Page 1 Headache Medicine for the Non‐ Neurologist Justin DeLange, DO, FAHS Northern Arizona Healthcare Medical Group- Neurology Objectives At the end of this talk you should be able to: • Explain why headache medicine matters • Diagnose migraine and diagnose cluster headache • Recognize red flag features • Know primary work-up for secondary headaches • Know available abortive and preventive treatment options for migraine as an outpatient • Know why abortive and preventive treatment is important • Know management options for headache on an inpatient basis
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Headache Medicine for the Non NeurologistHeadache Medicine for the Non‐ ... had tension-type headache as the primary diagnosis. • Migraine causes disability. Tension type headaches
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Page 1
Headache Medicine for the Non‐Neurologist
Justin DeLange, DO, FAHSNorthern Arizona Healthcare Medical Group-
Neurology
ObjectivesAt the end of this talk you should be able to:
• Explain why headache medicine matters• Diagnose migraine and diagnose cluster
headache• Recognize red flag features • Know primary work-up for secondary headaches• Know available abortive and preventive
treatment options for migraine as an outpatient• Know why abortive and preventive treatment is
important• Know management options for headache on an
inpatient basis
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Lecture Outline• Outpatient Management
o Migraineo Clustero Other common headache types
• Inpatient /ED Management of Migraine• Secondary Causes of Headache in the Hospital/ED
o Diagnostico Recognition
DisclosuresOff-Label: Numerous medications used for
headache or migraine do not carry an FDA indication.
Financial: none
Conflict of interest: none
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Why Headache Matters
The Numbers
• Migraine is a global problem (1 Billion people affected) .
• In the U.S. migraine affects around 12% of the population.
• 36 MILLION AMERICANS WITH MIGRAINE
• One in Four Households• Prevalence of Chronic
Daily Headache: 4%
Why Migraine Matters
The Burden• Migraine costs are in upwards of 20 billion dollars a year.
This includes office visits, ER visits, medications, and missed work/lost productivity.
• 4% of all visits to doctor are for headache.• World Health Organization places migraine in the Top 10
most disabling diseases on the planet. • Pain is not the only disabling factor.
o Nausea/vomitingo Aura symptomso Light/sound/smell sensitivity
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Why Migraine Matters in Primary Care
• The Landmark Study showed 94% of patients complaining in the office to primary care doctors of stable, episodic headaches had migraine or probable migraine. Only 3%had tension-type headache as the primary diagnosis.
• Migraine causes disability. Tension type headaches do not generally result in disability and seldom do patients with tension type headache seek medical attention.
• 40% of pts with migraine qualify for preventive treatment BUT only 13% actually get preventive treatment (Lipton RB et al. Neurology; 68:343-349.)
Diagnosis/Management of Headaches
Outpatient
MIGRAINES
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Migraine without auraInternational Headache Society 2013 Diagnostic Criteria
• A. At least five attacks fulfilling criteria B–D
• B. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)
• C. Headache has at least two of the following four characteristics:
o 1. unilateral locationo 2. pulsating quality o 3. moderate or severe pain intensityo 4. aggravation by or causing avoidance
of routine physical activity (e.g. walking or climbing stairs)
• D. During headache at least one of the following:
o 1. nausea and/or vomitingo 2. photophobia and phonophobia
• E. Not better accounted for by another ICHD-3 diagnosis.
Migraine Diagnosis Simplified
• Think: PUMA• Pulsating• Unilateral (60%)• Moderate to Severe on pain
scale• Activity makes worse
• Other sx’s of photophobia, nausea, vomiting, phonophobia, osmophobia.
• May occur with or without Aura.
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More Simplification:
ID Migraine Brief Screener• Yes or No Answers• With your Headaches
o 1. Do you have a dislike for light?o 2. Do you have nausea?o 3. Do your headaches have impact on work, home, school, or recreational
activities?
• 2/3 “Yes” Answers suggest Migraine• Sensitivity of 0.81 and Specificity of 0.75
Lipton (2003)
Clinical Pearls Regarding Migraine
ResponseTo Triptans
or ErgotsNot dx
Can be Chronic orEpisodic.
Bilateral LocationIn 40%
History of motion
sickness
Family historyOf HA
Neck Paincommon
Aura seenIn 20%
Red wine WeatherStress
Menstrualtriggers
Disabling
Migraine
Adapted from Tepper SJ and Tepper DE 2011 and Ward TN 2012
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What is Migraine with Aura?• Gradually progressive neurologic impairment that last 5-60 minutes,
precedes or coincides with headache, and is completely reversible.o Typical aura may include:
• Visual• Sensory• Language
o Atypical may include:• Weakness• Ataxia• Prolonged• Bulbar symptoms• Monocular visual disturbances/blindness
Migraine Aura is Important to Recognize
• Stroke Risk doubled in patients with Migraine with Aura (RR 2.16)
• OCP (estrogen) + Migraine with aura= 10-13 fold increase in stroke risk (relative risk)
o Absolute risk of stroke is low howevero Additive risk not multiplicative
• OCP (estrogen) + Migraine with Aura + Smoking=DANGEROUS (Odds Ratio 34)
• Stroke Risk mainly noted in woman less than age 45. • Migraine with Aura may also be associated with other
cardiovascular disease too.
If estrogen needed for compelling indication in
patient with migraine with aura patient: lowest dosage recommended.
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Case • A 24-year-old
woman presents to her PCP complaining of throbbing, disabling headaches 2 days/month.
• She notes nausea and photophobia with her attacks
• Pain is 8/10 and lasts for 6 hours.
• She notes that Tylenol and Aleve are not helping her headaches.
• She denies any aura symptoms prior to headache onset.
• Exam normal
What is the diagnosis?Are there any other questions we need to ask?
Algorithm for Headache Diagnosis
Detailed history and exam
Headache Red Flags Present?
Exclude Secondary headache using appropriate testing if necessary
Consider Primary HA.Atypical features present?
Reconsider Secondary Headache
Diagnose primary headache disorder
From Wolff’s Headache
Yes No
Yes
NoIf clearly migraine then imaging is not warranted!
• NEUROLOGIC SYMPTOMS or abnormal signs (confusion, impaired alertness or consciousness)
• ONSET: sudden, abrupt, or split-second (thunderclap)
• OLDER: new onset and progressive headache, especially in middle age >50 yr (giant cell arteritis)
• PREVIOUS HEADACHE HISTORY: first headache or different (change in frequency, severity, or clinical features), POSITIONAL, PAPILLEDEMA, or PRECIPITANTS (cough, sneeze, sex, Valsalva)
Dodick DW. Adv. Stud Med 2003;3:S550-555
History must be taken, not just accepted
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Yellow flags for Secondary
Headache Disorders
• Wakes patient from sleep at night• New onset side-locked headache
De Luca and Bartleson, Seminars in Neurology, 2010
Physical exam of headacheCheck Looking for To clue you towards
Marmura M, Silberstein SD, Schwedt TJ. Headache. 2015;55:3–20.
Note: Opiates/Opioids should never be used as a first line agent!
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Acute Pharmacotherapy for Migraine
Strength of Evidence• Level A: established as effective (First Line agents)• Triptans
• Almotriptan-Expensive, but less side effects• Eletriptan-Expensive, Quick and Effective• Frovatriptan-Expensive, long-acting (not quick)• Naratriptan-cheap, long-acting (not quick)• Rizatriptan-cheap, Quick and Effective• Sumatriptan-cheap, quick, most side effects.
Injectable form is gold standard but side effects.• Zolmitriptan-consistent, quick• Sumatriptan/naproxen-expensive, more effective
than sumatriptan alone.
Marmura M, Silberstein SD, Schwedt TJ. Headache. 2015;55:3–20.
Use full doses!
Acute Pharmacotherapy for Migraine
Strength of Evidence• Level A: established as effective (First Line agents)• Triptans
• Almotriptan-Expensive, but less side effects• Eletriptan-Expensive, Quick and Effective• Frovatriptan-Expensive, long-acting (not quick)• Naratriptan-cheap, long-acting (not quick)• Rizatriptan-cheap, Quick and Effective• Sumatriptan-cheap, quick, most side effects.
Injectable form is gold standard but side effects.• Zolmitriptan-consistent, quick• Sumatriptan/naproxen-expensive, more effective
than sumatriptan alone.
Marmura M, Silberstein SD, Schwedt TJ. Headache. 2015;55:3–20.
Use full doses!
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Acute Pharmacotherapy for Migraine
Triptans• Different Modalities/Delivery:• Consider alternate route if patient has bad
nausea • Tab
• All triptans• Disintegrating tab
• Zolmitriptan• rizatriptan
• Nasal Spray• Sumatriptan• zolmitriptan
• Injectable• Sumatriptan
• Iontophoretic Patch (FDA warning: skin burns!!!)pulled off market
• Sumatriptan• Intra-nasal powder (breath-powered) now FDA-approved
• Sumatriptan
Contraindications to triptans
• Known or suspected ischemic heart disease• Cerebrovascular disease• Peripheral vascular disease• Uncontrolled HTN• Severe hepatic disease• Use of ergot-alkaloid or other 5-HT1 agonist (i.e. a
different triptan) within preceding 24 hours• Patients should avoid sumatriptan, rizatriptan, and
zolmitriptan within 2 weeks of MAO inhibitor use (phenelzine)
• Hemiplegic attacks • Typically avoid during pregnancy (FDA Category C)
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Acute Pharmacotherapy for Migraine
DHE Nasal Spray
• DHE Nasal Spray is often overlooked and is useful if patient does not respond to triptans or NSAIDs.
• Does not need to be dosed at the onset of the attack to be effective.
• Drawbacks: Taste, medication going down the back of the throat.
• Can be expensive depending on patient’s insurance.
Contraindications to DHE
• Black box: Serious/life-threatening peripheral ischemia has been associated with the coadministration of DHE with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics
• Coadministration with other pressor/vasoconstrictivemedications
• Hypersensitivity to ergot alkaloid products • Myocardial infarction • Uncontrolled hypertension, ischemic heart disease, angina• Cerebrovascular disease, peripheral vascular disease • Onset of chest pain following test dose• Other ergot or 5-HT derivatives (triptan) within last 24 hr• Pregnancy and lactation (FDA Category X)• Prolonged hypotension, shock • Sepsis • Severely impaired liver/renal function • Following vascular surgery• Hemiplegic/basilar migraine
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Acute Pharmacotherapy for Migraine
Anti‐Emetics• Good for Rescue when nothing else is helping. • May help keep patient out of the ED.• May also help headache too!• Prochlorperazine 5-10 mg PO x1 (or suppositories at 25
mg PR x1)• Metoclopramide 10 mg PO X1• Promethazine 12.5-25 mg PO x1• Metoclopramide and Prochlorperazine have best
evidence in setting of migraine (IV forms). Watch for EPS!• Should only be used for Rescue therapy!
• Ondansetron if unable to tolerate anything else or has tremor history.
Primer on Acute Treatment• Significant nausea?: try triptan
injection or disintegrating tabs or nasal spray
• If no response to Triptans, Try NSAIDs alone or DHE nasal spray.
• Try to limit abortive medications to no more than 2 days/week (no more than 9 days/month) to avoid analgesic or triptan overuse headache.
• Make sure patient has anti-emetics for Rescue therapy (may help with headache along with nausea)
• In absence of vascular disease, consider migraine specific medication (e.g. triptans, DHE)
• For Triptans should be dosed at headache ONSET.
• Try adding NSAID with Triptans at onset for synergy or for breakthrough pain.
• NSAIDs do not need to be taken at headache onset to be effective
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Preventive Therapy for Migraine
o When to Initiate Migraine Prophylaxis:• >3 migraine days/month• >2 migraine days/week• Abortive medication overuse• Severe disability from headaches• Patient preference• Abortive medication side effects• Atypical cases: Hemiplegic Migraine, Prolonged aura,
Brainstem aura.
Preventive Therapy for Migraine
o Preventive therapy helps to avert chronification of migraine.
o Start Low and go slowo 2-3 month trialo Reassure patient they are not “married” to a certain
drug.• If side effects or no response after 2-3 months then try
another drug.o Realistic Goals:
• Goal is less disability, halving of frequency, and less abortive med usage.
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Preventive Therapy for Migraine
o Try to kill two birds with one stone if possible. • Topiramate for the obese patient• Propranolol for the anxious or tremulous patient• Amitriptyline for the insomnia patient.• Depakote or Topiramate for the Bipolar patient• Propranolol, Metoprolol, or Atenolol in the
hypertensive patient• Amitriptyline in the fibromyalgia or chronic pain
patient.
Preventive Therapy for Migraine
AAN Guidelines for Migraine Preventive Therapy
o FIRST LINE!o Level A: Meds with established efficacy (should be
offered)o Topiramate 100-200 mg/dailyo Metoprolol 50-100 mg/dailyo Propranolol 80-240 mg/dailyo Level B: Meds are probably effective (should be
considered)o Amitriptyline 10-150 mg/daily
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Preventive Therapy for Migraine
AAN Guidelines for Migraine Preventive Therapy
o SECOND LINE!o Level A: Meds with established efficacy (should be
offered)o Divalproex sodium or sodium valproate 250 mg-1500
mg/dailyo Level B: Meds are probably effective (should be
o Level A: Meds with established efficacyo Petasites (Butterbur): no longer safely recommended due
to liver toxicity issues!
o Level B: Meds are probably effective (should be considered)
o Magnesiumo Feverfewo Riboflavin
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Preventive Therapy for Migraine
onabotulinumtoxinA
o If patient has had 15 or more headache days/month for at least 3 months=Chronic Migraine
o If Chronic migraine patient has tried two or three different preventives and is still having 15 or more headache days/month then onabotulinumtoxinA may be indicated
o OnabotulinumtoxinA is only FDA-approved medication for Chronic Migraine
o Refer to Neurology or Headache Specialist.
Addressing Risk Factors for Developing Chronic Migraine
• Caffeine• Depression• Allodynia• Anxiety• Other chronic
pain
• Medication overuse
• Attack frequency• Obesity• Head Injury• Snoring
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New and Emerging Migraine Treatments
• Transcranial Magnetic Stimulation*
• Non-invasive Vagal nerve stimulation for Cluster and
Migrane*• Trigeminal nerve stimulation*
• Sumatriptan intranasal powder*
• CGRP monoclonal antibodies (Awaiting FDA
approval)
Photos credit: National Headache Foundation
*FDA approved
New and Emerging Migraine Treatments
• Transcranial Magnetic Stimulation*
• Non-invasive Vagal nerve stimulation for Cluster HA*
• A. At least five attacks fulfilling criteria B–D• B. Severe or very severe unilateral orbital, supraorbital• and/or temporal pain lasting 15–180 minutes (when• untreated)1• C. Either or both of the following:• 1. at least one of the following symptoms or signs,• ipsilateral to the headache:• a) conjunctival injection and/or lacrimation• b) nasal congestion and/or rhinorrhoea• c) eyelid oedema• d) forehead and facial sweating• e) forehead and facial flushing• f) sensation of fullness in the ear• g) miosis and/or ptosis• 2. a sense of restlessness or agitation• D. Attacks have a frequency between one every other• day and eight per day for more than half of the time• when the disorder is active• E. Not better accounted for by another ICHD-3• diagnosis.
Stillman 2011
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Cluster Headache Treatments
• Abortiveo Oxygen 10-15 L/min via NRB
mask x15 minuteso Sumatriptan 6 mg SC
• Oral triptans suboptimal in cluster!
o DHE injection or nasal sprayo Sumatriptan or zolmitriptan
nasal spray• Preventive
o Verapamil 240-480 mg/do Sodium valproate 500-1500
• Bridging (pain relief while waiting for preventive to “kick in”)• Prednisone 60-80
mg/d tapered over 14 days
• Greater occipital nerve block
Diagnosis/Management of Headaches
Outpatient
OTHER HEADACHE TYPES
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Other Common Headache Types
Tension-type Headache Post-Traumatic Headache• Usually does not present to
clinic (not disabling) unless chronic
• Typically bilateral, pressure-like• No migrainous features
o No nausea and vomitingo May have photophobia or
phonophobia but not both!• Activity does not make worse• Treatment
o Amitriptyline is preventive of choice if bothersome.
o NSAIDs for abortive care
• New-onset headache that appears after head injury, concussiono MRI Brain needed +/- vessel
imaging• Treat the phenotype
o Migrainouso Clustero Tension-type
Diagnosis/Management of Headaches
Inpatient/ED
MIGRAINES
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Inpatient Treatment Principles
ED/Inpatient
• Place the patient in a darkened, quiet room• Provide reassurance• Treat fluid depletion• Treat nausea and vomiting!!!• Implement treatment with parenteral medication• Use non-dependence producing agents when possible
(no opioids if possible)• Utilize doses which are likely to be effective
Inpatient Treatment Principles
ED/Inpatient
• Do not restrict antiemetics just to patients with nauseao Dopamine-blockade may be implicated in migraine relief
• Use “migraine-specific” therapy (DHE, Triptans)o But 50% of patients presenting to ED in 1 study had a
potential contraindication to migraine-specific therapy (Friedman et al. Headache 2009)
• Response to therapy is not a diagnostic tool!
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Inpatient/ED TreatmentMigraines
Migraine‐specific treatments Inpatient
Triptans
Sumatriptan 6 mg SC (Max 12 mg/24
hours)
Side effects: injection site reaction, paresthesias, hot/cold sensation, chest pressure/pain/tightness, dizziness, flushing, limb pain, vasoconstriction, and nausea.
Ergotamine derivatives
Dihydroergotamine mesylate (DHE) 0.5
mg‐1 mg IV ( Max 2‐3 mg/24 hours) (May
be dosed every 8 hours in hospital)
Side effects: paresthesias, dizziness, flushing, nausea/vomiting, diarrhea, dyspnea, rash, diaphoresis, elevated blood pressure, anxiety, and vasoconstriction.
For DHE: pre-treatment with anti-emetic +/-
diphenhydramine often needed!
Inpatient/ED TreatmentMigraines
Migraine‐specific treatments Inpatient
Triptans
Sumatriptan 6 mg SC (Max 12 mg/24
hours)
Side effects: injection site reaction, paresthesias, hot/cold sensation, chest pressure/pain/tightness, dizziness, flushing, limb pain, vasoconstriction, and nausea.
Ergotamine derivatives
Dihydroergotamine mesylate (DHE) 0.5
mg‐1 mg IV ( Max 2‐3 mg/24 hours) (May
be dosed every 8 hours in hospital)
Side effects: paresthesias, dizziness, flushing, nausea/vomiting, diarrhea, dyspnea, rash, diaphoresis, elevated blood pressure, anxiety, and vasoconstriction.
For DHE: pre-treatment with anti-emetic +/-
diphenhydramine often needed!
**AHS Guidelines for Acute Migraine in ED (2016): Should Offer
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Inpatient/ED TreatmentMigraines
Nonspecific Migraine treatments Inpatient
Antiemetics (D‐2 Antagonists)
Chlorpromazine 12.5‐25 mg IV/IM
Prochlorperazine 10 mg IV/IM **
Promethazine 25 mg IM
Haloperidol 5 mg IV in 500 ml normal saline over 20
minutes
Droperidol 2.5 mg IV
Metoclopramide 10 mg IV/IM
Side effects: drowsiness, dizziness, blurred vision, akathisia, dystonia, parkinsonism, fluid retention (metoclopramide), QT prolongation (Droperidol has Black Box warning due to risk of QT prolongation*), neuroleptic malignant syndrome, hypotension (especially chlorpromazine)
Inpatient/ED TreatmentMigraines
Nonspecific Migraine treatments Inpatient
Antiemetics (D‐2 Antagonists)
Chlorpromazine 12.5‐25 mg IV/IM
Prochlorperazine 10 mg IV/IM **
Promethazine 25 mg IM
Haloperidol 5 mg IV in 500 ml normal saline over 20
minutes
Droperidol 2.5 mg IV
Metoclopramide 10 mg IV/IM**
Side effects: drowsiness, dizziness, blurred vision, akathisia, dystonia, parkinsonism, fluid retention (metoclopramide), QT prolongation (Droperidol has Black Box warning due to risk of QT prolongation*), neuroleptic malignant syndrome, hypotension (especially chlorpromazine)
**AHS Guidelines for Acute Migraine
in ED (2016):Should Offer
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Inpatient/ED TreatmentMigraines
Nonspecific Migraine treatments Inpatient
Antiepileptics
Valproate sodium 500‐1000 mg IV (one
time dose)
Side effects: drowsiness, asthenia, nausea/vomiting, injection site reaction, dizziness, hepatotoxicity, hyperammonemia, pancreatitis.
• Useful for patients with cardiovascular or cerebrovascular contraindication to triptans,
DHE.
Inpatient/ED TreatmentMigraines
Nonspecific Migraine treatments Inpatient
Antiepileptics
Valproate sodium 500‐1000 mg IV (one
time dose)
Side effects: drowsiness, asthenia, nausea/vomiting, injection site reaction, dizziness, hepatotoxicity, hyperammonemia, pancreatitis.
• Useful for patients with cardiovascular or cerebrovascular contraindication to triptans,
• NEUROLOGIC SYMPTOMS or abnormal signs (confusion, impaired alertness or consciousness)
• ONSET: sudden, abrupt, or split-second (thunderclap)
• OLDER: new onset and progressive headache, especially in middle age >50 yr (giant cell arteritis)
• PREVIOUS HEADACHE HISTORY: first headache or different (change in frequency, severity, or clinical features), POSITIONAL, PAPILLEDEMA, or PRECIPITANTS (cough, sneezing, sex, Valsalva)
Dodick DW. Adv. Stud Med 2003;3:S550-555
History must be taken, not just accepted
Serious Secondary Causes of Headache• Subarachnoid hemorrhage
• CT or MRI myelogram may be needed to localize site of leak
• Treatment is blood patch
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Giant Cell Arteritis• New onset headache in
patient above age of 50• Jaw claudication• Temporal artery
tenderness• New visual disturbances• Polymyalgia rheumatica
sx’s• Fever or anemia• ESR and/or CRP elevated
Headache: The Journal of Head and Face PainVolume 55, Issue 6, pages 866-868, 11 MAR 2015 DOI: 10.1111/head.12541http://onlinelibrary.wiley.com/doi/10.1111/head.12541/full#head12541-fig-0003
Photo: uveitis.org
Giant Cell Arteritis• Temporal Artery Biopsy is
diagnostic• Steroids should not be
delayed to avoid ischemic complications
o Vision loss is irreversible
• Prednisone 60 mg daily• ASA 81 mg daily should
also be startedo Wide spread vasculitis of medium
to large vessels
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Conclusion• Migraine is a disabling, genetic brain disease• History is EVERYTHING in headache medicine• Be wary of red flag symptoms (2SNOOP4)• Migraine specific abortive therapy should be used when
possibleo Triptans or DHE if no risk factorso NSAIDs may be used for synergy with migraine specific therapy
• Migraine preventives are underutilized and important• Utilize Parenteral, non-opioid treatment in the
hospital/inpatient setting for migraine when possible• Be on the lookout for secondary causes of headache in
the ED/Hospital/Outpatiento Thunderclap Headache may herald an ominous cause!!!
Questions?
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Pregnant Migraineur?• No preventives if possible.
• Magnesium 350 mg (FDA recommends no higher)• Propranolol FDA Category C-lowest dose possible if needed.• Amitriptyline (no more than 50 mg) FDA Category C -lowest dose possible if needed.
• Abortives:• Tylenol• Tylenol/Caffeine• Metoclopramide 10 mg PRN (use sparingly)• Naproxen or Ibuprofen in 1st and 2nd Trimesters only!• Prednisone (not in 1st Trimester)
• Avoid opiates/opioids or butalbital if possible!• Triptans are Category C and use as a third line agent should
only be considered if nothing else is helping.• Registry data showing sumatriptan may be safe.
• DHE is Category X and is always contraindicated!!!
Consensus Statements on OCP use
in Migraine with Aura• European community: More restrictive of OCP use in
migraine.• ACOG position: no OCPs in a patient with migraine with
aura above 35 year old.• IHS position: individually assess and evaluate risk for
stroke in each patient• WHO: women with migraine with aura should not use
OCPs.
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In the clinic or at home:
Rescue Plan to Keep Out of ED!
Initial Therapy
Rescue Therapy
Back-up Therapy
First dose of triptan
And/Or NSAID
Repeat dose of triptan. Also try NSAID for breakthrough pain if not given initially.
Trying to keep out of ED Prochlorperazine PO or PR
(or other antiemetic of your choice)
Indomethacin 50 mg PR Ketorolac 30-60 mg IM or PO Consider steroids
If Fails
If Fails
Adapted from Whyte, Headache 2010; Turkewitz. Self-administration of parenteral ketorolac for head pain. Headache, 1992
Consider non-oral meds in patients with severe nausea/vomiting.
Injections/Nasal spray
Stop Status Migrainosus treatment if headache-free for 24 hours.