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HEADACHE. Andrew Charles, M.D. Professor Director, Headache Research and Treatment Program David Geffen School of Medicine at UCLA. COMMON TYPES OF HEADACHES. PRIMARY HEADACHES MIGRAINE TENSION TYPE CLUSTER HEADACHE AND OTHER TRIGEMINAL AUTONOMIC CEPHALGIAS SECONDARY HEADACHES

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Headache l.jpg

HEADACHE

Andrew Charles, M.D.

Professor

Director, Headache Research and Treatment Program

David Geffen School of Medicine at UCLA


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COMMON TYPES OF HEADACHES

  • PRIMARY HEADACHES

    • MIGRAINE

    • TENSION TYPE

    • CLUSTER HEADACHE AND OTHER TRIGEMINAL AUTONOMIC CEPHALGIAS

  • SECONDARY HEADACHES

    • Headaches due to infection

    • Headaches due to vascular causes

    • Headaches due to tumors

    • Etc., etc.


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MIGRAINE: Prevalence and Impact

LIFETIME CUMULATIVE INCIDENCE

  • 43% of women

  • 18% of men

    • Stewart et al., Cephalagia, 2008

  • 5% of women have headache more than 15 days per month – Migraine likely represents a significant component for these patients.

  • The majority of patients with migraine have not received an appropriate diagnosis, and are not receiving appropriate therapy


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    MIGRAINE – A MULTISYMPTOM COMPLEX

    AURA

    SENSORY SYMPTOMS

    VISUAL SYMPTOMS

    LANGUAGE SYMPTOMS

    COGNITIVE

    DYSFUNCTION

    MOTOR

    DYSFUNCTION

    PATHOPHYSIOLOGICAL

    MECHANISMS

    YAWNING,

    POLYURIA

    FATIGUE,

    MOOD CHANGE

    NAUSEA,

    VOMITING

    DIZZINESS,

    VERTIGO

    HEADACHE


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    CHANGING CONCEPTS OF MIGRAINE PATHOGENESIS

    • MIGRAINE IS A DISORDER OF BRAIN EXCITABILITY

    • VASODILATION MAY OCCUR AS PART OF THE DISORDER, BUT IS NOT REQUIRED FOR MIGRAINE PAIN


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    • Penfield W. A contribution to the mechanism of intracranial pain. Assoc Res NervMent Dis. 1935;15:399-416.

    • Ray BS, Wolff HG. Experimental studies in headache: Pain-sensitive structures of the head and their significance in headache. Arch Surg. 1940;41:813-856.


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    Issues with Studies of Ray and Wolff, Penfield

    • Stimulation of vessels was focal external stimulation or mechanical dilation

    • There is no evidence that physiological relaxation of smooth muscle and resultant dilation can cause pain

    • Multiple areas of brain that could evoke pain were not stimulated:

      • Cingulate cortex

      • Brainstem – Stimulation or lesions in brainstem can cause migraine


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    Vasoactive Drugs Cause Migraine After Significant Delay (hours), Not Correlated with Vasodilation

    • Nitric oxide donors

    • PDE inhibitors

    • Histamine

    • CGRP

    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.


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    Alternative Mechanisms of“ Vascular” Drugs

    • -blockers

      • Inhibit neuronal adrenergic signaling

    • Calcium channel blockers

      • Inhibit neuronal calcium channels

    • Caffeine

      • Neuronal/glial adenosine receptor antagonist

    • Ergotamines

      • Modulate central 5-HT receptors

    • Triptans

      • Activate neuronal 5-HT1 receptors in brainstem and thalamus


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    CORTICAL “WAVES” IN MIGRAINE WITH AURA

    Olesen, et al. 1981

    Hadjikhani et al., 2001

    Bereczki et al., 2008

    Cao et al., 1999


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    …AND MIGRAINE WITHOUT AURA

    Woods et al., 1994

    After sumatriptan

    4 to 6 h after the attack onset

    Before sumatriptan

    2 to 4 h after the attack onset

    Chalaupka, 2008

    Denuelle et al., 2008


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    Hypothalamic Activation in Migraine

    (Denuelle et al., Headache, 2007)


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    MIGRAINE – A MULTISYMPTOM COMPLEX

    PAIN

    Sensory, Cognitive, Motor Symptoms

    VISUAL SYMPTOMS

    Cortical

    Activation

    Brainstem

    Activation

    Nausea/Vomiting

    VESTIBULAR SYMPTOMS

    PAIN


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    MIGRAINE SHOULD BE IN DIFFERENTIAL DIAGNOSIS OF ANY EPISODIC NEUROLOGICAL DISORDER


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    Do most headache patients need an imaging study of the brain?


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    “I’ll want to get a few tests on you, just to cover my ass”


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    When Don’t You Need to Get a Scan?

    • Patient with established history of episodic headache

    • Current headache is consistent with previous headaches or is consistent with different manifestation of a primary headache.

    • Normal neurological exam


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    When You Do Need to Get a Scan

    • Extremely abrupt onset of headache

    • Persistent unremitting headache

    • New onset of headache in patient over age of 50

    • Fever

    • Papilledema

    • Abnormal neurological examination


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    General Approach to The Headache Patient

    • Make a diagnosis (or challenge the diagnosis that a patient has already been given)

    • Identify and change exacerbating environmental factors and medications

    • Establish regimen for acute therapy of headache

    • Determine if preventive therapy is appropriate


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    IHS CRITERIA FOR MIGRAINE WITHOUT AURA

    • At least 5 attacks fulfulling the following:

      • Headaches lasting 4 to 72 hours

      • During headache, at least one of the following:

        Nausea and/or vomiting

        Photophobia and phonophobia

      • At least 2 of the following criteria

        Unilateral location

        Pulsating quality

        Moderate or severe intensity

        Aggravated by physical activity


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    Simplified Diagnostic Criteria:ID Migraine

    • Light sensitivity with headache

    • Nausea with headache

    • Decreased ability to function with headache

    • Any 2 out of 3 = Migraine

      Migraine should be the default diagnosis for any headache that is brought to the attention of a health care provider


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    Migraine: Other Features

    • Perimenstrual timing

    • Stereotypical prodromal symptoms

    • Characteristic triggers

    • Abatement with sleep

    • Childhood precursors (motion sickness, somnambulism, episodic vomiting, episodic vertigo)

    • Osmophobia

    • Diarrhea during attack


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    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)

    Probable migraine (n=67)

    18%

    Migraine (n=288)

    76%

    Episodic tension-type (n=11)

    3%

    Unclassifiable (n=11)

    3%

    Adapted from Tepper SJ et al. Headache. 2004;44:856–864.


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    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

    Landmark: Patient and Physician Diagnoses

    In a prospective, open-label study of 1203 patients with episodic headache

    • 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 migraine

    Adapted from Tepper SJ et al. Headache. 2004;44:856–864.


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    MIGRAINES ARE OFTEN MISDIAGNOSED

    • SINUS HEADACHES

      • SIMILAR DISTRIBUTION OF PAIN

      • MIGRAINES CAN BE SEASONAL

      • DECONGESTANTS CAN “TAKE THE EDGE OFF” OF MIGRAINE

      • WITHDRAWAL FROM DECONGESTANTS CAN PRECIPITATE MIGRAINES


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    “SINUS HEADACHE”


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    OTHER COMMON MIGRAINE MISDIAGNOSES

    • TENSION HEADACHE/CERVICOGENIC HEADACHE

    • NECK PAIN IS A SYMPTOM OF MIGRAINE

      • MIGRAINE COMMONLY ASSOCIATED WITH NECK PAIN

      • NECK PAIN MAY OCCUR BEFORE, DURING, OR AFTER HEADACHE


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    ARE THERE MIGRAINE TRIGGERS?


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    COMMON HEADACHE TRIGGERS

    • IRREGULAR MEALS

    • IRREGULAR CAFFEINE, CHOCOLATE, NUTS, BANANAS, ETC.

    • IRREGULAR SLEEP (PARTICULARLY EXCESSIVE SLEEP)

    • STRESS OR “LET-DOWN” FROM STRESS

    • AIR TRAVEL, CHANGE IN BAROMETRIC PRESSURE

    • MENSTRUAL PERIOD


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    THE MIGRAINE LIFESTYLE

    • CONSISTENCY

      • TIMING OF MEALS, BALANCE OF DIET –- Don’t skip meals, mix of different food groups

      • SLEEP --- Don’t oversleep or undersleep

      • CAFFEINE – “Minimum daily dose” of caffeine on a daily basis

      • EXERCISE – The more aerobic exercise the better


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    MEDICATIONS THAT MAY MAKE MIGRAINES WORSE

    • ORAL CONTRACEPTIVES

    • HORMONE REPLACEMENT

    • SSRI ANTIDEPRESSANTS

    • STEROIDS (TAPERING)

    • DECONGESTANTS

    • SHORT ACTING SEDATIVES (e.g. Ambien (?)

    • BONE DENSITY MEDICATIONS (?)

    • BOTOX


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    FREQUENT OPIOID OR BARBITURATE (BUTALBITAL) USE IS A RISK FACTOR FOR MIGRAINE PROGRESSION

    • GROWING EVIDENCE THAT OVERUSE OF ANALGESIC MEDICATIONS LEADS TO WORSENING OF MIGRAINE

    • AMPP DATA (Bigal et al., Neurology 2008)

      • Frequent use of opioids or butalbital (more than 8 days/month) is a risk factor for progression to chronic migraine

      • Triptan use is neutral for progression

      • Nonsteroidal use is protective


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    ACUTE THERAPIES

    • TRIPTANS – Selective 5HT 1b 1d agonists

      • SUMATRIPTAN (IMITREX TABLETS, NASAL SPRAY, INJECTION), SUMATRIPTAN NAPROXEN COMBINATION

      • RIZATRIPTAN (MAXALT “MELTABS”, TABLETS)

      • NARATRIPTAN (AMERGE TABLETS)

      • ZOLMITRIPTAN (ZOMIG)

      • ALMOTRIPTAN (AXERT)

      • FROVATRIPTAN (FROVA)

      • ELETRIPTAN (RELPAX)

    • DHE NASAL SPRAY (MIGRANAL), INJECTION

    • NSAIDS

    • METACLOPRAMIDE


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    TRIPTAN NEWS

    • TRIPTANS ARE NOW AVAILABLE WIDELY WITHOUT A PRESCRIPTION IN EUROPE.

    • SUMATRIPTAN WILL SOON BE AVAILABLE AS A GENERIC IN MULTIPLE PREPARATIONS.

    • SUMATRIPTAN/NAPROXEN COMBINATION TABLET (TREXIMET) IS NOW AVAILABLE.


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    EVIDENCE-BASED NON-PRESCRIPTION APPROACHES TO MIGRAINE

    • Magnesium (300-500 mg. per day)

    • Riboflavin (400 mg. per day)

    • CoQ10 (300 -1200 mg. per day)

    • Melatonin (3 mg. qhs)

    • Petasites (Butterbur 75 mg. BID)


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    THERAPEUTIC OPTIONS FOR MIGRAINE PROPHYLAXIS

    • BETA BLOCKERS

    • TRICYCLICS

    • CALCIUM CHANNEL BLOCKERS

    • VALPROIC ACID (Depakote)

    • TOPIRAMATE (Topamax)

    • ?? MEMANTINE


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    MEMANTINE FOR MIGRAINE PREVENTION?

    • Activity dependent blocker of NMDA receptors

    • Identified as a blocker of CSD in rodents

    • Appears to be effective as a migraine preventive therapy for significant percentage of patients with frequent migraine who had failed other preventive therapies

    • It is generally very well tolerated

    • Well designed studies are warranted

      Peeters et al., JPET, 2007

      Charles, et al., Journal of Headache and Pain, 2007

      Bigal et al., Headache, 2008


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    MIGRAINE AND PREGNANCY

    • THE SIGNIFICANT MAJORITY OF WOMEN HAVE AN IMPROVEMENT IN MIGRAINE FREQUENCY DURING THE 2nd and 3rd TRIMESTERS OF PREGNANCY

    • THERE IS NO CONSENSUS OR EVIDENCED BASED APPROACH TO TREATMENT OF HEADACHE DURING PREGNANCY

    • REGULAR SMALL AMOUNTS OF CAFFEINE, MAGNESIUM SUPPLEMENTATION ARE REASONABLE NON-PRESCRIPTION ALTERNATIVES

    • THE ONLY ADVERSE EVENT THAT HAS BEEN IDENTIFIED WITH TRIPTANS AND PREGNANCY IS A SLIGHTLY INCREASED RISK OF PREMATURE DELIVERY….i.e. OK TO USE TRIPTANS IN SEVERE CASES


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    NEW THERAPIES ON THE HORIZON

    • ACUTE THERAPIES

      • CGRP Antagonist – Initial placebo controlled trials look very promising.

      • Transcranial magnetic stimulation

      • Inhaled ergotamines

    • PREVENTIVE THERAPIES

      • PFO Closure – Multiple closure devices in clinical trials

      • Memantine – Initial uncontrolled results are promising

      • Occiptial nerve stimulation

      • Tonabersat


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    TAKE HOME MESSAGES

    • MIGRAINE IS A COMPLEX DISORDER OF BRAIN EXCITABILITY AND NOT SIMPLY A “VASCULAR HEADACHE”

    • MIGRAINE IS EXTRAORDINARILY COMMON AND UNDERDIAGNOSED.

    • THE MAJORITY OF MIGRAINE PATIENTS CAN BE EFFECTIVELY AND SAFELY TREATED WITH AN ORGANIZED PLAN OF LIFESTYLE MANAGEMENT , ACUTE THERAPY, AND PREVENTIVE THERAPY IF NEEDED

    • PROMISING NEW THERAPIES ARE ON THE HORIZON


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