pathophysiology: migraine & headache

Headache & Migraine

Brian J. Piper, Ph.D., M.S.

October 23, 2012

Goals

• Describe differences in symptomology between migraines, cluster headaches, and tension-type headaches.

• List the vascular and neural substrates of migraine/headaches.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5503a6.htm

Importance

• WHO ranks migraine among world’s most debilitating chronic illnesses

• 3rd most common reason for ER visits (U.S.)• ≈$13 billion/year in lost productivity (U.S.)• underdiagnosed & undertreated

Menken et al. (2000). Archives of Neurology, 57(3), 418-420.

Migraine Terminology• migraineurs: person who experiences migraines• aura: collection of symptoms that may precede or co-

occur; typically visual, lasts less than 1 hour– positive features

• scintillations: a rapidly oscillating pattern of visual distortions• photopsia: perception of flashes of light• teichopsia: spot of flickering light

– negative features• scotoma: an area of diminished vision within the visual field• hemianopsia: blindness in half of the visual field, may involve one or

both eyes

– hemiplegic aura: occurring on one side of body– basilar type aura: aura is localized to the brainstem

DiPiro et al. (2008). Pharmacotherapy: A Pathophysiologic Approach. p. 1008.

George Cruikshank: The Head Ache (1819)

2:20: http://www.mayoclinic.com/health/migraine-aura/MM00659

International Headache Society Migraine Criteria• Migraine with aura (classic migraine)

– At least 2 attacks– Aura fulfills criteria for typical aura, hemiplegic aura, or basilar

type aura– Not attributed to another disorder

• Migraine without aura– At least 5 attacks– Headache lasts 4 to 72 hours (untreated or successfully treated)– Headache has at least 2 characteristics

• Unilateral location, pulsating quality, or moderate or severe intensity– Aggravation by or avoidance of routine physical activity

(walking, climbing stairs)– During headache, at least one of the following:

• Nausea, vomiting, or both• Photophobia and phonophobia

– Not attributed to another disorder

http://ihs-classification.org/en/02_klassifikation/02_teil1/01.00.00_migraine.html

Epidemiology: American Migraine Prevalence & Prevention Study

• Mailed Survey to 257K, response by 163K (64.9%) who are representative of U.S. population

• Migaine: IHS criteria, Chronic Migraine: >15 days/month over 3 months

Epidemiology: American Migraine Prevalence & Prevention Study

• Mailed Survey to 257K, response by 163K (64.9%) who are representative of U.S. population

• Migraine: IHS criteria, Chronic Migraine: >15 days/month over 3 months

Epidemiology: American Migraine Prevalence & Prevention Study

• Mailed Survey to 257K, response by 163K (64.9%) who are representative of U.S. population

• Migraine: IHS criteria, Chronic Migraine: >15 days/month over 3 months

• Demographic Correlates– Age (18-49)– Sex (Female)– SES: >$90K = 0.52; <$22K = 2.71; 5.2 fold!

• Primary versus Secondary (tumor, infection, stroke)

Buse et al. (2012-in press). Headache. doi: 10.1111/j.1526-4610.2012.02223.x

Pathophysiology

• limited animal models• theory: genetic (50% heritable) & neurovascular• 2 min: http://www.youtube.com/watch?v=yZr9Joe85wg• orthodromic: electrical potential following typical direction (soma

to axon)• antidromic: electrical potential traveling in the reverse direction

(axon to soma)

Neural Substrates of Migraine

• 1) meningeal vessels• 2) trigeminal: opthalmic nerve (V1)

Neural Substrates of Migraine

• 1) meningeal vessels• 2) trigeminal: opthalmic nerve (V1)• 3) pons (input from other structures)• 4) facial nerve

Neural Substrates of Migraine

Goadsby et al. (2002). New England Journal of Medicine, 346(4), 257-270.

5-HT1B: vasoconstriction5-HT1D: peripheral neuronal inhibition

Goadsby et al. (2002). New England Journal of Medicine, 346(4), 257-270.

Brainstem Activation During Migraine

• 43 year old man with history of migraine without aura

• Positron Emission Tomography completed at rest and following nitroglycerin

Bahra et al. (2001). Lancet, 357, 1016-1017.

Posterior

Anterior

Migraine Across Countries (Twins)

Mulder et al. (2003). Twin Research, 6(5), 422-431.

Genetic Contribution to Migraine

Mulder et al. (2003). Twin Research, 6(5), 422-431.

Environmental Factorsstresshead and neck infectionhead trauma/surgeryHormone changesaged cheesedairyred winenutsshellfishcaffeine withdrawalvasodilatorsperfumes/strong odorsirregular diet/sleeplight

Cluster Headache• unilateral pain• unilateral other:

– ptosis– miosis– rhinorrhoea

• circadian• males > females• brief ( < 3 hours)• rare

Dodick et al. (2001). Cluster headache. Cephalagia, 20(9), 787-803.http://ihs-classification.org/en/02_klassifikation/02_teil1/03.01.00_cluster.html

Hypothalamic & Insular Activation During Cluster Headache

• 9 patients with a history of cluster completed PET for regional cerebral blood flow at rest & following nitroglycerin

May et al. (1998). Lancet, 352(9124), 275-278.

Episodic Tension-type Headache (TTH)

A. Number of days with such headache < 180/year (<15/month) B. Headache lasting from 30 minutes to 7 days C. At least 2 of the following:

• Pressing/tightening (non-pulsating) quality• Mild or moderate intensity (may

inhibit, but does not prohibit activities)• Bilateral location• No aggravation by walking stairs

or similar routine physical activity D. Both of the following:

• No nausea or vomiting (anorexia may occur)• Photophobia and phonophobia are absent, or one but not

the other is present E. At least 10 previous headache episodes fulfilling these criteria

F. No evidence of organic disease

Substrates of TTH

Dorsal Horn: sensoryVentral Horn: motor

D

V

Tension-type Headache or Migraine

Tension-Type Migraine

Mild

Moderate

Severe

Unilateral

Bilateral

Photophobia

Nausea

Throbbing

Pressure

Aura

Vomiting

Aggravated by Activity

Comparison

• Frequency: TTH > Migraine > Cluster• Pain:

• Sex Ratio: F > M F > M M > F

Summary

• Headache and migraine are common but under-appreciated.

• Migraine & headache pathophysiology is an active, but far from complete, area of research.

0 to 1.5 min (skip ad): http://www.youtube.com/watch?v=eJZMnXG_Yw0

Medication Overuse Headache• Occurrence of rebound headache following

long-term treatment• Identification may take months, may involve

transition to prophylactic treatment (e.g. SSRI)

Smith & Stonerman (2004). Drugs, 64(22), 2503-2514.