headache andrew charles, m.d. professor director, headache research and treatment program david...
TRANSCRIPT
HEADACHEHEADACHE
Andrew Charles, M.D.Andrew Charles, M.D.ProfessorProfessor
Director, Headache Research and Treatment ProgramDirector, Headache Research and Treatment ProgramDavid Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLA
COMMON TYPES OF COMMON TYPES OF HEADACHESHEADACHES
PRIMARY HEADACHESPRIMARY HEADACHESMIGRAINEMIGRAINE
TENSION TYPE TENSION TYPE
CLUSTER HEADACHE AND OTHER CLUSTER HEADACHE AND OTHER TRIGEMINAL AUTONOMIC CEPHALGIASTRIGEMINAL AUTONOMIC CEPHALGIAS
SECONDARY HEADACHESSECONDARY HEADACHESHeadaches due to infectionHeadaches due to infection
Headaches due to vascular causesHeadaches due to vascular causes
Headaches due to tumorsHeadaches due to tumors
Etc., etc.Etc., etc.
HEADACHE: HEADACHE: Prevalence and Prevalence and ImpactImpact
PREVALENCE PREVALENCE 18-25 % women have migraine18-25 % women have migraine6-10 % men have migraine6-10 % men have migraine5% of women have headache more than 15 5% of women have headache more than 15 days per month days per month
112 million bedridden days per year112 million bedridden days per yearCost to U.S. Employers -- $13 Billion per Cost to U.S. Employers -- $13 Billion per yearyearThe majority of patients with migraine have The majority of patients with migraine have not received an appropriate diagnosis, and not received an appropriate diagnosis, and are not receiving appropriate therapyare not receiving appropriate therapy
MIGRAINE – A MULTISYMPTOM COMPLEXMIGRAINE – A MULTISYMPTOM COMPLEX
PATHOPHYSIOLOGICAL EVENTS
CHANGING CONCEPTS OF CHANGING CONCEPTS OF MIGRAINE PATHOGENESISMIGRAINE PATHOGENESIS
MIGRAINE IS A DISORDER OF BRAIN MIGRAINE IS A DISORDER OF BRAIN EXCITABILITYEXCITABILITY
VASODILATION MAY OCCUR AS PART VASODILATION MAY OCCUR AS PART OF THE DISORDER, BUT IS NOT OF THE DISORDER, BUT IS NOT REQUIREDREQUIRED FOR MIGRAINE PAIN FOR MIGRAINE PAIN
Penfield W. A contribution to the mechanism of intracranial pain. Penfield W. A contribution to the mechanism of intracranial pain. Assoc Res Nerv Ment Dis. 1935;15:399-416.Assoc Res Nerv Ment Dis. 1935;15:399-416.
Ray BS, Wolff HG. Experimental studies in headache: Pain-Ray BS, Wolff HG. Experimental studies in headache: Pain-sensitive structures of the head and their significance in headache. sensitive structures of the head and their significance in headache. Arch Surg. 1940;41:813-856.Arch Surg. 1940;41:813-856.
Issues with Studies of Issues with Studies of Ray and Wolff, PenfieldRay and Wolff, Penfield
Stimulation of vessels was focal external Stimulation of vessels was focal external stimulation or mechanical dilationstimulation or mechanical dilation
There is no evidence that physiological There is no evidence that physiological relaxation of smooth muscle and resultant relaxation of smooth muscle and resultant dilation can cause paindilation can cause pain
Multiple areas of brain that could evoke pain Multiple areas of brain that could evoke pain were not stimulated:were not stimulated:
Cingulate cortexCingulate cortex
Brainstem – Stimulation or lesions in brainstem can Brainstem – Stimulation or lesions in brainstem can cause migrainecause migraine
Vasoactive Drugs Cause Migraine After Vasoactive Drugs Cause Migraine After Significant Delay (hours), Significant Delay (hours), NotNot Correlated Correlated
with Vasodilation with Vasodilation
Nitric oxide donorsNitric oxide donors
PDE inhibitorsPDE inhibitors
HistamineHistamine
CGRPCGRP
Schoonman, et al. Migraine headache is not associated with cerebral or meningeal vasodilatation--a 3T magnetic resonance angiography study. Brain 131, 2192-2200, 2008.
Kruus, et al. Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain. 26:241-247, 2003.
Rahman et al., Vasoactive intestinal peptide causes marked cerebral vasodilation but does not induce migraine. Cephalalgia. 28, 226-236, 2008.
Alternative Mechanisms ofAlternative Mechanisms of“ Vascular” Drugs “ Vascular” Drugs
-blockers-blockersInhibit neuronal adrenergic signalingInhibit neuronal adrenergic signaling
Calcium channel blockersCalcium channel blockersInhibit neuronal calcium channelsInhibit neuronal calcium channels
CaffeineCaffeineNeuronal/glial adenosine receptor antagonistNeuronal/glial adenosine receptor antagonist
ErgotaminesErgotaminesModulate central 5-HT receptorsModulate central 5-HT receptors
TriptansTriptansActivate neuronal 5-HT1 receptors in brainstem Activate neuronal 5-HT1 receptors in brainstem and thalamusand thalamus
Olesen, et al. 1981 Hadjikhani et al., 2001
Cao et al., 1999
CORTICAL “WAVES” IN MIGRAINE WITH AURA
Bereczki et al., 2008
Woods et al., 1994
Chalaupka, 2008
Denuelle et al., 2008
Before sumatriptan2 to 4 h after the attack onset
After sumatriptan4 to 6 h after the attack onset
…AND MIGRAINE WITHOUT AURA
MIGRAINE – A MULTISYMPTOM COMPLEXMIGRAINE – A MULTISYMPTOM COMPLEX
Cortical Cortical ActivationActivation
BrainstemBrainstemActivationActivation
MIGRAINE SHOULD BE IN DIFFERENTIAL DIAGNOSIS
OF ANY EPISODIC NEUROLOGICAL DISORDER
Do most headache patients need an Do most headache patients need an imaging study of the brain? imaging study of the brain?
“I’ll want to get a few tests on you, just to cover my ass”
When Don’t You Need to When Don’t You Need to Get a Scan?Get a Scan?
Patient with established history of Patient with established history of episodic headache episodic headache
Current headache is consistent with Current headache is consistent with previous headaches or is consistent previous headaches or is consistent with different manifestation of a with different manifestation of a primary headache. primary headache.
Normal neurological examNormal neurological exam
When You Do Need to Get a When You Do Need to Get a ScanScan
Extremely abrupt onset of headacheExtremely abrupt onset of headache
Persistent unremitting headachePersistent unremitting headache
New onset of headache in patient New onset of headache in patient over age of 50over age of 50
FeverFever
PapilledemaPapilledema
Abnormal neurological examinationAbnormal neurological examination
General Approach to The General Approach to The Headache PatientHeadache Patient
Make a diagnosis (or challenge the diagnosis Make a diagnosis (or challenge the diagnosis that a patient has already been given)that a patient has already been given)
Identify and change exacerbating Identify and change exacerbating environmental factors and medicationsenvironmental factors and medications
Establish regimen for acute therapy of Establish regimen for acute therapy of headacheheadache
Determine if preventive therapy is Determine if preventive therapy is appropriateappropriate
IHS CRITERIA FOR MIGRAINE IHS CRITERIA FOR MIGRAINE WITHOUT AURAWITHOUT AURA
At least 5 attacks fulfulling the following:At least 5 attacks fulfulling the following:Headaches lasting 4 to 72 hoursHeadaches lasting 4 to 72 hours
During headache, at least one of the following: During headache, at least one of the following:
Nausea and/or vomitingNausea and/or vomiting
Photophobia and phonophobiaPhotophobia and phonophobia
At least 2 of the following criteriaAt least 2 of the following criteriaUnilateral locationUnilateral location
Pulsating qualityPulsating quality
Moderate or severe intensityModerate or severe intensity
Aggravated by physical activityAggravated by physical activity
Simplified Diagnostic Simplified Diagnostic Criteria:Criteria:
ID MigraineID MigraineLight sensitivity with headacheLight sensitivity with headache
Nausea with headacheNausea with headache
Decreased ability to function with Decreased ability to function with headacheheadache
Any 2 out of 3 = MigraineAny 2 out of 3 = Migraine
Migraine should be the default diagnosis Migraine should be the default diagnosis for any headache that is brought to for any headache that is brought to the attention of a health care providerthe attention of a health care provider
Migraine: Migraine: Other FeaturesOther Features
Perimenstrual timingPerimenstrual timingStereotypical prodromal symptomsStereotypical prodromal symptomsCharacteristic triggersCharacteristic triggersAbatement with sleepAbatement with sleepChildhood precursors (motion Childhood precursors (motion sickness, somnambulism, episodic sickness, somnambulism, episodic vomiting, episodic vertigo)vomiting, episodic vertigo)OsmophobiaOsmophobiaDiarrhea during attackDiarrhea during attack
Landmark: How Likely Is it That “Headache” Is Migraine?
In a prospective, open-label study of 1203 patients with episodic headache
• 94% (of 377 evaluable patients) had migraine or probable migraine
• 25% with migraine were not diagnosed by their physician
• Headaches had a severe impact (HIT–6 score 64)
Migraine (n=288)
76%
Probable migraine (n=67)18%
Episodic tension-type (n=11)3%
Unclassifiable (n=11)3%
Adapted from Tepper SJ et al. Headache. 2004;44:856–864.
Landmark: Patient and Physician Diagnoses
• Self-report or physician diagnosis of migraine was almost always correct • Self-report or physician diagnosis of non-migraine was almost always
later found out to be migraineAdapted from Tepper SJ et al. Headache. 2004;44:856–864.
Patient• If patient self-reports
migraine, 99.5% chance migraine or probable migraine
• If patient self-reports non-migraine, 86% chance migraine or probable migraine
Physician• If physician diagnoses
migraine, 98% chance migraine or probable migraine
• If physician diagnoses non-migraine, 82% chance migraine or probable migraine
In a prospective, open-label study of 1203 patients with episodic headache
MIGRAINES ARE OFTEN MIGRAINES ARE OFTEN MISDIAGNOSED MISDIAGNOSED
SINUS HEADACHESSINUS HEADACHESSIMILAR DISTRIBUTION OF PAINSIMILAR DISTRIBUTION OF PAIN
MIGRAINES CAN BE SEASONALMIGRAINES CAN BE SEASONAL
DECONGESTANTS CAN “TAKE THE EDGE DECONGESTANTS CAN “TAKE THE EDGE OFF” OF MIGRAINE OFF” OF MIGRAINE
WITHDRAWAL FROM DECONGESTANTS WITHDRAWAL FROM DECONGESTANTS CAN PRECIPITATE MIGRAINESCAN PRECIPITATE MIGRAINES
“SINUS HEADACHE”
OTHER COMMON MIGRAINE OTHER COMMON MIGRAINE MISDIAGNOSESMISDIAGNOSES
TENSION HEADACHE/CERVICOGENIC TENSION HEADACHE/CERVICOGENIC HEADACHEHEADACHE
NECK PAIN IS A NECK PAIN IS A SYMPTOMSYMPTOM OF OF MIGRAINEMIGRAINE
MIGRAINE COMMONLY ASSOCIATED MIGRAINE COMMONLY ASSOCIATED WITH NECK PAINWITH NECK PAIN
NECK PAIN MAY OCCUR BEFORE, NECK PAIN MAY OCCUR BEFORE, DURING, OR AFTER HEADACHE DURING, OR AFTER HEADACHE
ARE THERE MIGRAINE TRIGGERS?
COMMON HEADACHE COMMON HEADACHE TRIGGERSTRIGGERS
IRREGULAR MEALSIRREGULAR MEALS
IRREGULAR CAFFEINE, CHOCOLATE, IRREGULAR CAFFEINE, CHOCOLATE, NUTS, BANANAS, ETC.NUTS, BANANAS, ETC.
IRREGULAR SLEEP (PARTICULARLY IRREGULAR SLEEP (PARTICULARLY EXCESSIVE SLEEP)EXCESSIVE SLEEP)
STRESS OR “LET-DOWN” FROM STRESSSTRESS OR “LET-DOWN” FROM STRESS
AIR TRAVEL, CHANGE IN BAROMETRIC AIR TRAVEL, CHANGE IN BAROMETRIC PRESSUREPRESSURE
MENSTRUAL PERIODMENSTRUAL PERIOD
THE MIGRAINE LIFESTYLETHE MIGRAINE LIFESTYLE
CONSISTENCYCONSISTENCYTIMING OF MEALS, BALANCE OF DIET –- TIMING OF MEALS, BALANCE OF DIET –- Don’t skip meals, mix of different food Don’t skip meals, mix of different food groupsgroups
SLEEP --- Don’t oversleep or undersleepSLEEP --- Don’t oversleep or undersleep
CAFFEINE – “Minimum daily dose” of CAFFEINE – “Minimum daily dose” of caffeine on a daily basiscaffeine on a daily basis
EXERCISE – The more aerobic exercise EXERCISE – The more aerobic exercise the betterthe better
MEDICATIONS THAT MAY MEDICATIONS THAT MAY MAKE MIGRAINES WORSEMAKE MIGRAINES WORSE
ORAL CONTRACEPTIVESORAL CONTRACEPTIVES
HORMONE REPLACEMENTHORMONE REPLACEMENT
SSRI ANTIDEPRESSANTSSSRI ANTIDEPRESSANTS
STEROIDS (TAPERING)STEROIDS (TAPERING)
DECONGESTANTSDECONGESTANTS
SHORT ACTING SEDATIVES (e.g. Ambien SHORT ACTING SEDATIVES (e.g. Ambien (?)(?)
BONE DENSITY MEDICATIONS (?)BONE DENSITY MEDICATIONS (?)
BOTOXBOTOX
FREQUENT OPIOID OR BARBITURATE FREQUENT OPIOID OR BARBITURATE (BUTALBITAL) USE IS A RISK FACTOR (BUTALBITAL) USE IS A RISK FACTOR
FOR MIGRAINE PROGRESSIONFOR MIGRAINE PROGRESSION
GROWING EVIDENCE THAT OVERUSE GROWING EVIDENCE THAT OVERUSE OF ANALGESIC MEDICATIONS LEADS OF ANALGESIC MEDICATIONS LEADS TO WORSENING OF MIGRAINETO WORSENING OF MIGRAINE
AMPP DATA AMPP DATA (Bigal et al., Neurology 2008)(Bigal et al., Neurology 2008)
Frequent use of opioids or butalbital Frequent use of opioids or butalbital (more than 8 days/month) is a risk factor (more than 8 days/month) is a risk factor for progression to chronic migrainefor progression to chronic migraine
Triptan use is neutral for progressionTriptan use is neutral for progression
Nonsteroidal use is protectiveNonsteroidal use is protective
ACUTE THERAPIESACUTE THERAPIESTRIPTANS – Selective 5HT 1b 1d agonistsTRIPTANS – Selective 5HT 1b 1d agonists
SUMATRIPTAN (IMITREX TABLETS, NASAL SPRAY, SUMATRIPTAN (IMITREX TABLETS, NASAL SPRAY, INJECTION), SUMATRIPTAN NAPROXEN COMBINATIONINJECTION), SUMATRIPTAN NAPROXEN COMBINATIONRIZATRIPTAN (MAXALT “MELTABS”, TABLETS)RIZATRIPTAN (MAXALT “MELTABS”, TABLETS)NARATRIPTAN (AMERGE TABLETS)NARATRIPTAN (AMERGE TABLETS)ZOLMITRIPTAN (ZOMIG)ZOLMITRIPTAN (ZOMIG)ALMOTRIPTAN (AXERT)ALMOTRIPTAN (AXERT)FROVATRIPTAN (FROVA)FROVATRIPTAN (FROVA)ELETRIPTAN (RELPAX)ELETRIPTAN (RELPAX)
DHE NASAL SPRAY (MIGRANAL), INJECTIONDHE NASAL SPRAY (MIGRANAL), INJECTIONNSAIDSNSAIDSMETACLOPRAMIDEMETACLOPRAMIDE
TRIPTAN NEWSTRIPTAN NEWS
TRIPTANS ARE NOW AVAILABLE TRIPTANS ARE NOW AVAILABLE WIDELY WITHOUT A PRESCRIPTION WIDELY WITHOUT A PRESCRIPTION IN EUROPE.IN EUROPE.
SUMATRIPTAN WILL SOON BE SUMATRIPTAN WILL SOON BE AVAILABLE AS A GENERIC IN AVAILABLE AS A GENERIC IN MULTIPLE PREPARATIONS.MULTIPLE PREPARATIONS.
SUMATRIPTAN/NAPROXEN SUMATRIPTAN/NAPROXEN COMBINATION TABLET (TREXIMET) IS COMBINATION TABLET (TREXIMET) IS NOW AVAILABLE. NOW AVAILABLE.
EVIDENCE-BASED NON-EVIDENCE-BASED NON-PRESCRIPTION APPROACHES TO PRESCRIPTION APPROACHES TO
MIGRAINEMIGRAINE
Magnesium (300-500 mg. per day)Magnesium (300-500 mg. per day)
Riboflavin (400 mg. per day)Riboflavin (400 mg. per day)
CoQ10 (300 -1200 mg. per day)CoQ10 (300 -1200 mg. per day)
Melatonin (3 mg. qhs)Melatonin (3 mg. qhs)
Petasites (Butterbur 75 mg. BID)Petasites (Butterbur 75 mg. BID)
THERAPEUTIC OPTIONS FOR MIGRAINE THERAPEUTIC OPTIONS FOR MIGRAINE PROPHYLAXISPROPHYLAXIS
BETA BLOCKERSBETA BLOCKERS
TRICYCLICSTRICYCLICS
CALCIUM CHANNEL BLOCKERSCALCIUM CHANNEL BLOCKERS
VALPROIC ACID (Depakote)VALPROIC ACID (Depakote)
TOPIRAMATE (Topamax)TOPIRAMATE (Topamax)
?? MEMANTINE?? MEMANTINE
MEMANTINE FOR MIGRAINE MEMANTINE FOR MIGRAINE PREVENTION?PREVENTION?
Activity dependent blocker of NMDA Activity dependent blocker of NMDA receptorsreceptorsIdentified as a blocker of CSD in rodentsIdentified as a blocker of CSD in rodentsAppears to be effective as a migraine Appears to be effective as a migraine preventive therapy for significant percentage preventive therapy for significant percentage of patients with frequent migraine who had of patients with frequent migraine who had failed other preventive therapiesfailed other preventive therapiesIt is generally very well toleratedIt is generally very well toleratedWell designed studies are warrantedWell designed studies are warranted
Peeters et al., JPET, 2007Peeters et al., JPET, 2007Charles, et al., Journal of Headache and Pain, 2007Charles, et al., Journal of Headache and Pain, 2007Bigal et al., Headache, 2008Bigal et al., Headache, 2008
MIGRAINE AND PREGNANCYMIGRAINE AND PREGNANCYTHE SIGNIFICANT MAJORITY OF WOMEN HAVE AN THE SIGNIFICANT MAJORITY OF WOMEN HAVE AN IMPROVEMENT IN MIGRAINE FREQUENCY DURING THE IMPROVEMENT IN MIGRAINE FREQUENCY DURING THE 22ndnd and 3 and 3rdrd TRIMESTERS OF PREGNANCY TRIMESTERS OF PREGNANCY
THERE IS NO CONSENSUS OR EVIDENCED BASED THERE IS NO CONSENSUS OR EVIDENCED BASED APPROACH TO TREATMENT OF HEADACHE DURING APPROACH TO TREATMENT OF HEADACHE DURING PREGNANCYPREGNANCY
REGULAR SMALL AMOUNTS OF CAFFEINE, MAGNESIUM REGULAR SMALL AMOUNTS OF CAFFEINE, MAGNESIUM SUPPLEMENTATION ARE REASONABLE NON-SUPPLEMENTATION ARE REASONABLE NON-PRESCRIPTION ALTERNATIVESPRESCRIPTION ALTERNATIVES
THE ONLY ADVERSE EVENT THAT HAS BEEN IDENTIFIED THE ONLY ADVERSE EVENT THAT HAS BEEN IDENTIFIED WITH TRIPTANS AND PREGNANCY IS A SLIGHTLY WITH TRIPTANS AND PREGNANCY IS A SLIGHTLY INCREASED RISK OF PREMATURE DELIVERY….i.e. OK TO INCREASED RISK OF PREMATURE DELIVERY….i.e. OK TO USE TRIPTANS IN SEVERE CASESUSE TRIPTANS IN SEVERE CASES
NEW THERAPIES ON THE NEW THERAPIES ON THE HORIZONHORIZON
ACUTE THERAPIESACUTE THERAPIESCGRP Antagonist – Initial placebo controlled trials CGRP Antagonist – Initial placebo controlled trials look very promising.look very promising.
Transcranial magnetic stimulationTranscranial magnetic stimulation
Inhaled ergotaminesInhaled ergotamines
PREVENTIVE THERAPIESPREVENTIVE THERAPIESPFO Closure – Multiple closure devices in clinical trialsPFO Closure – Multiple closure devices in clinical trials
Memantine – Initial uncontrolled results are promisingMemantine – Initial uncontrolled results are promising
Occiptial nerve stimulationOcciptial nerve stimulation
TonabersatTonabersat
CGRP CGRP (Calcitonin Gene Related Peptide)(Calcitonin Gene Related Peptide) IN MIGRAINEIN MIGRAINE
CGRP IS RELEASED INTO JUGULAR VENOUS CGRP IS RELEASED INTO JUGULAR VENOUS SYSTEM DURING A MIGRAINE ATTACKSYSTEM DURING A MIGRAINE ATTACK
CGRP RECEPTOR ANTAGONISTS CGRP RECEPTOR ANTAGONISTS EFFECTIVELY ABORT A MIGRAINE ATTACKEFFECTIVELY ABORT A MIGRAINE ATTACKCalcitonin Gene–Related Peptide Receptor Antagonist BIBN 4096 BS for the Calcitonin Gene–Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine. NEJM, 350: 1104-1110, 2004.Acute Treatment of Migraine. NEJM, 350: 1104-1110, 2004.Jes Olesen, M.D., Hans-Christoph Diener, M.D., Ingo W. Husstedt, M.D., Peter J. Goadsby, M.D., David Jes Olesen, M.D., Hans-Christoph Diener, M.D., Ingo W. Husstedt, M.D., Peter J. Goadsby, M.D., David Hall, Ph.D., Ulrich Meier, Ph.D., Stephane Pollentier, M.D., and Lynna M. Lesko, M.D., for the BIBN Hall, Ph.D., Ulrich Meier, Ph.D., Stephane Pollentier, M.D., and Lynna M. Lesko, M.D., for the BIBN 4096 BS Clinical Proof of Concept Study Group4096 BS Clinical Proof of Concept Study Group
Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology 70: 1304-1312, 2008.in acute treatment of migraine. Neurology 70: 1304-1312, 2008.T. W. Ho, MD, L. K. Mannix, MD, X. Fan, PhD, C. Assaid, PhD, C. Furtek, BS, C. J. Jones, MS, C. R. Lines, PhD, A. T. W. Ho, MD, L. K. Mannix, MD, X. Fan, PhD, C. Assaid, PhD, C. Furtek, BS, C. J. Jones, MS, C. R. Lines, PhD, A. M. Rapoport, MD On behalf of the MK-0974 Protocol 004 study groupM. Rapoport, MD On behalf of the MK-0974 Protocol 004 study group**
MODULATORS OF CERVICAL INPUT TO HEADACHE
Occipital Nerve Stimulation
INHIBITORS OF CORTICAL SPREADING DEPRESSIONMemantine, Tonabersat, Transcranial Magnestic Stimulation
POTENTIAL NEW THERAPIES FOR MIGRAINE
Adapted from Jones HR. Netter’s Neurology, St. Louis, MO; Saunders; 2005.
INHIBITORS OF CGRP RECEPTORTelcagepant
CIRCULATORY TRIGGERS TO BRAIN EXCITABILITY?
PFO Closure
TAKE HOME MESSAGES TAKE HOME MESSAGES MIGRAINE IS A COMPLEX DISORDER OF BRAIN MIGRAINE IS A COMPLEX DISORDER OF BRAIN EXCITABILITY AND NOT SIMPLY A “VASCULAR EXCITABILITY AND NOT SIMPLY A “VASCULAR HEADACHE” HEADACHE” MIGRAINE IS EXTRAORDINARILY COMMON AND MIGRAINE IS EXTRAORDINARILY COMMON AND UNDERDIAGNOSED.UNDERDIAGNOSED.THE MAJORITY OF MIGRAINE PATIENTS CAN BE THE MAJORITY OF MIGRAINE PATIENTS CAN BE EFFECTIVELY AND SAFELY TREATED WITH AN EFFECTIVELY AND SAFELY TREATED WITH AN ORGANIZED PLAN OF LIFESTYLE MANAGEMENT , ORGANIZED PLAN OF LIFESTYLE MANAGEMENT , ACUTE THERAPY, AND PREVENTIVE THERAPY IF ACUTE THERAPY, AND PREVENTIVE THERAPY IF NEEDEDNEEDEDPROMISING NEW THERAPIES ARE ON THE HORIZONPROMISING NEW THERAPIES ARE ON THE HORIZON