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Headache ManagementHeadache ManagementMigraines and Persistent PainMigraines and Persistent Pain

STUART B BLACK, M.D; FAAN

MEDICAL DIRECTOR

DALLAS HEADACHE ASSOCIATION

1201 Migraine causes average of 11/2 hours lost work time per weekMigraine causes average of 11/2 hours lost work time per weekMigraine cost employers $13 billion per / yr in lost productivityMigraine cost employers $13 billion per / yr in lost productivity

69% have reduced work effectiveness during a MH attack 69% have reduced work effectiveness during a MH attack

Fortunately your headache isn’t a serious problem.

I don’t know what to do. I bet he thinks I just have a headache but I’m about to

lose my job

1201 91% of migraineurs experience functional impairment91% of migraineurs experience functional impairment25% or migraineurs have at least one attack per week25% or migraineurs have at least one attack per week

$14 Billion annual expense for direct & indirect medical costs $14 Billion annual expense for direct & indirect medical costs

Don’t worry. We have pain Medications to get rid of your migraine. You can even

repeat them if needed.

I am worried. If my headache isn’t gone within 1 to 2 hours, I’m done

for the day; not only will I not make it to work but tonight I will be in bed and won’t be able to enjoy

my family.

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Migraine Is an Episodic Recurrent Headache Lasting 4-72 Hours with:

International Headache SocietyInternational Headache SocietyCriteria For MigraineCriteria For Migraine

+unilateral pain

throbbing pain

nausea

vomiting

Any 2 of these pain qualities: Any 1 associated symptoms

Migraine With AuraSymptoms develop gradually over >5 minutesSymptoms last less than 60 minutesHeadache follows aura with free interval of < 60 minutes

Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders. 2nd edition. Cephalalgia. 2004;24(suppl 1):117-118.

+throbbing pain

pain worsened by movement movement

moderate / severe pain

vomiting

photophobia and / or phonophobia

The SelfThe Self--Administered 3Administered 3--Item ID Item ID Migraine Questionnaire in Primary CareMigraine Questionnaire in Primary Care

Dysfunction: Have you had “functional impairment due to headache in last 3 months”?Photophobia: Does “light bother you (a lot more than when you don’t have headaches)”?Nausea: Do “you feel nauseated or sick to yourNausea: Do you feel nauseated or sick to your stomach”?

Migraine indicated when more than 2 items are endorsed

Lipton RB, et al. Neurology. 2003;61:375-382.

The positive predictive value is 93% when 2 or more symptoms are present

Classic Vascular Theory Classic Vascular Theory of Migraineof Migraine

Aura PhaseSpasm of Cerebral Arteries

Headache PhaseVasodilation of Cerebral Arteries

Wolf HG. Headache and Other Head Pain. 1963.

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1201 How Does Migraine BeginHow Does Migraine BeginCortical Spreading DepressionCortical Spreading Depression

Platelet Activation

Glutamate ReleaseExcitotoxicity

Leaky BBBBrain Edema

VasodilatationInflammation

Slowed arterial flowOligemia

IntravascularCoagulation

Decreases CBF 20% to 30% for 2 -6 hours

CSD Stimulates Trigeminal Sensory Fibers CSD Stimulates Trigeminal Sensory Fibers

Trigeminal nerve fibers in the meningeal blood vessel

1

2 3

CSD Releases Inflammatory NeruopeptidesCSD Releases Inflammatory NeruopeptidesCGRP, Substance P & Inflammatory CytokinesCGRP, Substance P & Inflammatory Cytokines

2 31

4 5 6

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Vasodilation and Edema in Local Blood Vessels Vasodilation and Edema in Local Blood Vessels Leaky BBB with Tissue Edema and InflammationLeaky BBB with Tissue Edema and Inflammation

CGRP and prostaglandins cause inflammation and vasodilation of cerebral and meningeal blood vessels as well as inflammation and edema of surrounding tissue

Central Trigeminal SensitizationCentral Trigeminal Sensitization

Cutaneousallodynia

Sensitizedperipheral

neuron(trigeminal

Activatedcentral neuron

Throbbing pain

Muscletenderness

Burstein R et al. Ann Neurol. 2004;55:27-36.

ganglion)

Midbrain

Pons

V1 V1V2 V2

V3 V3

CN IX CN IXCN X CN X

T TN N

Brainstem

MedullaCN X CN X

C2 C2

C1 C1

NC C

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Pain V1

V2

V3 V3

V1

T T

(Ophthalmic Nerve)

Brainstem

Pons

MidbrainV2

Pain C1

C2

T

N N

T

C C

(Occipital Nerve)

Medulla

CN IXCN X

CN IXCN X

Pain

V3 V3

V1

T T

Brainstem

Pons

MidbrainV2(Ophthalmic Nerve)

V1V1

V2

PainC2

T

N N

T

C C

(Occipital Nerve)

Medulla

C1Emesis Center

Nausea and Vomiting

CN X CN XCN IX CN IX

N NT TS SD D

V VC C

Pain

V3 V3

V1

T T

Brainstem

Pons

MidbrainV2(Ophthalmic Nerve)

V1V1

V2

PainC2

T

N N

T

C C

(Occipital Nerve)

Medulla

C1Emesis Center

Nausea and Vomiting

CN X CN XCN IX CN IX

N NT TS SD D

V VC C

GI MotilityGI Stasis

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Pain

V3 V3

V1

T T

Brainstem

Pons

MidbrainV2(Ophthalmic Nerve)

V1V1

Locus CeruleusPhotophobia

Phonophobia

V2

PainC2

T

N N

T

C C

(Occipital Nerve)

Medulla

C1Emesis Center

Nausea and Vomiting

CN X CN XCN IX CN IX

N NT TS SD D

V VC C

GI MotilityGI Stasis

Prolonged TNC Stimulation Prolonged TNC Stimulation Leads to Central SensitizationLeads to Central Sensitization

Cutaneous allodynia is a marker for central sensitization, which when present during a migraine, may make the migraine episode more difficult to treat

A sustained pain-free response is harder to achieve

Symptoms of Central SensitizationSymptoms of Central Sensitization

• Combing hair• Pulling hair back (ponytail)• Sh i

• Allowing shower water to hit the face (“it feels like pins and needles”)

Patients often avoid 1 or more of the following activities because of cutaneous allodynia

Burstein R et al. Ann Neurol. 2000;47:614-624.Burstein R et al. Brain. 2000;123:1703-1709.

• Shaving• Wearing eyeglasses• Wearing contact lenses• Wearing jewelry• Wearing snug clothing• Using a heavy blanket in bed

• Resting the face on the pillow on the migraine side

• Rubbing back of neck• Cooking (“the heat is too

much”)• Breathing through the nose

on cold days (“it burns”)

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Case # 1Case # 1

31-year-old graphic artist; on OC for number of years

2 yr history of moderate-to-severe unilateral headaches, lasting 1 to 3 days, often associated with nausea and vomiting. Episodic headaches occur at least 4 -6 times per month. In addition has debilitating headaches during menses. Those headaches last 2 – 4 days .

Takes high doses of gOTC, mostly Excedrin, with moderate to little relief. Has never consulted her physician

Gastric distress has developed due to OTC use

Pattern of Migraine Around MensesPattern of Migraine Around MensesA Clinical ClassificationA Clinical Classification

Premenstrual migraine(Days -7 to -2)

Menstrual migraine(Days -2 to +3exclusively)

Cycle Days

Loder EL et al. Migraine in Women. BC Decker Inc; 2004.

Weeks 2-3

(Day menses begins)

-6 -5 -4-7 -3 -2 -1 1 2 3 4

Menstrually-related migraine peaks near menses, yet is present throughout the cycle

TRIPTANSTRIPTANS

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When to Consider Preventive TherapyWhen to Consider Preventive Therapy

The migraine attacks interfere with a patient’s daily routine with related dysfunction three or more days per month

Attacks occur more than two per week even with adequate acute care

Migraine duration > 48 hours

Acute medications are ineffective, contraindicated, overused, or not tolerated, ,

The patient prefers preventive therapy

The patient has an uncommon migraine condition(eg, hemiplegic migraine, migrainous infarction, migraine with prolonged aura)

Loder E, Biondi D. Headache 2005; 45 (suppl 1): S33 – S47.

American Migraine Prevalence and American Migraine Prevalence and Prevention study (AMPP)Prevention study (AMPP)

Migraine Prevention Is UnderutilizedMigraine Prevention Is Underutilized

40% of migraine sufferers may be eligible

for prevention

Migraine

Lipton RB et al. Poster presented at: American Headache Society 47th Annual Scientific Meeting; June 23-26, 2005; Philadelphia, Pa.

13% of all migraine sufferers currently receive prevention

PreventionCandidates

gSufferers

Case # 2Case # 236 year old woman with

disabling migraines

Excellent health; uses tobacco

Has visual aura lasting < 1 hr

Averages 3 migraines per month lasting up to 2-3 days. Sometimes misses work

Treats migraines with triptans and analgesics

Takes no other meds except Oral Contraceptives

1 to 2 ER visits per year

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Oral Contraceptives and the Oral Contraceptives and the Risk of StrokeRisk of Stroke

Low dose estrogens <50 µg estradiol have lower stroke risk than do high dose (≥50 µg estradiol) estrogens

Most of the increased stroke risk is considered to be attributable to the estrogen component of OCsbe attributable to the estrogen component of OCs

Limited data for progestin-only OCs

Relative risk of stroke is greatly increased if associated risk factors are present, in particular, hypertension, cigarette smoking, and migraine

Silberstein SD, Lipton RB, Goadsby PJ. Headache in Clinical Practice. 2nd Ed. New York, NY. Martin Dunitz. 2002:100-107.

Migraine as a Risk Factor for StrokeMigraine as a Risk Factor for Stroke

Stroke risk in young (<45 years) female population is generally very low

Estimated to be between 5 and 10 per 100,000 woman-years

However, there is increased stroke risk (odds ratio) in women migraineurs under age 45:

Odds Ratio (OR)( )Migraine 3Migraine with aura 6Migraine plus OCs 5−17Migraine plus OCs plus smoking 34

Relative risk seems high, but absolute risk in migraineurs is low 17 to 19 in 100,000

There is no evidence that migraine is a risk factor for stroke in women over age 45

Bousser MG et al. Cephalalgia. 2000;20:155-156.MacGregor EA, de Lignieres B. Cephalalgia. 2000;20:157-163.

Case # 3Case # 3History of headaches for 20

years. Initially migraine about 5 times a month. About 4 years ago, developed milder daily headaches with migrainous headache 2 times a week.

Started daily OTC 4 -5 years ago y y gand daily prescription medications 2 -3 years ago. Taking hydrocodone about 4 days a wk.

Daily headaches are now disabling without the use of daily analgesics. Prophylactic medications not helpful.

Missing work and social activities

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Chronic Daily HeadacheChronic Daily HeadacheClassificationClassification

CHRONIC MIGRAINE With/without medication overuse

CHRONIC TENSION-TYPE HEADACHEWith/ ith t di tiWith/without medication overuse

NEW DAILY PERSISTENT HEADACHE

With/without medication overuse

HEMICRANIA CONTINUA

With/without medication overuse

Risk Factors for Chronic Daily HeadacheRisk Factors for Chronic Daily Headache

Not readily modifiableMigraine

Female sexLow educational/

socioeconomic status Head injury

Readily modifiableAttack frequency

ObesityMedication overuseStressful life events

S i ( lHead injury

Other prognosticatorsMultiple migraine triggers (“migraine soup”)

Paternal history of headaches Surgical menopause

Complicated aura Cutaneous allodynia

Snoring (sleep apnea, sleep disturbance)

Lipton R, Bigal, M. Headache. 2005;45(suppl 1):S3-S13.

Medication Overuse HeadacheMedication Overuse HeadacheIHS Diagnostic Criteria Jun 06IHS Diagnostic Criteria Jun 06

A. Headache present for > 15 days / month

B. Regular overuse for >3 months of one or moreacute / symptomatic treatment drugs:1. Ergotamine, triptans, opioids, or combination analgesic

medications on > 10 days / month on a regular basis for >3 months

2. Simple analgesics or any combination of ergotamine, triptans, analgesics opioids on > 15 days / month on a

regular basis for > 3 months without overuse of any single class alone.

C. Headache has developed or markedly worsened during medication overuse

Headache Classification Committee: Cephalgia 2006; 26:742-746.

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Pharmacologic Treatment Of MOHPharmacologic Treatment Of MOH

Headache Diary for documentationBe explicit about medication doses, frequency and limits of useDiscourage PRN usage for mild headache during the washout periodProvide adequate rescue medication for moderate orProvide adequate rescue medication for moderate or severe headache with appropriate limitsRestrict total use of all acute headache drugs to 10 DAYS PER MONTH (2004 IHS recommendation)NO REFILLS FOR PRN MEDS during washout periodHospitalization for IV therapy may be necessary

Headache Classification Subcommitee of the International Headache SocietyThe International Classification of Headache Disorders. Cephalagia 2004 24. (suppl 1).Sheftell FD. Postgraduate Medicine 1996 (Oct) 40-46.

Inpatient Treatment PlanInpatient Treatment Plan

1. Detoxification and rehydration2. Pain control with IV therapy3. Establish prophylactic therapy4. Patient education5. Behavioral therapy6. Outpatient H/A programp p g

IV Treatment OptionsIV DHEIV CorticosteroidsIV NeurolepticsIV CaffeineIV MagnesiumIV AnticonvulsantsIV Diphenhydramine

34 Year Old Woman 34 Year Old Woman Ten Year History Of MigraineTen Year History Of Migraine

Two day history severe headache with nausea. Did not respond to usual migraine medications. “The worse migraine I ever had”. Developed persistent vomiting. Rescue medication not helpful.

Complained of “dizziness”. Noticed to have unsteadiness of gait.

Symptoms progressive.

P t M di l Hi tPast Medical History:Episodic migraine W/O aura On OC >15 yearsNo other risk factors

Became more debilitated.

Brought to ER

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Neurological Exam:Neurological Exam:Truncal and Appendicular ataxia; Horizontal NystagmusTruncal and Appendicular ataxia; Horizontal Nystagmus

Cerebellar InfarctionCerebellar InfarctionVertebral Artery DissectionVertebral Artery Dissection

Advances In Migraine PathogenesisAdvances In Migraine PathogenesisTherapeutic ImplicationsTherapeutic Implications