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Management of Migraine in this millennium

Management of Migraine in this millennium. PROF.A.V.SRINIVASAN , MD, D.M, PhD ,D.Sc (HON) , F.A.A.N, F.I.A.N , PATHOPHYSIOLOGY AND MANAGEMENT. I Emeritus Professor, The Tamilnadu Dr.M.G.R . MEDICAL University, Former HOD, and PROF OF NEUROLOGY INSTITUTE OF NEUROLOGY

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Management of Migraine in this millennium

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  1. Management of Migraine in this millennium PROF.A.V.SRINIVASAN, MD, D.M, PhD ,D.Sc (HON) , F.A.A.N, F.I.A.N, PATHOPHYSIOLOGY AND MANAGEMENT I Emeritus Professor, The TamilnaduDr.M.G.R. MEDICAL University, Former HOD, and PROF OF NEUROLOGY INSTITUTE OF NEUROLOGY MADRAS MEDICAL COLLEGE,CHENNAI 03-06-11

  2. Treating Migraines

  3. How Common is Migraine? • 30,000,000 Americans • 20% of women • 7% of men at any given time • Most of us have some migraine manifestations occasionally “My Opinions are founded on knowledge but modified by experience”

  4. Recognizing Migraine • Pounding unilateral headache • Preceded by visual or other aura • Nausea, vomiting • Light and sound sensitivity Expert is one who think to his chosen mode of ignorance

  5. Migraine without aura (MO) What is migraine? Migraine with aura (MA) • At least five attacks fulfilling these criteria: • Headache lasting 4–72 h • (2–48 h in children) • At least two attacks fulfilling these criteria: • At least three of the following: • one or more fully reversibleaura symptoms • gradually developing orsequential aura symptoms • no one aura symptom lastslonger than 1 h • headache shortly follows or accompanies aura • With at least two of: • unilateral location • pulsating quality • moderate/severe intensity • aggravated by activity • Accompanied by at least one of: • nausea • vomiting • photophobia and/or phonophobia • No evidence of organic disease • No evidence of organic disease Headache Classification Committee of IHS (1988)

  6. Switzerland 13% Denmark 10% France 8%† USA 12% Japan 8% Italy 16% • 1-year prevalence rates • Population-based studies • IHS criteria (or modified) Chile 7% Rasmussen and Olesen (1994); Rasmussen (1995);Lipton et al (1994); Lavados and Tenhamm (1997); Sakai and Igarashi (1997) †Prevalence measured over a few years World prevalence of migraine:A disorder of First World

  7. Diagnosis of migraine • Diagnosis depends on patient history • No specific tests or clinical markers • Positive diagnosis if attack history fulfils IHS criteria for migraine • Other pointers include: • family history of migraine • age of onset <45 • presence of aura • menstrual association • Organic disease must be excluded Cady (1999); Warshaw et al (1998)

  8. WORRISOME HEADACHE RED FLAGS“SNOOP” Systemic symptoms (fever, weight loss) or Secondary risk factors (HIV, systemic cancer) Neurologic symptoms or abnormal signs (confusion, impaired alertness, or consciousness) Onset: sudden, abrupt, or split-second Older: new onset and progressive headache, especially in ` Previous headache history: first headache or different (change in attack frequency, severity, or clinical features) “ He who cannot forgive others destroys the bridge over which he himself must pass” - Annoy

  9. Females Males Prevalence of migraine by sex and age Migraine prevalence (%) 30 25 20 15 10 5 0 20 30 40 50 60 70 80 100 Age (years) The American Migraine Study (n=2479 migraine sufferers) Lipton and Stewart (1993)

  10. Physiology • Vasospasm – Lance • Spreading Wave of Depression – Leao • Trigeminocentric • Allodynia If you think you can or you can’t You are always right

  11. Vasospasm • I. Aura: Arteries Spasm • Visual and focal neurological symtoms • Pial and Occipital small artery branches • II. Headache: Compensatory Vasodilation • Pounding unilateral sick headache • III. Inflammation and muscle spasm: second pain phase

  12. Phases of Migraine • Vague Prodrome: psychic change and cravings e.g. chocolate • Aura: Focal symptoms and vision • Headache: Throbbing unilateral pain • Inflammation: Prolonged phase and TTH • Postdrome • Migraine related stroke Experience can be defined as yesterday’s answer to today’s problems

  13. Spreading Wave • Brainstem controls Cortical Activity • Epileptic like phenomenon that spreads over Cortex • Visual Phenomenon that spreads over surface of brain like shimmering “C” • Cheiro-oral Jacksonian phenomena • Concurrence of migraine and epilepsy • Why epilepsy drugs work for migraine “Men of Genius Admired: Men of Wealth envied: women of power feared: But only women of character are trusted” -A- Friedman

  14. Trigeminal Theory • Serotonin again • Trigeminal Afferents: sensory function of face and meninges • Trigeminal efferents to vessels • Cause vessel spasm and sensitivity • This theory primarily explains action of Triptans: 5-HT 1b,d agonists “ Maintaining the right attitude is easier than regaining the right mental attitude”

  15. Migraine attack Trigger Increased serotonergic and noradrenergic stimulation in the brain stem Dilation or constriction of cerebral and scalp blood vessels Stimulation of branches of 5th cranial nerve (Trigeminal) Thalamus Cortex Pain Nausea Vomiting Chemoreceptor Hypothalamus - Photophobia J of Pharmacy Practice, Dec 1993; 253-270 “The Wise Man Before He Speaks , Will Consider Well What He Speaks

  16. Migraine Pathophysiology Goadsby NEJM 346 :257-70,2002

  17. Allodynia Theory • Migraine is a state of hypersensitivity • Light, sounds, smells, touch (head in headache) • Need for dark room • Best preventives decrease sensitivity. • Anticonvulsants, tricyclics, beta and calcium channel blockers The art of medicine is caring for the heart of the patient

  18. What is Central Sensitization? • Central Sensitization is a time-dependent physiological event • During a migraine attack, neuronal pathways become sensitized in stages • Peripheral neurons are activated early in the attack (mild pain phase throbbing) • Central neurons are activated later in the attack (full-blown migraine)

  19. Cutaneous allodynia • Phenomenon later in migraine attack • Once it develops pts less likely to respond to triptans • In small sample 15% of pts with and 93% of pts without CA responded to triptan (Burstein et al) Many Ideas grow better when transplanted into another mind than in the one where they sprang UP O.W. Holmos

  20. Each of these Theories explains some migraine phenomena When they tell you to grow up, they mean stop growing - P. Diccaso

  21. Migraine Phenomena • Focal and paroxysmal onset of symptoms • Specific visual phenomena • Spreading numbness and moving visual phenomena and sensory distortions. • Nausea, vomiting “sick” headache • Pounding unilateral or bilateral pain • Psychic changes • Light and sound sensitivity even between attacks • Effectiveness of triptans • Effect of anticonvulants • Role of serotonin

  22. Some Dicta • Any paroxysmal headache is likely to be migraine unless proven otherwise • “Sinus” headaches and “tension” headaches are almost always migraine headaches • First ever severe headache or sudden “thunderclap” headaches may be SAH “By Nature All Men/ Women are alike butby Education widely different” - Chinese

  23. Trigeminal nerve INHIBITION 5-HT1D 5-HT1F triptan CGRP NK SP CONSTRICTION 5-HT1B CGRP calcitonin gene related peptide NK neurokinin A SP substance P Blood vessel Adapted from Goadsby (1997) Mechanisms for treatment

  24. Acute Attack • Triptans: • sumatriptan, zolmitriptan, almotriptan, naratriptan, frovatriptan, elitriptriptan, riaztriptan • NSAID’s • Fioricet • Midrin (isometheptane, chlorphenoxazone, apap • OTC: Caffeine, apap, phenacitin, asa • Ergots: Caffergot, DHE nasal, injected • Narcotics • Depacon The True Art of Memory is The Art of Attention - S.Johnson

  25. Plea • Listen to patients • Migraine is mixed up with a lot of things • Emotional factors: ennui, husbands, bosses, general dissatisfaction with life • Sleep disturbances • Hormonal changes • If you do not address these you will not be treating your patients • Don’t just throw drugs at your patients • Be attentive and empathetic

  26. THE TREATMENTAPPROACH TO MIGRAINE

  27. LONG-TERM TREATMENT GOALS FOR THE MIGRAINE SUFFERER • Reducing the attack frequency and severity • Avoiding escalation of headache medication • Educating and enabling the patient to manage the disorder • Improving the patient’s quality of life A great man is he, who can forgive any sin

  28. MIGRAINE MANAGEMENT • Non-pharmacological treatment • Identification of triggers • Meditation • Relaxation training • Psychotherapy • Pharmacotherapy non-specific • Abortive therapy specific • Preventive therapy

  29. MIGRAINE: ABORTIVE THERAPY Non-specific treatment Expert is one who think to his chosen mode of ignorance

  30. ABORTIVE THERAPY FOR MIGRAINE Specific treatment Discipline Weighs ounces Regret weighs Tons

  31. Selective 5-HT1B/1D/1F agonists Silberstein SD. Neurology. 2000. TRIPTANS • As a class, relative to nonspecific therapies, triptans provide • Rapid onset of action • High efficacy • Favorable side effect profile Adverse events and contraindications

  32. Triptans • Learn to use one or two • Effective medicines “Social Isolation is in itself a pathogenicFactor for disease production”

  33. Are there differences between the triptans? If one triptan fails, will another triptan work? • Sumatriptan • Tablet (25, 50, 100 mg) • Injection (6 mg) • Nasal spray (5, 20 mg*) Question and Answer • Eletriptan • Tablet (20, 40 mg) * Pediatric efficacy shown Ferrari MD et al. Lancet. 2001. TRIPTANS:TREATMENT CHOICES • Almotriptan • Tablet (6.25, 12.5 mg) • Frovatriptan • Tablet (2.5 mg) • Zolmitriptan • Tablet (2.5, 5 mg) • Nasal spray (5 mg) • Naratriptan • Tablet (1, 2.5 mg) • Rizatriptan • Tablet (5, 10 mg)

  34. Elitriptan or RelpaxAdvantages Quick oral absorption Reliable oral absorption Relatively long half life Numerous Clinical trials where proven superior to Imitrex Gets in fast, and stays around Low “rebound” recurrence rate Works for all migraine phenonena Pain, photosonophobia, nausea

  35. Relpax Cautions • Available only in oral form • CYP 3A4 • Do not give within 72 hours of: Ketoconazole, Nefazadone, clarithromycin, rotonavir, nelfinavir, others. caution with verapamil, erythromycin. • Contraindications (all triptans) • Suspected Coronary disease • Basilar or hemiplegic, ophthalmoplegic migraine • Uncontrolled hypertension • <18 or >65 • Within a day of any other triptan • Hypersensitivity to the drug Maintaining the right attitude is easier than regaining the right mental attitude

  36. Relpax Dosing • 40 mg. May repeat X1 in 2 hours • Max dose in 24 hours is 80 mg • Repeating dose most efficacious if headache returns Opinion is ultimately determined by the feelings and not by the intellect

  37. “Parenteral” triptans • Imitrex injections: Very good fast reliable onset but peaks quickly with short half life • Imitrex and Zomig nasal: absorption not reliable, taste not so good but may be tried if a lot of nausea • Zomig ZMT and Maxalt MLT on tongue: not strictly parenteral absorbed thru gut Truth comes out of error sooner than that of confusion

  38. Triptan worries • Not released under age 18 • If you even suspect CAD don’t use or get proper exclusionary tests. • Man or woman of a certain age • Smoker or other risk factors • Cerebrovascular disease or complicated migraine - contraindicated • Watch for overuse. These are rescue medicines Every discovery contains an irrational element or 4 creative intuition - Karl Popper

  39. Consider Combinations • Triptan + NSAID • Triptan + anti-nausea • Unconventional agents • Phenergan, Compazine alone or in combination. Zyprexa or atypicals • We don’t have enough alternatives The secret of walking on water is Knowing where the stones are

  40. ANTI-NAUSEANT DRUGS FOR MIGRAINE TREATMENT Thought is the labour of the intellect Reverie is its pleasure

  41. WHY THE NEED FOR PROPHYLAXIS ? • Abortive drugs should not be used more than 2-3 times a week • Long-term prophylaxis improves quality of life by reducing frequency and severity of attacks • 80% of migraineurs may require prophylaxis Memory, the daughter of attention , is the teeming mother of knowledge - Martin Tupper

  42. WHEN IS PROPHYLAXIS INDICATED? According to the US Headache Consortium Guidelines, indications for preventive treatment include: • Patients who have very frequent headaches (more than 2 per week) • Attack duration is > 48 hours • Headache severity is extreme • Migraine attacks are accompanied by prolonged aura • Unacceptable adverse effects occur with acute migraine treatment • Contraindication to acute treatment • Migraine substantially interferes with the patient’s daily routine, despite acute treatment • Special circumstances such as hemiplegic migraine or attacks with a risk of permanent neurologic injury • Patient preference

  43. PREVENTIVE THERAPY FOR MIGRAINE Every thing should be made as simple as possible; but not simpler

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