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