Migraine Primary Care Conference July 29, 2010 Samuel Ash, MD Resident, Internal Medicine University of Washington [email protected].

MigraineMigraine

Primary Care ConferencePrimary Care ConferenceJuly 29, 2010July 29, 2010

Samuel Ash, MDSamuel Ash, MDResident, Internal MedicineResident, Internal MedicineUniversity of WashingtonUniversity of Washington

[email protected]@uw.edu

OutlineOutline CasesCases EpidemiologyEpidemiology CostsCosts PathophysiologyPathophysiology DiagnosisDiagnosis TreatmentTreatment

• AbortiveAbortive• PreventativePreventative

Special considerationsSpecial considerations SummarySummary

CasesCases

Case Number 1: 32 year old woman Case Number 1: 32 year old woman with no other significant medical with no other significant medical history who states that she has history who states that she has frequent severe headaches and has frequent severe headaches and has previously been diagnosed with previously been diagnosed with migraine.migraine.

CasesCases

Case Number 2: 43 year old woman with Case Number 2: 43 year old woman with self-reported history of:self-reported history of:• Migraine without auraMigraine without aura• Seizure disorderSeizure disorder• DepressionDepression• AnxietyAnxiety• PMDDPMDD

Chart history of:Chart history of:• Axis II, cluster B disorderAxis II, cluster B disorder• Benzodiazepine and opiate dependence/abuseBenzodiazepine and opiate dependence/abuse

EpidemiologyEpidemiology 1 year prevalence:1 year prevalence:

• overall: 11.7%overall: 11.7% women: 17.1%women: 17.1% men: 5.6%men: 5.6%

• additional 4.5% additional 4.5% have "probable have "probable migraine“migraine“

Lifetime Lifetime prevalence:prevalence:• Women: 25%Women: 25%• Men: 8%Men: 8%

Image from yourhealth.net.au

EpidemiologyEpidemiology

EpidemiologyEpidemiology

Chronic migraine:Chronic migraine:• 1-year period 1-year period

prevalence 1-2%prevalence 1-2%

Migraine among Migraine among neurologistsneurologists• 50% prevalence50% prevalence

Migraine among Migraine among headache specialistsheadache specialists• 75% prevalence75% prevalence

EpidemiologyEpidemiology Famous migraineurs Famous migraineurs

(suspected or known)(suspected or known)• Lewis CarrollLewis Carroll• Elvis PresleyElvis Presley• Joan of ArcJoan of Arc• Elizabeth TaylorElizabeth Taylor• Julius CaesarJulius Caesar• Napoleon BonaparteNapoleon Bonaparte• Thomas JeffersonThomas Jefferson• Ulysses GrantUlysses Grant• Frederich NietzscheFrederich Nietzsche• Sigmund FreudSigmund Freud• Claude MonetClaude Monet• Alexander Graham BellAlexander Graham Bell• Terrell DavisTerrell Davis

http://www.aiws.info/

Cost to SocietyCost to Society Direct Costs:Direct Costs:

• Total cost of annual medical care:Total cost of annual medical care: Family with migraineur: $7007 per yearFamily with migraineur: $7007 per year Family without migraineur: $4435 per yearFamily without migraineur: $4435 per year

• National Burden: $11 billionNational Burden: $11 billion $4.6 billion was in prescription drugs$4.6 billion was in prescription drugs $5.2 billion in outpatient costs$5.2 billion in outpatient costs $0.5 billion in ER$0.5 billion in ER $0.7 billion in inpatient costs $0.7 billion in inpatient costs

Cost to SocietyCost to Society

Indirect Costs:Indirect Costs:• Estimated to be approximately $13.3 billionEstimated to be approximately $13.3 billion• Due to missed work days and impaired work Due to missed work days and impaired work

performance performance • Does not include:Does not include:

unemployment or underemployment unemployment or underemployment burden experienced between attacksburden experienced between attacks lost home-worker time due for choreslost home-worker time due for chores lost time because of caring for family members with lost time because of caring for family members with

migraine. migraine.

PathophysiologyPathophysiology

??

GeneticsGenetics

Familial hemiplegic migraineFamilial hemiplegic migraine• Three different abnormal genesThree different abnormal genes• Mutations relate to ion channel function Mutations relate to ion channel function

and neuronal hyperexcitabilityand neuronal hyperexcitability

GeneticsGenetics 1p13.31p13.3Glutathione S-Transferase Glutathione S-Transferase

(GST)(GST) MOMO

1 p361 p36 MTHF-RMTHF-R MAMA

4 q244 q24 ?? MA & MOMA & MO

4 q214 q21

4q31.24q31.2Endothelin type A (ETA-231 Endothelin type A (ETA-231

A/G)A/G) Not specifiedNot specified

6p21.36p21.3Tumor necrosis factor α Tumor necrosis factor α

(TNFα)(TNFα) Not specifiedNot specified

6p21.36p21.3 HLA-DRB1HLA-DRB1 MOMO

6q25.16q25.1 Estrogen receptor 1 (ESR1)Estrogen receptor 1 (ESR1) MA & MOMA & MO

6q25.16q25.1 Estrogen receptor 1 (ESR1)Estrogen receptor 1 (ESR1)Not specified Not specified

Females onlyFemales only

9q349q34Dopamine β-hydroxylase Dopamine β-hydroxylase

(DBH)(DBH) Not specifiedNot specified

11 q2411 q24 ?? MAMA

11 p1511 p15 DRD4DRD4 MOMO

11q22-2311q22-23 Progesterone receptor (PGR)Progesterone receptor (PGR) MA & MOMA & MO

11q2311q23

DRD2 Allele 1 TG DRD2 Allele 1 TG dinucleotide non-dinucleotide non-codingcoding MOMO

11q2311q23 Dopamine D2 (DRD2) NcoIDopamine D2 (DRD2) NcoI MAMA

14 q21-2214 q21-22 ?? MOMO

17q11.1-q1217q11.1-q12Human serotonin Human serotonin

transporter (SLC6A4)transporter (SLC6A4) MA & MOMA & MO

17q2317q23Angiotensin converting Angiotensin converting

enzyme (ACE)enzyme (ACE) MOMO

19p13.3/219p13.3/2 Insulin receptor INSRInsulin receptor INSR Not specifiedNot specified

22q11.222q11.2

Catechol-Catechol-OO--methyltransferase methyltransferase (COMT)(COMT) not specifiednot specified

X q24-28X q24-28 ?? MOMO


Syndromic approach with migraine Syndromic approach with migraine as “final common pathway”as “final common pathway”

Maladaptive activation of trigeminal Maladaptive activation of trigeminal cervical pain apparatuscervical pain apparatus• Early warning system to protect the Early warning system to protect the

brain and cervical cord from injurybrain and cervical cord from injury


AuraAura• cortical spreading cortical spreading

depressiondepression• initially decreased initially decreased

and then increased and then increased blood flowblood flow

• may be related to may be related to initiation of initiation of migraine migraine

Image courtesy of http://migraine.co.nz/

PathophysiologyPathophysiology Micro-emboliMicro-emboli

• Increased prevalence of PFO in patients with Increased prevalence of PFO in patients with migraine with auramigraine with aura

• Uncontrolled of PFO closure trials promisingUncontrolled of PFO closure trials promising• Controlled studies thus far not as promisingControlled studies thus far not as promising

Types of MigraineTypes of Migraine

Migraine without aura (common migraine)

Migraine with aura (classic migraine)• Typical aura with migraine headache• Typical aura with non-migraine headache• Typical aura without headache• Familial hemiplegic migraine• Sporadic hemiplegic migraine• Basilar-type migraine

DiagnosisDiagnosis

International International Classification of Classification of Headache Headache Disorders (ICHD)Disorders (ICHD)

Very detailed set of Very detailed set of criteria available criteria available at:at:

http://www.ihs-http://www.ihs-classification.org/enclassification.org/en

DiagnosisDiagnosis

Alternative (ie shorter) history:Alternative (ie shorter) history:• POUNDPOUND

PPulsatile quality of headacheulsatile quality of headache OOne day duration (usually 4-72 hours)ne day duration (usually 4-72 hours) UUnilateral locationnilateral location NNausea or vomitingausea or vomiting DDisabling intensityisabling intensity

• 3/5 criteria = likely migraine3/5 criteria = likely migraine• 4/5 criteria = very likely to be migraine4/5 criteria = very likely to be migraine

DiagnosisDiagnosis

Prodrome vs. AuraProdrome vs. Aura• ProdromeProdrome

Euphoria, depression, fatigue, hypomania, Euphoria, depression, fatigue, hypomania, food cravings, dizziness, cognitive slowing, food cravings, dizziness, cognitive slowing, or astheniaor asthenia

Occurs in 60-70% of migraine patientsOccurs in 60-70% of migraine patients

• AuraAura Visual changes, loss of vision, hallucinations, Visual changes, loss of vision, hallucinations,

numbness, tingling, weakness, or confusionnumbness, tingling, weakness, or confusion Occurs in 15-20% of migraine patientsOccurs in 15-20% of migraine patients

DiagnosisDiagnosis Consider headache diary to better Consider headache diary to better

determine triggers, etc.determine triggers, etc.

http://www.relieve-migraine-headache.com/diary-headache-migraine.html

Developmental HistoryDevelopmental History

Childhood periodic syndromes that are commonly precursors of migraine• Cyclical vomiting• Abdominal migraine• Benign paroxysmal vertigo of childhood

Alarm FeaturesAlarm Features

Alarm FeaturesAlarm FeaturesBased on HistoryBased on History

Changes in headache pattern/freq/intensityChanges in headache pattern/freq/intensity Daily headacheDaily headache Blurred visionBlurred vision Dizziness/syncope/discoordination/focal neuro Dizziness/syncope/discoordination/focal neuro

deficitsdeficits Sudden/explosive onsetSudden/explosive onset Pain worse with coughingPain worse with coughing Change in personalityChange in personality Headache that wakes you up from sleepHeadache that wakes you up from sleep Onset after 50 years of ageOnset after 50 years of age

Alarm FeaturesAlarm FeaturesBased on PhysicalBased on Physical

• Vitals: fever or hypertension (diastolic >120)Vitals: fever or hypertension (diastolic >120)• Mental status changeMental status change• Meningeal signsMeningeal signs• Diminished pulse or tenderness of temporal Diminished pulse or tenderness of temporal

arteryartery• Focal neurologic deficits: including visual Focal neurologic deficits: including visual

acuityacuity• PapilledemaPapilledema• Intraocular pressureIntraocular pressure• Necrotic or tender scalp lesionsNecrotic or tender scalp lesions• Other signs of infectionOther signs of infection

LabsLabs

ESRESR• Indicated for new onset headache if Indicated for new onset headache if

age>50 age>50 • Screens for temporal arteritis and other Screens for temporal arteritis and other

vasculitidesvasculitides• Obtain even if symptoms consistent with Obtain even if symptoms consistent with

migrainemigraine• Headache is predominant feature in 65-Headache is predominant feature in 65-

80% of patients with temporal arteritis80% of patients with temporal arteritis

Neuro-ImagingNeuro-Imaging

Neuro-ImagingNeuro-Imaging

Consider if:Consider if:• Atypical migraine featuresAtypical migraine features• Substantial change in headache patternSubstantial change in headache pattern• Signs or symptoms of neurologic Signs or symptoms of neurologic

abnormalitiesabnormalities

EEGEEG

Consider only if associated Consider only if associated symptoms suggest a seizure symptoms suggest a seizure disorder.disorder.

No useful headache subtype groups No useful headache subtype groups are defined by EEGare defined by EEG

EEG is not able to identify patients EEG is not able to identify patients with structural cause of headacheswith structural cause of headaches

TreatmentTreatment ““My migraine only gets better with that ‘d’ My migraine only gets better with that ‘d’

drug. You know, d…d…dilaudid…”drug. You know, d…d…dilaudid…” ““My dilaudid only works IV and only if I get My dilaudid only works IV and only if I get

at least 8mg at once.”at least 8mg at once.” ““I have to get benadryl with it or I get I have to get benadryl with it or I get

itchy – I need 50mg… It has to be IV.”itchy – I need 50mg… It has to be IV.” ““I’m sooo nauseated too. I’m allergic to all I’m sooo nauseated too. I’m allergic to all

the anti-nausea medications except IV the anti-nausea medications except IV phenergan.”phenergan.”

- Patient from my last night in the UWMC ED - Patient from my last night in the UWMC ED

TreatmentTreatment

Brust’s Rule: if we have a lot of Brust’s Rule: if we have a lot of treatments for a disease… none treatments for a disease… none must work very well…must work very well…

Images from migraine support blogs

Treatment: Non-PharmacologicTreatment: Non-Pharmacologic


DietDiet• Some benefit to elimination dietsSome benefit to elimination diets• 20% of patients report dietary triggers20% of patients report dietary triggers• Common triggers:Common triggers:

Caffeine Caffeine withdrawalwithdrawalPackaged meatsPackaged meatsMSGMSGDairyDairyFatty foodsFatty foods

Aged cheeseAged cheeseRed wineRed wineBeerBeerChampagneChampagneChocolateChocolate

Treatment: Non-PharmacologicTreatment: Non-Pharmacologic AlcoholAlcohol

• ““If you must drink, no If you must drink, no more than two normal more than two normal size drinks”size drinks”

• ““Suggested drinks:Suggested drinks: RieslingRiesling Seagram’s VOSeagram’s VO Cutty SarkCutty Sark Vodka”Vodka”

- As per Diamond S and - As per Diamond S and Dalessio DJ. The practicing Dalessio DJ. The practicing physician’s approach to physician’s approach to headache. New York: headache. New York: Williams and Wilkings. 1982.Williams and Wilkings. 1982.


BehavioralBehavioral• Shown to be effective Shown to be effective

30-50% reduction of migraine frequency30-50% reduction of migraine frequency ModalitiesModalities

• Relaxation trainingRelaxation training• Thermal biofeedback with relaxation trainingThermal biofeedback with relaxation training• Electromyogram biofeedbackElectromyogram biofeedback• Cognitive behavioral therapyCognitive behavioral therapy

• No data to guide selection of modality…No data to guide selection of modality…

Treatment: AbortiveTreatment: Abortive

Tenets:Tenets:• Educate migraine sufferersEducate migraine sufferers• Use migraine specific agents in severe Use migraine specific agents in severe

diseasedisease• Non-oral route for patients with Non-oral route for patients with

significant nausea and vomitingsignificant nausea and vomiting• Be aware of medication overuse and Be aware of medication overuse and

reboundrebound

Treatment: AbortiveTreatment: Abortive

When to treat?When to treat?• EARLYEARLY• Within 2 hoursWithin 2 hours• Treatment during Treatment during

prodrome or aura is prodrome or aura is even more effectiveeven more effective

Image courtesy of denverpost.com

Treatment: Mild to ModerateTreatment: Mild to Moderate

NSAIDSNSAIDS• IbuprofenIbuprofen• NaproxenNaproxen• DiclofenacDiclofenac• Tolfenamic acidTolfenamic acid• Indomethacin suppositoryIndomethacin suppository

AspirinAspirin TylenolTylenol CombinationsCombinations

Treatment: SevereTreatment: Severe

If severe symptoms present then If severe symptoms present then don’t bother with OTC preparationsdon’t bother with OTC preparations• Improved outcomes with migraine Improved outcomes with migraine

specific therapyspecific therapy Consider route of administrationConsider route of administration Consider contraindications/PMHConsider contraindications/PMH

Treatment: TriptansTreatment: Triptans

First lineFirst line• More effectiveMore effective• Less nauseaLess nausea

ContraindicationsContraindications• CADCAD• CostCost

RoutesRoutes• OralOral• IntranasalIntranasal• SubcutaneousSubcutaneous Image courtesy of headaches.about.com


Mechanism of ActionMechanism of Action• Selective serotonin agonistSelective serotonin agonist• 5HT1B/1D5HT1B/1D

Pharmacokinetics/dynamicsPharmacokinetics/dynamics• Both long and short acting availableBoth long and short acting available• Long acting more effective during aura Long acting more effective during aura

but take longer to actbut take longer to act• Short acting have more side effects Short acting have more side effects


OptionsOptions• Sumatriptan (subq/nasal/oral)Sumatriptan (subq/nasal/oral)• Almotriptan (oral)Almotriptan (oral)• Eletriptan (oral)Eletriptan (oral)• Frovatriptan (oral)Frovatriptan (oral)• Naratriptan (oral)Naratriptan (oral)• Rizatriptan (oral/ODT)Rizatriptan (oral/ODT)• Zolmitriptan (oral)Zolmitriptan (oral)


Which one to choose…Which one to choose…• No class effectNo class effect• Recurrent headache may indicate need Recurrent headache may indicate need

for repeat dose, not new triptanfor repeat dose, not new triptan• Pharmacokinetics/dynamicsPharmacokinetics/dynamics• Side effect profileSide effect profile


Which one to choose…Which one to choose…• Specific concernsSpecific concerns

TeratogenicityTeratogenicity Menstrual migraineMenstrual migraine Subq Subq

• not effective during prodrome/auranot effective during prodrome/aura• More contraindicationsMore contraindications

Treatment: DihydroergotamineTreatment: Dihydroergotamine Mechanism of ActionMechanism of Action

• Non-selective serotonin agonistNon-selective serotonin agonist RoutesRoutes

• NasalNasal• SubqSubq• IMIM• IVIV

ContraindicationsContraindications• Pregnancy (category X)Pregnancy (category X)• Cannot be used with a triptanCannot be used with a triptan• IV contraindicated in CADIV contraindicated in CAD

Treatment: AdjunctsTreatment: Adjuncts

Anti-emeticsAnti-emetics• Metoclopromide both as adjunct and Metoclopromide both as adjunct and

mono-therapymono-therapy• Ondansetron IV/oral/ODTOndansetron IV/oral/ODT

CaffeineCaffeine• ReboundRebound

SteroidsSteroids• DexamethasoneDexamethasone• PrednisonePrednisone

Treatment: RescueTreatment: Rescue

OpiatesOpiates• Should be used only a few times per Should be used only a few times per

yearyear

Up to ½ of patients with recurrent Up to ½ of patients with recurrent headache do not adhere to drug headache do not adhere to drug treatment regimentreatment regimen

Treatment: PreventionTreatment: Prevention


Definitely consider:Definitely consider:• Disabling Disabling

headaches > 2x per headaches > 2x per monthmonth

• Poor relief from Poor relief from abortive therapyabortive therapy

• Uncommon Uncommon migrainemigraine

BasilarBasilar HemiplegicHemiplegic

Might consider:Might consider:• Contraindication to Contraindication to

acute therapyacute therapy• Failure of acute Failure of acute

therapytherapy• Preference for Preference for

preventative preventative therapytherapy

Treatment: PreventionTreatment: Prevention Rules to live by:Rules to live by:

• Headache diaryHeadache diary• PatiencePatience• No right agentNo right agent• Consider:Consider:

Side effectsSide effects Other benefitsOther benefits


AntihypertensivesAntihypertensives• All agents effectiveAll agents effective• Best evidence for Best evidence for beta blockersbeta blockers• Limited evidence for Limited evidence for CCBCCB• ACEACE and and ARBARB also effective also effective• No evidence for diureticsNo evidence for diuretics


AntidepressantsAntidepressants• Depression or other psychiatric disorder Depression or other psychiatric disorder

often co-morbid conditionoften co-morbid condition• Lack of evidence for Lack of evidence for SSRIsSSRIs• TricyclicsTricyclics and and mirtazepine mirtazepine shown to shown to

have some benefithave some benefit


AnticonvulsantsAnticonvulsants• Valproate (FDA approved)Valproate (FDA approved)

At least as effective as b-blockerAt least as effective as b-blocker May be better toleratedMay be better tolerated

• Topiramate (FDA approved)Topiramate (FDA approved) Requires slightly higher dosesRequires slightly higher doses Weight loss benefitWeight loss benefit

• GabapentinGabapentin Not FDA approved but appears effectiveNot FDA approved but appears effective


Other agentsOther agents• Botulinum toxin injections: not Botulinum toxin injections: not

recommendedrecommended• Coenzyme Q10: small studiesCoenzyme Q10: small studies• Magnesium: mixed resultsMagnesium: mixed results• Butterbur (herbal): minimal evidenceButterbur (herbal): minimal evidence• Feverfew (herbal): resultsFeverfew (herbal): results

Special Consideration: Special Consideration: Rebound and OveruseRebound and Overuse

Can occur with almost any headache Can occur with almost any headache medicationmedication

To avoid:To avoid:• Limit acute medications to no more than 10 Limit acute medications to no more than 10

days per monthdays per month• Preventative therapies as mainstay of Preventative therapies as mainstay of

treatmenttreatment• Use headache diaryUse headache diary

Special Consideration: Special Consideration: HospitalizationHospitalization

Status migranosisStatus migranosis• Prolonged (>72h), intractable migraineProlonged (>72h), intractable migraine• Associated nausea and vomitingAssociated nausea and vomiting

Overuse headacheOveruse headache• Inpatient weaningInpatient weaning

Special Consideration: Special Consideration: Menstrual MigraineMenstrual Migraine

Estrogen effectsEstrogen effects Two typesTwo types

• Pure menstrual migrainePure menstrual migraine• Menstrually related migraineMenstrually related migraine

TreatmentTreatment• Usual abortive therapyUsual abortive therapy• Estrogen-progestin OCP in extended cycleEstrogen-progestin OCP in extended cycle• Menstrually targeted supplemental estrogenMenstrually targeted supplemental estrogen• Long acting triptan prophylaxisLong acting triptan prophylaxis• Some evidence for SERMsSome evidence for SERMs

Special Consideration: Special Consideration: Migraine and StrokeMigraine and Stroke

WHOWHO• Avoid estrogen containing OCPs:Avoid estrogen containing OCPs:

Migraine + over age of 35Migraine + over age of 35 Migraine with auraMigraine with aura

ACOGACOG• Avoid estrogen containing OCPs:Avoid estrogen containing OCPs:

Migraine + over age of 35Migraine + over age of 35 Migraine + focal neurologic signsMigraine + focal neurologic signs Migraine + smokingMigraine + smoking

Special Consideration: Special Consideration: Other Migraine DisordersOther Migraine Disorders

Retinal migraine Complications of migraine

• Chronic migraine• Status migrainosus• Persistent aura without infarction• Migrainous infarction• Migraine-triggered seizure

Special Consideration: Special Consideration: Other Migraine DisordersOther Migraine Disorders

Probable migraine• Probable migraine without aura• Probable migraine with aura• Probable chronic migraine

SummarySummary

Migraine is exceedingly commonMigraine is exceedingly common• 1 in 4 women, nearly 1 in 10 men1 in 4 women, nearly 1 in 10 men

Unclear pathophysiologyUnclear pathophysiology Diagnosis based primarily on historyDiagnosis based primarily on history

• POUNDPOUND TreatmentTreatment

• Abortive: focus on migraine specific therapiesAbortive: focus on migraine specific therapies• Preventative: focus on patiencePreventative: focus on patience

Special casesSpecial cases

Resources and Further ReadingResources and Further Reading

Bartleson JD and Cutrer M. Migraine Update: Diagnosis and Treatment. Minn Med. May 2010.

In the Clinic: Migraine. Annals of Int Med. 2007;9:1-16.

Dr. Natalia Murinova• UWMC Headache Clinic

ReferencesReferences Catterall WA, Dib-Hajj S, Meisler MH, Pietrobon D. Inherited

neuronal ion channelopathies: new windows on complex neurological diseases. J Neurosci. 2008;28(46):11768-77.

Charles A. Advances in the basic and clinical science of migraine. Ann Neurol. 2009;65(5):491-8.

Cutrer FM. Pathophysiology of Migraine. Semin Neurol 2010; 30(2): 120-130.

Evans RW, Lipton RB, Silberstein SD. The prevalence of migraine in neurologists. Neurology 2003;61:1271-2.

Evans RW. Migraine: A question and answer review. Med Clin N Am 2009;93:245-62.

General Household Survey, Office for National Statistics. Fourth National Morbidity Study from General Practice 1991/92, Office for National Statistics. http://www.statistics.gov.uk/

Hawkins K, Rupnow M, Wang S. Direct cost burden of migraine among members of US employers. Value Health 2006;9:A85.

ReferencesReferences Hazard E, Munakata J, Bigal ME, Rupnow MF, Lipton RB. The

burden of migraine in the United States. Value Health 2009;12:55-64.

Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med 1999;159:813–8.

IHS – International Headache Society; http://www.ihs-classification.org/en/

Lipton RB, Bigal, ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007;68:348-9.

Michel P, Dartigues JF, Henry P, et al. Validity of the IDHS criteria for migraine. Neuroepidemiology. 1993;12:51-7.

Silberstein S, Loder E, Diamond S, et al. Probable migraine in the United States: results of the American Migraine Prevalence and Prevention Study. Cephalagia 2007;27:220-34.

UpToDate. Online 18.2.

Migraine Primary Care Conference July 29, 2010 Samuel Ash, MD Resident, Internal Medicine University of Washington [email protected].

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