Why do I get migraines?

What triggers them?

Why do I get migraines?

What triggers them?

Herbert G. Markley, M.D.

New England Regional Headache Center

Worcester, MA

Reprinted from Cell. 87, Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner P, Hoffman SMG, Lamerdin JE, Mohrenweiser HW,Bulman DE, Ferrari M, Haan J, Lindhout D, van Ommen GJB, Hofker MH, Ferrari MD, Frants RR. Familial hemiplegic migraine and episodicataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. 543-552, Copyright 1996, with permission from Elsevier Science.

Neuronal Hyperexcitability: Genetic EvidenceNeuronal Hyperexcitability: Genetic Evidence

Mutations inneuronal ionchannels: gene for

neuronal/ vascular

calcium channel

CACNA1A4 locus

S4S4 S4S4 S4S4S4S4

FHMFHM

CytoplasmCytoplasm

NN FHM + CerebellarFHM + Cerebellarataxiaataxia

Migraine is More Common than Asthma & Diabetes Combined

Migraine is More Common than Asthma & Diabetes Combined

1%

5%6%

7%

12%

Rheumatoidarthritis

Asthma Diabetes Osteoarthritis Migraine

Data from the Centers for Disease Control and Prevention, US Census Bureau, and the Arthritis Foundation.

Disease Prevalence in the US Population

The Migraine AttackThe Migraine Attack

PostdromePostdromeProdromeProdrome

Associated Associated FeaturesFeatures

HeadacheHeadacheAuraAura

TimeTime

Intensity of Symptoms or Phases

The Migraine AttackThe Migraine Attack

PostdromePostdromeProdromeProdrome

Associated Associated FeaturesFeatures

HeadacheAuraAura

TimeTime

Intensity of Symptoms or Phases

ProdromeMood changesFatigueCognitive ChangeMuscle PainFood Craving

AuraFully reversibleNeurological changes:VisualSomatosensory

Early HeadacheDull headacheNasal congestionMuscle pain

“Tension Headache of Migraine”

Mild

Moderate

Evolving HeadacheLocalization of headacheAssociated symptoms begin to appear

Severe

Advanced HeadacheUnilateralThrobbingNauseaPhotophobiaPhonophobia Postdrome

FatigueCognitive changesMuscle pain

Anatomical pathophysiology of migraineAnatomical pathophysiology of migraine

Goadsby, Lipton, Ferrari. N Engl J Med;346:257-270.2002.

PAIN

CSD

NAUSEA

PHOTOPHOBIA +

SONOPHOBIA

NEUROGENICINFLAMMATION

Lipton, Diamond et al, 2000

Migraine Prevalence by Age and GenderMigraine Prevalence by Age and Gender

Migraine Prevalence %

Age (years)

0 20 30 40 50 60 70 80 1000

5

10

15

20

25

30

Adapted from Lipton RB, Stewart WF. Neurology. 1993

MalesMales

FemalesFemales

Female Life Events that Influence MigraineFemale Life Events that Influence Migraine

• Menarche

• Menses

• Oral Contraception

• Pregnancy

• Lactation

• Menopause

• Hormone Replacement Therapy

Migraine and MenarcheMigraine and Menarche

• Females suffer from migraine at a 3:1 ratio to males

• Beginning with puberty, migraine is more common in girls

• Menstrually associated migraine begins at menarche in 33% of women

• 60-70% of female sufferers experience migraine in association with menses

Silberstein SD. Neurology. 1991; 41:786-793MacGregor EA. Neruologic Clinics. 1997; 15(1): 125-141Benedetto, C et al. Cephalalgia. 1997; 20: 32-34

Menstrual Migraine: DefinitionsMenstrual Migraine: Definitions

• Menstrually-associated Migraine (MAM):– Women who experience attacks that occur both

perimenstrually and at other times of the month – 60-70% of female migraineurs report a

menstrual relationship to their headaches

• Menstrual Migraine (MM):– Women who experience attacks that occur only

perimenstrually– In female migraineurs, true menstrual migraine

occurs in only 7-14%

Benedetto, C et al. Cephalalgia. 1997; 20: 32-34

Migraine Vulnerability During the Menstrual CycleMigraine Vulnerability During the Menstrual Cycle

• Can occur before, during, and after menstruation– Migraine may be part of premenstrual

syndrome (PMS), now a part of the DSM-IIIR criteria for Late Luteal Phase Dysphoric Disorder (LLPDD)

– Greatest likelihood of menstrual migraine on Day -1 to Day +4, but can vary

– Decrease in estrogen levels in the late luteal phase is a likely trigger for migraine

Silberstein SD. Neurology. 1991; 41: 786-793

Hormone Levels During Menstrual CycleHormone Levels During Menstrual Cycle

Adapted from Silberstein SD, Lipton RB, Goadsby PJ. Headache in Clinical Practice. 2nd Ed. New York, NY: Martin Dunitz; 2002:102

Follicular phase Luteal phase

Endocrine cycle

LH

FSH

E2

POvulation

HORMONAL FLUCTUATIONS DURING THE MENSTRUAL CYCLEHORMONAL FLUCTUATIONS DURING THE MENSTRUAL CYCLE

Estradiol Treated CycleEstradiol Treated Cycle

Somerville BW, Neurology, 1972;22:355-365.

100

50

20

5

2

1

-6 -5 -4 -3 -2 -1 0

Days From Onset of Menstruation

EstradiolTreatedCycle

NormalCycle

Migraine-unilateral,duration 8 hours.

Nausea.

Migraine-unilateralduration 12 hours.

Nausea.

Estradiolvalerate10 mg

Pla

sma

Est

radi

ol (

ng/1

00 m

l)

1 2 3 4 5 6

10

200

Other Migraine TriggersOther Migraine Triggers

• Vasoactive foods– Chocolate (phenylethylamine)– Caffeine or its withdrawal (caffeine is a

phosphodiesterase inhibitor)– Smoked meats, fish (nitrites, dilate arteries)– Alcohol, esp. beer, red wine (direct vasodilator,

congeners with vasoactive effects)– Monosodium glutamate (excitatory neurotransmitter)– Cold foods (ice cream headache more common in

migraine patients)

Other Migraine TriggersOther Migraine Triggers

• Strong odors – fragrances, gasoline

• Certain foods

• Weather changes

• Exercise

Avoidance techniques: identify and avoid factors which trigger migraine

Avoidance techniques: identify and avoid factors which trigger migraine

• Oral contraceptives– May precipitate migraine, also increase risk of stroke in

women with migraine– Migraine associated with use of these agents sometimes

resolves completely when they are discontinued

• Other precipitating factors: seek and eliminate– Foods: chocolate, cheddar cheese, alcohol (red wine)– Alterations in sleep schedule, stress, vacation– Weather changes, missing meals or strong odors– “Phobic approach” works well in children with food

sensitivities, but adults may find stringent dietary and activity restrictions too confining

The Headache Patient's Bill of RightsThe Headache Patient's Bill of Rights

• The right to be taken seriously

• The right to a complete medical evaluation, including complete history and neurological examination

• The right to neurodiagnostic testing: CT/MRI scans

• The right of referral to a specialist: neurologist or a Headache Clinic

• The right to receive specific headache therapy, instead of non-prescription drugs, narcotics, or combination analgesics which may increase the headache problem