Headache

Paul G. Mathew, M.D.,1,2 and Ivan Garza, M.D.3

ABSTRACT

Headache is one of the most common complaints among patients presenting to an

outpatient neurology practice. The evaluation, diagnosis, and treatment of headache can be
rather cumbersome and at times quite challenging for even the most seasoned neurologist.
Many complex issues that although not causative, can play an exacerbating role in the
genesis of headaches. In this article, the authors review some of the essential elements that

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are part of headache evaluation including headache-specific history, physical examination,
warning signs of secondary headache disorders, and when to consider further studies. They
then provide a brief review on the diagnosis of primary headache disorders according to the
International Headache Societys International Classification of Headache Disorders, 2nd
Edition (ICHD-2), and treatment strategies of the more common primary headache
disorders with a focus on migraine, trigeminal autonomic cephalalgias, tension-type
headache, and chronic daily headache.

KEYWORDS: Primary headache, migraine, trigeminal autonomic cephalgias, cluster

headache, tension-type headache

EVALUATION tory. The history should be chronological, and should

The first major step that a neurologist must take when
evaluating a headache patient in an outpatient neurology
practice is to establish whether the headache is a pri-
mary or secondary type of headache. Primary head-
aches are those that cannot be attributed to an
underlying disorder, whereas secondary headaches are
due to a specific underlying cause or disorder. In the case
of secondary headaches, addressing the underlying dis-
order can often, but not always, lead to resolution of the
headaches. Some of the common causes of secondary
headaches are listed in Table 1.
History
The most fundamental and essential component in the
evaluation of headaches is a thorough history. Table 2
summarizes the important elements of a headache his-
document the evolution of all associated symptoms. It is
vital to have the patient recall when the headaches
began, and whether there were any triggering events
around the time of onset. Events such as head trauma,
the presence of infectious diseases or inflammatory
processes, and other neurologic disorders can all be
associated with the development of headaches. Other
details that should be elicited include the location,
radiation, quality, frequency, and duration of pain. For
female patients with headaches, seeking any prior or
current association with menstruation, pregnancy, and/
or hormone therapy can be useful.
In addition, assessing the presence of photopho-
bia, phonophobia, osmophobia, nausea, vomiting, cuta-
neous allodynia, unilateral runny/stuffy nose, monocular
tearing, monocular eye redness, and unilateral eyelid
ptosis can be helpful in classifying headaches. Patients

1
Department of Neurology, Brigham and Womens Faulkner Hospital,
John R. Graham Headache Center, Jamaica Plain, Massachusetts;
2
Division of Neurology, Cambridge Health Alliance, Cambridge,
Massachusetts; 3Department of Neurology, Mayo Clinic, Rochester,
Minnesota.
Address for correspondence and reprint requests: Paul G. Mathew,
M.D., John R. Graham Headache Center, 1153 Centre Street, Suite
4970, Jamaica Plain, MA 02130 (e-mail: PMATHEW@partners.org).
Office-Based Neurology; Guest Editor, Devon I. Rubin, M.D.
Semin Neurol 2011;31:517. Copyright # 2011 by Thieme
Medical Publishers, Inc., 333 Seventh Avenue, New York, NY
10001, USA. Tel: +1(212) 584-4662.
DOI: http://dx.doi.org/10.1055/s-0031-1271313.
ISSN 0271-8235.
5
6 SEMINARS IN NEUROLOGY/VOLUME 31, NUMBER 1 2011
Table 1 Causes of Secondary Headache
Cause
Cerebrovascular diseases
Altered CSF dynamics
Intracranial space-occupying lesion
Infection
Trauma
Musculoskeletal
Medications
CSF, cerebrospinal fluid.
often deny many of these features, but the presence of
these features can be assessed by asking about typical
pain behaviors during more severe headaches. For exam-
ple, migraine patients often deny photo- or phonopho-
bia, but will admit to the preference of a dark, quiet
room.
Establishing the presence of a visual, sensory,
language, or motor aura can be useful in migraine
headache classification, but determining whether a
symptom is a true aura or secondary to another cause
can often be challenging. Common aura pretenders
include blurred vision secondary to an ophthalmologic
cause, tingling due to a peripheral nerve disorder such as
carpal tunnel, and concentration issues rather than true
aphasia due to chronic pain or sleep issues. Several
factors can help delineate true aura from symptoms
from another cause. A true aura typically occurs before
or during the early portion of the pain phase of migraine
headaches. Auras tend to have a gradual progression over
minutes, such as enlarging scotomas, or a marching
progression of numbness, weakness, and/or tingling
Table 2 Essential Elements of a Headache History
Age of onset
Frequency
Duration
Time of onset
Time to maximum intensity
Characteristics location, quality, severity
Associated symptoms and signs before, during, and after
headache
Precipitating factors
Aggravating factors
Relieving factors
Previous treatments
Review of systems
Past medical history
Family history
Social history occupation, habits, etc.
Emotional state
Examples
Carotid or vertebral artery dissension, cerebral venous sinus thrombosis,
arteriovenous malformations, subdural hematoma, giant cell arteritis
Idiopathic intracranial hypertension, hydrocephalus, spontaneous CSF leak
Neoplasm, abscess
Meningitis, encephalitis, abscess, sinusitis
Cervical spine disorders, temporomandibular joint disorders
Medication overuse headache
through an extremity. True language auras will manifest
as the inability to name objects, read, write, understand
others, and/or carry out simple conversation, rather than
vague word-finding difficulties. Accompanying family
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members or friends can help to clarify features of
language involvement. Classic visual auras consist of
flashing or scintillating lights in the periphery of the
vision, rather than just blurry vision, which is a common
complaint, but not a true aura.
Sleep is another behavior that should be scruti-
nized routinely during a headache history because poor
sleep hygiene can worsen headaches. Total hours of
sleep, sleep interruptions and awakenings, the presence
of snoring, restlessness, waking up feeling poorly rested,
and excessive daytime sleepiness are all aspects of sleep
that should be analyzed.
Triggering or worsening of headaches with posi-
tion changes, physical activity, coughing, sneezing, talk-
ing, chewing, and/or popping or clicking of the jaw are
important details, especially when considering secondary
causes of headaches. The clinician should remain vigilant
of the red flags that could suggest a secondary head-
ache rather than a primary headache disorder. These
include age of headache onset >50 years, a new, first,
or worst headache, a significant change in the charac-
teristics of prior headaches, a headache always on the
same side, increasingly worsened frequency and/or se-
verity of headache, headache not responding to treat-
ment, known systemic illnesses that predispose to
secondary headaches (e.g., cancer or human immunode-
ficiency virus [HIV]), signs of systemic illness (e.g.,
fever, weight loss), posttraumatic headache, neurologic
symptoms not consistent with typical aura (e.g., seiz-
ures), or an abnormal neurologic examination. Table 3
lists disorders that should be considered when certain
red flags are present.
Finally, a detailed history should also include past
medical history, surgical history, social history, family
history (especially of headaches), medication history, and
procedural history. Medication history is of particular
importance, and this should include the medication
dose, length of treatment, outcome, and adverse effects.
 HEADACHE/MATHEW, GARZA 7

Table 3 Headache Red Flags and Diagnostic Considerations

Sign/Symptom Possible Causes Testing to Consider

Thunderclap headache is a sudden Secondary CT in the acute setting

onset severe headache, maximum in
intensity immediately, or in less
than 60 seconds.
Primary
Subarachnoid hemorrhage MRI with gadolinium
Other intracerebral hemorrhage MRA head and neck
Carotid/vertebral dissection MRV
CNS angiopathy CSF if imaging normal
Intracranial aneurysm Pheochromocytoma evaluation
CSF leak
Pituitary apoplexy
Third ventricle colloid cyst
Ischemic stroke
Cerebral venous sinus thrombosis
Hypertensive crisis
Reversible cerebral
vasoconstrictive syndrome

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Primary orgasmic headache
Migraine
Primary thunderclap headache
During or after Secondary causes (43% had Acute setting or with
physical exertion structural lesions in one series) first occurrence:
Subarachnoid hemorrhage CT head
Intracranial neoplasm Consider CSF
Third ventricle colloid cyst MRI brain with gadolinium
Arterial dissection and MRA head/neck
Pheochromocytoma
Cardiac ischemia
Primary causes
Migraine
Primary exertional headache
Nocturnal, Secondary MRI brain with contrast
wakening from sleep Intracranial space-occupying Cervical spine X-ray or MRI
lesions Possibly overnight oximetry
Raised intracranial pressure
Idiopathic intracranial hypertension
(pseudotumor cerebri)
Medication overuse headache
(rebound headache)
Obstructive sleep apnea
Cervicogenic
Primary
Hypnic headache
Cluster headache
Migraine
Orthostatic CSF leak MRI head with gadolinium if
(worse while standing) Secondary (following lumbar spontaneous CSF leak suspected
puncture, ENT surgery, ENT or neurosurgery referral
neurosurgery, etc.)
Spontaneous (no clear cause)
With papilledema Secondary CT brain without contrast (acute setting)
Intracranial space-occupying lesions MRI and MRV brain
Cerebral venous sinus thrombosis Lumbar puncture with opening
pressure only if no intracranial
space-occupying lesions found
8 SEMINARS IN NEUROLOGY/VOLUME 31, NUMBER 1 2011

Table 3 (Continued )
Sign/Symptom Possible Causes Testing to Consider

Intracranial hemorrhage Ophthalmology exam required

During sexual activity and
increases with sexual
excitement
At orgasm, typically an
explosive or thunderclap
Primary
Idiopathic intracranial hypertension
(IIH or pseudotumor cerebri)
Tend to be young, obese women
Transient visual obscurations
Primary preorgasmic headache Less worrisome for secondary cause
when compared with orgasmic headache
Secondary causes On first onset, it is mandatory to exclude a
Subarachnoid hemorrhage subarachnoid hemorrhage and
Arterial dissection arterial dissection
CSF leak Nonacute setting: MRI brain with gadolinium
Primary orgasmic headache if other and MRA head/neck
causes ruled out

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Brief headache with coughing, Secondary causes (
50% have MRI brain with gadolinium
sneezing, straining, or Valsalva structural disease) Possibly MRA head
Posterior fossa lesions (e.g., tumor)
Arnold-Chiari malformation
CSF leak
Intracranial aneurysms
Primary cough headache
CNS, central nervous system; CSF, cerebrospinal fluid, CT, computed tomography; ENT, ear, nose, throat; MRA, magnetic resonance
angiography; MRI, magnetic resonance imaging; MRV, magnetic resonance venography.

Physical Examination and Diagnostic Testing
All patients that present with a chief complaint of
headaches should have a thorough physical examination
and neurologic examination, which should always in-
clude funduscopy to assess for papilledema or signs of
increased intracranial pressure. For headache patients,
additional examination maneuvers should be considered
as a supplement to the neurologic examination to help
identify certain etiologies. Palpation of the head and
neck can be useful in assessing for cutaneous allodynia,
temporal arteritis, and muscular tension. Examination of
the temporomandibular joint can be helpful, as pain
associated with popping and clicking of this joint can
exacerbate headaches. Percussion over the occipital
nerves (Tinel sign) may often reproduce a painful neu-
ralgic paroxysm in occipital neuralgia. In addition, as-
sessing neck stiffness on active and passive range of
motion can suggest a cervicogenic component or men-
ingismus.
Imaging studies, and the type of imaging ob-
tained, should be considered on an individual case basis.
In general, imaging studies should be pursued in new-
onset headaches, worsening headaches with changes in
character, headaches with focal neurologic signs, and
any time the patient claims to be having the worse
headache of his or her life. In patients with typical
migraine headaches, imaging is seldom needed, but
should be considered when the headache is associated
with a protracted or atypical aura, occurs after trauma,
occurs after age 50 years, fits a basilar-type or hemi-
plegic form (see ICHD-2), is associated with increasing
frequency, quality, or severity, or if a patient is in status
migrainosus. Additionally, if the patient presents with
their first or most severe migraine, imaging should
be considered. Table 3 reviews suggested neuroimaging
studies that should be performed in certain circum-
stances.
PRIMARY HEADACHE DIAGNOSIS
Once the clinician has ruled out a secondary headache,
making an accurate primary headache diagnosis is critical
because each type of primary headache disorder has
known treatment options that differ among the different
primary headaches. The International Headache Societys
International Classification of Headache Disorders 2nd
Edition (ICHD-2) is the current guideline that headache
specialists use for the accurate classification of primary
headache disorders. Since its publication in 2004, it has
undergone minor revisions and is expected to continue
to evolve through time.1 The diagnostic criteria and
classification are available online at the International
Headache Societys Web site (http://ihs-classificatio-
n.org/en). Although a detailed discussion of all primary
headache disorders is beyond the scope of this article,
here we will review the diagnosis and management of

several of the more common primary headache disorders
presenting to an outpatient neurology practice.
Migraine
Migraine is the most common primary headache
disorder for which patients present for evaluation
and treatment. In U.S. population studies, the preva-
lence of migraine is
18% in women and 6% in
men.24 Migraine is divided into migraine with and
migraine without aura. The ICHD-2 criteria for
migraine are listed in Table 4. Chronic migraine is
diagnosed when the migraine headache frequency is
greater than 15 days per month (tension-type and/or
migraine) and when 8 of those days involve headaches
that satisfy criteria for migraine and that respond to
treatment with triptans or ergots for greater than
3 months.5 Medication overuse headache (previously
called rebound headache) must be excluded when a
diagnosis of chronic migraine is considered (see
chronic daily headache section). If a patient is using
acute headache treatments more than 2 days a week on
average, the clinician should suspect medication over-
use headache.
ABORTIVE MIGRAINE TREATMENT
Nonsteroidal anti-inflammatory medications (NSAIDs),
antiemetics, triptans, and dihydroergotamine are the
mainstays of abortive treatment for migraine headaches.
Other commonly used nonspecific analgesics include
acetaminophen, aspirin, cyclooxygenase 2 inhibitors, opi-
ates, and combination analgesics that vary in content. Of
the various medications used for migraine headaches,
only triptans and dihydroergotamine are specific for
migraines.
Several different triptans are available for treat-
ment of migraines (Table 5). All oral triptans can be
effective and relatively well tolerated. As a class of
medications, the differences between oral triptans are
generally relatively small, but the effects can vary
among individual patients.6 One of the factors for
initial consideration in choosing a triptan is cost and
formulary coverage of an individuals insurance plan.
Sumatriptan is currently the only generic triptan on the
market. If sumatriptan is tolerated, but only somewhat
beneficial, it can be combined with an NSAID and/or
an antiemetic such as promethazine. In cases where
sumatriptan is ineffective, switching to a different
triptan or formulation would be reasonable. In addition
to oral formulations, triptans are available as orally
dissolving, intranasal, and injectable preparations.
These routes of administration that may be particularly
useful for these migraine patients with early and
prominent vomiting.
It is essential to warn patients that triptans often
induce transient side effects including chest or throat
HEADACHE/MATHEW, GARZA 9
Table 4 The International Classification of Headache
Disorders, 2nd Edition (IHCH-2) Migraine Diagnostic
Criteria1
Migraine without aura
A. At least five attacks fulfilling criteria BD
B. Headache attacks lasting 472 hours (untreated or
unsuccessfully treated)
C. Headache has at least two of the following characteristics:
Unilateral location
Pulsating quality
Moderate or severe pain intensity
Aggravation by or causing avoidance of routine physical
activity (e.g., walking or climbing stairs)
D. During headache at least one of the following:
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Nausea and/or vomiting
Photophobia and phonophobia
E. Not attributed to another disorder
Migraine with aura
A. At least two attacks fulfilling criteria BD
B. Aura consisting of at least one of the following,
but no motor weakness:
Fully reversible visual symptoms including positive
features (e.g., flickering lights, spots or lines) and/or
negative features (i.e., loss of vision)
Fully reversible sensory symptoms including positive
features (i.e., pins and needles) and/or negative
features (i.e., numbness)
Fully reversible dysphasic speech disturbance
C. At least two of the following:
Homonymous visual symptoms and/or unilateral sensory
symptoms
At least one aura symptom develops gradually over 5 minutes
and/or different aura symptoms occur in succession
over 5 minutes
Each symptom lasts 5 and 60 minutes
D. Headache fulfilling criteria BD for migraine without aura
begins during the aura or follows aura within 60 minutes
E. Not attributed to another disorder
tightness, flushing, a heat sensation, dizziness, nausea,
drowsiness, and tingling. Warning patients of these
transient side effects can prevent patient anxiety related
to the future triptan use and even emergency room visits
for what patients confuse to be an anaphylactic reaction.
Triptans should be avoided in patients with a history of
coronary artery disease, stroke or transient ischemic
10 SEMINARS IN NEUROLOGY/VOLUME 31, NUMBER 1 2011
Table 5 Formulations and Half-Lives of Triptan Medications6
Generic Name Brand Name
Almotriptan Axert1
Eletriptan Relpax1
Frovatriptan Frova1
Naratriptan Amerge1
Rizatriptan Maxalt1
Sumatriptan Imitrex1
Zolmitriptan Zomig1
Adapted from Ferrari MD, Goadsby PJ. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of
53 trials. Cephalalgia 2002;22(8):633658.
attacks, and peripheral vascular disease. Other relative
contraindications include uncontrolled blood pressure,
smoking, hormone replacement, pregnancy, and breast-
feeding. Concomitant use of selective norepinephrine
reuptake inhibitors (SNRIs) or selective serotonin reup-
take inhibitors (SSRIs) and triptans carry a very low risk
of serotonin syndrome, and should not prevent appro-
priate patients from receiving treatment with triptans.7
Patients, however, should be warned of the symptoms of
serotonin syndrome, and should seek medical attention
immediately if those symptoms occur. In patients that
fail to respond to over-the-counter analgesics and trip-
tans, dihydroergotamine is a reasonable next option.
Dihydroergotamine has similar contraindications to
triptans.
PREVENTATIVE MIGRAINE TREATMENT
Preventative medications should be considered in cases
where migraines occur with high frequency or signifi-
cantly interfere with the patients daily routines. Pre-
ventatives should also be considered when abortive
treatments are contraindicated, have failed, have adverse
effects, or are being overused. Preventative treatments
for migraine span several different classes, including
b-blockers (propranolol, atenolol, nadolol, metoprolol,
timolol), calcium-channel blockers (verapamil), anticon-
vulsants (topiramate, divalproex sodium, gabapentin),
and tricyclic antidepressants (amitriptyline, nortripty-
line, protriptyline) (Table 6).
There are several factors to be considered when
choosing a preventative medication. A medication
should be chosen that has proven efficacy. Propranolol,
topiramate, divalproex sodium, and amitriptyline have
proven efficacy and are considered first-line medications.
The presence of a comorbid condition, such as hyper-
tension or seizures, may lead to choosing a medication
that may treat the condition as well as the migraine
headaches. In some cases, a medication may be initiated
for the comorbid condition in a patient whose headaches
may not have necessarily warranted a preventative med-
ication, such as in a patient with infrequent headaches in
whom a b-blocker is initiated for hypertension. As a
Half-Life (Hours) Administration and Dose
34 Oral 6.25, 12.5 mg
4 Oral 20, 40 mg
26 Oral 2.5 mg
6 Oral 1, 2.5 mg
23 Oral 5, 10 mg ODT 5, 10 mg
2.5 Oral 25, 50, 100 mg Intranasal 5,
20 mg Subcutaneous 4, 6 mg
3 Oral 2.5, 5 mg ODT 2.5, 5 mg Intranasal 5 mg
general guideline, all preventative medications should be
started at low doses and titrated slowly until the mini-
mum effective dose is reached.
A reasonable goal of prophylaxis is not to elimi-
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nate headaches but to decrease their frequency and
intensity. All preventative medication trials should have
a duration of at least 3 months at a therapeutic dose
before a decision regarding efficacy can be made. It is
important to realize that adequate doses and durations of
medications may cause some level of mild improvement
in headache frequency and intensity that does not meet
the expectations of the patient and at times the provider.
A preventive medication should be considered successful
if it decreases headache frequency by 50%. Although
monotherapy is preferred, in clinical practice some pa-
tients with refractory headaches may receive additive
benefit from combinations of preventative treatments.8
Botulinum toxin type A injections may be an
effective preventative treatment for certain migraine
patients.9 This treatment is usually selected in patients
with prophylactic medication failure, medication intol-
erance, limiting comorbidities, and/or poor compli-
ance. If botulinum toxin type A is found to be
effective, the benefits of botulinum toxin can be as
short as 2 months and as long lasting as 4 months,
and repeating injections at 3-month intervals is usually
required.10 Figure 1 illustrates common injection sites
utilized for botulinum toxin type A injections for
migraine treatment. Infrequently, patients can develop
neutralizing antibodies to botulinum toxin. This risk
can be limited by minimizing the frequency of dosing to
no more than every 3 months, and using the lowest
effective dose.11,12 Based on negative trials and a recent
evidence-based review, episodic migraine does not
appear to be a good indication for botulinum toxin
type A injections.13 Recent randomized, double-blind,
parallel-group, placebo-controlled phase followed by
open-label phase trials involving over 1200 subjects
have yielded encouraging results for the use of botu-
linum toxin A in chronic migraine and suggested that
botulinum toxin A is an effective, safe, and well tol-
erated treatment for chronic migraine.14,15
 HEADACHE/MATHEW, GARZA 11

Table 6 Commonly Used Migraine Prophylactic Medications

Typical Total Adverse Effects
Initial Dose Daily Dose
Drug (mg) Range (mg) Common Serious

Amitriptyline 10 25150 Weight gain, constipation, Cardiac dysrhythmias

sedation
Nortriptyline 10 25150 Same as above Same as above
Divalproex sodium 25500 7501500 Alopecia, weight gain, Pancreatitis, liver failure,
nausea, tremor thrombocytopenia
Propranolol 4060 40240 Depression, fatigue Bradyarrhythmia
Atenolol 25 50100 Same as above Same as above
Verapamil 80160 160480 Edema, constipation Hypotension, dysrhythmias
Gabapentin 300 9002400 Edema, sedation, fatigue, dizziness
Topiramate 1525 75200 Paresthesias, fatigue, weight loss Acute angle glaucoma,
hyperthermia, metabolic acidosis,
nephrolithiasis
Reprinted from Garza I, Swanson JW. Prophylaxis of migraine. Neuropsychiatr Dis Treat 2006;3(1):281291. Copyright (2006), with permission

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from Dove Medical Press Ltd.

There is a frequent association between migraines administration of a nonsteroidal anti-inflammatory

and menstrual periods in women with migraine head-
aches. If migraines occur only during their menstrual
period, the label of pure menstrual migraine is applied.
If they tend to have increased frequency and/or intensity
of their migraines around the time of their menstrual
periods, but also have migraines outside of their men-
strual periods, the label of menstrually associated mi-
graine is applied. In either case, specific prophylactic
strategies can be applied around the time of menstrual
periods and used in addition to more continuous pre-
ventative treatment. One strategy is the use of longer-
acting triptans, such as frovatriptan or naratriptan, taken
twice a day on a standing basis starting 2 days prior to the
onset of menses, and continuing for 3 days into
menses.16,17 Another strategy for menstrual migraine is
medication, such as naproxen sodium, twice a day on a
standing basis starting 2 days prior to the onset of
menses, and continuing for 3 days into menses.18,19
Trigeminal Autonomic Cephalgias
Trigeminal autonomic cephalgia (TAC) is a category of
headaches that manifests as unilateral head pain associ-
ated with ipsilateral autonomic features. By definition,
individual attacks can only occur on one side of the head,
but infrequently sufferers can have attacks on the other
side of the head. However, TACs never present as
bilateral pain during an individual attack. Autonomic
features include lacrimation, conjunctival injection, pto-
sis, and/or rhinorrhea that are ipsilateral to the pain.20

Figure 1 Common botulinum toxin type A injection sites for chronic migraine. (From Garza I, Cutrer F. Pain relief and
persistence of dysautonomic features in a patient with hemicrania continua responsive to botulinum toxin type A. Cephalalgia
2010; 30(4):500503. Reprinted with permission from Mayo Foundation for Medical Education and Research. All rights
reserved.)
12 SEMINARS IN NEUROLOGY/VOLUME 31, NUMBER 1 2011

Table 7 Trigeminal Autonomic Cephalgias20

Hemicrania Cluster Headache Paroxysmal SUNCT/SUNA

Sex 3 M to 1 F MF 1.5 M to 1 F
Frequency (per day) 18 20 100
Length (min) 30180 230 15
Circadian/circannual Present Absent Absent
Episodic:Chronic 90:10 35:65 10:90
Nausea 50% 40% 25%
Photophobia/phonophobia 65% 65% 25%
Agitation/restlessness 90% 80% 65%
Triggers
Alcohol
Cutaneous
Treatment effects
Oxygen 70% No effect No effect
Sumatriptan, 6 mg 90% 20% <10%
Indomethacin No effect 100% No effect

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SUNCT, short-acting unilateral neuralgiform headache with conjunctival injection and tearing; SUNA, short-lasting unilateral neuralgiform
headache attacks with cranial autonomic symptoms.
Adapted from Goadsby PJ, Cittadini E, et al. Trigeminal autonomic cephalalgias: diagnostic and therapeutic developments. Curr Opin Neurol
2008;21(3):323330.

The category of TAC includes several types of head-
aches, such as cluster headache, paroxysmal hemicrania,
and short-acting unilateral neuralgiform headache with
conjunctival injection and tearing (SUNCT). The pri-
mary differences between these headaches are the dura-
tion and frequency of the attacks. Table 7 provides a
summary that compares the different TACs. Cluster
headache is the most common TAC and will be dis-
cussed in greater detail below. Paroxysmal hemicrania,
by definition, responds to indomethacin. Whether hem-
icrania continua is a TAC or not remains a matter of
debate.
Cluster Headache
Cluster headache is the most common of the TACs.
Unlike migraine, which has a female predilection, cluster
headache has an approximate 3:1 male to female ratio
although different ratios have been published in different
populations.20 Meta-analysis of recent prevalence studies
suggests a lifetime prevalence of cluster headaches of
1
in 1000.21 The criteria for cluster headache are listed in
Table 8. It is important to note that symptomatic,
secondary, or cluster-like headaches have been re-
ported in the setting of intracranial neoplasms, paranasal
sinus disease, and cerebrovascular disease. Therefore, at
the time of diagnosis of cluster headaches and other
TACs, brain magnetic resonance imaging (MRI) with
gadolinium is indicated. Clinical judgment should guide
whether additional forms of neuroimaging are needed.
Cluster headaches typically occur in series known as a
cluster period, which can last for weeks to months.
During a cluster period, headache frequency is highly
variable occurring once every other day to as frequently
as eight headache attacks a day. After a cluster period,
there can be months to years of remission before the next
attack in the episodic form of the disorder.1 Cluster
periods often follow patterns linked to seasonal varia-
tion, and individual headache attacks tend to follow
temporal regularity, suggesting hypothalamic regula-
tion.22 Chronic cluster is defined as recurring attacks
for greater than one year without remission or remission
periods less than 1 month. Among cluster sufferers, 10 to
15% suffer from chronic cluster headaches.1
ABORTIVE CLUSTER HEADACHE TREATMENT
Subcutaneous sumatriptan and concentrated oxygen
are the abortive treatment options of choice for cluster
Table 8 The International Classification of Headache
Disorders, 2nd Edition (IHCH-2) Cluster Headache
Diagnostic Criteria1
A. At least five attacks fulfilling criteria BD
B. Severe or very severe unilateral orbital, supraorbital and/or
temporal pain lasting 15180 minutes if untreated
C. Headache is accompanied by at least one of the following:
Ipsilateral conjunctival injection and/or lacrimation
Ipsilateral nasal congestion and/or rhinorrhea
Ipsilateral eyelid edema
Ipsilateral forehead and facial sweating
Ipsilateral miosis and/or ptosis
A sense of restlessness or agitation
D. Attacks have a frequency from one every other day to
eight per day
E. Not attributed to another disorder

headache. Intranasal sumatriptan, as well as oral and
intranasal zolmitriptan have also demonstrated efficacy
in aborting cluster attacks.2326 Pure (100%) oxygen
should be administered by a non-rebreathing mask at a
rate of at least 7 L/min for 15 minutes.27 For patients
that fail to respond to these treatments, dihydroergot-
amine (DHE) may be an effective alternative.28 DHE
is available in intranasal and intramuscular prepara-
tions, as well as intravenous formulations.
PREVENTATIVE CLUSTER HEADACHE TREATMENT
Two major categories of preventative treatments are
used for cluster headaches transitional preventives
and maintenance preventives. Transitional preventives
are medications that are used for days to weeks with the
primary goal of stopping a cluster period and inducing
remission. Maintenance preventatives are used contin-
uously to maintain remission. Steroid tapers and occi-
pital nerve blocks are transitional preventative
treatments that can be employed to treat cluster peri-
ods. Steroid tapers have proven to be the most effective
in helping terminate cluster periods, but are limited by
relapses and side effects. There is no standardized
corticosteroid treatment strategy, and the type of cor-
ticosteroid and taper schedule vary among headache
specialists. Oral prednisone tapers can be started at
doses of 80 mg and tapered over 18 to 21 days.
Alternatively, studies have demonstrated the efficacy
of dexamethasone at 4 mg twice a day for one week,
followed by 4 mg daily for one week.29 Occipital nerve
blocks may be effective in treating cluster periods in
some patients, but the parameters of the blocks vary
between studies. The total volume of the block can
range anywhere from 0.5 to 10 mL. Blocks are typically
composed of varying strengths and combinations of
lidocaine, bupivacaine, and/or prilocaine with or with-
out a steroid component. The steroids utilized in the
blocks may include methylprednisolone, triamcinolone,
and dexamethasone.30
Maintenance preventative treatments for cluster
headache include verapamil, lithium, divalproex so-
dium, and topiramate among others less frequently
used. Verapamil is the first-line treatment for cluster
headaches in terms of efficacy and side effect profile. It
is typically started at doses of 80 to 240 mg daily (with
240 mg total dose per day being a usual goal starting
dose), and titrated up by 80 mg per week if needed.
Occasionally, doses as high as 960 mg daily are re-
quired. The titration should be slow because many
patients may find benefit at lower doses. Routine
electrocardiograms (ECGs) should be checked while
titrating the medication to monitor for atrioventricular
block and symptomatic bradycardia, especially when
doses of verapamil exceed 240 mg/day.31
Lithium is an effective treatment for chronic
cluster headaches, but is limited by its side effect profile
HEADACHE/MATHEW, GARZA 13
and need for monitoring blood levels. Lithium does not
appear to be as effective for episodic cluster as it is for
the chronic form. Lithium is typically dosed at 600 to
1200 mg daily with a target serum concentration of 0.4
to 0.8 mEq/L. Side effects include weakness, nausea,
thirst, tremor, slurred speech, and blurred vision.
Lithium toxicity may manifest as nausea, vomiting,
anorexia, diarrhea, confusion, nystagmus, ataxia, ex-
trapyramidal signs, and seizures. Lithium can also
affect thyroid and kidney function, and therefore base-
line function testing is necessary prior to initiation of
the medication. Lithium drug levels, creatinine, so-
dium, TSH, and ECG should be performed periodi-
cally while on lithium.29
In patients refractory to a single medication,
combinations of preventative medications are often
required, usually administering verapamil with other
agents (topiramate, lithium, divalproex sodium, etc.).
Downloaded by: World Health Organization ( WHO). Copyrighted material.
Although botulinum toxin has not demonstrated the
same efficacy as is seen with chronic migraine, there
have been some limited cases that suggest its potential
benefit.32,33
In patients that fail to respond adequately to oral
medications for long-term prophylaxis, surgical inter-
ventions can be considered. Surgical interventions for
cluster headache have historically been performed on the
ipsilateral side of the headache. Although some of these
destructive procedures have demonstrated efficacy in
some refractory cases, they do not always consistently
provide relief of symptoms. In addition, they can involve
serious side effects including corneal anesthesia, anes-
thesia dolorosa, and jaw deviation. In responsive cases,
surgical treatment may relieve symptoms ipsilateral to
the surgery, but cluster attacks may start to occur on the
nonsurgical side.34,35
More recently, as an alternative to these destruc-
tive procedures in patients with medically refractory
cluster headache, neurostimulation has been utilized.
Neurostimulation involves central targets such as the
posterior hypothalamus with deep brain stimulation
(DBS), or peripheral targets, such as in occipital nerve
stimulation (ONS). Although DBS has demonstrated
efficacy with about two-thirds of patients having com-
plete remission of pain in large studies, it is an invasive
procedure that carries a small risk of fatal cerebral
hemorrhage.36 Occipital nerve stimulation trials have
not demonstrated as high of a responder rate as DBS,
but ONS is much less invasive. Complications associ-
ated with ONS included battery depletion, lead migra-
tion, muscle recruitment, neck stiffness, skin
discomfort, superficial infections, occipital paresthesias,
and painful overstimulation.37 Some patients have good
control of their pain with ONS, but continue to have
cranial autonomic features, which can be bothersome.38
As with surgery, neurostimulation is typically a unilat-
eral procedure (although some groups advocate for
14 SEMINARS IN NEUROLOGY/VOLUME 31, NUMBER 1 2011
bilateral stimulation in some cases), and therefore
cluster sufferers that have had unilateral ONS or
DBS run the risk of their symptoms occurring on the
contralateral side. Since neurostimulation has been
available for medically refractory cluster headache, it
has been a favored intervention over trigeminal destruc-
tive procedures. Surgery for medically refractory cluster
headache should be performed at a center with expertise
in these procedures.
Tension-Type Headache
Tension-type headache (TTH) is the most common
primary headache disorder with a lifetime prevalence
of 88% in women and 68% in men.39 The criteria for
TTH are listed in Table 9. In general, the headache is
described as a dull pressure pain that often is in a cap or
bandlike distribution around the head. Tension-type
headache is generally less painful and debilitating than
other primary and secondary headache disorders, and
thus sufferers are less likely to present to a physician for
evaluation.40 Tension-type headache can be divided into
three categories based on frequency: (1) episodic infre-
quent TTH, which involves an average of fewer than one
headache day per month for no greater than 10 head-
aches per year; (2) episodic frequent TTH, which
involves 1 to 14 headache days per month; and (3)
chronic TTH, which involves greater than 15 headache
days per month. Progression from episodic to chronic
TTH is usually a gradual process that occurs over years,
and increasing frequency tends to be associated with
increasing intensity of the headache.41,42 Pericranial
tenderness with palpation is a feature that can be seen
in patients with TTH, and this tenderness seems to be
worse during a headache. In addition, the presence of
pericranial tenderness tends to correlate with high fre-
quency and intensity of TTH.4345
Table 9 The International Classification of Headache
Disorders, 2nd Edition (IHCH-2) Tension Type Headache
Diagnostic Criteria1
A. At least 10 episodes occurring on <1 day per month on
average (<12 days per year) and fulfilling criteria BD
B. Headache lasting from 30 minutes to 7 days
C. Headache has at least two of the following characteristics:
Bilateral location
Pressing/tightening (non-pulsating) quality
Mild or moderate intensity
Not aggravated by routine physical activity such as walking
or climbing stairs
D. Both of the following:
No nausea or vomiting (anorexia may occur)
No more than one of photophobia or phonophobia
E. Not attributed to another disorder
ABORTIVE TENSION-TYPE HEADACHE TREATMENT
Aspirin, acetaminophen, and NSAIDs have all demon-
strated efficacy as abortive treatments for TTH in
clinical trials.4649 Triptans in general have not been
found to be effective for the abortive treatment of pure
TTH.50
PREVENTATIVE TENSION-TYPE HEADACHE TREATMENT
Because TTH tends to be a low-intensity headache, high
frequency or high levels of disability are two reasons to
consider prophylactic treatment. The mainstays of pre-
ventative treatment for TTH are tricyclic antidepres-
sants. Among the tricyclic antidepressants, amitriptyline
has the most clinical data to support its efficacy in
TTH.40,51,52 For patients that benefit from amitripty-
line, but cannot tolerate side effects, nortriptyline or
protriptyline may be reasonable alternatives with better
side effect profiles. Other options with proven efficacy in
Downloaded by: World Health Organization ( WHO). Copyrighted material.
TTH include topiramate, divalproex sodium, mirtaza-
pine, and tizanidine.5255 Tricyclic antidepressants are
considered to be superior to selective serotonin reuptake
inhibitors and selective norepinephrine reuptake inhib-
itors for the prevention of TTH.56 The use of botulinum
toxin injections for chronic TTH has not been well
supported in double-blind clinical trials.57,58 Some stud-
ies suggest that in TTH involving myofascial trigger
points, injecting directly into the trigger points may
provide efficacy that was not appreciated in earlier
studies.59
Chronic Daily Headache
Chronic daily headache (CDH) is a term that encom-
passes a heterogenous group of headache disorders. It is
estimated that
4 to 5% of the population suffers from
CDH. Chronic migraine, chronic tension-type head-
ache, hemicrania continua, and new daily persistent
headache are four primary headaches of long duration
(>4 hours) that fit under this broad category. Other
primary headache disorders of shorter duration (cluster
headache, hypnic headache, etc.), however, may also
present as CDH. Chronic migraine and chronic ten-
sion-type headache compose the largest subsets of
CDH.60 The criteria for hemicrania continua and
new daily persistent headache are listed in Tables 10
and 11.
When considering chronic headache syndromes
such as CDH, medication overuse can worsen the
frequency and intensity of headaches. Previous names
given to medication overuse headaches include rebound
headache, drug-induced headache, and medication-mis-
use headache. The criteria for medication overuse head-
aches are listed in Table 12. According to ICHD criteria,
medication overuse headache is considered to be a
secondary headache disorder, and occurs in the setting
of a preceding primary headache disorder. It is estimated

Table 10 The International Classification of Headache
Disorders, 2nd Edition (IHCH-2) Hemicrania Continua
Diagnostic Criteria1
A. Headache for >3 months fulfilling criteria BD
B. All of the following characteristics:
Unilateral pain without side-shift
Daily and continuous, without pain-free periods
Moderate intensity, but with exacerbations of severe pain
C. At least one of the following autonomic features occurs
during exacerbations and ipsilateral to the side of pain:
Conjunctival injection and/or lacrimation
Nasal congestion and/or rhinorrhea
Ptosis and/or miosis
D. Complete response to therapeutic doses of indomethacin
E. Not attributed to another disorder1
Table 11 The International Classification of Headache
Disorders, 2nd Edition (IHCH-2) New Daily Persistent
Headache Diagnostic Criteria1
A. Headache that within 3 days of onset fulfills criteria BD
B. Headache is present daily, and is unremitting for >3 months
C. At least two of the following pain characteristics:
Bilateral location
Pressing/tightening (nonpulsating) quality
Mild or moderate intensity
Not aggravated by routine physical activity such as walking
or climbing
D. Both of the following
No more than one of photophobia, phonophobia or mild nausea
Neither moderate or severe nausea nor vomiting
E. Not attributed to another disorder2
that medication overuse headache has a prevalence of 1
to 1.4% in the general population, and women in their
50s have the highest subset prevalence of 5%.61
In the setting of medication overuse, both abor-
tive and preventative treatments tend to be less effective.
Table 12 Medication Overuse Headache Diagnostic
Criteria5
A. Headache present on 15 days/month fulfilling criteria
B and C
B. Regular overuse for 3 months of one or more acute/
symptomatic treatment drugs as defined under sub
forms of 8.2
Ergotamine, triptans, opioids, or combination analgesic
medications on 10 days/month on a regular basis
for >3 months
Simple analgesics or any combination of ergotamine,
triptans, analgesics, opioids on 15 days/month on a
regular basis for >3 months without overuse of any
single class alone
C. Headache has developed or markedly worsened
during medication overuse
HEADACHE/MATHEW, GARZA 15
In one study, opiates usage of at least 8 days per month
and barbiturates usage of at least 5 days per month for
migraines were both associated with progression of
migraines into medication overuse headaches. For this
reason, opiates and barbiturates should be avoided as
much as possible as abortive treatments of primary
headache disorders, or the frequency of administration
should not exceed these limits. To a lesser extent,
triptans can cause some progression of headaches in
those with high frequency of headaches at baseline;
therefore, triptan use should be limited to not more
than 9 days per month.62 Given their high risk for
medication overuse headache, combination analgesics
should also be limited to not more than 8 or 9 days a
month.
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CONCLUSION
The management of headaches can be a complex and
challenging task for the office based neurologist. It
cannot be stressed enough that only through a thorough
evaluation, and the establishment of the correct primary
or secondary headache diagnosis can therapeutic efficacy
be achieved. This article provides a basic foundation in
the essential elements of office based headache manage-
ment, and hopefully serves as a means to the advance-
ment of headache care in the setting of a highly
underserved subspecialty.
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