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Headache & Migraine Brian J. Piper, Ph.D., M.S. October 23, 2012

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Goals• Describe differences in symptomology between migraines, cluster headaches, and tension-type headaches.• List the vascular and neural substrates of migraine/headaches.

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

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

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

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George Cruikshank: The Head Ache (1819)2:20: http://www.mayoclinic.com/health/migraine-aura/MM00659

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

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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

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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

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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

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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)

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Neural Substrates of Migraine • 1) meningeal vessels • 2) trigeminal: opthalmic nerve (V1)

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

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

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5-HT1B: vasoconstriction 5-HT1D: peripheral neuronal inhibitionGoadsby et al. (2002). New England Journal of Medicine, 346(4), 257-270.

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Brainstem Activation During Migraine Posterior• 43 year old man with history of migraine without aura• Positron Emission Tomography completed at rest and following nitroglycerin AnteriorBahra et al. (2001). Lancet, 357, 1016-1017.

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Migraine Across Countries (Twins)Mulder et al. (2003). Twin Research, 6(5), 422-431.

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Genetic Contribution to MigraineMulder et al. (2003). Twin Research, 6(5), 422-431.

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Environmental Factorsstresshead and neck infectionhead trauma/surgeryHormone changesaged cheesedairyred winenutsshellfishcaffeine withdrawalvasodilatorsperfumes/strong odorsirregular diet/sleeplight

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Cluster Headache • unilateral pain • unilateral other: – ptosis – miosis – rhinorrhoea • circadian • males > females • brief ( < 3 hours) • rareDodick et al. (2001). Cluster headache. Cephalagia, 20(9), 787-803.http://ihs-classification.org/en/02_klassifikation/02_teil1/03.01.00_cluster.html

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Hypothalamic & Insular Activation During Cluster Headache • 9 patients with a history of cluster completed PET for regional cerebral blood flow at rest & following nitroglycerinMay et al. (1998). Lancet, 352(9124), 275-278.

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Episodic Tension-type Headache (TTH)A. Number of days with such headache < 180/year (<15/month)B. Headache lasting from 30 minutes to 7 daysC. 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 activityD. Both of the following: • No nausea or vomiting (anorexia may occur) • Photophobia and phonophobia are absent, or one but not the other is presentE. At least 10 previous headache episodes fulfilling these criteriaF. No evidence of organic disease

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DSubstrates of TTH V Dorsal Horn: sensory Ventral Horn: motor

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Tension-type Headache or Migraine Mild Moderate Severe Aura Unilateral Vomiting Bilateral Photophobia Aggravated by Activity Nausea Throbbing Pressure Tension-Type Migraine

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Comparison• Frequency: TTH > Migraine > Cluster• Pain:• Sex Ratio: F > M F>M M>F

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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

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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.