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The Science of Migraine - Neuro Expo 2013


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Brian M. Plato, DO
Norton Headache and Concussion Center
Norton Neuroscience Instittute

Published in: Health & Medicine
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The Science of Migraine - Neuro Expo 2013

  1. 1. The Science of MigraineBrian M. Plato, DONorton Headache and Concussion CenterNorton Neuroscience Institute
  2. 2. A Common Problem• 45 million Americans with headache disorders• 30 million Americans with migraine, the mostcommon disabling form of headache• 12% of the US population has migraine• 18% of women, 6% of men are affected bymigraine
  3. 3. One Year Prevalence of MigraineLipton R B et al. Neurology 2007;68:343-349
  4. 4. Migraine is more common thandiabetes and asthma combined!1%7%6%7%13%0% 5% 10% 15% 20%MigraineOsteoarthritisDiabetesAsthmaRheumatoidArthritis
  5. 5. Commonly Mis- / Un-DiagnosedDiagnosed MigraineUndiagnosedMigraine39%61% 52%48%19891999Lipton et al., 2001American Migraine Study II
  6. 6. A Costly Problem• Chronic headache disorders are among thetop 20 causes of disability in the US accordingto the World Health Organization (WHO)• 4% of Americans experience 4 hours ofheadaches per day, at least 15 days per month• Headache disorders are responsible for morethan $31B in economic costs in the USannually
  7. 7. Diagnosis of Migraine Without Aura• No single feature required or sufficient for diagnosis• Characteristics (2/4)– Unilateral (40% bilateral or generalized)– Throbbing (50% non-pulsating)– Moderate-severe intensity (~20% mild)– Pain worsened by exertion (>95%)• Associated symptoms (1/2)– Nausea (86% – 95%) or vomiting (47% – 62%)– Photophobia (82% – 95%), phonophobia (61% – 98%)Russell MB et al. Cephalalgia. 1996.Pryse-Phillips WEM et al. Can Med Assoc J. 1997.
  8. 8. Additional Features of Migraine• Predictable timing around menstruation andovulation• Stereotyped prodromal symptoms• Characteristic triggers• Improves with sleep (more effective in young pts)• Positive family history• Childhood precursors (cyclic vomiting, abdominal“migraine”, episodic vertigo, probably motionsickness)• Osmophobia (smell sensitivity)
  9. 9. “I have sinus headaches”Eross E, Dodick D, Eross M. The sinus, allergy and migraine study (SAMS)86% Migraine3% Sinus related headachePatients self diagnosing “sinus headaches”
  10. 10. What Causes Migraine?• The Vascular Theory• Blood vessels constricting (aura)Followed by• Blood vessels dilating
  11. 11. The Vascular Theory• Does not explain prodrome• Not supported by blood flow studies• There are effective nonvascular drugs, such asNSAIDs• Most patients do not have aura• THIS IS NOT CORRECT
  12. 12. The Neurovascular Theory• Referred pain from dura mater and bloodvessels• Peripheral Neural Processing• Central Neural Processing
  13. 13. Pain Perceiving Structures Inside the SkullThe most important structures that register pain in the head are the large cranial vessels,proximal cerebral vessels and dural arteries and the large veins and venous sinuses
  14. 14. A More Sensitive BrainPain control mechanisms are partially defective in migraine patients
  15. 15. Wang, Schoenen. Cephalalgia. 1998.People with migraine process visual and auditory stimulation differently that peoplewithout migraine. In this example with repeated stimulation non-migraine patientshave decreased response with repeated stimulation whereas migraine patients havean increased response.
  16. 16. Migraine Aura
  17. 17. Migraine Aura• A reversible focal neurological deficit– Most commonly visual• Cortical spreading depression– Think a wave of activity moving across the brainfollowed by decreased activity– The part of the brain inactivated causes theneurological deficit• Occipital lobes = vision
  18. 18. Spreading Depression of LeãoEEG activity is suppressed and moves in a wave, correlates with symptoms
  19. 19. Aura is from brain cells (neurons)
  20. 20. The Pain
  21. 21. Neuropeptides• Cranial levels of both substance P andcalcitonin gene-related peptide (CGRP) areincreased by stimulation of the trigeminalganglion in humans• In migraine CGRP is elevated in externaljugular vein blood, whereas substance P is not• CGRP infusions can trigger headache andmigraine
  22. 22. A Growing Snowball• Trigeminal nerve and its blood supply(neurovascular)– Release of neuropeptides• CGRP• Substance P• 5-HT (serotonin) --> “triptans”• Nitric oxide– Vasodilatation (CGRP) leads to further activation, and theprocess spreads– Brainstem, thalamus, cortex become activated leading to“central sensitization”• Amplified pain signaling in the central nervous system– Allodynia: pain due to a non-noxious stimulant
  23. 23. Cutaneous AllodyniaMigraineurs develop increasedsensitivity to stimuli as a result ofincreased nerve excitability80% of migraine patients hadcutaneous allodynia during attacksNon painful stimuli perceived aspainfulAfter allodynia occurs, triptans loseeffectiveness
  24. 24. Burstein R, et al. Brain. 2000.1-PeripheralTrigeminal Sensitization2-Central TrigeminalSensitization3-Forehead Allodynia4-ExtracephalicAllodynia
  25. 25. Importance of treating earlyNo Allodynia AllodyniaPain free @2hrs 28 (93%) 5 (15%)Not pain free @2hrs 2 (7%) 29 (85%)30 34R Burstein, 2003
  26. 26. Allodynia is a risk factor fordeveloping chronic migraine
  27. 27. Earliest Possible Treatment to StopMigraine Progression and ChronificationInheritedthreshold fortrigeminalactivationTriggers orstressorsEpisodicmigraineIneffectivepaincontrolMedicationoveruseIncreasedheadachefrequencyChronicmigraineGraphic adapted from: Calhoun AH. In: Headache Newsletter: American Headache SocietyCommittee for Headache Education; Veteran’s Day, 2010.
  28. 28. Medication Overuse Headache• Headache present on ≥15 days/month• Regular overuse for ≥3 months of one or more drugsthat can be taken for acute and/or symptomatictreatment of headache• Headache has developed or markedly worsenedduring medication overuse• Headache resolves or reverts to its previous patternwithin 2 months after discontinuation of overusedmedication
  29. 29. Chronification of MigraineMedication Overuse HeadacheThe Cleveland Clinic Manual of Headache Therapy p. 156Bigal ME, et al. Headache. 2008;48:1157-1168.Bigal ME, et al. Pain. 2009;142:179-182.
  30. 30. Medication Overuse Headache• Simple analgesics:• Acetaminophen (Tylenol)• Ibuprofen (Advil, Motrin)• Aspirin (Bayer)• Naproxen (Aleve)• Combination products:• Fioricet• Excedrin• Opiates:– Lortab (hydrocodone)– Percocet (oxycodone)– Many others• Triptans:– Imitrex, Maxalt, Relpax,Zomig, Frova, Amerge,Axert, Treximet• DHE
  31. 31. Why opiates are bad
  32. 32. Other Associated Symptoms
  33. 33. Nausea• Gastroparesis occurs frequently,both during and outside of acutemigraine attacks1-3– May correlate with intensity ofheadache, nausea, and photophobia4• Absorption of orally administereddrugs used to treat migraine may bedelayed by gastroparesis,postponing the drug’s onset of action1,5-71. Krymchantowski AV, et al. Cephalalgia. 2006;26(7):871-874; 2. Aurora SK, et al. Headache. 2006;46(1):57-63; 3. AuroraS, et al. Headache. 2007;47(10):1443-1446; 4. Boyle R, et al. Br J Clin Pharmacol. 1990;30(3):405-409; 5. Thomsen LL, etal. Cephalalgia. 1996;16(4):270-275; 6. Volans GN. Br J Clin Pharmacol. 1975;2(1):57-63; 7. Tokola RA and Neuvonen PJ.Br J Clin Pharmacol. 1984;18(6):867-871; 8. Tfelt-Hansen P. Headache. 2007;47(6):929-930; 9. Dahlöf C. Curr OpinNeurol. 2002;15:317-322; 10. Lychkova AE. Bull Exp Biol Med. 2004;138(2):127-130.
  34. 34. Other Associated Symptoms• Blurry vision (29%)• Neck pain (31%)• Nasal congestion (28%)• Sweating (30%)• Dizziness (16%)
  35. 35. Why is it important to understandthe science of migraine?• Treatment– Prevention of triggers– Preventative medications– Rescue medications
  36. 36. Triggers• We now understand that patients withmigraine have an “excitable” brain– Need to be careful with:• Sleep• Diet• Medication overuse• Stress management
  37. 37. Preventative Medications• Antiseizure drugs– Topamax– Depakote• Antidepressants– Amitriptyline (Elavil)– Effexor• Blood pressure medications– Propranolol (Inderal)– Verapamil
  38. 38. Rescue Medications• Triptans• NSAIDs• DHE
  39. 39. TriptansSelective agonists (activators) of serotoninblocking the release of other inflammatorychemicals during a migraine attackTriptans work here
  40. 40. Triptans• Prevent release of neuropeptides• Once enough activation has occurred theprocess of central sensitization begins– Manifested by allodynia– Remember 15% vs. 93% chance of success
  41. 41. NSAIDs• Ketorolac infusion has been shown to reversecentral sensitization• IV ketorolac is not practical in the outpatientsetting• Ibuprofen, naproxen, diclofenac
  42. 42. DHE• Can also reverse central sensitization• More side effects• A little less convenient to give in the homesetting
  43. 43. Summary• Hyperexcitable brain: more susceptible totriggers• Aura: spreading excitation and depression• Throbbing head pain: trigeminal inflammation• Allodynia: common, important and due tocentral sensitization
  44. 44. Learn More at Headache School• Women and Headaches• June 13 • 6 to 7:30 p.m.• Biofeedback and stressmanagement• July 11 • 6 to 7:30 p.m.• Headache related to injury• August 8 • 6 to 7:30 p.m.• What is a migraine aura?• September 12 • 6 to 7:30p.m.• Alternative headachetreatments• October 17 • 6 to 7:30 p.m.
  45. 45. Thank you!