Presentation on theme: "HEADACHE Andrew Charles, M.D. Professor"— Presentation transcript:
1 HEADACHE Andrew Charles, M.D. Professor Director, Headache Research and Treatment ProgramDavid Geffen School of Medicine at UCLA
2 COMMON TYPES OF HEADACHES PRIMARY HEADACHESMIGRAINETENSION TYPECLUSTER HEADACHE AND OTHER TRIGEMINAL AUTONOMIC CEPHALGIASSECONDARY HEADACHESHeadaches due to infectionHeadaches due to vascular causesHeadaches due to tumorsEtc., etc.
3 MIGRAINE: Prevalence and Impact LIFETIME CUMULATIVE INCIDENCE43% of women18% of menStewart et al., Cephalagia, 20085% 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
5 CHANGING CONCEPTS OF MIGRAINE PATHOGENESIS MIGRAINE IS A DISORDER OF BRAIN EXCITABILITYVASODILATION MAY OCCUR AS PART OF THE DISORDER, BUT IS NOT REQUIRED FOR MIGRAINE PAIN
6 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:Ray BS, Wolff HG. Experimental studies in headache: Pain-sensitive structures of the head and their significance in headache. Arch Surg. 1940;41:
7 Issues with Studies of Ray and Wolff, Penfield Stimulation of vessels was focal external stimulation or mechanical dilationThere is no evidence that physiological relaxation of smooth muscle and resultant dilation can cause painMultiple areas of brain that could evoke pain were not stimulated:Cingulate cortexBrainstem – Stimulation or lesions in brainstem can cause migraine
8 Nitric oxide donors PDE inhibitors Histamine CGRP Vasoactive Drugs Cause Migraine After Significant Delay (hours), Not Correlated with VasodilationNitric oxide donorsPDE inhibitorsHistamineCGRPSchoonman, et al. Migraine headache is not associated with cerebral or meningeal vasodilatation--a 3T magnetic resonance angiography study. Brain 131, , 2008.Kruus, et al. Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain. 26: , 2003.Rahman et al., Vasoactive intestinal peptide causes marked cerebral vasodilation but does not induce migraine. Cephalalgia. 28, , 2008.
9 Alternative Mechanisms of “ Vascular” Drugs -blockersInhibit neuronal adrenergic signalingCalcium channel blockersInhibit neuronal calcium channelsCaffeineNeuronal/glial adenosine receptor antagonistErgotaminesModulate central 5-HT receptorsTriptansActivate neuronal 5-HT1 receptors in brainstem and thalamus
10 CORTICAL “WAVES” IN MIGRAINE WITH AURA Olesen, et al. 1981Hadjikhani et al., 2001So by now we see that events c temporal, spatial, blood flow characteristics of CSD appear to occur in migraine pts, correlate with aura sx.Bereczki et al., 2008Cao et al., 1999
11 …AND MIGRAINE WITHOUT AURA Woods et al., 1994Denuelle et al., 2008Before sumatriptan2 to 4 h after the attack onsetAfter sumatriptan4 to 6 h after the attack onsetChalaupka, 2008
12 The image on this slide is a PET scan from one individual in the Weiller et. al. study. The red area or locus of activity is located in the brain stem. The authors of this study identified the raphe nuclei, the locus ceruleus, and the peri-aqueductal gray as brain stem regions that are selectively activated during a migraine attack. These regions are thought to be involved in the generation of headache pain.Reference: Weiller C, May A, Limmroth V, et. al. Brain stem activation in spontaneous human migraine attacks. Nat Med. 1995;1:
13 Hypothalamic Activation in Migraine (Denuelle et al., Headache, 2007)
14 Sensory, Cognitive, Motor Symptoms MIGRAINE – A MULTISYMPTOM COMPLEXPAINSensory, Cognitive, Motor SymptomsVISUAL SYMPTOMSCorticalActivationBrainstemActivationNausea/VomitingVESTIBULAR SYMPTOMSPAIN
15 MIGRAINE SHOULD BE IN DIFFERENTIAL DIAGNOSIS OF ANY EPISODIC NEUROLOGICAL DISORDER
16 Do most headache patients need an imaging study of the brain?
17 “I’ll want to get a few tests on you, just to cover my ass”
18 When Don’t You Need to Get a Scan? Patient with established history of episodic headacheCurrent headache is consistent with previous headaches or is consistent with different manifestation of a primary headache.Normal neurological exam
19 When You Do Need to Get a Scan Extremely abrupt onset of headachePersistent unremitting headacheNew onset of headache in patient over age of 50FeverPapilledemaAbnormal neurological examination
20 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 medicationsEstablish regimen for acute therapy of headacheDetermine if preventive therapy is appropriate
21 IHS CRITERIA FOR MIGRAINE WITHOUT AURA At least 5 attacks fulfulling the following:Headaches lasting 4 to 72 hoursDuring headache, at least one of the following:Nausea and/or vomitingPhotophobia and phonophobiaAt least 2 of the following criteriaUnilateral locationPulsating qualityModerate or severe intensityAggravated by physical activity
22 Simplified Diagnostic Criteria: ID Migraine Light sensitivity with headacheNausea with headacheDecreased ability to function with headacheAny 2 out of 3 = MigraineMigraine should be the default diagnosis for any headache that is brought to the attention of a health care provider
23 Migraine: Other Features Perimenstrual timingStereotypical prodromal symptomsCharacteristic triggersAbatement with sleepChildhood precursors (motion sickness, somnambulism, episodic vomiting, episodic vertigo)OsmophobiaDiarrhea during attack
24 Landmark: How Likely Is it That “Headache” Is Migraine? In a prospective, open-label study of 1203 patients with episodic headache94% (of 377 evaluable patients) had migraine or probable migraine25% with migraine were not diagnosed by their physicianHeadaches had a severe impact (HIT–6 score 64)Probable migraine (n=67)18%Migraine (n=288)76%Episodic tension-type (n=11)3%The Landmark Study evaluated the diagnosis of patients consulting their primary care physicians with headache, and was conducted in 128 practices (93% primary care) in 15 countries. This prospective, open-label study included patients (aged 18–65 years) who consulted their physician with headache as a primary or secondary complaint. Patients were excluded if they had chronic daily headache or if they had a known or suspected secondary headache disorder. A total of 1203 patients were included.During the screening visit, patients self-reported a headache diagnosis, and were then assigned a headache diagnosis by their physician following his or her usual practice. Patients with a physician diagnosis of migraine or non-migraine primary headache completed diaries to record headache symptoms for 3 months or 6 attacks, whichever occurred first. Members of an expert panel (Carl Dahlöf, Sweden; Andrew Dowson, UK; and Lawrence Newman and Stewart Tepper, US), who were unaware of the physician diagnosis, then used the diary data to assign a headache diagnosis according to IHS criteria.The expert panel reviewed diary data for 448 patients (306 with a new physician diagnosis of migraine and 142 with a diagnosis of non-migraine primary headache). Of these, 377 diaries were evaluable for making a headache diagnosis.Of the 377 patients, 355 (94%) were assigned a diagnosis of migraine (76%) or probable migraine (18%) by the expert panel.The Landmark Study found that if a patient presents to their physician with complaint of headache, there is a 94% likelihood it is migraine or migrainous headache.Unclassifiable (n=11)3%Adapted from Tepper SJ et al. Headache. 2004;44:856–864.
25 Landmark: Patient and Physician Diagnoses In a prospective, open-label study of 1203 patients with episodic headachePatientIf patient self-reports migraine, 99.5% chance migraine or probable migraineIf patient self-reports non-migraine, 86% chance migraine or probable migrainePhysicianIf physician diagnoses migraine, 98% chance migraine or probable migraineIf physician diagnoses non-migraine, 82% chance migraine or probable migraineOf the 206 patients in the Landmark study who self-reported migraine at the screening visit, almost all (99.5%) were confirmed as having migraine or probable migraine by the expert panel (88% migraine, 11.5% probable migraine). No patient who self-reported migraine was subsequently diagnosed with episodic tension-type headache. Of the 272 patients who were given a new diagnosis of migraine by their physician, 98% were diagnosed with migraine or probable migraine by the expert panel. Therefore, a patient or a physician diagnosis of migraine is likely to be accurate, according to this study.However, if the patient or the physician diagnosed non-migraine, there was a high probability that the patient actually had migraine. Of the 148 patients who self-reported non-migraine headache, 86% were diagnosed by the expert panel with migraine or probable migraine. Likewise, of the 105 patients diagnosed by their physicians as having non-migraine headache, 82% were assigned a diagnosis of migraine or probable migraine by the expert panel.A self-report or physician diagnosis of migraine was almost always correct. On the other hand, a self-report or physician diagnosis of non-migraine was almost always later found out to be migraine.It may be helpful to provide such tools as migraine diaries for patients, and request them to fill it out over several migraine attacks before asking the patient to return to the clinic. During this followup visit, the physician can review the diary and refer to the I.H.S. diagnostic criteria in order to help reach a final diagnosis.Self-report or physician diagnosis of migraine was almost always correctSelf-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.
26 MIGRAINES ARE OFTEN MISDIAGNOSED SINUS HEADACHESSIMILAR DISTRIBUTION OF PAINMIGRAINES CAN BE SEASONALDECONGESTANTS CAN “TAKE THE EDGE OFF” OF MIGRAINEWITHDRAWAL FROM DECONGESTANTS CAN PRECIPITATE MIGRAINES
28 OTHER COMMON MIGRAINE MISDIAGNOSES TENSION HEADACHE/CERVICOGENIC HEADACHENECK PAIN IS A SYMPTOM OF MIGRAINEMIGRAINE COMMONLY ASSOCIATED WITH NECK PAINNECK PAIN MAY OCCUR BEFORE, DURING, OR AFTER HEADACHE
31 COMMON HEADACHE TRIGGERS IRREGULAR MEALSIRREGULAR CAFFEINE, CHOCOLATE, NUTS, BANANAS, ETC.IRREGULAR SLEEP (PARTICULARLY EXCESSIVE SLEEP)STRESS OR “LET-DOWN” FROM STRESSAIR TRAVEL, CHANGE IN BAROMETRIC PRESSUREMENSTRUAL PERIOD
32 THE MIGRAINE LIFESTYLE CONSISTENCYTIMING OF MEALS, BALANCE OF DIET –- Don’t skip meals, mix of different food groupsSLEEP --- Don’t oversleep or undersleepCAFFEINE – “Minimum daily dose” of caffeine on a daily basisEXERCISE – The more aerobic exercise the better
33 MEDICATIONS THAT MAY MAKE MIGRAINES WORSE ORAL CONTRACEPTIVESHORMONE REPLACEMENTSSRI ANTIDEPRESSANTSSTEROIDS (TAPERING)DECONGESTANTSSHORT ACTING SEDATIVES (e.g. Ambien (?)BONE DENSITY MEDICATIONS (?)BOTOX
34 AMPP DATA (Bigal et al., Neurology 2008) FREQUENT OPIOID OR BARBITURATE (BUTALBITAL) USE IS A RISK FACTOR FOR MIGRAINE PROGRESSIONGROWING EVIDENCE THAT OVERUSE OF ANALGESIC MEDICATIONS LEADS TO WORSENING OF MIGRAINEAMPP 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 migraineTriptan use is neutral for progressionNonsteroidal use is protective
36 TRIPTAN NEWSTRIPTANS 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.
37 EVIDENCE-BASED NON-PRESCRIPTION APPROACHES TO MIGRAINE Magnesium ( mg. per day)Riboflavin (400 mg. per day)CoQ10 ( mg. per day)Melatonin (3 mg. qhs)Petasites (Butterbur 75 mg. BID)
39 MEMANTINE FOR MIGRAINE PREVENTION? Activity dependent blocker of NMDA receptorsIdentified as a blocker of CSD in rodentsAppears to be effective as a migraine preventive therapy for significant percentage of patients with frequent migraine who had failed other preventive therapiesIt is generally very well toleratedWell designed studies are warrantedPeeters et al., JPET, 2007Charles, et al., Journal of Headache and Pain, 2007Bigal et al., Headache, 2008
40 MIGRAINE AND PREGNANCY THE SIGNIFICANT MAJORITY OF WOMEN HAVE AN IMPROVEMENT IN MIGRAINE FREQUENCY DURING THE 2nd and 3rd TRIMESTERS OF PREGNANCYTHERE IS NO CONSENSUS OR EVIDENCED BASED APPROACH TO TREATMENT OF HEADACHE DURING PREGNANCYREGULAR SMALL AMOUNTS OF CAFFEINE, MAGNESIUM SUPPLEMENTATION ARE REASONABLE NON-PRESCRIPTION ALTERNATIVESTHE 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
41 NEW THERAPIES ON THE HORIZON ACUTE THERAPIESCGRP Antagonist – Initial placebo controlled trials look very promising.Transcranial magnetic stimulationInhaled ergotaminesPREVENTIVE THERAPIESPFO Closure – Multiple closure devices in clinical trialsMemantine – Initial uncontrolled results are promisingOcciptial nerve stimulationTonabersat
42 TAKE HOME MESSAGESMIGRAINE 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 NEEDEDPROMISING NEW THERAPIES ARE ON THE HORIZON