Presentation on theme: "Migraine Headache – Update on Diagnosis & Treatment"— Presentation transcript:
1 Migraine Headache – Update on Diagnosis & Treatment Herbert L. Muncie, Jr., M.D.
2 What is the diagnosis?Sarah, a previously very healthy 14 year old female complains of a severe headache & nausea. It is the start of the Thanksgiving holiday and all she wants to do is lay on the sofa.PMHH. flu meningitis age 7 monthsCar motion sickness as a childFamily history positive for migraines – maternal grandmother & mother
3 Diagnosing Migraine Headache Any severe or recurrent headache most likely is a form of migraineAlmost all patients will have family history of migraines or at least “sick” headachesOnly 15% have preceded or accompanied focal neurologic symptomsUsually visualVision loss or distortion in one eye – ‘ocular migraine’“Classic migraine”
4 Sarah Spent most of Thanksgiving holiday resting on the sofa Diagnosed with onset of migraine headaches
5 Recurrent Headaches Primary Migraine Tension Cluster Other benign – cough, cold temperature, post coital, exertion
7 Migraine with aura – Criteria* At least 2 attacks with 3 of the following:Fully reversible aura symptomsAt least 1 aura symptom develops gradually during more than 4 minutes or 2 symptoms occur in successionAny aura symptom lasts less than 60 minutesHeadache follows the aura within 60 minutes*International Headache Society
8 Migraine with aura Visual aura common Slowly evolving scintillating scotoma that moves or passes through visual fieldDuration of aura – 22 minutesShould not be called ocular migraine if bilateral eye involvementJust call them migraine with aura
9 Visual aura rating scale (VARS) Visual SymptomRisk ScoreDuration minutes3Develops gradually over 5 min2ScotomaZigzag line (fortification)Unilateral (homonymous)1MIGRAINE with AURA DIAGNOSIS≥ 5
10 Migraine with aura – vascular risk? Migraine with aura is associated with 2 fold risk of ischemic stroke & cardiovascular eventAbsolute risk is low (4 per women years)May be indication for aggressive treatment of other risk factorsUnclear if more intense treatment & prevention of migraines will alter the risk
11 Migraine without aura – Criteria* At least 5 attacks (bunch of them)Lasting 4-72 hours untreated or unsuccessfully treated (didn’t just go away quickly)Must have one of these to be migraine:Nausea or vomitingPhotophobiaPhonophobia*International Headache Society
12 Migraine without aura – Criteria* Then usually have at least 2 of these:Unilateral painThrobbing/pulsatingAggravation on movementModerate or severe intensityAnd of course to be sure not something else:H & P does not suggest organic disorderH & P suggests an organic disorder which is then ruled outAn organic disorder is present but attacks do not occur for the 1st time in close time to the disorder*International Headache Society
13 Diagnosing the acute headache The classification criteria are best suited for a between-attack assessment of their typical headacheHowever, they are often used for the acute attackOnce acute pain relieved, take time to make an accurate diagnosisUp to 1/3 of ED patients cannot be assigned a diagnosisDespite a through questionnaire-based assessment
14 ER Clinical Decision Rule “ID Migraine” – three featuresSensitivity to lightNausea or vomitingDisabling intensity of headache0 - 1 positive - low probabilityIf 2 positive higher probability of migraineCriteria focus on typical attacks not the current acute attack
15 Epidemiology - Migraine Can start at any age, however,Peak incidence of onset is mid-adolescence (age 13-16)History of colic or motion sickness support DxMedian frequency - 1.5/monthGreater increase in prevalence with aging in womenFemales - 6.4% age ; 17.3% ageMales % age ; 5.0% age 18 – 29Usually more severe in women
16 Pathophysiology Migraine is a primary neural event Something lowers threshold for a cortical spreading depression (CSD)Which causes regional hypoperfusion (aura)Release of proinflammatory neurochemicalsNeural event results in vasodilationWhich leads to pain & more nerve activationMigraine headache is not a primary vascular event
17 Why does it hurt? Substance of brain is largely insensate Pain could come from:Cranial blood vesselsTrigeminal innervations of vesselsReflex connection of trigeminal system with cranial parasympathetic flowNo clear explanation for why it hurts
18 Testing Indications*Laboratory tests not helpful or needed to make the diagnosisEEG not indicated as routine evaluationNeuroimaging guidelinesTypical migraine with normal neurologic examNeuroimaging not warranted (SOR-B)Insufficient evidence regarding imaging in presence of neurologic symptoms (SOR-C)*U.S. Headache Consortium (2000)
19 Neuroimaging - EBMFor non-acute HA with unexplained abnormal finding on neurologic examination – obtain neuro image (SOR-B)If atypical features or headache does not fulfill definition of migraine – lower the threshold for obtaining imaging (SOR-C)CT vs. MRI?Insufficient data to recommend MRI compared to CT in evaluation of migraine or other nonacute headache (Grade C)
20 Red Flags! Strongly consider neuroimaging if New onset > age 50 Thunderclap onsetFocal and nonfocal symptomsAbnormal signsHeadache with change in postureValsalva headacheHIV or cancer diagnosis
21 Prodrome (before headache) Some patients experience symptoms hours to days before the headache (prodrome)FatigueInattentiveness/confusionRestlessness, elation, +/- irritabilityInsomnia +/- depressionJoint painHunger or food cravingYawning
22 Treatment Goals of treatment Reduce frequency, severity, & duration of headachesImprove quality of life (QOL)Avoid acute medication escalationTreatment Guidelines are based upon having a specific diagnosisOften difficult initially to make specific DxTherefore, significant uncertainty about ‘best’ initial treatment
23 Treatment - MigraineThe brain of patients with migraines does not tolerate peaks or troughs of lifePatients should get:Regular sleepGo to bed and awaken same time every dayRegular mealsEat same time every dayNever skip meals – fasting associated with precipitating headacheRegular exerciseAvoid peaks of stress, troughs of relaxationAvoid unique dietary triggers
24 Migraine & Diet - EBMFrequency, duration & severity are NOT increased by dietary choices (SOR-A)Cheese, alcohol, chocolate, citrus are not universal triggersLow-fat diet reduced frequency of migraines (SOR-B)
25 Migraine & Supplements - EBM Supplements reduced frequency & intensityRiboflavin – 400 mg qdEffect begins at 1 month, 3 monthsMagnesium – 600 mg qdDiarrhea common - almost 20%360 mg qd during luteal phase reduced menstrual migraineOthersButterbur mg/dCoQ mg/dFeverfew mg/dNational Guideline Clearing HouseSOR – AAnswer to TQ#2
26 27250Question22 yo female presents with throbbing headache, nausea, photophobia for 5 hours. BP 116/76, P 86. Which of these treatments would be appropriate for her?Ketorolac (Toradol®) 60 mg IMMetoclopramide (Reglan®) 20 mg IVProchlorperazine (Compazine®) 10 mg IVD.H.E mg IVSumatriptan (Imitrex®) 6 mg SQ
27 Treatment of Acute Pain NSAID (SOR-A)Ketorolac (Toradol®) – 10 mg oral, 60 mg IM, or 30 mg IV(SOR-C)CombinationsIsometheptene mucate, dichloralphenazone and acetaminophen (Midrin®)Butalbital has not been effective in controlled trials (butalbital/acetaminophen/caffeine- 50/325/40 Fioricet®, butalbital/ASA/caffeine-50/325/40 Fiorinal®)Answer to TQ#1
28 Treatment of Acute Pain NSAIDs – more effective when:Taken earlyWith adequate initial doseCombined with antiemeticASA 1000 mgCombined with metoclopramide IM (Reglan®) reduces nausea/vomiting but not better pain controlAnswer to TQ#1
29 Treatment of Acute Pain IV fluids may benefit patients, although benefit is not well establishedUnlikely to be harmful especially in patients with persistent GI symptomsParenteral therapy preferred due to gastric stasis & delayed absorption of oral medicationsAnswer to TQ#1
30 Treatment of Acute Pain Droperidol (Inapsine®) probably most effective of dopamine agonistsPain relief at 2 hours approaching 100%Ideal dose – 2.5 mg IVFDA warning about QT prolongation
31 Treatment of Acute Pain Prochlorperazine (Compazine®) 10 mg IVEffective with diphenhydramine (Benadryl®) – 25 mg IV [Friedman 2008]Superior to SC sumatriptan in ED setting [Kostic 2010]Children 0.15 mg/kg IV over 15 minutes (max 10 mg)If EPS develop give diphenhydramine 1mg/kg (max 50 mg)Randomized blinded trial of IV Compazine (10 mg with mg Benadryl IV) vs SC sumatriptan (6 mg) superior. Also probably less costly overall. [Kostic 2010]Although time for IV insertion and patient acceptance may alter the decision process.
32 Treatment of Acute Pain Metoclopramide* (Reglan®)IV – monotherapy mg IVIM – 10 mg adjunct to other therapies (SOR-C)* FDA boxed warning 2/26/09 – Long-term or high-dose use of metoclopramide has been linked to tardive dyskinesia.
33 Treatment of Acute Pain Ergot alkaloidsDihydroergotamine (D.H.E. 45®) – 1 mg IM/IV/SCSince it may cause nausea, more effective with metoclopramide (Reglan®) to reduce nauseaNasal spray effectiveErgotamine/caffeine (1/100) (Cafergot®)Little evidence effective aloneHigh risk of overuse & rebound headache
34 Treatment of Acute Pain Sodium valproate (Depacon®)500 – 1000 mg in 10 ml normal saline IV over 30 minMay be effective but less than prochlorperazine (Compazine®)
35 Treatment of Acute Pain Complementary medicineTopical menthol 10% was more effective at complete pain relief than placebo at 2 hours (38.3% vs 12.1%) [Haghighi 2010]10% solution of menthol crystals in ethanolForehead and the temporal area most painful are washed with tap waterAfter drying 1 ml is applied with sponge on a surface area of 5 x 5 cmCan be reapplied in 30 min
36 Treatment of Acute Pain - EBM Patients with substantial disability will benefit from serotonin 5-HT1B/1D agonists (‘triptans’)SOR – AClinical Evidence
37 Triptan EfficacyNo one triptan is superior in all pain relief parametersUse one triptan for 2-3 attacks before abandoning that medicationIf one does not work try another oneAnswer to TQ#3
38 How is pain relief measured? Was pain better within 2 hours?Did the pain go away at 2 hours?Did the pain stay away for at least hours? (No immediate recurrence)Did the patient consistently obtain pain relief from that medication?
39 Oral Triptan Efficacy Was pain better within 2 hours? 55-65% of patients experience improvement at 2 hoursCan be repeated in 1 – 2 hours if partial response
40 Oral Triptan Efficacy Did pain go away within 2 hours? 25-35% of patients are pain free at 2 hours
41 Oral Triptan Efficacy Did pain stay away for 24 hours? Freedom from pain at 2 hours, no rescue medication, no recurrence of pain in 24 hours% of patients have sustained freedom from pain
42 Oral Triptan Efficacy Intra-patient Consistency? The same patient experiences pain relief with the same medicationRizatriptan (Maxalt®) has highest intra-patient consistency of the oral medications
43 Sumatriptan (Imitrex®) – Parenteral 6 mg SCPain decreased within 2 hours - 76%Pain gone within 2 hours - 48%Consistent pain relief for that patient - 90%In ER best candidates are those with previous response to this treatmentAdverse events more frequent than with oral medicationAnd more intense
44 Sumatriptan (Imitrex®) – Parenteral Cutaneous allodynia - sensation of pain in response to normally non-toxic touch stimuli (e.g. brushing hair, taking shower, putting hair in ponytail)Presence of cutaneous allodynia associated with reduced response to SC sumatriptanNeedle-free injection available (Sumavel® DosePro™)Causes as much pain as needle & more swelling, bruising & bleeding at site
46 27250Question22 yo female presents with throbbing headache, nausea, photophobia for 5 hours. BP 116/76, P 86. Which of these treatments would be appropriate for her?Ketorolac (Toradol®) 60 mg IMMetoclopramide (Reglan®) 20 mg IVProchlorperazine (Compazine®) 10 mg IVD.H.E mg IVSumatriptan (Imitrex®) 6 mg SQ46
47 Triptans – Side Effects TinglingParesthesiasWarmth head, neck, chest & limbsNasal spray associated with taste disturbance
48 Triptans – CautionsContraindicated with CAD, uncontrolled hypertension or cerebrovascular disease, hemiplegic migraineShould not be taken within 24 hrs of another triptan or ergotamine-containing/ergot-type medicationTaking them with an SSRI or SNRI can cause life-threatening serotonin syndrome
49 Combining Medications Sumatriptan 85 mg & Naproxen 500 mg (Treximet®) more effective than either alone for acute pain reliefUnknown effect of taking 2 separate pills (not tested)The combination may have some increased benefit in mild/moderate pain but no evidence of need for fixed dose combination (Medical Letter 2008)
50 Early RecurrenceUp to 75% of patients will experience a recurrence of pain within 48 hoursNaproxen (500 mg) or sumatriptan (100 mg) equally effective treating the recurrence [Friedman 2010]Naproxen prophylactically can prevent recurrence (NNT – 3)Triptans should not be used prophylacticly
51 Preventing Early Recurrence Parenteral dexamethasone (10-25 mg IV)Produced 26% relative reduction in recurrence within 72 hours [Colman 2008]Modest benefit in the ED – prevented 1 in 10 patients from experiencing moderate or severe recurrence [Singh 2008]Later trials failed to find benefit with oral dexamethasone or prednisone
52 Acute Pain & Parenteral Opioids Should not be used as 1st line therapyInternational Headache ConsortiumCanadian Association of Emergency PhysiciansAmerican Academy of NeurologyMeperidine (Demerol®) less effective than DHE and there is an:Increased risk of sedationToxic metabolite with repetitive useFriedman BW et al 2008;52:No trials have compared morphine or hydromorphone for the treatment of migraine nor has a trial compared sumatriptan to opioid.
53 New Treatments Acute Pain Diclofenac oral solution (Cambia®) – dissolve contents in waterSumatriptan patch (Zelrix™) – similar levels to SCCambia was approved in June 2009 and is now being marketed. It has a faster tmax and onset of action compared to tablet.Levadex approval is anticipated in 2011.
54 New Treatments Acute Pain DHE inhaled (Levadex®) – patients not responding to triptans or more than 6 hours into headache?Calcitonin gene-related peptide (CGRP) antagonist (telcagepant) – as effective as zolmitriptan 5 mg oralSingle-pulse transcranial magnetic stimulation (sTMS)More effective than placebo in pain-free at 2 hours (39% vs 22%)
55 After the Migraine - Postdrome Some patients may have:Mood changes“Hangover”TiredWeakDisoriented“Not right”
56 Chronic Migraine (CM) or Medication Overuse Headache (MOH) Chronic migraine previously called ‘transformed migraine’Consider medication overuse if ≥ 2 days/week for > 3 months analgesic useOver period of time (months to years) can become almost daily headacheResembles mixture of tension & migraineOccasionally called ‘tension-vascular’Hint – if awaken with headache consider medication overuseMOH is more prevalent during ages and affects about 3 times more women than men.Diagnosis of MOH is based on history and clinical presentation.Prescriptions for acute migraine should be closely monitored to prevent overuse and to detect possible MOH earlier.Chronic migraine treatment requires a team based comprehensive strategy. Most patients will be candidates for referral to a center specializing in the treatment of headaches. For additional information refer to:Silberstein S et al. Epidemiology, risk factors, and treatment of chronic migraine: a focus on topiramate. Headache 2008;48:Walker BB et al. An evidence-based practice approach. J Clin Psychol 2006:62:
57 CM Modifiable Risk Factors Risk factor associated with increased risk of developing CMStressful life eventsSleep disturbance (i.e. Snoring/sleep apnea)ObesityBaseline headache frequencyMedication overuseHowever, there is no evidence that treatment of these modifiable risk factors reduces the risk of CM. Their treatment with non-pharmacologic means would be appropriate but has not been proven in randomized trials.
58 CM & MOH Treatment Must stop acute medication to determine Headaches will go away in a few days if medication overuse is etiologyNo controlled trials of medication withdrawalMay get severe withdrawal headacheSevere withdrawal headache can be treated with short course of prednisoneRandomized trial found no difference with steroid compared to placeboDuration of withdrawal headache varied by the previous treatments. It was 4.1 days for triptans, 6.7 days for ergots and 9.5 days for analgesics.Relapse is high especially during the first year. Expect almost 50% of patients to relapse.
59 Preventive Medication Candidates:Unresponsive to acute attack medication & disabling headache≥ 2 attacks/monthIncreasing frequency of attacksMigraines with potential neurological sequelaePatient preference (just wants to use medication to prevent headaches)
60 29250Audience Question23 y. o. female with recurrent migraine headaches. You advise starting preventive therapy. Which medication would be appropriate?Anticonvulsant medicationBipolar/anticonvulsant medicationBeta-blocker medicationTricyclic medication60
61 Prevention therapy - EBM First line treatment should be:Propranolol (Inderal®)20 – 240 mg/dayTimolol10 – 30 mg/dayLess evidence to support other beta-blockersAmitriptyline10 – 150 mg/day
62 Prevention therapy - EBM First line treatment should be:Divalproex sodium (Depakote®)125 – 500 mg BIDTopiramate (Topamax®)mg BIDMay be as good as propranololAnti-epileptic drugs had greater suicidal ideation vs. placebo (0.43% vs 0.22%)Topiramate – start with 50 mg nightly for 1 week and increase increments of 25 mg every week. Goal dosage is 50 mg bid.May be considered in overweight patients, have epilepsy or β-blockers are contraindicated.European Federation of Neurological Societies recommends β -blockers, topiramate and valproic acid as 1st line therapies for prevention.
63 Prevention therapy Second line (SOR-B) Gabapentin - pregnancy category DCarbamazepine* - pregnancy category D* FDA Alert 12/12/07 – Dangerous or even fatal skin reactions can be caused by Carbamazepine therapy in patients with a particular HLA-B*1502 allele.
64 Prevention Therapies - EBM Relaxation training (SOR-A)Progressive muscular relaxationBreathing exercisesDirected imageryCognitive-behavioral (SOR-A)Combined with medication (SOR-B)Acupuncture appears to be effective (SOR-A)Sham acupuncture just as effective as real [Linde 2009]Thermal biofeedback with relaxation trainingFor complete review of evidence-based treatments of migraine go to:Campbell JK et al. Evidence-based guidelines for migraine headache: behavioral and physical treatments.
65 29250Audience Question23 y. o. female with recurrent migraine headaches. You advise starting preventive therapy. Which medication would be appropriate?Anticonvulsant medicationBipolar/anticonvulsant medicationBeta-blocker medicationTricyclic medication65
66 Menstrual Migraine – two classes Pure menstrual migraine without auraMigraine without aura on days -2 to of cycleDuring at least 2 of 3 cyclesMenstrual related migraine without auraMigraine without aura as above andAt other times of the month
67 Menstrual Migraine Strongly associated with estrogen Steep drop in estrogen just prior to menses may trigger headachePeak incidence is 1st day and preceding day of cycleOther clinical featuresGreater severity of painIncreased risk of nausea & vomitingLess responsive to acute treatment
68 Menstrual Migraine Acute therapy the same as other migraines Short-term preventionNSAID on days -7 to +6 helpedNaproxen sodium (Anaprox®) & mefenamic acid (Ponstel®) orally have been studiedTriptans starting day -2 for 5-6 days helpedFrovatriptan (Frova®), naratriptan (Amerge®) & sumatriptan (Imitrex®) orally have been studied
69 Prognosis of Migraines Study with 10 year follow-up of year olds at onset of migraines40% no longer had headache20% had episodic tension headache20% had migraine type that was different from the original diagnosed headacheFrequency & intensity usually decreases after menopauseTwo fold increased risk of CVA [Spector 2010]May influence how aggressive to be with other therapies to reduce risk of CVA
70 Areas of UncertaintyCausal relationship between patent foramen ovale (PFO) & migraine postulatedClosure of PFO suggested for treatmentRelationship remains uncertain & treatment of unselected patients is questionableIntranasal lidocaine provided no relief of migraine pain in ED
71 Tension Type Headache (TTH) - Criteria FirstNo vomiting – if vomiting probably a migraineNot worsened by routine physical activityBut can have one of these clinical featuresPhotophobiaPhonophobia
72 TTH - CriteriaIf no vomiting & only 1 other symptom - then need 2 of the following:Pressing, tightening or non-pulsatile painMild to moderate intensity of painBilateralNo aggravation with movementDiagnosis best made with use of headache diary for 4 weeks
73 TTH Underlying cause uncertain Muscle tenderness & psychological tension associated with aggravating themBut are not clearly the causeSusceptibility influenced by genetic factors
74 TTH Gender ration female:male 5:4 Age of onset – 25-30 years old Peak prevalence – years oldPrevalence increases with higher educational level
75 TTH – Treatment OTC analgesic medications NSAID (prescription) May be augmented with:Promethazine (Phenergan®)Diphenhydramine (Benadryl®)Metoclopramide (Reglan®)Efficacy tends to decrease with increasing frequency of headaches
76 Chronic Tension Headache Tension headache that occurs15 or more days a monthFor at least 6 months
77 Treatment of Chronic Tension Headache – EBM Beneficial (1st choice)Amitriptyline (Start 10 – 25/day; increase up to 150 mg daily)If no effect in 4 weeks, change therapyOther effective therapies (second choice)Mirtazapine (Remeron®)Venlafaxine (Effexor®)Likely to be beneficialCognitive behavioral therapy
78 Treatment of Chronic Tension Headache – Clinical Evidence Unknown effectivenessAcupunctureIndian head massageRelaxation or EMG biofeedbackSSRITricyclics other than amitriptylineLikely to be ineffective or harmfulBenzodiazepinesRegular acute pain medicationBotulism toxin
79 Cluster Headaches - Criteria Severe unilateral, bilateral, supraorbital or temporal pain lasting minutes (untreated) and one of following on same sideLacrimationRhinorrheaForehead or facial swellingPtosisMiosisEyelid edema
80 Cluster Headaches - Criteria Sense of restlessness (93% patients) or agitationPrefer to be erect & move about5 attacks with frequency of 1-8 on any given day from no other cause75% of attacks last < 60 minutes
81 Cluster Headaches Male : female – 2.1 : 1 Peak onset in 40’s 60% right sidedProbably most severe pain known to humansFemale patients describe attacks as worse than childbirth
82 Episodic cluster≥ 2 cluster periods lasting days & separated by pain-free remission ≥ 1 monthAbsence of aura, nausea, vomitingDistinguishes it from migraine
83 Cluster Headache Treatment AcuteSumatriptan6 mg SC – relief in 15 minIntranasal spray sumatriptan or zolmitriptan – relief in 30 minTriptans limits on daily usageLimit to 2 SC or 3 nasal sprays per day to prevent tachyphylaxis or reboundHigh flow O2 effective & safe [Cohen 2009]O2 – L/min with loose fitting nonrebreathing facial mask for 15 min
84 Cluster Headache Treatment AcuteDHE mg IM or IV useful as abortive agentOctreotide (Sandostatin®) 100 mcg SC can abort an attackNNT 5 for complete relief in 30 minPrednisone mg – short course
86 Daily HeadacheWhen chronic daily headache is strictly unilateral, same side, consider diagnosis to be:Hemicrania continuaIpsilateral side one or more autonomic symptoms (ptosis, lacrimation, etc.)Defined by absolute response to indomethacin (25 – 300 mg daily, must be continued indefinitely)If intolerant of indomethacin conside COX2 inhibitor
87 Key Points Diagnosis of migraine headache is clinical Almost always positive family historyTriptans are preferred treatment for frequent migrainesDiscuss preventive therapy with all patientsProvide treatment plan for breakthrough pain
89 ReferencesCohen AS et al. High-flow oxygen for treatment of cluster headache. JAMA 2009;302:Colman I et al. Parenteral dexamethasone for acute severe migraine headache: meat-analysis of randomized controlled trials for preventing recurrence. BMJ 2008;336:Friedman BW et al. The relative efficacy of meperidine for the treatment of acute migraine: a meta-analysis of randomized controlled trials. Ann Emerg Med 2008;52:Friedman BW et al. A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine. Ann Emerg Med 2008;52:Friedman BW et al. Treating headache recurrence after emergency department discharge: A randomized controlled trial of naproxen versus sumatriptan. Ann Emerg Med 2010;
90 ReferencesHaghighi AB et al. Cutaneous application of menthol 10% solution as an abortive treatment of migraine without aura: a randomised, double-blind, placebo-controlled, crossed-over study. Int J Clin Pract 2010;64:Kostic MA et al. A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the Emergency Department. Ann Emerg Med 2010;56:1-6.Linde K et al. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev 2009;(1):CD001218Schurks M et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 2009;339:b3914.
91 ReferencesSingh A et al. Does the addition of dexamethasone to standard therapy for acute migraine headache decrease the incidence of recurrent headache for patient treated in the emergency department. Acad Emerg Med 2008;15:Spector JT et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med 2010;123: