studies focusing on natural history following RVCL-S patients at different disease stages, will be critical to help elucidate RVCL-S pathophysiology. These studies will also provide the tools to identify appropriate biomarkers and therapeutic agent options for RVCL-S patients.

Cerebellar hemorrhages in patients with Dutch-type hereditary cerebral amyloid angiopathy.

BACKGROUND: Recent studies suggest that superficially located cerebellar intracerebral hemorrhage (ICH) and microbleeds might point towards sporadic cerebral amyloid angiopathy (CAA). AIMS: We investigated the proportion of cerebellar ICH and asymptomatic macro- and microbleeds in Dutch-type hereditary CAA (D-CAA), a severe and essentially pure form of CAA. METHODS: Symptomatic patients with D-CAA (defined as ≥1 symptomatic ICH) and presymptomatic D-CAA mutation-carriers were included. We assessed magnetic resonance imaging scans for symptomatic (cerebellar) ICH and asymptomatic cerebellar macro- and microbleeds according to the STRIVE-criteria. Location was assessed as superficial-cerebellar (cortex, vermis or juxta-cortical) or deep-cerebellar (white matter, pedunculi cerebelli and gray nuclei). RESULTS: We included 63 participants (mean age 58 years, 60% women, 42 symptomatic). In total, the 42 symptomatic patients with D-CAA had 107 symptomatic ICH (range 1-7). None of these ICH were located in the cerebellum. Six of 42 (14%, 95%CI 4-25%) symptomatic patients and none of the 21 (0%, 95%CI 0-0%) presymptomatic carriers had ≥ 1 asymptomatic cerebellar macrobleed(s). All macrobleeds were superficially located. Cerebellar microbleeds were found in 40 of 63 (64%, 95%CI 52-76) participants (median 1.0, range 0-159), 81% in symptomatic patients and 29% in presymptomatic carriers. All microbleeds were strictly or predominantly superficially (ratio superficial versus deep 15:1) located. CONCLUSIONS: Superficially located asymptomatic cerebellar macrobleeds and microbleeds are common in D-CAA. Cerebellar microbleeds are already present in the presymptomatic stage. Despite the high frequency of cerebellar micro and macrobleeds, CAA pathology did not result in symptomatic cerebellar ICH in patients with D-CAA.

Depressive symptoms during the different phases of a migraine attack: A prospective diary study.

BACKGROUND: The relationship between migraine and depression has been thoroughly investigated, indicating a bidirectional comorbidity. The exact temporal relationship between acute depressive symptoms (mood changes) and the various phases of the migraine attack has not yet been examined. METHODS: We performed a prospective diary study in n = 487 participants with migraine. Participants filled out a daily diary on migraine and acute depressive symptoms during a 1-month period. We randomly selected one migraine attack per participant, consisting of six days around an attack, including the interictal, premonitory, ictal, and postdromal phases. Acute depressive symptoms covered five major items from the DSM-5 classification. Primary analysis was performed using a mixed model with post-hoc testing. We also tested whether lifetime depression influenced the presence of acute depressive symptoms. RESULTS: During a migraine headache day, patients scored higher on acute depressive symptoms than on all other days of the migraine attack (p < 0.001). There were no early warning signs for an upcoming headache attack through acute depressive symptomatology. Migraine patients with lifetime depression scored overall higher during the migraine attack than those without lifetime depression (p < 0.001). LIMITATIONS: Migraine attacks were based on self-reported migraine and one migraine attack per patient was randomly selected. CONCLUSION: We now clearly demonstrate that during the migraine headache phase, but not in the prodromal phase, patients report increased depressive symptomatology. No evidence was found for mood changes as an early warning sign for an upcoming migraine attack.

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is caused by TREX1 mutations. High-quality systematic follow-up neuroimaging findings have not been described in presymptomatic and symptomatic mutation carriers. We present MR imaging findings of 29 TREX1 mutation carriers (20-65 years of age) and follow-up of 17 mutation carriers (30-65 years of age). Mutation carriers younger than 40 years of age showed a notable number of punctate white matter lesions, but scan findings were generally unremarkable. From 40 years of age onward, supratentorial lesions developed with long-term contrast enhancement (median, 24 months) and diffusion restriction (median, 8 months). In these lesions, central susceptibility artifacts developed, at least partly corresponding to calcifications on available CT scans. Some lesions (n = 2) additionally showed surrounding edema and mass effect (pseudotumors). Cerebellar punctate enhancing lesions developed mainly in individuals older than 50 years of age. These typical neuroimaging findings should aid neuroradiologic recognition of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, which may enable early treatment of manifestations of the disease.

Striped occipital cortex and intragyral hemorrhage: Novel magnetic resonance imaging markers for cerebral amyloid angiopathy.

BACKGROUND AND AIM: To investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH). METHODS: We performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features. RESULTS: We included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging. CONCLUSION: Whereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA.

Optical coherence tomography detects retinal changes in hereditary cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers. METHODS: Twenty-one D-CAA mutation carriers (n = 8 presymptomatic, n = 13 symptomatic, median age 50 years) and nine controls (median age 53 years) were scanned using spectral-domain OCT. Symptomatic mutation carriers were defined as having a history of ≥1 symptomatic intracerebral hemorrhage. D-CAA mutation carriers and controls were recruited from our D-CAA cohort and a healthy control cohort. Total peripapillary retinal nerve fiber layer (pRNFL) thickness, six regions of pRNFL, total macular volume (TMV), and individual macular region thickness were measured and analysed, adjusted for age. RESULTS: The overall median (interquartile range) thickness of pRNFL was lower in symptomatic, but not presymptomatic D-CAA mutation carriers compared with controls [91 (86-95) µm vs. 99 (87-108) µm; P = 0.006]. Both presymptomatic [111 (93-122) µm vs. 131 (123-143) µm; P < 0.001] and symptomatic carriers [119 (95-128) µm vs. 131 (123-143) µm; P = 0.034] had a thinner temporal-superior quadrant of the pRNFL versus controls. TMV or individual macular layer thickness did not differ between carriers and controls. CONCLUSIONS: Thinning of the retinal nerve fiber layer may be a candidate marker of disease in hereditary CAA. Further studies are needed to determine whether retinal thinning is present in sporadic CAA and estimate its value as a marker for disease progression.

Cold extremities in migraine: a marker for vascular dysfunction in women.

BACKGROUND AND PURPOSE: Migraine is recognized as a vascular risk factor, especially in women. Presumably, migraine, stroke and cardiovascular events share pathophysiological mechanisms. Self-reported cold extremities were investigated as a marker for vascular dysfunction in migraine. Secondly, it was hypothesized that suffering from cold extremities affects sleep quality, possibly exacerbating migraine attack frequency. METHODS: In this case-control study, a random sample of 1084 migraine patients and 348 controls (aged 22-65 years) from the LUMINA migraine cohort were asked to complete questionnaires concerning cold extremities, sleep quality and migraine. RESULTS: A total of 594 migraine patients and 199 controls completed the questionnaires. In women, thermal discomfort and cold extremities (TDCE) were more often reported by migraineurs versus controls (odds ratio 2.3, 95% confidence interval 1.4-3.7; P < 0.001), but not significantly so in men (odds ratio 2.5, 95% confidence interval 0.9-6.9; P = 0.09). There was no difference in TDCE comparing migraine with or without aura. Female migraineurs who reported TDCE had higher attack frequencies compared to female migraineurs without TDCE (4 vs. 3 attacks per month; P = 0.003). The association between TDCE and attack frequency was mediated by the presence of difficulty initiating sleep (P = 0.02). CONCLUSION: Women with migraine more often reported cold extremities compared with controls, possibly indicating a sex-specific vascular vulnerability. Female migraineurs with cold extremities had higher attack frequencies, partly resulting from sleep disturbances. Future studies need to demonstrate whether cold extremities in female migraineurs are a predictor for cardiovascular and cerebrovascular events.

Efficacy of galcanezumab in patients with episodic migraine and a history of preventive treatment failure: results from two global randomized clinical trials.

BACKGROUND AND PURPOSE: The efficacy of galcanezumab, a monoclonal antibody for migraine prevention, has been demonstrated in two pivotal trials in patients with episodic migraine. METHODS: EVOLVE-1 and EVOLVE-2 were identical phase 3, randomized, double-blind, placebo-controlled studies in patients with episodic migraine. Mean migraine headache days per month at baseline was 9. Patients were randomized 2:1:1 to monthly injections of placebo, galcanezumab 120 mg/240 mg during the 6-month double-blind treatment period. Key efficacy outcomes were assessed in subgroups amongst patients for whom, previously, for efficacy and/or safety/tolerability reasons (i) one or more (≥1) preventives failed, (ii) two or more (≥2) preventives failed and (iii) preventives were never used, or used but not failed (no prior failure). RESULTS: In an integrated analysis of EVOLVE studies, galcanezumab 120 mg/240 mg versus placebo led to larger overall mean (SE) reductions in monthly migraine headache days across 6 months in patients with prior preventive failures (P < 0.001): ≥1 failure: 120 mg: -4.0 (0.4); 240 mg: -4.2 (0.5); placebo: -1.3 (0.4); ≥2 failures: 120 mg: -3.1 (0.7); 240 mg: -3.8 (0.8); placebo: -0.5 (0.6). Similar results were observed amongst patients with no prior failure, but the placebo response was larger: 120 mg: -4.7 (0.2); 240 mg: -4.5 (0.2); placebo: -3.0 (0.2) (P < 0.001 versus placebo). Significant improvements were observed with galcanezumab versus placebo for ≥50% and ≥75% reduction in monthly migraine headache days. CONCLUSION: In patients with episodic migraine treated with galcanezumab, those with ≥1 or ≥2 prior preventive failures had significantly larger improvements, versus placebo, in efficacy outcomes. Similar results were observed in patients with no prior failure, with a larger placebo response.

Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Alcoholic beverages as trigger factor and the effect on alcohol consumption behavior in patients with migraine.

BACKGROUND AND PURPOSE: Alcoholic beverages are frequently reported migraine triggers. We aimed to assess self-reported alcohol consumption as a migraine attack trigger and to investigate the effect on alcohol consumption behavior in a large migraine cohort. METHODS: We conducted a cross-sectional, web-based, questionnaire study among 2197 patients with migraine from the well-defined Leiden University MIgraine Neuro-Analysis (LUMINA) study population. We assessed alcoholic beverage consumption and self-reported trigger potential, reasons behind alcohol abstinence and time between alcohol consumption and migraine attack onset. RESULTS: Alcoholic beverages were reported as a trigger by 35.6% of participants with migraine. In addition, over 25% of patients with migraine who had stopped consuming or never consumed alcoholic beverages did so because of presumed trigger effects. Wine, especially red wine (77.8% of participants), was recognized as the most common trigger among the alcoholic beverages. However, red wine consistently led to an attack in only 8.8% of participants. Time of onset was rapid (<3 h) in one-third of patients and almost 90% had an onset <10 h independent of beverage type. CONCLUSIONS: Alcoholic beverages, especially red wine, are recognized as a migraine trigger factor by patients with migraine and have a substantial effect on alcohol consumption behavior. Rapid onset of provoked migraine attacks in contrast to what is known about hangover headache might point to a different mechanism. The low consistency of provocation suggests that alcoholic beverages acting as a singular trigger is insufficient and may depend on a fluctuating trigger threshold.