Migraine is een hersenziekte: als het eenvoudig was hadden we het al opgelost

Een verkorte versie van deze tekst is uitgesproken door Prof.dr. Gisela M. Terwindt bij de aanvaarding van het ambt van hoogleraar Neurologie, in het bijzonder paroxysmale neurologische aandoeningen aan de Universiteit Leiden op vrijdag 3 juni 2022 Een verkorte versie van deze tekst is uitgesproken door Prof.dr. Gisela M. Terwindt bij de aanvaarding van het ambt van hoogleraar Neurologie, in het bijzonder paroxysmale neurologische aandoeningen aan de Universiteit Leiden op vrijdag 3 juni 2022LUMC / Geneeskund

Effect of lockdown during COVID-19 on migraine: a longitudinal cohort study

BackgroundThe objective of this study was to assess whether migraine-related outcomes changed during intelligent lockdown when compared with the prior period.MethodsThis was a cohort study evaluating the first month of intelligent lockdown in the Netherlands (12 March to 8 April 2020) compared with one baseline month (13 February to 11 March 2020). We identified 870 migraine patients treated at the Leiden Headache Center with headache e-diaries during the period of interest. Adherence to the e-diary had to be ≥80%, yielding 592 enrolled patients.ResultsIntelligent lockdown led to a decrease in monthly migraine days (-0.48; 95% CI: -0.78 to -0.18, p = 0.002) and acute medication days (-0.48; 95% CI: -0.76 to -0.20, p p ConclusionsOur findings imply that intelligent lockdown measures can improve migraine disability despite of the potential negative effects of COVID-19 and lockdown. We hypothesise that this effect is a combined result of working from home, scaling down demanding social lives, and freedom to choose how to organise one's time.Paroxysmal Cerebral Disorder

Migraine prevalence in visual snow with prior illicit drug use (hallucinogen persisting perception disorder) versus without

Background and purpose This study was undertaken to investigate migraine prevalence in persons with hallucinogen persisting perception disorder (HPPD) presenting as visual snow syndrome (VSS).Methods Persons with visual snow as a persisting symptom after illicit drug use (HPPD) were recruited via a Dutch consulting clinic for recreational drug use. A structured interview on (visual) perceptual symptomatology, details of drugs use, and medical and headache history was taken. As a control group, persons with visual snow who had never used illicit drugs prior to onset were included. The primary outcome was lifetime prevalence of migraine. Symptom severity was evaluated by the Visual Snow Handicap Inventory (VHI), a 25-item questionnaire.Results None of the 24 HPPD participants had migraine, whereas 20 of 37 (54.1%) controls had migraine (p < 0.001). VHI scores did not differ significantly between the two groups; in both groups, the median score was 38 of 100. In most HPPD cases (17/24, 70.9%), visual snow had started after intake of ecstasy; other psychedelic drugs reported included cannabis, psilocybin mushrooms, amphetamine, 4-fluoroamphetamine, 3-methylmethcathinone, 4-Bromo-2,5-dimethoxypenethylamine, and nitrous oxide.Conclusions Whereas none of the HPPD participants had migraine, more than half of the visual snow controls without prior use of illicit drugs had migraine. This suggests that at least partly different pathophysiological factors play a role in these disorders. Users of ecstasy and other hallucinogens should be warned of the risk of visual snow. Further studies are needed to enhance understanding of the underlying neurobiology of HPPD and VSS to enable better management of these conditions.Paroxysmal Cerebral Disorder

Behavioural intervention in medication overuse headache: a concealed double-blind randomized controlled trial

Background 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 effectParoxysmal Cerebral Disorder

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study

Background To compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls. Methods We performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression. Results The questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression. Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference +/- SE: migraine 5.44 +/- 0.90, p < 0.001; cluster headache 5.62 +/- 0.99, p < 0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: - 3.16 +/- 0.50, p < 0.001; cluster headache: - 5.25 +/- 0.56, p < 0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001). Conclusion Men with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.Paroxysmal Cerebral Disorder

Jealousy in women with migraine: a cross-sectional case-control study

BACKGROUND: Estrogen influences susceptibility to migraine attacks and it has been suggested to affect jealousy in romantic relationships in women. Therefore, we hypothesized that migraine women may be more jealous. METHODS: Jealousy levels and hormonal status were determined based on a cross-sectional, web-based, questionnaire study among female migraine patients and controls. A random sample of participants was selected from a validated migraine database. Participants with a serious and intimate monogamous relationship were included (n = 498) and divided into the following subgroups: menstrual migraine (n = 167), non-menstrual migraine (n = 103), postmenopausal migraine (n = 117), and premenopausal (n = 57) and postmenopausal (n = 54) controls. The primary outcome was the difference in mean jealousy levels between patients with menstrual migraine, non-menstrual migraine and premenopausal controls. Results were analyzed with a generalized linear model adjusting for age, relationship duration and hormonal status (including oral contraceptive use). Additionally, the difference in jealousy levels between postmenopausal migraine patients and controls was assessed. Previous research was replicated by evaluating the effect of combined oral contraceptives on jealousy. RESULTS: Jealousy levels were higher in menstrual migraine patients compared to controls (mean difference ± SE: 3.87 ± 1.09, p = 0.001), and non-menstrual migraine patients compared to controls (4.98 ± 1.18, p < 0.001). No difference in jealousy was found between postmenopausal migraine patients and controls (- 0.32 ± 1.24, p = 0.798). Women using combined oral contraceptives were more jealous compared to non-users with a regular menstrual cycle (2.32 ± 1.03, p = 0.025). CONCLUSION: Young women with migraine are more jealous within a romantic partnership

Treatment with the monoclonal calcitonin gene-related peptide receptor antibody erenumab: a real-life study

Background and purpose New prophylactics for migraine, targeting calcitonin gene-related peptide (CGRP), have recently emerged. Real-world data are important for a comprehensive understanding of treatment response. We assessed the consistency of response to erenumab, a monoclonal CGRP receptor antibody, in a real-world setting, in order to determine which patients may be considered responders in clinical practice. Methods All erenumab-treated patients (n = 100) completed a time-locked daily electronic diary, and an automated algorithm was used to monitor treatment response. Monthly migraine days (MMD), non-migrainous headache days, days of acute medication use (MAMD), well-being and coping with pain were assessed for a 6-month period. The primary outcome was reduction in MMD compared to baseline. Results The numbers of MMD and MAMD decreased in all months, in both episodic and chronic migraine patients, compared to baseline (p = 50% in >= 3/6 months, and 6% had such a reduction in all 6 months. For a >= 30% MMD reduction, the figures were 60% and 24%, respectively. Almost 90% of patients with an average MMD reduction of >= 30% over the first 3 months had a sustained response in the last 3 months. In addition, 20% of patients without an initial response (average = 30%) in the last 3 months. Conclusion Erenumab was effective in migraine patients who were highly refractory to previous prophylactics. As a practical guideline, we propose that treatment be continued for at least 6 months and that patients with a >= 30% MMD reduction in at least half of the treatment period should be considered to be responders.Paroxysmal Cerebral Disorder

Pain perception in women with menstrually-related migraine

BackgroundCyclic hormonal fluctuations influence migraine incidence and severity. Previously, we described reduced menstrual cyclicity in estradiol levels and dermal blood flow reaction to capsaicin in female migraineurs. It is unclear whether pain perception in women with migraine is influenced by the menstrual cycle.MethodsWomen with menstrually-related migraine (n = 14), healthy age-matched controls (n = 10) and postmenopausal women (n = 15) were asked to grade trigeminal and non-trigeminal painful stimuli on a numeric pain rating scale on menstrual cycle day 19-21 (mid-luteal) and day 1-2 (early follicular).ResultsIn women with menstrually-related migraine, trigeminal pain remained low throughout the cycle. Controls showed increased trigeminal pain during the mid-luteal phase compared to the early follicular phase. Changes throughout the cycle were significantly different between women with MRM and controls.ConclusionThe compromised menstrual cyclicity of pain perception in women with menstrually-related migraine parallels our earlier findings on estradiol levels and dermal blood flow.Paroxysmal Cerebral Disorder

The potential danger of blocking CGRP for treating migraine in CADASIL patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease characterised by recurrent ischemic stroke, cognitive decline progressing to dementia, psychiatric disturbances and apathy. More than half of mutation carriers suffer from migraine, most often migraine with aura. Recently, a CADASIL patient was treated with a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor. Monoclonal antibodies targeting the CGRP system have been demonstrated to be safe, well tolerated, and effective in reducing migraine attacks. There is, however, abundant evidence that CGRP is important in maintaining cardiovascular homeostasis under (patho)physiological conditions. CGRP may act as a vasodilatory safeguard during cerebral and cardiac ischemia and blockage of the system could, therefore, potentially worsen ischemic events. Therefore, we caution against treating patients with small vessel diseases, such as the monogenic disorder CADASIL, with these drugs until relevant safety data and long term follow up results are available. Alternative preventive migraine treatments in CADASIL may be acetazolamide, sodium valproate, lamotrigine, topiramate, verapamil, or flunarizine