Migraine Headache Update on Diagnosis Treatment

Migraine Headache – Update on Diagnosis & Treatment Herbert L. Muncie, Jr. , M. D.

What is the diagnosis? n 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. ¡ PMH n H. flu meningitis age 7 months n Car motion sickness as a child ¡ Family history positive for migraines – maternal grandmother & mother

Diagnosing Migraine Headache n n n Any severe or recurrent headache most likely is a form of migraine Almost all patients will have family history of migraines or at least “sick” headaches Only 15% have preceded or accompanied focal neurologic symptoms ¡ Usually visual n ¡ Vision loss or distortion in one eye – ‘ocular migraine’ “Classic migraine”

Sarah n n Spent most of Thanksgiving holiday resting on the sofa Diagnosed with onset of migraine headaches

Recurrent Headaches n Primary ¡ ¡ Migraine Tension Cluster Other benign – cough, cold temperature, post coital, exertion

Recurrent Headaches n Secondary (pain from complications) ¡ ¡ Intracranial tumor Intracranial aneurysm Intracranial A-V malformation Temporal arteritis

Migraine with aura – Criteria* n At least 2 attacks with 3 of the following: ¡ ¡ Fully reversible aura symptoms At least 1 aura symptom develops gradually during more than 4 minutes or 2 symptoms occur in succession Any aura symptom lasts less than 60 minutes Headache follows the aura within 60 minutes *International Headache Society - 2004

Migraine with aura n Visual aura common ¡ ¡ ¡ Slowly evolving scintillating scotoma that moves or passes through visual field Duration of aura – 22 minutes Should not be called ocular migraine if bilateral eye involvement n Just call them migraine with aura

Migraine with aura – vascular risk? n Migraine with aura is associated with 2 fold risk of ischemic stroke & cardiovascular event ¡ ¡ ¡ Absolute risk is low (4 per 10000 women years) May be indication for aggressive treatment of other risk factors Unclear if more intense treatment & prevention of migraines will alter the risk

Migraine without aura – Criteria* n n n 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 vomiting Photophobia Phonophobia *International Headache Society - 2004

Migraine without aura – Criteria* n Then usually have at least 2 of these: ¡ ¡ n Unilateral pain Throbbing/pulsating Aggravation on movement Moderate or severe intensity And of course to be sure not something else: ¡ ¡ ¡ H & P does not suggest organic disorder H & P suggests an organic disorder which is then ruled out An organic disorder is present but attacks do not occur for the 1 st time in close time to the disorder *International Headache Society - 2004

Diagnosing the acute headache n The classification criteria are best suited for a between-attack assessment of their typical headache ¡ ¡ n However, they are often used for the acute attack Once acute pain relieved, take time to make an accurate diagnosis Up to 1/3 of ED patients cannot be assigned a diagnosis ¡ Despite a through questionnaire-based assessment

ER Clinical Decision Rule n “ID Migraine” – three features ¡ ¡ Sensitivity to light Nausea or vomiting Disabling intensity of headache n 0 - 1 positive - low probability n If 2 positive higher probability of migraine Criteria focus on typical attacks not the current acute attack

Epidemiology - Migraine n Can start at any age, however, ¡ ¡ n n Peak incidence of onset is mid-adolescence (age 13 -16) History of colic or motion sickness support Dx Median frequency - 1. 5/month Greater increase in prevalence with aging in women ¡ ¡ ¡ Females - 6. 4% age 12 - 17; 17. 3% age 18 - 29 Males - 4. 0% age 12 - 17; 5. 0% age 18 – 29 Usually more severe in women

Pathophysiology n Migraine is a primary neural event ¡ Something lowers threshold for a cortical spreading depression (CSD) n n ¡ ¡ n Which causes regional hypoperfusion (aura) Release of proinflammatory neurochemicals Neural event results in vasodilation Which leads to pain & more nerve activation Migraine headache is not a primary vascular event

Testing Indications* n n n Laboratory tests not helpful or needed to make the diagnosis EEG not indicated as routine evaluation Neuroimaging guidelines Typical migraine with normal neurologic exam n Neuroimaging not warranted (SOR-B) ¡ Insufficient evidence regarding imaging in presence of neurologic symptoms (SOR-C) ¡ *U. S. Headache Consortium (2000)

Neuroimaging - EBM n n n For 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)

Red Flags! n Strongly consider neuroimaging if ¡ ¡ ¡ ¡ New onset > age 50 Thunderclap onset Focal and nonfocal symptoms Abnormal signs Headache with change in posture Valsalva headache HIV or cancer diagnosis

Treatment n Goals of treatment ¡ ¡ ¡ n Reduce frequency, severity, & duration of headaches Improve quality of life (QOL) Avoid acute medication escalation Treatment Guidelines are based upon having a specific diagnosis ¡ ¡ Often difficult initially to make specific Dx Therefore, significant uncertainty about ‘best’ initial treatment

Treatment - Migraine n n The brain of patients with migraines does not tolerate peaks or troughs of life Patients should get: ¡ ¡ ¡ Regular sleep n Go to bed and awaken same time every day Regular meals n Eat same time every day n Never skip meals – fasting associated with precipitating headache Regular exercise Avoid peaks of stress, troughs of relaxation Avoid unique dietary triggers

Migraine & Diet - EBM n Frequency, duration & severity are NOT increased by dietary choices (SOR-A) ¡ n Cheese, alcohol, chocolate, citrus are not universal triggers Low-fat diet reduced frequency of migraines (SOR-B)

Migraine & Supplements - EBM n Supplements reduced frequency & intensity ¡ ¡ ¡ n Riboflavin – 400 mg qd n Effect begins at 1 month, maximal @ 3 months Magnesium – 600 mg qd n Diarrhea common - almost 20% n 360 mg qd during luteal phase reduced menstrual migraine Others n Butterbur 100 -150 mg/d n Co. Q 10 300 mg/d n Feverfew 18. 75 mg/d National Guideline Clearing House ¡ SOR – A ¡ http: //www. guideline. gov/summary. aspx? doc_id=6231&nbr=004002&string=migraine

Question 22 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? a. b. c. d. e. Ketorolac (Toradol®) 60 mg IM Metoclopramide (Reglan®) 20 mg IV Prochlorperazine (Compazine®) 10 mg IV D. H. E. 45 1 mg IV Sumatriptan (Imitrex®) 6 mg SQ

Treatment of Acute Pain n NSAID (SOR-A) Ketorolac (Toradol®) – 10 mg oral, 60 mg IM, or 30 mg IV(SOR-C) Combinations ¡ ¡ Isometheptene 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®)

Treatment of Acute Pain n NSAIDs – more effective when: ¡ ¡ ¡ n Taken early With adequate initial dose Combined with antiemetic ASA 1000 mg ¡ Combined with metoclopramide IM (Reglan®) reduces nausea/vomiting but not better pain control

Treatment of Acute Pain n IV fluids may benefit patients, although benefit is not well established ¡ ¡ Unlikely to be harmful especially in patients with persistent GI symptoms Parenteral therapy preferred due to gastric stasis & delayed absorption of oral medications

Treatment of Acute Pain n Droperidol (Inapsine®) probably most effective of dopamine agonists ¡ ¡ ¡ Pain relief at 2 hours approaching 100% Ideal dose – 2. 5 mg IV FDA warning about QT prolongation

Treatment of Acute Pain n Prochlorperazine (Compazine®) 10 mg IV ¡ ¡ ¡ Effective 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) n If EPS develop give diphenhydramine 1 mg/kg (max 50 mg)

Treatment of Acute Pain n Metoclopramide* (Reglan®) ¡ ¡ IV – monotherapy 10 - 20 mg IV IM – 10 mg adjunct to otherapies (SOR-C) * FDA boxed warning 2/26/09 – Long-term or high-dose use of metoclopramide has been linked to tardive dyskinesia.

Treatment of Acute Pain n Ergot alkaloids ¡ Dihydroergotamine (D. H. E. 45®) – 1 mg IM/IV/SC n n ¡ Since it may cause nausea, more effective with metoclopramide (Reglan®) to reduce nausea Nasal spray effective Ergotamine/caffeine (1/100) (Cafergot®) n n Little evidence effective alone High risk of overuse & rebound headache

Treatment of Acute Pain n Complementary medicine ¡ Topical menthol 10% was more effective at complete pain relief than placebo at 2 hours (38. 3% vs 12. 1%) [Haghighi 2010] n 10% solution of menthol crystals in ethanol n Forehead and the temporal area most painful are washed with tap water n After drying 1 ml is applied with sponge on a surface area of 5 x 5 cm n Can be reapplied in 30 min

Treatment of Acute Pain - EBM n Patients with substantial disability will benefit from serotonin 5 -HT 1 B/1 D agonists (‘triptans’) ¡ ¡ SOR – A Clinical Evidence n http: //www. clinicalevidence. com/ceweb/conditio ns/nud/1208. jsp

Triptan Efficacy n n n No one triptan is superior in all pain relief parameters Use one triptan for 2 -3 attacks before abandoning that medication If one does not work try another one

How is pain relief measured? 1) Was pain better within 2 hours? 2) Did the pain go away at 2 hours? Did the pain stay away for at least 24 hours? (No immediate recurrence) 3) 4) Did the patient consistently obtain pain relief from that medication?

Oral Triptan Efficacy n Was pain better within 2 hours? ¡ ¡ 55 -65% of patients experience improvement at 2 hours Can be repeated in 1 – 2 hours if partial response

Oral Triptan Efficacy n Did pain go away within 2 hours? ¡ 25 -35% of patients are pain free at 2 hours

Oral Triptan Efficacy n Did pain stay away for 24 hours? ¡ Freedom from pain at 2 hours, no rescue medication, no recurrence of pain in 24 hours n 20 - 25% of patients have sustained freedom from pain

Oral Triptan Efficacy n Intra-patient Consistency? ¡ The same patient experiences pain relief with the same medication n Rizatriptan (Maxalt®) has highest intrapatient consistency of the oral medications

Sumatriptan (Imitrex®) – Parenteral n 6 mg SC ¡ ¡ ¡ Pain 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 treatment Adverse events more frequent than with oral medication n And more intense

Sumatriptan (Imitrex®) – Parenteral n Cutaneous allodynia - sensation of pain in response to normally non-toxic touch stimuli (e. g. brushing hair, taking shower, putting hair in ponytail) ¡ n Presence of cutaneous allodynia associated with reduced response to SC sumatriptan Needle-free injection available (Sumavel® Dose. Pro™) ¡ Causes as much pain as needle & more swelling, bruising & bleeding at site

Question 22 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? a. b. c. d. e. Ketorolac (Toradol®) 60 mg IM Metoclopramide (Reglan®) 20 mg IV Prochlorperazine (Compazine®) 10 mg IV D. H. E. 45 1 mg IV Sumatriptan (Imitrex®) 6 mg SQ

Triptans – Side Effects n Tingling n Paresthesias Warmth head, neck, chest & limbs Nasal spray associated with taste disturbance n n

Triptans – Cautions n Contraindicated with CAD, uncontrolled hypertension or cerebrovascular disease, hemiplegic migraine n Should not be taken within 24 hrs of another triptan or ergotaminecontaining/ergot-type medication Taking them with an SSRI or SNRI can cause life-threatening serotonin syndrome n

Combining Medications n ¡ ¡ Sumatriptan 85 mg & Naproxen 500 mg (Treximet®) more effective than either alone for acute pain relief Unknown 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)

Early Recurrence n Up to 75% of patients will experience a recurrence of pain within 48 hours ¡ ¡ ¡ Naproxen (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

Preventing Early Recurrence n 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

Acute Pain & Parenteral Opioids n Should not be used as 1 st line therapy ¡ ¡ ¡ n International Headache Consortium Canadian Association of Emergency Physicians American Academy of Neurology Meperidine (Demerol®) less effective than DHE and there is an: ¡ ¡ Increased risk of sedation Toxic metabolite with repetitive use

New Treatments Acute Pain n n Diclofenac oral solution (Cambia®) – dissolve contents in water Sumatriptan patch (Zelrix™) – similar levels to SC

New Treatments Acute Pain n 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 oral Single-pulse transcranial magnetic stimulation (s. TMS) ¡ More effective than placebo in pain-free at 2 hours (39% vs 22%)

After the Migraine - Postdrome n Some patients may have: ¡ ¡ ¡ Mood changes “Hangover” Tired Weak Disoriented “Not right”

Chronic Migraine (CM) or Medication Overuse Headache (MOH) n n n Chronic migraine previously called ‘transformed migraine’ Consider medication overuse if ≥ 2 days/week for > 3 months analgesic use Over period of time (months to years) can become almost daily headache ¡ ¡ ¡ Resembles mixture of tension & migraine Occasionally called ‘tension-vascular’ Hint – if awaken with headache consider medication overuse

CM Modifiable Risk Factors n Risk factor associated with increased risk of developing CM ¡ ¡ ¡ Stressful life events Sleep disturbance (i. e. Snoring/sleep apnea) Obesity Baseline headache frequency Medication overuse

CM & MOH n Treatment ¡ Must stop acute medication to determine n ¡ ¡ Headaches will go away in a few days if medication overuse is etiology No controlled trials of medication withdrawal May get severe withdrawal headache n n Severe withdrawal headache can be treated with short course of prednisone Randomized trial found no difference with steroid compared to placebo

Preventive Medication n Candidates: ¡ ¡ ¡ Unresponsive to acute attack medication & disabling headache ≥ 2 attacks/month Increasing frequency of attacks Migraines with potential neurological sequelae Patient preference (just wants to use medication to prevent headaches)

Audience Question 23 y. o. female with recurrent migraine headaches. You advise starting preventive therapy. Which medication would be appropriate? a) b) c) d) Anticonvulsant medication Bipolar/anticonvulsant medication Beta-blocker medication Tricyclic medication

Prevention therapy - EBM n First line treatment should be: ¡ Propranolol (Inderal®) n ¡ Timolol n n ¡ 20 – 240 mg/day 10 – 30 mg/day Less evidence to support other beta-blockers Amitriptyline n 10 – 150 mg/day

Prevention therapy - EBM n First line treatment should be: ¡ Divalproex sodium (Depakote®) n ¡ 125 – 500 mg BID Topiramate (Topamax®) n n n 50 - 100 mg BID May be as good as propranolol Anti-epileptic drugs had greater suicidal ideation vs. placebo (0. 43% vs 0. 22%)

Prevention therapy n Second line (SOR-B) ¡ ¡ Gabapentin - pregnancy category D Carbamazepine* - 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-

Prevention Therapies - EBM n Relaxation training (SOR-A) ¡ ¡ ¡ n Cognitive-behavioral (SOR-A) ¡ n Combined with medication (SOR-B) Acupuncture appears to be effective (SOR-A) ¡ n Progressive muscular relaxation Breathing exercises Directed imagery Sham acupuncture just as effective as real [Linde 2009] Thermal biofeedback with relaxation training

Audience Question 23 y. o. female with recurrent migraine headaches. You advise starting preventive therapy. Which medication would be appropriate? a) b) c) d) Anticonvulsant medication Bipolar/anticonvulsant medication Beta-blocker medication Tricyclic medication

Menstrual Migraine – two classes A. Pure menstrual migraine without aura ¡ ¡ B. Migraine without aura on days -2 to +3 of cycle During at least 2 of 3 cycles Menstrual related migraine without aura ¡ ¡ Migraine without aura as above and At other times of the month

Menstrual Migraine n Strongly associated with estrogen ¡ ¡ n Steep drop in estrogen just prior to menses may trigger headache Peak incidence is 1 st day and preceding day of cycle Other clinical features ¡ ¡ ¡ Greater severity of pain Increased risk of nausea & vomiting Less responsive to acute treatment

Menstrual Migraine n n Acute therapy the same as other migraines Short-term prevention ¡ NSAID on days -7 to +6 helped n ¡ Naproxen sodium (Anaprox®) & mefenamic acid (Ponstel®) orally have been studied Triptans starting day -2 for 5 -6 days helped n Frovatriptan (Frova®), naratriptan (Amerge®) & sumatriptan (Imitrex®) orally have been studied

Prognosis of Migraines n Study with 10 year follow-up of 11 -14 year olds at onset of migraines ¡ ¡ ¡ n n 40% no longer had headache 20% had episodic tension headache 20% had migraine type that was different from the original diagnosed headache Frequency & intensity usually decreases after menopause Two fold increased risk of CVA [Spector 2010] ¡ May influence how aggressive to be with otherapies to reduce risk of CVA

Tension Type Headache (TTH) - Criteria n First ¡ ¡ ¡ No vomiting – if vomiting probably a migraine Not worsened by routine physical activity But can have one of these clinical features n n Photophobia Phonophobia

TTH - Criteria n If no vomiting & only 1 other symptom then need 2 of the following: ¡ ¡ n Pressing, tightening or non-pulsatile pain Mild to moderate intensity of pain Bilateral No aggravation with movement Diagnosis best made with use of headache diary for 4 weeks

TTH n n Underlying cause uncertain Muscle tenderness & psychological tension associated with aggravating them ¡ n But are not clearly the cause Susceptibility influenced by genetic factors

TTH n n Gender ration female: male 5: 4 Age of onset – 25 -30 years old Peak prevalence – 30 -39 years old Prevalence increases with higher educational level

TTH – Treatment n n n OTC analgesic medications NSAID (prescription) May be augmented with: ¡ ¡ ¡ n Promethazine (Phenergan®) Diphenhydramine (Benadryl®) Metoclopramide (Reglan®) Efficacy tends to decrease with increasing frequency of headaches

Cluster Headaches - Criteria n Severe unilateral, bilateral, supraorbital or temporal pain lasting 15 -180 minutes (untreated) and one of following on same side ¡ ¡ ¡ Lacrimation Rhinorrhea Forehead or facial swelling Ptosis Miosis Eyelid edema

Cluster Headaches - Criteria n Sense of restlessness (93% patients) or agitation ¡ n Prefer to be erect & move about 5 attacks with frequency of 1 -8 on any given day from no other cause ¡ 75% of attacks last < 60 minutes

Cluster Headaches n n Male : female – 2. 1 : 1 Peak onset in 40’s 60% right sided Probably most severe pain known to humans ¡ Female patients describe attacks as worse than childbirth

Cluster Headache Treatment n Acute ¡ Sumatriptan n ¡ ¡ Intranasal spray sumatriptan or zolmitriptan – relief in 30 min Triptans limits on daily usage n ¡ 6 mg SC – relief in 15 min Limit to 2 SC or 3 nasal sprays per day to prevent tachyphylaxis or rebound High flow O 2 effective & safe [Cohen 2009] n O 2 – 7 - 15 L/min with loose fitting nonrebreathing facial mask for 15 min

Cluster Headache Treatment n Acute ¡ ¡ ¡ DHE 0. 5 - 1 mg IM or IV useful as abortive agent Octreotide (Sandostatin®) 100 mcg SC can abort an attack n NNT 5 for complete relief in 30 min Prednisone 50 -80 mg – short course

Cluster Headache Treatment n Prophylactic ¡ Verapamil 240 -960 mg/day

Daily Headache n When chronic daily headache is strictly unilateral, same side, consider diagnosis to be: ¡ Hemicrania continua n ¡ Ipsilateral side one or more autonomic symptoms (ptosis, lacrimation, etc. ) Defined by absolute response to indomethacin (25 – 300 mg daily, must be continued indefinitely) n If intolerant of indomethacin conside COX 2 inhibitor

Key Points n Diagnosis of migraine headache is clinical ¡ Almost always positive family history n Triptans are preferred treatment for frequent migraines n Discuss preventive therapy with all patients n Provide treatment plan for breakthrough pain

What Questions do you have?