Noon friedman

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Migraine in Women Deborah Friedman, MD, MPH Professor, Neurology and Ophthalmology University of Texas Southwestern Medical Center Dallas, Texas

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Transcript of Noon friedman

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Migraine in Women

Deborah Friedman, MD, MPH

Professor, Neurology and Ophthalmology

University of Texas Southwestern Medical

Center

Dallas, Texas

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Disclosure:

Consultant: Iroko, MAP Pharmaceuticals, Zogenix 

Grant Support: AGA Pharmaceuticals, Merck, Pfizer, MAP Pharmaceuticals, Quark Pharmaceuticals

Honoraria: Allergan 

Other: Neurology News Editorial Board

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Migraine is a Female Disorder

Average 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 migraine

Hormonally associated migraine affect 12 million women in the U.S.

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Is it Migraine? Migraine without Aura

At least 5 attacks

Headache lasts 4-72 hours (untreated) in adults,

1-72 hours in children

At least 2 of the following:

Unilateral location

Pulsating quality

Moderate or severe intensity

Aggravated by routine physical activity

During the headache, at least 1 of the following:

Nausea and/or vomiting

Photophobia and phonophobia

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Migraine with Aura

At least 2 attacks Scintillating scotoma

At 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

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Sensory

Paresthesias (tongue; hand-mouth)

Motor

Unilateral or bilateral weakness (spreads)

Olfactory

Gustatory hallucinations

Vertigo/dizziness

Common (50%) but does not distinguish migraine with/without aura

Fortification spectra

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Speech

Dysarthria

Aphasia

Behavioral

Depersonalization

Automatic behavior

Transient global amnesia

Emotional (anxiety, euphoria)

Déjà vu (strange things look familiar) Jamais vu (familiar things look strange)

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Other

Diplopia

Ptosis

Altered level of consciousness

Ataxia

Unilateral episodic mydriasis

Auditory

What’s not aura

Blurred vision

Premonitory photophobia, phonophobia, nausea

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Quick and Easy Migraine Diagnosis:“I.D. Migraine”

1. Headache related disability

2. Photophobia3. Nausea

93% of migraineurs have 2 of 3 features81% sensitivity, 75% specificityAura 100% sensitive

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Phases of Migraine

*Yawning, mood change, sleepiness,

food cravings, excessive thirst or

urination

Pre-HeadachePremonitory symptoms*

AuraHeadache Post-Headache

Postdrome

Mild Moderate Severe

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Taking the History: The American Migraine Communication Study

60 visits (approximately 12 minutes each) between healthcare professionals (primary care, neurologists, NP) and patients were video and audio-recorded

Post-visit interviews were conducted separately with patients and healthcare professionals

All interviews were transcribed and analyzed looking for discordance

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Findings

91% of the questions asked were closed-ended or short-answer

90% 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 visit

Prevention was only mentioned in 50% of the 25 patients who would qualify for one based on standard guidelines

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Suggestions for Improving Communication

Patient-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?”

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Other General Features

Migraine changes throughout life

Migraine may change with hormones

You can have a migraine without a headache

Children get migraines too

People with migraine often get other kinds of headaches as well

It runs in the family

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Occurs in the peak productive years

Migraine affects:18% of women6.5% of men

7% of children

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Estrogen Paradox

Being female increases the likelihood of having migraine (estrogen)

Sudden decreases in estrogen can trigger migraine headaches

Fall in estrogen

Prior to menses

Pill free week of oral contraceptives

Perimenopause

Postpartum

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Migraine Throughout the (Hormonal) Life CycleChildren

Adolescence – Puberty

Menstruation

Pregnancy

Menopause

Other:

Hormone replacement therapy

Oral contraceptives

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Migraine in Children

Boys=girls prior to puberty Peak incidence of migraine with aura

Boys – age 5

Girls – age 12-13

Peak incidence of migraine without aura

Boys – age 10-11

Girls – age 14-17

After puberty ratio is 3 to 1

(girls to boys)

Boys often outgrow them

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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

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Think about migraine in children with:

Episodes of unexplained vomiting and abdominal pain lasting an hour or more

Attacks of imbalance or dizziness lasting minutes

Recurring attacks of head tilt, vomiting, imbalance lasting hours to days

Alternating one-sided weaknessHeadaches followed by droopy eyelid and

double vision (lasting days to weeks)

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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 cycles

Menstrually-Related MigraineWithin the above window and at other times of the month

Perimenstrual MigraineAttacks 2-7 days prior to menses

Keep a diary! Compare menstrual and non-menstrual attacks.

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May Be Associated with Other Features of PMS

(DSM-4: 5 days before to 4 days into menses, interfere with activities)

Affective

Depression

Angry outbursts

Irritability

Anxiety

Confusion

Social withdrawal

Food cravings

Increased appetite

Sexual disinterest

Physical

Breast tenderness

Abdominal bloating

Headache

Peripheral edema

Acne

Cramping

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What’s Different During Menses?

No difference in sex hormones between migraineurs and controls (testosterone, LH, FSH)

Headaches more severe, more

nausea and vomiting

Treatments may not

be as effective during

menses (?)

Loder E. Neurol Sci 2005;26:S121-124

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Treatment of Menstrual MigraineAcute symptomatic treatment

Migraine specific, anti-inflammatoriesStandard preventive treatmentShort-term preventive treatment (“mini-

prevention”)Non-steroidal anti-inflammatoriesLong-acting triptans (frova) or ergots MagnesiumHormonal therapy (estradiol gel)Increase usual preventative

Non-pharmacologic therapy

**Pringsheim T, et al. Acute treatment and prevention of menstrually related migraine headache. Neurology 2008;70:1555-1563

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Use of Oral Contraceptives to Prevent Menstrual Migraine

1. 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 month

3. Contraceptive patch + vaginal ringLess daily fluctuation in estrogen level

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Migraine and Pregnancy

Better (50-60+%)

Worse (15-%)

The Same (25%)

May worsen during the first trimester

May only occur during pregnancy

May be headache free in last trimester

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New Onset of Headaches During Pregnancy

Increased intracranial pressure

Tension-type headache

Cerebral venous sinus thrombosis

Stroke

Tumor

Vasculitis

Intracranial hemorrhage

Reversible cerebrovasoconstrictive syndrome (RCVS)

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Headache Medications and Pregnancy – General Concepts

Pharmakokinetics vary during gestation

Increased plasma volume – increase unbound drug

Decreasing albumin – increase free fraction (total assays unreliable)

Increased renal clearance

Changes 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.

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Symptomatic Treatment of Migraine During Pregnancy (Category B – no evidence of risk but no studies)

AcetaminophenCaffeineIbuprofen*Indomethacin*Naproxen*MeperidineMorphinePrednisone

*Avoid in third trimester

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Barbiturates, opioids, benzodiazepines

Neonatal withdrawal syndrome

Opioids are category B

Beware medication overuseTriptans are all category CErgots are contraindicated

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Treatment of Migraine-Related Nausea (Category B)

Dimenhydramine Meclizine

Metoclopramide

Ondansetron

Anticholinergics – meconium ileus

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Migraine Prevention During Pregnancy (Category B/C)

Avoid migraine triggers

Beta blockers (C)

Fluoxetine (C)

Venlafaxine (C)

Vitamin B2 (B)

Coenzyme Q-10 (B)

Magnesium (B)

Avoid valproate, topiramate, AEDs, lithium (D)

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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

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Is the drug necessary?

Use the safest one

Consider measuring blood levels in the infant

Take medication after completing a breast feeding to minimize exposure to the baby

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Symptomatic Treatment While Breast Feeding

Compatible

Acetaminophen, caffeine, NSAID

Caution

Aspirin, barbiturates

Triptans

Concern

Benzodiazepines

Contraindicated

Antihistamines

Ergotamine/DHE

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Preventive Treatment While Breast Feeding

CompatibleBeta blockersCalcium blockersValproateCorticosteroidsAmitriptyline

CautionSSRI

ConcernTricyclic antidepressantsVerapamil

ContraindicatedBromocriptine

**Hale TW. Medications and Mother’s Milk. Amarillo, TX, Hale Publishing, 2008.

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Perimenopause

Women with a history of menstrual migraine (“hormonally sensitive”) may have worsening of migraines in peri-menopause

Treatment:Hormone replacement therapy

Low dose OC (without placebo week)

Standard migraine therapies

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MenopauseMigraine and natural

menopause:

20-40% worsen

20-30% improve

30-50% unchanged

Effect of surgical menopause:

(hysterectomy, oophorectomy)

38-87% worsen

Some women develop migraines for the first time at menopause

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Hormone Replacement Therapy?

Conflicting data regarding migraineConsiderations:

Delivery (patch*, cream, pill, injection)Need for continuous useType and dosage

Natural estrogens (estradiol) are better tolerated than conjugated estrogen

One size does not fit allRisk-benefit ratio

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Migraine and Stroke

Women under 45

Posterior circulation strokes and white matter lesions more likely in MWA and high attack frequency of migraine than controls

Women 45 years and older

MWA twice as likely to develop ischemic stroke and MI over 10 years of follow-up

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Ferrari M, et al. Brain 2005

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Migraine and Stroke

Numerous studies document increase risk:

National Health and Nutrition Examination Survey – prospective (11,777 men and women; RR 2.1)

Meta-analysis of 14 observational studies

Risk among all migraineurs, OR = 2

MWA, OR = 2.9

MWOA, OR = 1.6

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Women’s Health StudyProspective cohort study of 39,754 health

professionals ages 45 and olderNo migraine or MWOA – no increased risk

MWA – Adjusted hazards ratio

1.53 for total stroke

1.71 for ischemic stroke

No increased risk for hemorrhagic stroke

Women < 55 with MWA had greatest risk:

1.75 for total stroke

2.25 for ischemic stroke

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Stroke Risk: Low Dose OCs

Meta analysis of 16 studies (Gillum)RR = 1.92 (1.4-2.7) controlling for smoking and hypertension = 1 additional stroke per 24,000

Meta analysis of 14 studies (Baillargeon)RR 1.84 (1.4-2.4) with low dose OC useAlso risk of 2nd and 3rd generation OC use

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Risk of Stroke Varies by Age: Women

9 per 100,000 in 20-year-old MWA

3 per 100,000 in 20-year-old w/o migraine

80 per 100,000 in 40-year-old MWA

11 per 100,000 in 40 year-old w/o migraine

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Summary of Risk

Migraine 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 = 2OC increase risk of venous sinus thrombosis, OR = 22OC increase risk of subarachnoid hemorrhage, OR = 1.6

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Recommendations (ACOG, WHO, IHS)

Women with migraine should minimize other vascular risks

Women with MWOA on hormone therapy should stop if aura develops or headache worsens

Women with migraine over 35 who smoke should not use OCs

Women with a history of stroke or venous clot should not use OCs

Controversy: Women with MWA should not use hormonal therapy

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Migraine and Cardiovascular Disease (Women’s Health Study)

580 major CVD events occurredActive MWA: hazard ratio 2.15 overall

1.91 for ischemic stroke2.08 for MI1.74 for coronary revascularization1.71 for angina2.33 for ischemic CVD death

18 additional major CVD events/10,000 women per year, after adjusting for age

MWOA: No increased risk

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Migraine as a Clinically Progressive Disorder

Episodic migraine evolves over time in some patients, AKA “transformed migraine”

Attacks increase in frequency (medication overuse)

Chronic daily headache (>180 days yearly) with superimposed migraine

Development of allodynia

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Risk Factors for Development of Chronic Daily Headache

Definition: Headache on more days than not (> 15 days monthly X 3 months

Case-control, cross sectional population study

Longitudinal follow-up for progression

800 people with episodic headache

3% developed CDH

6% developed 105-179 HA days

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Predictors of Progression

Medication overuse

Especially OTC with caffeine combinations, narcotic combinations, barbiturate combinations

Weight: Overweight = 2X, Obesity = 5X!!

Baseline headache frequency (>1/wk)

Low socioeconomic status

Head injury

Lipton RB, Bigal M. Headache 2005; 45 (suppl 1) S3-S13Goadsby PJ. Med J Austr 2005;182(3):103-4

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Stressful life events (moving, death in family, work-related changes)

Snoring

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Risk Factors and Development of CDH

Not readily modifiable

Migraine as a disorder

(predisposition)

Female sex

Low SES

Head injury

Modifiable

Attack frequency

Obesity

Medication overuse

Stressful life events

Snoring (OSA and other sleep disorders)

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Central Sensitization and Allodynia

Allodynia – a normally non-painful stimulus becomes painful

Occurs in 75% of migraineurs during migraine

Usually takes years to develop

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Allodynia – Taking the HistoryPositive in 70%

Peripheral sensitizationThrobbing qualityHair / eye glasses / earrings hurtHurts to touch: shave, sleep, wash

Central sensitizationPain is worse with coughing, sneezingTriptans less likely to work when central allodynia is present

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Implications for Treatment

Stratified care based on disability

Reduce environmental triggers, if present

Weight management

Investigate for sleep disorder when appropriate

Prophylaxis

Reduce modifiable cardiovascular risk

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Stratified Care by Overall DisabilityLittle to none “Low end” Triptans

Moderate Combination treatments

Triptans Anti-emetics

Prophylaxis

Severe “High end” Triptans

Prophylaxis Narcotics

Anti-emetics Ergots

Refer to specialist

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Summary

Women are different.Migraines change throughout the reproductive cycle.Estrogen is important.Migraine may be progressive – consider preventive treatment.

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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

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Kurth T, Gaziano JM, Cook NR, et al. Migraine and risk of cardiovascular disease in women. JAMA 2006;296;283-291

Lipton RB, Bigal ME. Ten lessons on the epidemiology of migraine. Headache 207;46(Suppl1):S2-S9

McGregor EA. Prevention and treatment of menstrual migraine. Drugs 2010;70:1799-818

Sullivan E, Bushnell C. Management of menstrual migraine: a review of current abortive and prophylactic therapies. Curr Pain Headache Rep 2010;14:376-84