Approach to a Patient with Headacheweb.brrh.com/msl/IM2018/Day-3_Sunday/Sunday 5... · If You are Concerned About a Secondary Cause •Diagnostic testing is warranted to exclude or

©2014 MFMER | slide-1

J.D. Bartleson, MD Professor of Neurology

Mayo Clinic College of Medicine

15th Annual Internal Medicine Conference March 25, 2018 Boca Raton, FL

Approach to a Patient with Headache


Disclosures

I have no financial or other entanglements to disclose

Many of the medications used to treat migraine are not specifically approved by the FDA for this indication


Objectives

• Determine when to obtain diagnostic tests in the patient with

headache and know what tests to order

• Learn how to treat migraine headaches focusing on:

• Avoidance of headache triggers

• Treatment of the acute attack

• Preventive therapy, if appropriate


Diagnosing Headache

• The gold standard for headache diagnosis is:

• A careful history

• Neurological examination

• Pertinent physical examination

• Spend most of your time on the history!


International Classification of Headache Disorders, 3rd Edition (ICHD-3)-Beta

• Four parts

• Primary headaches

• Secondary headaches

• Painful cranial neuropathies, other facial pains, and other headaches

• Appendix

• Full version pdf at https://www.ichd-3.org/wp-content/uploads/2016/08/International-Headache-Classification-III-ICHD-III-2013-Beta-1.pdf

• Full version (hyperlink) at https://www.ichd-3.org

Cephalalgia 2013 33:629-808

https://www.ichd-3.org/wp-content/uploads/2016/08/International-Headache-Classification-III-ICHD-III-2013-Beta-1.pdf






















https://www.ichd-3.org/





International Classification of Headache Disorders, 3rd Edition

• The Primary Headaches

• Migraine

• Tension-type

• Cluster and other Trigeminal Autonomic Cephalalgias

• Other primary headaches

• Primary Stabbing HA, Cough HA, Exertional HA, HA

with Sexual Activity, Hypnic HA, Thunderclap HA,

Hypnic HA, and New Daily-persistent HA

• Secondary headaches which can mimic any primary HA

Cephalalgia 2013;33:629-808


ICHD, 3rd Edition

The Secondary Headaches Cephalalgia 2013;33:629-808

• Trauma

• Vascular disorder

• Non-vascular intracranial

• Substance or substance

withdrawal

• Infection

• Disorder of homeostasis

• Skull and HEENT causes

• Psychiatric condition

• Other


Headache Red Flags

• Abrupt onset – split second or ‘thunderclap’ headache • Recent head or neck injury • New onset or new type or worsening of existing headache • New level of pain – ‘worst ever’ • Triggered by Valsalva or cough • Triggered by exertion • Triggered by sexual activity • Onset during pregnancy or puerperium • Age > 50 years • Neurologic signs or symptoms (seizures, confusion, findings) • Systemic illness (fever, weight loss, scalp artery tenderness) • Secondary risk factors (cancer, immunosuppressed, travel) De Luca + Bartleson Semin Neurol 2010;30:131-144




Headache Yellow Flags Not as Worrisome

• Headaches that wake patient from sleep at night

• Migraine, cluster, sleep apnea, rebound withdrawal, mass lesion, severe hypertension

• New onset side-locked headaches

• Trigeminal autonomic cephalalgias, head trauma, dissection, aneurysm, lung cancer

• Postural HA worse when upright suggests low CSF pressure (e.g., after LP or spontaneously)

• Postural HA worse if supine suggests brain tumor

De Luca + Bartleson Semin Neurol 2010;30:131-144


If You are Concerned About a Secondary Cause

• Diagnostic testing is warranted to exclude or confirm a secondary cause for the headache(s)

• Other factors that influence the decision:

• Need for diagnostic certainty, reassurance, meet patient and family expectations, medicolegal concerns, financial incentives, and faulty medical reasoning

• Brain imaging is the first, the best, and often the only diagnostic test needed

• Alternatively, could try treating as a primary HA disorder

Bartleson Semin Neurol 2006;26:163-170


MRI vs CT Brain Imaging

• CT better for acute onset symptoms and after

trauma – CT shows blood and fractures

• CT preferred for paranasal sinus disease

• MRI better for everything else – shows pituitary,

craniocervical junction, tumors, stroke, venous

disease, MS, low and high CSF pressure, etc

• MR + CT angiography and venography are = for

atherosclerosis, aneurysm, dissection, vasculitis

• MRI does not use X-rays and ‘dye’ is safer

• MRI shows too much!


MRI Shows Too Much Rotterdam Population Study of 2,000 Persons

• Asymptomatic brain infarcts in 7.2%

• Cerebral aneurysms in 1.8%

• Benign primary brain tumors in 1.6%

• Arachnoid cysts 1%

• Type I Chiari malformation 1%

• Also shows incidental sinus disease

Vernooij et al N Engl J Med 2007;357:1821-8


Other Headache Diagnostic Tests

• Myelogram, isotope cisternogram for low CSF pressure

• Dental and TMJ radiographs for face and jaw pain

• Blood tests for systemic illnesses (e.g., temporal arteritis)

• Polysomnography for sleep apnea

• CSF for meningitis, low and high CSF pressure

• Plasma + urine catecholamines for pheochromocytoma

• CO level for carbon monoxide poisoning

• Blood tests for thyroid function, insulinoma

• Chest imaging for ipsilateral pain due to apical lung tumor


Migraine is Extremely Common Up to 20% of Women, 10% of Men

• Any episodic headache should be considered migraine

with the likelihood increasing if:

• Pain is asymmetric or unilateral

• Pain has a throbbing quality

• Pain is severe

• Pain is accompanied by nausea and/or sensitivity to

light, noise, and/or smells

• Typical migraine aura symptoms

• Positive family history of migraine (found in 2/3rds)


Treatment Strategies for Migraine (and Other Headaches)

• Identify and avoid headache triggers

•Acute therapy of the individual attack

•Preventive therapy, if needed

Bartleson + Cutrer Minnesota Medicine 2010;93:36-41


Migraine Triggers

• Going too long without eating

• Alcohol

• Hormonal contraceptives

• Hormone replacement therapy

• Caffeine and caffeine withdrawal

• Stress or release from stress

• Too little or too much sleep


Migraine Triggers Continued

• Menstruation

• Fatigue

• Exposure to bright or flickering lights, loud noises, smoke, and strong scents

• Change in the weather

• Acute head trauma


Migraine Food Triggers Usually Within 12 to 24 Hours

• Chocolate • Aged cheeses • Processed meats • Fermented foods • Aspartame • Monosodium glutamate • Citrus fruits • Nuts • Supplements


The Trouble with Triggers

• Most migraine attacks are not triggered

• Many triggers are unavoidable

• Response to a trigger is variable

• Impairs trigger recognition

• Reduces the patient’s willpower to regularly avoid a recognized trigger








Goals of Acute Migraine Treatment

• Treat attacks rapidly, effectively, and consistently

• Restore the patient’s sustained ability to function

• Minimize need for rescue treatments, ER visits

• Optimize self-care and reduce resource utilization

• Be cost-effective

• Have minimal or no adverse side effects

• Avoid medication overuse and rebound withdrawal


Acute Therapy of Migraine

• Early treatment is critical

• Rest early in the course can be very helpful

• Many medication options are available

• The mainstay of therapy for most patients

• Early treatment is critical – many patients wait too

long and miss a window of opportunity


Acute Migraine Treatment Options

• Nonspecific

• NSAIDs

• Acetaminophen

• Combination drugs

• Antinauseants and

neuroleptics

• Opioid analgesics

• Specific antimigraine

• Triptans

• Dihydroergotamine

and ergotamine


Acute Migraine Therapy

• Single ingredient oral OTC and prescription analgesics

• Acetaminophen 650-1,000 mg max 3 gm/day

• Aspirin 650-1,000 mg

• Naproxen sodium 220-550 mg max 1100 mg/day

• Ibuprofen 200-800 mg max 3200 mg/day

• Ketoprofen 50-75 mg max 300 mg/day

• Diclofenac potassium oral solution 50-100 mg max

200 mg/day



• Combination OTC analgesics

• Excedrin Migraine = Excedrin Extra Strength = 250 mg acetaminophen, 250 mg aspirin, and 65 mg caffeine

• Anacin = aspirin and caffeine

• Tylenol PM = Excedrin PM = acetaminophen and diphenhydramine

• Aleve PM and Advil PM also contain diphenhydramine



• Multi-ingredient prescription medications

• Midrin = isometheptene, dichloralphenazone, APAP

• Acetaminophen (APAP) with codeine

• Vicodin, Lorcet, Lortab, Norco = hydrocodone/APAP

• Percocet, Roxicet, Tylox, Endocet = oxycodone/APAP

• Fiorinal, Fioricet, Esgic, Phrenilin = butalbital with ASA

or APAP with/without caffeine and some with codeine

• Ergotamine ± caffeine tablets and suppositories

APAP = acetaminophen



• Ketorolac (Toradol) 15 - 60 mg IM

• Tramadol (Ultram) 50 - 100 mg PO

• Stronger opioid analgesics, parenterally or PO,

often with an adjuvant

• Adjuvants include:

• Hydroxyzine (Vistaril) 25 - 100 mg IM or PO

• Metoclopramide (Reglan) 10 mg IV or PO

• Prochlorperazine (Compazine) 5 - 10 mg

IV, IM or PO; 12.5 - 25 mg PR

• Promethazine (Phenergan) 12.5 - 50 mg IV,

IM, PO or PR

• Caffeine ≥ 65 mg PO


Acute Migraine Therapy Antinauseants

• Prochlorperazine (Compazine)

• 5 - 10 mg IM/IV/PO or 12.5 - 25 mg PR

• Promethazine (Phenergan)

• 10 - 50 mg IM/IV/PO/PR

• Metoclopramide (Reglan)

• 10 mg IV/PO (also prokinetic)

• Droperidol 2.5 - 5 mg IM/IV

• Ondansetron (Zofran) 4 - 8 mg PO


5-Hydroxytryptamine Agonist Therapy “The Triptans”

Almotriptan = Axert

Eletriptan = Relpax

Frovatriptan = Frova

Naratriptan = Amerge

Rizatriptan = Maxalt

Sumatriptan = Imitrex

Zolmitriptan = Zomig


Acute Rx with 5 HT1B/1D Agonists

• Sumatriptan (Imitrex) is available as:

• 6 mg SQ autoinjector, MR once after ≥ 1 hour

• Intranasal spray 20 mg or 5 mg to one nostril or 5 mg

to each nostril, MR once after ≥ 2 hours

• 25 mg, 50 mg or 100 mg tablets PO, MR q ≥ 2 hours,

not > 200 mg in 24 hours

• Treximet® (a tablet with 85 mg of sumatriptan and

500 mg of naproxen), MR once after ≥ 2 hours

• Needle-free injectable (Sumavel®)

• Breath actuated intranasal powder (Onzetra®)

MR = May Repeat

Underlined is the usual optimum dose



• Rizatriptan (Maxalt) 5 or 10 mg regular or oral

dissolving tablets PO, MR x 2 at intervals of ≥ 2

hours not to exceed 30 mg in 24 hours. Use 5

mg dose if patient is on propranolol. Pretty

quick and effective.

• Eletriptan (Relpax) 20 mg vs 40 mg PO, MR q

≥ 2 hours not to exceed 80 mg in 24 hours.

Fairly quick and effective. Avoid in patients on

potent CYP3A4 enzyme inhibitors.




• Zolmitriptan (Zomig) 2.5 or 5 mg regular or oral

dissolving tablets PO, MR once after ≥ 2 hours

not to exceed 10 mg in 24 hours. Use lower

dose if on cimetidine. Zomig Nasal Spray 2.5 or

5 mg intranasally, MR once after ≥ 2 hours not to

exceed 10 mg in 24 hours.

• Almotriptan (Axert) 6.25 or 12.5 mg PO, MR q ≥

2 hours, not to exceed 25 mg in 24 hours. Pretty

quick, fairly long duration, fewer side effects.




• Frovatriptan (Frova) 2.5 mg PO, MR q ≥ 2 hours,

not to exceed 7.5 mg in 24 hours. Longer duration

of action.

• Naratriptan (Amerge) 1 mg or 2.5 mg PO, MR

once after ≥ 4 hours not to exceed 5 mg in 24

hours. Longer duration of action. Contraindicated

with severe hepatic or renal impairment.



Acute Rx with Dihydroergotamine (DHE) a Non-triptan 5 HT1B/1D Agonist

• Dihydroergotamine (Migranal) nasal spray 0.5 mg

to each nostril, repeated once after 15 minutes.

Avoid in severe hypertension, pregnancy, if

nursing, on potent CYP3A4 inhibitors.

• DHE also available for SQ, IM, or IV injection -

0.5 - 1 mg q ≥ 1 hour, not > 3 mg in 24 hours.

• Ergotamine tartrate (Wigraine, Cafergot)

available 1 or 2mg PO or PR is little used.




• Recent meta-analysis found eletriptan (Relpax) most effective at 2 and 24 hours followed by rizatriptan (Maxalt) then zolmitriptan (Zomig)

• Sumatriptan (Imitrex) and DHE injections work faster than sumatriptan (Imitrex), zolmitriptan (Zomig), and DHE (Migranal) nasal sprays which act faster than tablets

• Rizatriptan (Maxalt) enters the blood stream more rapidly than other oral triptans

• Naratriptan (Amerge), frovatriptan (Frova), and DHE (Migranal nasal spray or by injection) have longest half-lives

• Dissolving tablets don’t reach bloodstream faster!

Thorlund et al Cephalalgia 2014;34:258-67



• Use shot, nasal spray, or oral dissolving tablet or add an

antinauseant if patient has early vomiting

• If a patient does not respond to one triptan, they may

respond to another

• Make sure they use an adequate dose soon enough

• If headache returns, should repeat dose as allowed

• Try at least 2 triptans for 2-3 attacks each

• If oral triptan doesn’t work, try SQ sumatriptan

• Triptans help 4 out of 5 patients

• Does response to a triptan confirm diagnosis of migraine?

• No, but I sleep better


New Therapies

• Cefaly®: Electrical stimulation of medial brow can be

used acutely or daily as a preventive

• sTMS®: Transcranial Magnetic Stimulation acutely for

migraine with or without aura or daily for migraine

prevention

• GammaCore®: External vagal nerve stimulation acutely

• Sphenopalatine ganglion blocks with local anesthetic

• May include insertion of a delivery device

• Can be used acutely or preventively



Acute Treatment Strategies

• Step or staged care

• Start with a ‘weaker’ medication

• If needed, increase ‘strength’ of drug

• Stratified care

• Use best medication for this headache based on

• The current headache (e.g., type, severity)

• Patient’s experience with different treatments

• “Hit me with your best shot”

• Use the medication most likely to help every time


Rational Polypharmacy of the Acute Attack

• NSAID or APAP plus an antinauseant

• Triptan plus NSAID (see Treximet) or APAP

• Triptan plus an antinauseant

• Triptan plus NSAID or APAP plus an antinauseant

APAP = acetaminophen


The Trouble With Triptans

• Triptans cause chest and neck pressure, tingling, nausea

• Estimated risk of a serious CV event is 1 in 4 million uses

• Avoid triptans in patients with or at high risk for CAD

• DHE has a lower risk of chest discomfort but a high incidence of GI side effects

• If there is concern about underlying coronary artery disease and a great need to treat the headaches:

• Evaluate and treat the heart disease, then try triptan

• Give triptan under medical surveillance

• Risk of serotonin syndrome if triptans used with SSRIs or SNRIs is almost nil

• But I inform patients about possible symptoms Loder New Engl J Med 2010;363:63-70


Contra-indications to 5 HT1B/1D Agonists

• Known or suspected:

• Ischemic heart disease (atherosclerotic or vasospastic)

• Peripheral vascular disease

• Cerebrovascular disease

• WPW syndrome

• Uncontrolled hypertension

• Other 5 HT1B/1D agonists within preceding 24 hours

• Hemiplegic or basilar migraine (latter is now called migraine with brainstem aura)

• MAO inhibitor therapy in preceding 2 weeks

• For DHE and ergotamine, above plus pregnancy and lactation








When to Consider Preventive Antimigraine Treatment

• More than 4 to 6 headache days per month

• When acute therapy is contraindicated or ineffective

• When acute treatment is needed more than twice a week

• For severe migraine attacks (e.g., hemiplegic migraine)

• For even infrequent attacks that affect safety (e.g., pilot)

or livelihood (e.g., professional athlete)

• Patient preference


Goals of Preventive Therapy

• Decrease attack

• Frequency

• Severity

• Duration

• Improve response of attacks to acute therapy

• Improve function, decrease disability

• Prevent medication overuse and chronic

migraine headaches


Preventive Antimigraine Rx

• Dose response relationship is variable

• Start low and slowly increase dose

• To reduce side effects

• To avoid overshooting a beneficial response

• Medications take 3-4 weeks to 3-4 months to work

• Full benefit may take 6 months

• ≥ 50% decrease in headache burden is a good result

• If helpful, continue for 6-12 months then reassess

• Preventive therapy is underutilized


Preventive Antimigraine Therapies from American Academy of Neurology (AAN)

Silberstein et al Neurology 2012;78:1337-45

Level A Evidence

• Antiepileptic drugs

• Divalproex

• Topiramate

• Beta blockers

• Metoprolol

• Propranolol

• Timolol

Level B Evidence

• Antidepressants

• Amitriptyline

• Venlafaxine

• Beta blockers

• Atenolol

• Nadolol


Preventive Antimigraine Therapies Level A from Recent AAN Evidence-based Guideline

• Divalproex start at 250-500 aim for 750-1500 mg/day

• Alopecia, weight gain, tremor, birth defects

• Topiramate start at 15-25 aim for 100-200 mg/day

• Mental slowing, kidney stones, weight loss, birth defects

• Metoprolol start at 25-50 aim for 100-200 mg/day

• Depression, fatigue, hypotension, bradycardia

• Propranolol start at 60-80 aim for 120-240 mg

• Same side effects as metoprolol

• Timolol start at 10-20 mg aim for 40-60 mg/day

• Same side effects as metoprolol



Preventive Antimigraine Therapies Level B from Recent AAN Evidence-based Guideline

• Amitriptyline start at 10-25 aim for 50-150 mg/day

• Weight gain, dry mouth, sedation, constipation

• Venlafaxine start at 37.5-75 aim for 150-225 mg/day

• Nausea, sleep disturbance, asthenia, nervousness

• Atenolol start at 12.5-25 aim for 50-100 mg/day

• Depression, fatigue, hypotension, bradycardia

• Nadolol start at 40-60 aim for 160-240 mg/day

• Same side effects as atenolol



Preventive Antimigraine Therapies with Less Evidence from AAN Guideline

Holland et al Neurology 2012;78:1346-53

Prescription drugs

• Verapamil

• Gabapentin

• Some Rx NSAIDs

• On a daily basis

• Lisinopril

• Candesartan

Non-prescription drugs

• Some OTC NSAIDs

• On a daily basis

• Magnesium

• Riboflavin (vitamin B2)

• Co-Q10

• Petasites (butterbur root, Petadolex®) with Level A evidence but recent reports of liver damage


Preventive Antimigraine Therapies That are Used with Less Evidence

• Verapamil start at 80-160 aim for 180-240 mg/day

• Hypotension, constipation, swelling

• Gabapentin start at 100-300 aim for 900-2700 mg/day

• Edema, sedation, fatigue, weight gain, dizziness

• Regular use of NSAID (ibuprofen, ketoprofen, naproxen)

• GI upset, hypertension, kidney damage

• Magnesium 300 mg/day: Diarrhea and other GI effects

• Riboflavin (vitamin B2) 400 mg/day: Itching, dark urine

• Co-Q10 100 mg three times/day: Mostly GI side effects

• I would not recommend use of Petasites (butterbur root)

due to reports of hepatoxicity Holland et al Neurology 2012;78:1346-53


How to Choose a Preventive Antimigraine Treatment

• Pick a medication that will treat another condition

• Beta blocker in a patient with hypertension

• Avoid a drug that could aggravate an existing condition

• Divalproex in someone who is overweight

• Consider the cost, risk/safety, side effects, ease of use

• But don’t avoid a preventive with good evidence

• Be aware of potential drug interactions (e.g., topiramate and BCPs)

• Avoid drugs that could cause birth defects in women

• Neural tube defects with divalproex

• Cleft lip/palate with topiramate

• Obtain input from patient – they have the final say

Margulis et al Am J Obstet Gynecol 2012;207:405.e1-7


Why Preventives Don’t Work in Migraine

• Starting dose was too high and side effects occurred

• Dose advanced too quickly and side effects occurred

• Dose was not pushed high enough

• Trial was too short

• Preventive helped but patient not satisfied or didn’t notice

• Patient was in rebound due to medication overuse when preventive therapy is less likely to be beneficial

• Occasionally using 2 preventives together is helpful

• Tricyclic agent with a beta blocker or verapamil

• Without good evidence for synergism


New Preventive Antimigraine Therapy

• Recent reports of benefit from injections of monoclonal antibodies directed at calcitonin gene-related peptide receptors (CGRP) or CGRP itself

• Found to be helpful for chronic migraine and preventing episodic migraine headaches

• New mechanism of action

• High hopes for benefit from this class of drugs

Hershey N Engl J Med 2017;377:2190-1

Silberstein et al N Engl J Med 2017;377:2113-22

Goadsby et al N Engl J Med 2017;377:2123-32


Chronic Migraine Can be Treated with

Onabotulinum A Injections into Scalp Muscles

• Chronic migraine (CM) is defined as:

• Headache on ≥ 15 days per month for > 3 months

• The headaches have features of migraine on ≥ 8 days

per month for > 3 months

• CM can be caused or simulated by overuse of acute

drugs (analgesic or triptan) or substances (caffeine)

• So-called medication overuse headache

• Can have both CM and medication overuse

• CM patients usually referred to headache specialist

The International Classification of Headache Disorders, 3rd Ed

Onabotulinumtoxin A Injections FDA Approved in 2010 for Chronic Migraine, not Frequent Migraine


J.D. Bartleson, MD

Professor of Neurology

Mayo Clinic College of Medicine

[email protected]

Approach to a Patient with Headache

I Look Forward to Your Questions

Documents

Approach to a Patient with Headacheweb.brrh.com/msl/IM2018/Day-3_Sunday/Sunday 5... · If You are Concerned About a Secondary Cause •Diagnostic testing is warranted to exclude or