Chronic migraine is a highly disabling and difficult to treat form of migraine. In this thesis, various clinical aspects and the management of chronic migraine are investigated, in order to enhance... Show moreChronic migraine is a highly disabling and difficult to treat form of migraine. In this thesis, various clinical aspects and the management of chronic migraine are investigated, in order to enhance prevention and treatment of chronic migraine. Important risk factors for chronic migraine are depression, anxiety, cutaneous allodynia and especially overuse of acute anti-headache medication. The studies in this thesis conform that withdrawal of the overused medication results into a meaningful improvement in many patients. A double-blind randomised controlled trial did not show any additional benefit of treatment with Botulinum toxin A adjacent to acute withdrawal. Another double-blind randomised controlled trial did suggest effectiveness of a behavioural intervention during acute withdrawal on the reduction of medication intake during and shortly after withdrawal. Cutaneous allodynia (the perception of pain upon a non-painful stimuli) is a clinical marker of central sensitisation, an important mechanism in the pathophysiology of chronic migraine. The presence of cutaneous allodynia in general, and the extent of allodynia symptoms, appear to be a predictor for response to withdrawal therapy. Show less
Background and purpose Medication overuse headache is a prevalent disorder, with a strong biobehavioural component. Hence, behavioural interventions might effectuate reduction of the overused... Show moreBackground and purpose Medication overuse headache is a prevalent disorder, with a strong biobehavioural component. Hence, behavioural interventions might effectuate reduction of the overused medication. We assessed in a double-blind manner the efficacy of a behavioural intervention during medication withdrawal therapy. Methods In this concealed, double-blind, randomized controlled trial in medication overuse headache, conducted at the Leiden University Medical Centre, we compared the effect of maximal versus minimal behavioural intervention by a headache nurse during withdrawal therapy. Maximal intervention consisted of an intensive contact schedule, comprising education, motivational interviewing, and value-based activity planning during 12 weeks of withdrawal therapy. Minimal intervention consisted of a short contact only. Patients were unaware of the existence of these treatment arms, as the trial was concealed in another trial investigating botulinum toxin A. Endpoints were successful withdrawal and monthly days of acute medication use after the withdrawal period. Results We enrolled 179 patients (90 maximal, 89 minimal intervention). At Week 12, most patients achieved withdrawal in both groups (82/90 [93%] maximal intervention vs. 75/89 [86%] minimal intervention, odds ratio = 2.44, 95% confidence interval [CI] = 0.83-7.23, p = 0.107). At Week 24, patients in the maximal intervention group had fewer medication days (mean difference = -2.23, 95% CI = -3.76 to -0.70, p = 0.005). This difference receded over time. Change in monthly migraine days did not differ between groups (-6.75 vs. -6.22). Conclusions This trial suggests modest benefit of behavioural intervention by a headache nurse during withdrawal therapy for medication overuse headache, to reduce acute medication use during and shortly after intervention, but extension seems warranted for a prolonged effect Show less
ObjectiveTo identify a plasma metabolomic biomarker signature for migraine.MethodsPlasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a H-1... Show moreObjectiveTo identify a plasma metabolomic biomarker signature for migraine.MethodsPlasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a H-1-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses.ResultsDecreases in the level of apolipoprotein A1 (beta -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (beta -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (beta -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status.ConclusionsMetabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs. Show less
Onderwater, G.L.J.; Ligthart, L.; Bot, M.; Demirkan, A.; Fu, J.Y.; Kallen, C.J.H. van der; ... ; BBMRI Metabolomics Consortium 2019
