Headache Evaluation & Treatment
2014
Elizabeth Waterhouse, M.D., FAAN
Department of Neurology
Virginia Commonwealth University School of Medicine
                       Objectives
   Describe the features of common headache disorders, so that
    appropriate treatment can be initiated.
   Differentiate primary and secondary headaches
   Recognize the clinical features of migraine, chronic migraine,
    cluster headache, and trigeminal neuralgia. Distinguish between
    these headache disorders.
   Identify the preventive and acute treatment options for migraine.
   Review forthcoming treatments for migraine
Clinical presentation of headaches
 Primary               Secondary
   Migraine              Infection
   Tension-type          Hemorrhage
   Cluster               Increased
   Other                  ICP
                          Brain tumor
 Diagnostic evaluation
                 Headache
      NO       Warning signs
                                YES
                 present?
 Primary                         Secondary
Headache                         Headache
    Atypical
   Features    Investigations
                  “SSNOOPP”
Systemic symptoms (fever, weight loss) or
Secondary risk factors (HIV, systemic cancer)
Neurologic symptoms or signs (focal, or altered mental
    status)
Onset: sudden, abrupt,    split-second
Older: new onset and progressive headache, especially
in middle-age > 50 (arteritis)
Previous headache history: first headache or different
(change in attack frequency, severity or clinical features)
Postural
When is imaging indicated?
In patients with recurrent migraine, and normal
exam, neither CT nor MRI is warranted except in
cases with:
      Recent substantial change in headache pattern
      History of seizures
      Focal neurological symptoms or signs
In patients with non-migraine
headache, CT or MRI should be
considered on a case by case basis
 Consensus expert opinion
      MRI is more sensitive
      Use CT if looking for acute blood
Report of Quality Standards Subcommittee of AAN. Neurology.
Nonacute headache/ Normal neuro exam
    Headache type             n            Significant    Prevalence
     (# of studies)                      abnormality on      (%)
                                         neuro-imaging
      MIGRAINE
                            1086                 2           0.18
         (11)
          TTH
                             83                  0           0.0
           (2)
    UNSPECIFIED
                            2788                49           1.8
        (10)
  Headache Consortium Guidelines. Neurology. 2000.
Disorders not excluded by normal CT
   Vascular                   Tumor
 Venous sinus           Posterior fossa lesion
                        (tumor, Chiari malformation)
 thrombosis
 Arterial dissection    Infiltrative CNS glioma
 CNS vasculitis         Pituitary tumor/apoplexy
 Temporal arteritis     Leptomeningeal cancer
  Infectious                  Other
 Encephalitis           Idiopathic intracranial
                        hypertension
 Meningitis             Low-pressure headache
                        syndrome (CSF leak)
 Sinusitis (Sphenoid)   Isodense subdural
             Lumbar puncture
   The first unusually severe       Acute:
    headache
                                      Subarachnoid hemorrhage
   Thunderclap headache with
                                      Meningoencephalitis
    normal head CT
                                      High or low pressure
   Subacute progressive
    headache
   Headache with fever,             Subacute:
    confusion, meningismus, or        Fungal or Lyme infection
    seizures                          Vasculitis
   High or low CSF pressure          Neurosarcoid
    suspected (even if papilledema    Leptomeningeal disease
    is absent.)
Primary Headaches
               Case Scenario
   36-year-old man, computer programmer,
    married with 2 children
   Has severe, stabbing pain behind his right eye
   Headaches accompanied by
    lacrimation and nasal congestion
   Pain lasts 30 to 45 minutes;
    attacks occur daily and nightly for
    several weeks, then stop
    for months at a time
Show you tube video
http://www.youtube.com/watch?v=RAOqWOV-
y0s&feature=channel&list=UL
             Cluster headache
   Relatively uncommon
   More prevalent in men than
    in women                              January
   Genetic predisposition         February
                                         March
   Attack frequency: 1 every    May Jun         April
    other day to 8 daily                       July
                                        e
                                      August
                                         September
   Clusters usually last 2
    weeks - 3 months               October
                                 November
                                         December
   Circadian and annual
    periodicity
        Cluster headache: pain
   Severe
   Unilateral
   Short: 15 - 180 minutes (untreated)
   Orbital, suborbital, or temporal pain
   Unilateral autonomic features
    –   Lacrimation
    –   Congestion
    –   Rhinorrhea
    –   Horner’s
     Adapted from Lance JW and Goadsby PJ (eds). Mechanisms and Management of Headache.
      Cluster headache - treatment
   Acute symptomatic
     – Oxygen, 7 – 12 L/min for 15 – 20 mins
     – Sumatriptan injection
     – DHE IM, IV or nasal spray
   Preventative
     – Lithium
     – Verapamil
     – Methysergide
     – Corticosteroids
     – Topiramate
           Cranial neuralgias
   Categorized separately from primary or secondary
    headaches
   Stabbing or constant pain
   Trigeminal neuralgia is the most common
     – Brief unilateral stabs of pain
     – Distribution of one or more divisions of CN V
     – Triggered by minor stimulation
     – Patient is asymptomatic between paroxysms of
       pain
                    Trigeminal neuralgia
                     diagnostic criteria
   Paroxysmal brief attacks of pain
   Pain has at least one of the following characteristics:
     – Intense, sharp, superficial or stabbing
     – Precipitated from trigger areas or by trigger factors
   Attacks are stereotyped in the individual patient
   There is no clinically evident neurological deficit
   Not attributed to another disorder
     Trigeminal neuralgia--treatment
   Obtain MRI to look for lesion impinging on the
    trigeminal nerve
   Preventive therapy
    –   Carbamazepine
    –   Gabapentin (high dose is often needed)
    –   Baclofen
    –   Tricyclic antidepressants
   Surgical treatments
    – Decompression
    – Ablation procedures on the trigeminal ganglion
Case Scenario
    27-year-old woman,
     administrative assistant
    Experiences throbbing
     headache in left temple with
     nausea and vomiting
    Headache generally lasts
     12 to 24 hours
    NSAIDs are usually effective
     for the headache, but nausea
     and vomiting cause her to miss
     time from work
IHS criteria for migraine without aura
     Recurrent attacks (at least 5) lasting 4 - 72 hours
     At least 2 of the following
       – Unilateral
       – Pulsating quality of pain
       – Moderate/severe intensity
       – Aggravated by routine activity
     At least 1 of the following
       – Nausea and/or vomiting
       – Photophobia/phonophobia
     Rule out organic disease
            Migraine with aura
   Also called “Classic Migraine”
   The aura is very distinctive
    from other types of headaches
   15 - 20% of all migraineurs
    suffer from migraine with aura
   Gradual onset over minutes
   Persists for 20 - 60 minutes
          Prevalence of migraine
    30
                                                                                Female
    25                                                                          Male
    20
    15
    10
    0
          20        30       40       50       60          70              80            90
                                    Age (y)
   1 in 6 American women
   1 in 11 men
    Up to 90% of patients have a family history of migraine
                                                    Lipton & Stewart. Neurology. 1993;43(suppl 3):S6-10
        Reported quality of life is worse for
     migraine than for other chronic conditions
                                    Diabetes                     Migraine
                                    Angina                       Hypertension
                                    No chronic condition
              0.5
             -0.5
                -1
             -1.5
                         Physical      Everyday        Social   Mental Health Pain   Global
                        activity       health          perceptions
Stewart WF, Lipton RB. Eur Neurol. 1994;34(suppl 2):12-17.
 Acute migraine medications
Nonspecific
 NSAIDs
 Combination   analgesics
 Opioids
 Neuroleptics/antiemetics
 Corticosteroids
Specific
 Ergotamine/DHE
 Triptans
     Acute therapies for migraine
   GROUP 1: Substantial empirical evidence and
   pronounced clinical benefit
   OTC Analgesics             Migraine Specific Meds
     Aspirin                 Triptans
     Acetaminophen, aspirin,
      plus caffeine           DHE
                                                                SC, IM, IN, IV (plus
                                                                 antiemetic)
   Nonspecific Rx Meds
        Butorphanol IN
        Ibuprofen
        Naproxen sodium
        Prochlorperazine IV
Silberstein et al, AAN evidence based guideline for migraine headache, Neurology, .55, 754-762, 2000
                 Triptans
Selective 5HT-1B/1D agonists – site of action
is the interface between trigeminal nerve
endings and blood vessel walls
Relative to nonspecific therapies, as a class
they provide
 Rapid onset of action
 High efficacy
 Favorable side effect profile
Adverse events and contraindications
      Triptans: treatment choices
   Sumatriptan (Imitrex)        Available as tablets only:
    – Tablet
    – Nasal Spray Subcut.           Naratriptan (Amerge)
      Injection
                                    Almotriptan (Axert)
   Zolmitriptan (Zomig)
    – Tablet Orally dissolving
      tablet                        Frovatriptan (Frova)
    – Nasal spray
                                    Eletriptan (Relpax)
   Rizatriptan (Maxalt)
    – Tablet Orally dissolving      Sumatratiptan + naprosyn
      tablet                         (Treximet)
   Acute treatment principles
 Treat early in attack
 Use correct dose and formulation
 Use a maximum of 2-3 days a week
 Everyone needs acute treatment
 Add on preventive therapy in selected
  patients
            Lifestyle issues
Risk factors/triggers        Protective Factors
   Hormonal changes            Regular sleep
   Chronobiologic changes      Regular meals
   Foods & additives –         Regular exercise
   Alcohol                     Biofeedback/stress
   Drugs                        reduction
   Sensory input               Healthy lifestyle
   Stress                      Avoidance of “prn”
   Trauma                       medication overuse
   Weather changes
   Dehydration
FDA-approved migraine preventatives
    Topiramate                      2004
    Divalproex sodium (Depakote®)   1996
    Timolol (Blocadren®)            1990
    Propranolol (Inderal®)          1979
    Methysergide (Sansert®)         1962
2012 AAN evidence-based guidelines
   Effective for episodic migraine prevention
    –   Divalproex sodium, sodium valproate
    –   Topiramate
    –   Metoprolol, propranolol, timolol
    –   Frovatriptan (menstrual migraine)
   NSAIDs, probably effective
    – Ibuprofen, ketoprofen, naproxen, fenoprofen
   Supplements
    – Butterbur - effective in 2 studies
    – Feverfew, magnesium, riboflavin, and subcutaneous
      histamine are probably effective
                                              Neurology 2012;78:1337-1345 and 1346-1353
Treatment and comorbid conditions
                                                                 COMORBID CONDITION
                                    SIDE              RELATIVE                      RELATIVE
       DRUG       EFFICACY*       EFFECTS*        CONTRAINDICATION                 INDICATION
Anticonvulsants    *On a scale of 0 to 4
    Divalproex        4+              2+     Liver disease, bleeding disorders,   Mania, epilepsy, anxiety
                                             overweight, pregnancy                disorders
                                             Kidney stones, underweight,          Epilepsy, obesity
    Topiramate        4+              2+     pregnancy
    Gabapentin        2+              2+     ESRD, pregnancy                      Epilepsy, neuropathy, pain
Antidepressants
    TCAs              3+              2+     Mania, urinary retention, heart      Pain, depression, anxiety
                                             block, tachycardia                   disorders, insomnia
    SSRIs             2+              1+     Mania                                Depression, OCD
                  Preventive treatment
                                                            COMORBID CONDITION
                                 SIDE                                              RELATIVE
       DRUG        EFFICACY*   EFFECTS*   RELATIVE CONTRAINDICATION               INDICATION
Beta-Blockers         4+          2+      Asthma, depression, CHF, Raynaud’s   HTN, angina
                                          disease, diabetes
Calcium channel
blockers
    Verapamil         2+          1+      Constipation, hypotension            Migraine with aura,
                                                                               HTN, angina, asthma
Preventive treatment - supplements
                                            SIDE          RELATIVE
    SUPPLEMENT               EFFICACY*    EFFECTS*       INDICATION
    Butterbur           2+               1+          Preference for
                                                     supplement
Other
    Riboflavin          2+               1+          Preference for natural
                                                     products, pregnancy
    Magnesium           2+               2+           Preference for natural
                                                      products, pregancy
*On a scale of 0 to 4
\
              Case Scenario
   37 year old woman with history of severe headaches in
    her teens and twenties
   7 month history of daily mild to moderate bifrontal
    headache, waxing and waning in intensity. Most of the
    time she is able to continue her activities.
   About twice per week the headache pain becomes
    throbbing and severe, with associated nausea,
    photophobia and photobia, and she feels she has to lie
    down to try and sleep.
   She has been taking 8 – 10 over-the-counter
    analgesic tablets per day for the past 6
    months.
          Medication overuse
   Analgesic overuse plays a role in 80% of
    chronic daily headaches
   Female > male (3.5:1)
   Risk factors
    – Simple analgesics: > 5 days / week
    – Triptans / combination analgesics: > 3 days / week
    – Opioids / ergotamine: > 2 days / week
                                Adapted from Diener C & Dahlof K. The Headaches
               Chronic migraine
   Daily or almost daily (> 15 days/month) head pain for > 3 months
   Average headache duration of > 4 hours per day (untreated)
   Sometimes called “transformed migraine”
     – Episodic migraine “transformed” into a chronic waxing and waning
       headache
     – Frequently analgesic overuse is the agent of “transformation”
   At least one:
     – History of episodic migraine (IHS)
     – History of increasing headache frequency with decreasing average
         severity of migrainous features over > 3 months
     – Headache at some time meets IHS criteria for migraine
              Chronic Migraine
   Therapy
    – Give preventive medication(s)
    – Wean off “prn” medications
    – Consider onabotulinumtoxin A
          Reduced mean frequency of headache days by 8.4 days per month
           (compared with placebo 6.6 days)
          Repeat injections are needed about every 3 months
                                                        Dodick et al., Headache 2010;50:921-936
    What to do when all else fails?
   Make sure your diagnosis is correct
   Work on lifestyle factors
    –   Sleep
    –   Mood
    –   Hydration
    –   Gradual caffeine reduction
    –   Exercise (walking)
    –   Diet/weight loss
   Review preventive options
   Do not keep escalating the “prn” meds
    What to do when all else fails?
   Consider a supplement
    – Magnesium citrate 400 mg daily
    – Riboflavin 400 mg daily
    – Butterbur 75 mg BID
   Consider injections
    – Botulinum toxin
    – Occipital nerve block
A new FDA-approved device
                  Cerena TMS
   Transcranial magnetic stimulator
   FDA approved in December, 2013, but not yet
    marketed in U.S.
   Randomized controlled clinical trial of 201 patients
    with moderate – severe migraine with auras
    preceding at least 30% of their migraines.
           Cerena study results
   Of the study subjects, 113 recorded treating a
    migraine at least once when pain was present.
   38 % of subjects who used the device were pain-free
    two hours after using it, compared to 17 % of
    controls.
   After 24 hours, nearly 38 % of the active device users
    were pain-free compared to 10 % of the controls.
         Caveats and side effects
   It cannot be used in people who have implanted
    devices (pacemaker, VNS, etc.)
   There were 7 adverse events in 5 subjects (9.43%) of
    the Cerena group and 11 reported in 7 subjects
    (11.67%) of the sham group.
   Events possibly related to the use of the device
    include dizziness (N=2). Other reported events
    included sinusitis, aphasia, and vertigo (N=1 each).
    No seizures were reported.
Other devices in development
                      Summary
   The appropriate headache diagnosis must be made before
    a treatment can be selected.
   History and exam help to differentiate primary and
    secondary headaches.
   Migraine is the most common primary headache disorder.
   Effective options for acute treatment include the triptans,
    which are serotonin 1B/D agonists.
   Numerous choices for preventive migraine therapy are
    available.