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Noon friedman

  1. 1. Migraine in Women Deborah Friedman, MD, MPH Professor, Neurology and Ophthalmology University of Texas Southwestern Medical Center Dallas, Texas
  2. 2. Disclosure:Consultant: Iroko, MAP Pharmaceuticals,ZogenixGrant Support: AGA Pharmaceuticals,Merck, Pfizer, MAP Pharmaceuticals,Quark PharmaceuticalsHonoraria: AllerganOther: Neurology News Editorial Board
  3. 3. Migraine is a Female DisorderAverage lifetime percent of population with migraine: 22.6% women (range 13-32%) 10.5% men (range 5.7-9%)Women are roughly 3 times as likely as men to have migraineHormonally associated migraine affect 12 million women in the U.S.
  4. 4. Is it Migraine?Migraine without AuraAt least 5 attacksHeadache lasts 4-72 hours (untreated) in adults, 1-72 hours in childrenAt least 2 of the following: Unilateral location Pulsating quality Moderate or severe intensity Aggravated by routine physical activityDuring the headache, at least 1 of the following: Nausea and/or vomiting Photophobia and phonophobia
  5. 5. Migraine with AuraAt least 2 attacks Scintillating scotomaAt least 3 of the following: Fully reversible aura symptoms explained by focal brain dysfunction At least one aura symptoms evolving over at least 4 minutes or two or more symptoms in succession Each symptom lasts less than 60 minutes Headache usually begins during or follows the aura
  6. 6. Sensory Paresthesias (tongue; hand-mouth)Motor Unilateral or bilateral weakness (spreads)Olfactory Gustatory hallucinationsVertigo/dizziness Common (50%) but does not distinguish migraine with/without aura Fortification spectra
  7. 7. Speech Dysarthria AphasiaBehavioral Depersonalization Automatic behavior Transient global amnesia Emotional (anxiety, euphoria) Déjà vu (strange things look familiar) Jamais vu (familiar things look strange)
  8. 8. Other Diplopia Ptosis Altered level of consciousness Ataxia Unilateral episodic mydriasis AuditoryWhat’s not aura Blurred vision Premonitory photophobia, phonophobia, nausea
  9. 9. Quick and Easy Migraine Diagnosis:“I.D. Migraine”1. Headache related disability2. Photophobia3. Nausea93% of migraineurs have 2 of 3 features81% sensitivity, 75% specificityAura 100% sensitive
  10. 10. Phases of MigrainePre-Headache Headache Post-Headache Premonitory Aura Postdrome symptoms* Mild Moderate Severe *Yawning, moodchange, sleepiness, food cravings, excessive thirst or urination
  11. 11. Taking the History: The AmericanMigraine Communication Study60 visits (approximately 12 minutes each) between healthcare professionals (primary care, neurologists, NP) and patients were video and audio-recordedPost-visit interviews were conducted separately with patients and healthcare professionalsAll interviews were transcribed and analyzed looking for discordance
  12. 12. Findings91% of the questions asked were closed- ended or short-answer90% of visits did not address impairment in any way (60% were severely impaired during attacks; average frequency 5/month)Of the 50 patients, 35 were not on a preventive medication after the first visitPrevention was only mentioned in 50% of the 25 patients who would qualify for one based on standard guidelines
  13. 13. Suggestions for ImprovingCommunicationPatient-centered interviewing focused on disability:“How do migraines affect your daily life?”“How does migraine affect your work and family?”“How does migraine make you feel – even when you aren’t having one?”
  14. 14. Other General FeaturesMigraine changes throughout lifeMigraine may change with hormonesYou can have a migraine without a headacheChildren get migraines tooPeople with migraine often get other kinds of headaches as wellIt runs in the family
  15. 15. Occurs in the peak productiveyearsMigraine affects: 18% of women 6.5% of men 7% of children
  16. 16. Estrogen ParadoxBeing female increases the likelihood of having migraine (estrogen)Sudden decreases in estrogen can trigger migraine headachesFall in estrogen Prior to menses Pill free week of oral contraceptives Perimenopause Postpartum
  17. 17. Migraine Throughoutthe (Hormonal) Life CycleChildrenAdolescence – PubertyMenstruationPregnancyMenopauseOther: Hormone replacement therapy Oral contraceptives
  18. 18. Migraine in ChildrenBoys=girls prior to puberty Peak incidence of migraine with aura Boys – age 5 Girls – age 12-13Peak incidence of migraine without aura Boys – age 10-11 Girls – age 14-17After puberty ratio is 3 to 1 (girls to boys)Boys often outgrow them
  19. 19. Migraine in Childhood Under-diagnosed Young children may not be able to describe pain or associated features Nausea, vomiting, sensitivity to light and noise is inferred Headaches are often shorter than in adults
  20. 20. Think about migraine in children with:Episodes of unexplained vomiting and abdominal pain lasting an hour or moreAttacks of imbalance or dizziness lasting minutesRecurring attacks of head tilt, vomiting, imbalance lasting hours to daysAlternating one-sided weaknessHeadaches followed by droopy eyelid and double vision (lasting days to weeks)
  21. 21. Migraine and Menstruation60-70% of women with migraine have them with menstruationPure Menstrual Migraine 2 days prior to menses to 4th day of menses only (14% of women) for 2 of 3 cyclesMenstrually-Related Migraine Within the above window and at other times of the monthPerimenstrual Migraine Attacks 2-7 days prior to mensesKeep a diary! Compare menstrual and non-menstrual attacks.
  22. 22. May Be Associated with Other Features of PMS(DSM-4: 5 days before to 4 days into menses, interfere with activities) Affective Physical Depression Breast tenderness Angry outbursts Abdominal bloating Irritability Headache Anxiety Peripheral edema Confusion Acne Social withdrawal Cramping Food cravings Increased appetite Sexual disinterest
  23. 23. What’s Different During Menses?No difference in sex hormones between migraineurs and controls (testosterone, LH, FSH)Headaches more severe, more nausea and vomitingTreatments may not be as effective during menses (?)Loder E. Neurol Sci 2005;26:S121-124
  24. 24. Treatment of Menstrual MigraineAcute symptomatic treatment Migraine specific, anti-inflammatoriesStandard preventive treatmentShort-term preventive treatment (“mini- prevention”) Non-steroidal anti-inflammatories Long-acting triptans (frova) or ergots Magnesium Hormonal therapy (estradiol gel) Increase usual preventativeNon-pharmacologic therapy **Pringsheim T, et al. Acute treatment and prevention of menstrually related migraine headache. Neurology 2008;70:1555-1563
  25. 25. Use of Oral Contraceptives toPrevent Menstrual Migraine1. Extended cycle OCsSuppress ovulation for monthsMay have breakthrough bleeding in first few months (accompanied by migraine)2. Reduce monthly decline in estrogenUse low-dose estrogen instead of 7 placebo pills each month3. Contraceptive patch + vaginal ringLess daily fluctuation in estrogen level
  26. 26. Migraine and PregnancyBetter (50-60+%)Worse (15-%)The Same (25%)May worsen during the first trimesterMay only occur during pregnancyMay be headache free in last trimester
  27. 27. New Onset of Headaches DuringPregnancyIncreased intracranial pressureTension-type headacheCerebral venous sinus thrombosisStrokeTumorVasculitisIntracranial hemorrhageReversible cerebrovasoconstrictive syndrome (RCVS)
  28. 28. Headache Medications andPregnancy – General ConceptsPharmakokinetics vary during gestationIncreased plasma volume – increaseunbound drugDecreasing albumin – increase freefraction (total assays unreliable)Increased renal clearanceChanges in CYP and glucuronidation **Lucas S. Medication Use in the Treatment of Migraine During Pregnancy and Lactation. Curr Pain Headache Rep 2009;13:392-398.
  29. 29. Symptomatic Treatment of Migraine During Pregnancy (Category B – no evidence of risk but no studies)Acetaminophen Caffeine Ibuprofen* Indomethacin* Naproxen* Meperidine Morphine Prednisone*Avoid in third trimester
  30. 30. Barbiturates, opioids,benzodiazepines Neonatal withdrawal syndrome Opioids are category B Beware medication overuseTriptans are all category CErgots are contraindicated
  31. 31. Treatment of Migraine-RelatedNausea (Category B) Dimenhydramine Meclizine Metoclopramide Ondansetron Anticholinergics – meconium ileus
  32. 32. Migraine Prevention DuringPregnancy (Category B/C)Avoid migraine triggersBeta blockers (C)Fluoxetine (C)Venlafaxine (C)Vitamin B2 (B)Coenzyme Q-10 (B)Magnesium (B)Avoid valproate, topiramate, AEDs, lithium (D)
  33. 33. Breast Feeding – General Principles No evidence that lactation worsens migraine Safe in pregnancy ≠ safe in lactation Amount passed to breast milk depends on: • average plasma concentration • amount excreted into breast milk • volume of milk ingested
  34. 34. Is the drug necessary?Use the safest oneConsider measuring blood levels in the infantTake medication after completing a breast feeding to minimize exposure to the baby
  35. 35. Symptomatic Treatment While BreastFeeding ConcernCompatible Benzodiazepines Acetaminophen, Contraindicated caffeine, NSAID AntihistaminesCaution Ergotamine/DHE Aspirin, barbiturates Triptans
  36. 36. Preventive Treatment While BreastFeeding ConcernCompatible Tricyclic Beta blockers antidepressants Calcium blockers Verapamil Valproate Contraindicated Corticosteroids Bromocriptine Amitriptyline **Hale TW. Medications andCaution Mother’s Milk. Amarillo, TX, Hale Publishing, 2008. SSRI
  37. 37. PerimenopauseWomen with a history of menstrual migraine (“hormonally sensitive”) may have worsening of migraines in peri-menopauseTreatment: Hormone replacement therapy Low dose OC (without placebo week) Standard migraine therapies
  38. 38. MenopauseMigraine and natural menopause: 20-40% worsen 20-30% improve 30-50% unchangedEffect of surgical menopause:(hysterectomy, oophorectomy) 38-87% worsenSome women develop migraines for the first time at menopause
  39. 39. Hormone Replacement Therapy?Conflicting data regarding migraineConsiderations: Delivery (patch*, cream, pill, injection) Need for continuous use Type and dosageNatural estrogens (estradiol) are better tolerated than conjugated estrogenOne size does not fit allRisk-benefit ratio
  40. 40. Migraine and StrokeWomen under 45Posterior circulation strokes and white matter lesions more likely in MWA and high attack frequency of migraine than controlsWomen 45 years and olderMWA twice as likely to develop ischemic stroke and MI over 10 years of follow-up
  41. 41. Ferrari M, et al. Brain 2005
  42. 42. Migraine and StrokeNumerous studies document increase risk:National Health and Nutrition Examination Survey – prospective (11,777 men and women; RR 2.1)Meta-analysis of 14 observational studiesRisk among all migraineurs, OR = 2MWA, OR = 2.9MWOA, OR = 1.6
  43. 43. Women’s Health StudyProspective cohort study of 39,754 health professionals ages 45 and olderNo migraine or MWOA – no increased riskMWA – Adjusted hazards ratio 1.53 for total stroke 1.71 for ischemic stroke No increased risk for hemorrhagic strokeWomen < 55 with MWA had greatest risk: 1.75 for total stroke 2.25 for ischemic stroke
  44. 44. Stroke Risk: Low Dose OCsMeta analysis of 16 studies (Gillum) RR = 1.92 (1.4-2.7) controlling for smoking and hypertension = 1 additional stroke per 24,000Meta analysis of 14 studies (Baillargeon) RR 1.84 (1.4-2.4) with low dose OC use Also risk of 2nd and 3rd generation OC use
  45. 45. Risk of Stroke Varies by Age: Women9 per 100,000 in 20-year-old MWA3 per 100,000 in 20-year-old w/o migraine80 per 100,000 in 40-year-old MWA11 per 100,000 in 40 year-old w/o migraine
  46. 46. Summary of RiskMigraine increases risk of stroke, OR = 2-3Aura, female sex, age > 45, high frequency, migraine duration – higher risk > 12 attacks/year, > 12 years of migraine)OC increases risk of ischemic stroke, OR = 2 OC increase risk of venous sinus thrombosis, OR = 22 OC increase risk of subarachnoid hemorrhage, OR = 1.6
  47. 47. Recommendations (ACOG, WHO, IHS)Women with migraine should minimize other vascular risksWomen with MWOA on hormone therapy should stop if aura develops or headache worsensWomen with migraine over 35 who smoke should not use OCsWomen with a history of stroke or venous clot should not use OCsControversy: Women with MWA should not use hormonal therapy
  48. 48. Migraine and CardiovascularDisease (Women’s Health Study)580 major CVD events occurredActive MWA: hazard ratio 2.15 overall 1.91 for ischemic stroke 2.08 for MI 1.74 for coronary revascularization 1.71 for angina 2.33 for ischemic CVD death18 additional major CVD events/10,000 women per year, after adjusting for ageMWOA: No increased risk
  49. 49. Migraine as a Clinically Progressive DisorderEpisodic migraine evolves over time in some patients, AKA “transformed migraine”Attacks increase in frequency (medication overuse)Chronic daily headache (>180 days yearly) with superimposed migraineDevelopment of allodynia
  50. 50. Risk Factors for Development ofChronic Daily HeadacheDefinition: Headache on more days than not (> 15 days monthly X 3 monthsCase-control, cross sectional population studyLongitudinal follow-up for progression800 people with episodic headache 3% developed CDH 6% developed 105-179 HA days
  51. 51. Predictors of ProgressionMedication overuse Especially OTC with caffeine combinations, narcotic combinations, barbiturate combinationsWeight: Overweight = 2X, Obesity = 5X!!Baseline headache frequency (>1/wk)Low socioeconomic statusHead injury Lipton RB, Bigal M. Headache 2005; 45 (suppl 1) S3-S13 Goadsby PJ. Med J Austr 2005;182(3):103-4
  52. 52. Stressful life events (moving, death in family, work-related changes)Snoring
  53. 53. Risk Factors and Development of CDHNot readily modifiable ModifiableMigraine as a disorder Attack frequency (predisposition) ObesityFemale sex Medication overuseLow SES Stressful life eventsHead injury Snoring (OSA and other sleep disorders)
  54. 54. Central Sensitization and AllodyniaAllodynia – a normally non-painful stimulus becomes painfulOccurs in 75% of migraineurs during migraineUsually takes years to develop
  55. 55. Allodynia – Taking the HistoryPositive in 70% Peripheral sensitization Throbbing quality Hair / eye glasses / earrings hurt Hurts to touch: shave, sleep, wash Central sensitization Pain is worse with coughing, sneezing Triptans less likely to work when central allodynia is present
  56. 56. Implications for TreatmentStratified care based on disabilityReduce environmental triggers, if presentWeight managementInvestigate for sleep disorder when appropriateProphylaxisReduce modifiable cardiovascular risk
  57. 57. Stratified Care by OverallDisabilityLittle to none “Low end” TriptansModerate Combination treatments Triptans Anti-emetics ProphylaxisSevere “High end” Triptans Prophylaxis Narcotics Anti-emetics Ergots Refer to specialist
  58. 58. SummaryWomen are different.Migraines changethroughout thereproductive cycle.Estrogen isimportant.Migraine may beprogressive –consider preventivetreatment.
  59. 59. Additional Recommended Reading Dodick DW. Chronic daily headache. NEJM 2008;354:158-165 Elliott D. Migraine and stroke: current perspectives. Curr Pain Headache Rep 2008;30(8):801-12 Ferrante E, Tassorelli C, Rossi P, et al. Focus on the management of thunderclap headache: from nosography to treatment. J Headache Pain 2011;12:251-258 Klein AM, Loder E. Postpartum headache. Int J Obstet Anesth. 2010;19:422-30
  60. 60. Kurth T, Gaziano JM, Cook NR, et al. Migraineand risk of cardiovascular disease in women.JAMA 2006;296;283-291Lipton RB, Bigal ME. Ten lessons on theepidemiology of migraine. Headache207;46(Suppl1):S2-S9McGregor EA. Prevention and treatment ofmenstrual migraine. Drugs 2010;70:1799-818Sullivan E, Bushnell C. Management ofmenstrual migraine: a review of currentabortive and prophylactic therapies. Curr PainHeadache Rep 2010;14:376-84