1 Migraine Course, natural history and prognosis - PowerPoint Presentation

1. 1MigraineCourse, natural history and prognosis

2. Migraine without aura≥5 attacks lasting 4–72 hours when untreated≥2 of the following: Unilateral locationPulsating qualityModerate-to-severe painAggravation by physical activityEither nausea/vomiting and/or photo/phonophobia Migraine with aura≥1 of the following reversible aura symptoms: visual, sensory, speech, motor, brainstem, retinal≥3 of the following: Gradual spread of aura≥2 aura symptoms in succession≥1 positive symptom≥1 unilateral symptom, followed by headache within 60 mins MigraineDiagnosis and segmentation in migraine ICD-10=International Classification of Diseases, 10th edition; ICHD-3=International Classification of Headache Disorders, 3rd edition1. Headache Classification Committee of the International Headache Society (IHS). Cephalalgia 2018;38(1):1–211; 2. ICD-10. https://www.icd10data.com/ICD10CM/Codes. Accessed Jun 2020; 3. Katsarava et al. Curr Pain Headache Rep 2012;16(1):86–92; 4. Buse et al. Headache 2012;52(10):1456–1470; 5. Bigal & Lipton. Curr Neurol Neurosci Rep 2011;11(2):139–148; 6. Bigal & Lipton. Curr Opin Neurol 2008;21(3):301–3082The ICHD-3 defines as:Headache occurring on ≥15 days/ month for >3 monthsWith ≥8 days/month, having features of migraine headacheThe clinical criteria for episodic migraine with and without aura apply to the chronic diagnosis, with the only differentiator being frequency and duration of symptomsChronic migraine also has its own ICD-10 code (G43.7)2The majority of people with migraine have episodic migraine – estimates suggest up to 8% of people with migraine have chronic migraine3,4 Estimates suggest that episodic migraine progresses to chronic migraine in approximately 3% of people annually3,5,6Episodic migraine1(1–14 headache days per month)Chronic migraine1(≥15 headache days per month)People with ≥5 attacks of migraine lasting 4–72 hours during their lifetime, but who do not meet criteria for chronic migraine

3. Episodic migraineChronic migraine~3% of people with episodic migraine per yearMigraineEpisodic and chronic migrainePAG=periaqueductal gray; QoL=quality of lifeAdapted from: Aurora. Cephalalgia 2009;29(6):597–605; Aurora & Brin. Headache 2017;57(1):109–125; Katsarava et al. Curr Pain Headache Rep 2012;16(1):86–92; Bigal & Lipton. Curr Neurol Neurosci Rep 2011;11(2):139–1483QoLDisability associated with acute attacksProlonged, pervasive disabilityClinicalLower frequency of headachesSymptoms include lateralised pulsating pain (worsened by physical activity), nausea, photophobia/phonophobia More severe painHigher frequency of headachesFewer associated symptomsOften associated with analgesic overuseLess severe painTreatmentCan be difficult to treat – triptans are frequently ineffectiveFor patients who remain affected despite optimized acute treatment, preventive treatment should be considered.Triptans often effectivePresence of risk factors for progression may influence treatmentPathologicalAlteration in PAG iron homeostasisIncreased blood flow in pons during migraineSome baseline cortical hyperexcitabilityAlteration in processing of cutaneous painPAG iron homeostasis changes possibly progressiveIncreased blood flow in pons during interictal periodExcessive baseline cortical hyperexcitabilityFurther alteration in processing of cutaneous pain

4. A migraine attackMigraine4

5. MigraineProposed phases of a migraine attackSymptoms in bold denote criteria in the ICHD-3 classificationICHD-3=International Classification of Headache Disorders, 3rd editionAdapted from: Dodick. Lancet 2018;391(10127):1315–1330; Cady et al. Headache 2002;42(3):204–216; Goadsby et al. Physiol Rev 2017;97(2):553–622;Headache Classification Committee of the International Headache Society (IHS). Cephalalgia 2018;38(1):1–211;The American Migraine Foundation. https://americanmigrainefoundation.org/resource-library/timeline-migraine-attack/. Accessed May 2020;Migraine Buddy website. Available at: https://migrainebuddy.com/migraine/2018/11/22/the-stages-of-a-migraine-postdrome-phase. Accessed May 20205ProdromeAuraHeadachePostdromeFatigueCognitive difficultiesMood changesFood cravingsNeck painYawningVisual aura (scotoma, fortification spectrum)Sensory disturbanceSpeech disturbanceMotor symptomsHeadacheNausea with or without vomitingPhotophobiaPhonophobiaOsmophobiaFeeling tired or wearyDifficulty with concentration Neck stiffnessHeadache4–72 hrs<12–48 hrs5–60 minutesA few hoursto 48 hours

6. MigraineBothersome migraine symptoms and unmet treatment needsThe MAST study followed 6,045 people for 6 months, and surveyed people with migraine about their symptoms and treatment1Considering the 3 cardinal symptoms of migraine, respondents reported which of the 3 symptoms they considered to be ‘most bothersome’:1Photophobia – 49% of respondents, more commonly reported as most bothersome by men, obese participants, and those with auraNausea – 28% of respondents, more commonly reported as most bothersome by women, participants with low incomes, and those with less well-optimised acute treatmentPhonophobia – 23% of respondents, more commonly reported as most bothersome by participants with allodynia, and participants without auraAmong MAST study respondents, 96% had at least 2 cardinal migraine-associated symptoms, and 65% reported all 3 symptoms1In the IBMS survey, photophobia and phonophobia were reported by more people with chronic migraine than with episodic migraine, adding to the burden of chronic migraine2IBMS=International Burden of Migraine Study; MAST=Migraine in America Symptoms and Treatment1. Munjal et al. Headache 2020;60(2):416–429; 2. Blumenfeld et al. Cephalalgia 2011;31(3):301–3156

7. Migraine triggersMigraine7

8. EmotionalPhysicalDietaryEnvironmentalMigraineMigraine triggersAdapted from: Migraine Trust website. https://www.migrainetrust.org/about-migraine/trigger-factors/common-triggers/ Accessed July 2020; Park et al. PLoS One 2016;11(2):e0149577; Pavlovic et al. Headache 2014;54(10):1670–1679; Sarchielli. J Headache Pain 2006;7(4):172–1738StressSleep deprivationFatigueWeather changesOvereatingFastingCaffeineAlcoholSmokingNoiseSunlightOdoursHormonal changes in womenExcessive sleepRelaxation from stress

9. MigraineTriggers of a migraine attack in a large-scale studyRespondents were asked to rate triggers on a 0–3 scale (0, never; 1, occasional, 1–33%; 2, frequent, 34–66%; 3, very frequent, 66–100%)Adapted from: Kelman. Cephalalgia 2007;27(5):394–4029People with migraine reporting triggers as occurring very frequently or at least occasionally (n=1,207)

10. MigraineStress as a migraine triggerStress, anxiety, excitement, and tension may all lead to a migraine attack1Moreover, some people report reduction or relief of stress as a trigger – so-called ‘weekend’, or ‘let-down’ headaches1,2Because migraine itself is stressful, stress can be self-propagating, in a vicious cycle:3 A 3-month electronic diary study followed 17 people with migraine and tracked stress levels using the PSS and SRSS:2Level of stress was not associated with migraine attacksHowever, decline in stress was associated with headache onset within 6–18 hours (OR: 1.5–1.9, p<0.05)The authors concluded that, rather than stress per se being a migraine trigger, reduced stress from one day to the next was associated with increased risk of a migraine attackSeveral lines of evidence link stress and migraine, making the management of stress using approaches such as relaxation training and BFT powerful tools in treating migraine3BFT=biofeedback therapy; OR=odds ratio; PSS=Perceived Stress Scale; SRSS=Self-Reported Stress Scale1. Migraine Trust website. https://www.migrainetrust.org/about-migraine/trigger-factors/common-triggers/ Accessed July 2020; 2. Lipton et al. Neurology 2014;82(16):1395–1401; 3. Kajal et al. Int J Cur Res Rev 2017;9(12):23–2610Migraine attacks lead to more stressStress acts as a migraine trigger

11. MigraineAlcohol as a migraine triggerWine was identified as a migraine trigger almost two thousand years ago1The IHS describes 2 types of alcohol-induced headache:2An ‘immediate alcohol-induced headache’, which develops within 3 hours of alcohol ingestionA ‘delayed alcohol-induced headache’, which develops 5-12 h after ingestion, i.e., a so-called ‘hangover headache’Roughly a third of people with migraine report alcohol as a migraine trigger, although there does appear to be considerable variation between individuals and between countries1,3Potential mechanisms linking alcohol and migraineChemicals in alcoholMany chemicals in different alcoholic drinks have been linked to headache, including histamine, tyramine, flavonoids, and sulphites1Interaction with 5-HT receptorsWine, particularly red wine, appears to modulate 5-HT levels in the blood, and may stimulate the release of 5-HT from central stores1Vasodilating effectsEthanol has a vasodilating effect1,3Ethanol has been shown to release CGRP;4 a key protein in the pathology of migraine55-HT=5-hydroxytryptamine (serotonin); CGRP=calcitonin gene-related peptide; IHS=International Headache Society1. Panconesi. J Headache Pain 2008;9(1):19–27; 2. Headache Classification Committee of the International Headache Society (IHS). Cephalalgia 2018;38(1):1–211; 3. Panconesi. J Neurosci Rural Pract 2016;7(2):269–275; 4. Gazzieri et al. Cardiovasc Res 2006;70(3):589–599; 5. Edvinsson et al. Nat Rev Neurol 2018;14(6):338–35011

12. MigraineIs chocolate a trigger or not?The connection between chocolate and migraine has long been contested1Across a range of epidemiological studies, including thousands of people with migraine, up to 22.5% of people report chocolate as a headache trigger1The tyramine in chocolate has been investigated in migraine, however, a link has not been established1The phenylethylamine contained in chocolate has been shown experimentally to cause headaches1In one seminal study, 25 people with migraine were given either 44 g of chocolate or a matched placebo;a participants were told these were two different sorts of chocolate2Participants were asked to respond 48 hours after the experiment indicating whether or not they had experienced a migraine2In total, 9 headaches occurred after chocolate ingestion, whilst 6 occurred after placebo, without a significant difference between the two groups (p=0.54)1,2Other provocative studies have failed to show a significant difference in headache attacks between chocolate and placebo1aConsisting of a synthetic fat which approximated in physical quality to cocoa butter, but which was made from non-cocoa containing vegetable oils1. Lippi et al. Acta Biomed 2014;85(3):216–221; 2. Moffett et al. J Neurol Neurosurg Psychiatry 1974;37(4):445–44812Many people report chocolate as a migraine trigger, but the basis for chocolate precipitating migraine attacks is largely anecdotal1

13. MigraineMonitoring potential trigger factorsThe migraine trust recommends that people with migraine keep a diary, logging factors including:1The timing of migraine attacks can also provide clues, e.g., experiencing migraine at the weekend resulting from caffeine withdrawal, or from changes in sleep routines1Migraine attacks that are typically triggered by a single factor are easier for an individual to accommodate in their lifestyle than attacks caused by multiple triggers11. Migraine Trust website. https://www.migrainetrust.org/about-migraine/trigger-factors/what-is-a-trigger/. Accessed August 202213Sleep habits, including waking time and time going to sleepActivities throughout the dayThe environment throughout the dayFood and drink consumptionTiming of eating and drinkingTiming of bowel movementsExercise and travelMoodWeather conditions Menstrual cycle (for women) Severity and symptoms of a migraine attackMedications takenOther changing lifestyle factors

14. MigraineDistinguishing triggers from prodrome symptomsMigraine triggers are argued by some to be an example of the post hoc ergo propter hoc logical fallacy – the falsehood that states that because one event was followed by another, the former must have caused the latter1In the context of migraine pathology, it is possible that changes in the brain that precede headache and migraine onset are misinterpreted, e.g., brain changes causing temporary food cravings lead to a belief that that food causes a migraine1Studying migraine triggers and prodrome symptoms is methodologically difficult, because all potential study designs have flaws:2Patient surveys are influenced by recall bias and by beliefsDiary studies are burdensome for the patient and may be affected by recall bias of retrospective completionClinical studies are expensive and time consuming, and some potential trigger factors cannot be controlled or changed, making them difficult to studyDespite the difficulties, understanding migraine triggers, and distinguishing triggers from prodrome symptoms, is a clinically worthwhile exercise, and would allow for better treatment, and potentially a more complete understanding of the biology and pathology of migraine21. Hoffmann & Recober. Curr Pain Headache Rep 2013;17(10):370; 2. Lipton et al. Headache 2014;54(10):1661–166914

15. MigraineThe usefulness of triggers for migraine preventionBlanket advice to avoid exposure to migraine triggers has been criticised as impractical, and unhelpful:1There is little empirical support for avoidance as a coping strategyIn other clinical fields avoidance is not a useful strategySome research suggests that whilst short exposure to a headache trigger results in increased sensitivity, prolonged exposure results in decreased sensitivityThis has led to the idea of coping with triggers, rather than avoiding them1Moreover, the idea of forecasting migraine attacks using triggers (e.g., environmental conditions) is gaining some traction2Currently, people with migraine are treated with acute, abortive medications, or with preventive medications that consider risk as equal from day-to-day2Forecasting opens up a third possibility: pre-emptive therapy would allocate a treatment specifically on days of heightened headache risk, e.g., pharmacotherapy at the weekend if an individual experiences ‘let-down’ headaches21. Martin. Cephalalgia 2010;30(5):634–637; 2. Turner et al. Curr Pain Headache Rep 2018;22(9):6215

16. MigraineMigraine triggers and preventive medicationAn electronic diary study followed 62 people with migraine over 3 months1The most the frequent trigger factors on headache days were stress, fatigue, and sleep deprivation1Headaches with trigger factors were more severe than those without trigger factors1Travelling, hormone changes, noise, alcohol, overeating, and stress were significantly associated with migraine compared with non-migraine headaches1Hormonal changes and noise increased the risk of migraine regardless of preventive medication1Stress, overeating, alcohol, and travelling increased the risk of migraine in situations without preventive medication1Investigating trigger factors is a useful tool for understanding the biology of migraine and devising and targeting pre-emptive therapies11. Park et al. PLoS One 2016;11(2):e014957716

17. Evolution of migraine from episodic to chronicMigraine17

18. MigraineMigraine ‘chronification’Adapted from: Torres-Ferrús et al. J Headache Pain 2020;21(1):42; Buse et al. Headache 2019;59(3):306–338; Katsarava et al. Curr Pain Headache Rep 2012;16(1):86–92; Bigal & Lipton. Neurology 2008;71(11):848–855;Lipton et al. Managing Migraine: A Healthcare Professional’s Guide to Collaborative Migraine Care. 200818Mild impairmentSevere impairmentModerate impairmentDepressionMuscle painComorbiditiesSleep disordersObjective of treatmentSeverityFrequencyRecovery time between attacksPoor recovery timeNo recovery time between attacks

19. MigraineSwitching from episodic to chronic migraine and back again1. Blumenfeld et al. Cephalalgia 2011;31(3):301–315; 2. Bigal & Lipton. Curr Neurol Neurosci Rep 2011;11(2):139–148; 3. Torres-Ferrús et al. J Headache Pain 2020;21(1):42; 4. Buse et al. Headache 2019;59(3):306–338; 5. Manack et al. Neurology 2011;76(8):711–718; 6. Bigal & Lipton. Curr Opin Neurol 2008;21(3):301–30819People with migraine (%)Number of headache days per monthEpisodicChronicFrequency of headache days per month in people with migraine (n=8,281)1Approximately 3% of people with episodic migraine develop chronic migraine over a period of 1 year – a process known as chronification2-6Approximately 26% of people with chronic migraine will transition to episodic migraine over a 2-year period5

20. MigraineEvolution from episodic to chronic migraineThe AMPP study followed people with chronic migraine over 2 years, and found that 26% of people had remitted by 2 yearsA multivariate model identified the following predictors of remission:Low baseline headache frequency (OR: 0.29; 95% CI: 0.11, 0.75)Absence of allodynia (OR: 0.45; 95% CI: 0.23, 0.89)AMPP=American Migraine Prevalence and Prevention; CI=confidence interval; OR=odds ratioAdapted from: Manack et al. Neurology 2011;76(8):711–71820People with chronic migraine(n=383)Baseline20052006Follow up2007Chronic migraine(n=130)Remitted(n=100)34% of people had persistent chronic migraine26% of people had remitted The AMPP studyThe population of people with chronic migraine is in a relatively fluid state

21. MigraineComorbidities and migraine ‘chronification’In the AMPP survey, several comorbidities were more common in chronic migraine compared with episodic migraine, based on data from 18,500 respondents:1DepressionAnxietyChronic painRespiratory disorders including asthma, bronchitis, and chronic obstructive pulmonary diseaseCardiac risk factors including hypertension, high cholesterol, and obesityAlong with managing acute migraine symptoms, reducing the overall burden of migraine must also include management of comorbid disorders, behavioural traits and associated risk factors that increase the risk of ischaemic vascular events and of progression from episodic to chronic migraine2Reducing cardiovascular risk factors, and encouraging the cessation of smoking and the use of non-oestrogen-containing contraceptives, reduces the risk of ischaemic events in people with migraine2Comorbid disorders that may influence the risk of migraine complications – ischaemic events or migraine ‘chronification’2AMPP=American Migraine Prevalence and Prevention1. Buse et al. J Neurol Neurosurg Psychiatry 2010;81(4):428–432; 2. Dodick. Cephalalgia 2009;29(Suppl 3):7–1421VascularPsychiatricOtherNeurologicalRaynaud’s syndromeSymptomatic and asymptomatic ischaemic strokeWhite matter hyperintensitiesHypertensionMyocardial infarctionPatent foramen ovaleMitral valve prolapseAtrial septal aneurysmDepressionAnxietyBipolar disorderPanic disorderSnoringSleep apnoeaAllergy/asthmaSystemic lupus erythematosusNon-headache painEpilepsyTourette’s syndromeA variety of risk factors and comorbid disorders have been linked to migraine progression2

22. MigraineRisk factors for migraine ‘chronification’AMPP=American Migraine Prevalence and Prevention 1. Bigal & Lipton. Curr Neurol Neurosci Rep 2011;11(2):139–148; 2. Bigal & Lipton. Curr Opin Neurol 2008;21(3):301–308; 3. Dodick. Cephalalgia 2009;29(Suppl 3):7–14;4. Lipton & Bigal. Headache 2005;45(Suppl 1):S3–S13; 5. Aguggia & Saracco. Neurol Sci 2010;31(Suppl 1):S15–S172284%NonmodifiableGenderAgeRaceGeneticsModifiable Headache frequencyCentral sensitisationObesityMedication overuseStressSnoringIn some people, migraine is episodic; in others, migraine presents as a chronic–progressive disease4Preventing disease progression, including by modification of risk factors, should be among the goals when treating migraine4,51-year prognosis of migraine from the AMPP study1,213%3%Risk factors for migraine ‘chronification’1-5

23. MigraineICHD-3 differential diagnosis – medication-associated headacheICHD-3=International Classification of Headache Disorders, 3rd edition1. Headache Classification Committee of the International Headache Society (IHS). Cephalalgia 2018;38(1):1–211;23a. Patients should be coded for one or more subtypes of ‘8.2 Medication-overuse headache’ according to the specific medication(s) overused and the criteria for each below. For example, a patient who fulfils the criteria for ‘8.2.2 Triptan-overuse headache’ and the criteria for one of the sub-forms of ‘8.2.3 Non-opioid analgesic-overuse headache’ should receive both these codes. The exception occurs when patients overuse combination-analgesic medications, who are coded ‘8.2.5 Combination analgesic-overuse headache’ and not according to each constituent of the combination analgesic medicationb. Patients who use multiple drugs for acute or symptomatic treatment of headache may do so in a manner that constitutes overuse even though no individual drug or class of drug is overused; such patients should be coded ‘8.2.6 Medication-overuse headache attributed to multiple drug classes not individually overused’c. Patients who are clearly overusing multiple drugs for acute or symptomatic treatment of headache but cannot give an adequate account of their names and/or quantities are coded ‘8.2.7 Medication-overuse headache attributed to unspecified or unverified overuse of multiple drug classes’ until better information is available. In almost all cases, this necessitates diary follow-upHeadache occurring on ≥15 days/month in a patient with a pre-existing headache disorderRegular overuse for >3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headachea-cNot better accounted for by another ICHD-3 diagnosis8.2 Medication-overuse headache1

24. Short-term pain reliefRebound headacheHigher medication doseMigraineMedication overuseICHD-3 thresholds for overuse: regular intake of ≥1 opioid or triptan on ≥10 days/month for >3 months, or regular intake of acetaminophen or ≥1 NSAID on ≥15 days/month for >3 months2ICHD-3=International Classification of Headache Disorders, 3rd edition; NSAID=non-steroidal anti-inflammatory drugAdapted from: 1. Da Silva & Lake. Headache 2014;54(1):211–217; 2. Headache Classification Committee of the International Headache Society (IHS). Cephalalgia 2018;38(1):1–21124MedicationHeadachePain reliefSuccessful acute treatment of migraine involves treatment and resolution of the migraine attack and symptomsMedication-overuse headache can occur with several classes of migraine therapy, including acetaminophen, caffeine combinations, opioids, barbiturates, NSAIDs, and triptansThe vicious cycle of medication overuse1

25. People with chronic migraine (who may have failed to experience any benefits from preventive treatments in the past)MigraineMedication-overuse headache in chronic migraineChronic migraine can be complicated by the addition of medication-overuse headache – a headache due to excessive intake of acute migraine medication1Medication overuse can lead to rebound headaches, and is also thought to cause structural brain changes that underly treatment refractoriness1Chronic migraine coupled with medication-overuse headache is associated with poor quality of life, and large costs to society1There is good evidence that the rate of medication-overuse headache associated with analgesics and opioids is considerably higher than the rate associated with triptans and ergot derivatives2,3Management of medication-overuse headache11. Ferrari et al. Expert Opin Drug Metab Toxicol 2015;11(7):1127–1144; 2. Bigal & Lipton. Neurology 2008;71(22):1821–1828;3. Thorlund et al. J Headache Pain 2016;17(1):10725To prevent medication-overuse headache in the future, effective pharmacological and non-pharmacological strategies must be used effectively, alongside biomarkers and predictors of response to allow personalisation of migraine therapy whilst migraine is episodic1Primary preventionSecondary preventionTertiary preventionPeople with refractory migrainePeople with episodic migraineEffective acute treatmentEarly initiation of preventive treatmentIdentification and treatment of risk factors for disease progressionIdentification and withdrawal of overused medicationInitiation of effective preventive treatmentReduction of disabilitiesOptimisation of symptomatic treatmentExploration of preventive and alternative treatments

26. Migraine prognosisMigraine26

27. MigraineStructural brain changes associated with migraineA meta-analysis of 19 studies found evidence that migraine was a risk factor for several different structural changes within the brain:1Migraine with aura was a risk factor for white matter abnormalities: OR: 1.68; 95% CI: 1.07, 2.65; p<0.05Migraine with aura was a risk factor for infarct-like lesions: OR: 1.44; 95% CI: 1.02, 2.03; p<0.05Volumetric brain changes have been reported in people with migraine with aura relative to control individuals, including changes in neuron density in the periaqueductal gray and in the dorsolateral pons, correlated with attack frequency and disease durationThe Reykjavik study followed a cohort of 4,689 individuals over a period of 26 years, and found that people with migraine with aura had a greater risk of late-life infarcts than control individuals (OR: 1.4; 95% CI: 1.1, 1.8)2An MRI study of 69 people with migraine found that people with white matter hyperintensities were more likely to be older, and have a longer disease duration (median of 180 versus 84 months, p<0.05), compared with people without white matter hyperintensities3Where necessary, people with structural brain changes should be evaluated for stroke risk factors1CI=confidence interval; MRI=magnetic resonance imaging; OR=odds ratio1. Bashir et al. Neurology 2013;81(14):1260–1268; 2. Scher et al. JAMA 2009;301(24):2563–2570; 3. Xie et al. BMC Neurol 2018;18(1):9327More research is needed to understand structural brain changes within the context of the longitudinal course of migraine1

28. MigrainePrognosis of migraine in childrenThe Monreale 10-year study followed 55 children with migraine into adulthood, monitoring symptoms at 5 and 10 yearsAfter 10 years, 38% of people had remitted Females showed a higher tendency for persistent migraine than males, but this did not reach statistical significance (p=0.18)In the univariate analysis, family history of migraine was the only significant predictor of 10-year persistence of migraineAdapted from: Monastero et al. Neurology 2006;67(8):1353–135628Children aged 11–14 years with migraine (n=55)Baseline19895-year follow up199410-year follow up1999Persistent migraine (n=23)Remitted(n=21)Monreale 10-year study

29. MigraineLong-term follow-up studies of migraineA 16-year Danish study followed 53 people with migraine with aura1Attacks ceased in 36% of people 55% of males and 31% of females1Among non-remitted individuals, attack frequency improved in 44%, and intensity improved in 41% of people1Migraine tended to persist in women, in people with sensory or aphasic aura besides their visual aura, and in people with early onset of migraine, but with less frequent and less severe attacks1These results indicated that remission of migraine with aura is more likely among:1MalesIndividuals who only experience visual auraIndividuals with late-onset migraine with auraA 12-year Danish study followed 64 people with migraine:242% of people achieved remission38% had low migraine frequency20% had >14 migraine days per year (poor outcome) at follow-upPoor outcome was associated with:2High migraine frequency at baseline Age at migraine onset younger than 20 yearsIn a univariate analysis of the results, frequent use of analgesics was associated with poor outcome2Other long-term follow-up studies of migraine suggest that remission from migraine increases with age – that the decline in migraine prevalence with age is accounted for partly by cessation of migraine31. Eriksen et al. Cephalalgia 2004;24(1):18–22; 2. Lyngberg et al. Neurology 2005;65(4):580–585;3. Bigal & Lipton. Curr Opin Neurol 2008;21(3):301–30829

30. Migraine is a chronic disorder with episodic attacks with a highly variable long-term prognosis. In many, migraine may have a verybenign (complete remission) or relatively benign (partial remission) prognosis. In some, migraine persists and in others, it progresses. Identifying predictors of migraine prognosis is, therefore, of great scientific and clinical interestBigal & Lipton. Curr Opin Neurol 2008;21(3):301–30830