Headache
Steven J. Scrivani, Steven B. Graff-Radford,
Shehryar N. Khawaja, and Egilius L. H. Spierings
Abstract
Headache is defined as a pain in the region
above the orbitomeatal line. Headache
disorders are common and considered a major
health problem that affects a large percentage
of the population worldwide. The International
Headache Society (IHS) has an updated
classification of headache referred to as
the International Classification of Headache
Disorders III (ICHD-III). This classification
divides headache into primary and secondary
headache and, additionally, categorizes painful
cranial neuralgias and other facial pain
S.J. Scrivani (*)
Chief, Division of Oral and Maxillofacial Pain,
Department of Oral and Maxillofacial Surgery,
Massachusetts General Hospital, Boston, MA, USA
e-mail: sscrivani1@partners.org
S.B. Graff-Radford
Director, Division of Headache and Orofacial Pain, Pain
Center, Cedar Sinai Medical Center, Los Angeles, CA,
USA
e-mail: steven.graff-radford@cshs.org
S.N. Khawaja
Resident, Orofacial Pain Program, Department of Oral and
Maxillofacial Surgery, Massachusetts General Hospital,
Boston, MA, USA
e-mail: khawajashehryar@gmail.com
E.L.H. Spierings
Professor, Craniofacial Pain Center, Tufts University
School of Dental Medicine, Headache and Facial Pain
Program, Department of Neurology, Tufts Medical Center
and Tufts School of Medicine, Boston, MA, USA
e-mail: spierings@medvadis.com
# Springer International Publishing AG 2017
C.S. Farah et al. (eds.), Contemporary Oral Medicine,
DOI 10.1007/978-3-319-28100-1_33-2
conditions. This chapter discusses the epidemi-
ology, clinical presentation, and management
of the most common primary headache disor-
ders (migraine headache, tension-type head-
aches, and trigeminal autonomic cephalgias)
and important secondary headache disorders
(headaches attributed to ischemic stroke or
transient ischemic attack, trauma or injury to
head and neck region, nontraumatic intracra-
nial hemorrhage, giant cell arteritis, increase or
decrease in cerebrospinal fluid, and intracranial
neoplasia). In addition, it reviews the associa-
tion between headache and temporomandibu-
lar disorders.
Keywords
Primary headache disorders • Migraine • Ten-
sion-type headaches • Trigeminal autonomic
cephalgias • Secondary headache disorders •
Cluster headache • Hemicrania continua • Par-
oxysmal hemicrania • Short-lasting unilateral
neuralgiform headache attacks
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Epidemiology and Classification of Headache
Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Evaluation of Headache . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Physical Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Diagnostic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1
2 S.J. Scrivani et al.

Diagnosis and Treatment of Primary Headache listed. Secondary headache is due to a specific
Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 and identifiable underlying pathology (Table 3).
Migraine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Tension Type Headache . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Trigeminal Autonomic Cephalgia . . . . . . . . . . . . . . . . . . . . 13
Epidemiology and Classification
Diagnosis and Treatment of Important Secondary
Headache Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 of Headache Disorders
Headache Attributed to Ischemic Stroke or Transient
Ischemic Attack . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 The lifetime prevalence of headache (irrespective
Headache Attributed to Trauma or Injury to the of type) has been reported to be 93% in men and
Head and/or Neck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Headache Attributed to NonTraumatic Intracranial 99% in women. The point prevalence of headache
Hemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 is 11% in men and 22% in women. Tension-type
Headache Attributed to Giant Cell Arteritis . . . . . . . . . . 21 headache (TTH) and migraine are the most com-
Headache Attributed to Increased Cerebrospinal mon types of headache affecting the population
Fluid Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Headache Attributed to Low Cerebrospinal Fluid (Rasmussen et al. 1991, Rasmussen et al. 1991;
Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Lipton et al. 2007). TTH is more prevalent than
Headache Attributed to Intracranial Neoplasia . . . . . . . 23 migraine and its lifetime prevalence is 85%. In a
Headaches Attributed to Cervicogenic Disorders . . . . 23 cross-sectional population study of 740 adult sub-
Headaches Associated with Disorders of Nose
and Paranasal Sinuses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 jects, 74% had experienced TTH within the pre-
Medication Overuse Headache . . . . . . . . . . . . . . . . . . . . . . . 24 vious year and 31% had experienced TTH for
Temporomandibular Disorders and Headache . . . . . . . . 24 more than 14 days. In another study, the 1-year
Conclusion and Future Directions . . . . . . . . . . . . . . . . . . 26 prevalence rate of TTH was 63% in males and
86% in females. The onset is usually between
Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
20 and 40 years of age with peak prevalence in
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 the fifth decade of life. However, up to 25% of
school children report TTH and in the mature
population (60 years), the prevalence is 20% to
Introduction 30%. There is evidence that chronic TTH
(15 days of headaches, for at least 3 months)
Headache is defined as a pain in the region above has a genetic predisposition. It is estimated that
the orbitomeatal line. Headache disorders are com- first-degree relatives of chronic TTH patients are
mon and considered a major health problem that three times more likely to suffer from headache in
affects a large percentage of the population world- comparison to the general population (Rasmussen
wide (Rasmussen et al. 1991; Lipton et al. 2007). It et al. 1991, Rasmussen et al. 1991).
may affect the individual’s daily activities, psycho- The American Migraine Study found the over-
social functioning, and quality of life. Headache is all 1-year prevalence of migraine in the United
one of the leading causes of absence from work and States to be 17% to 18% for women and 6% for
accounts for millions of workdays lost each year men, increasing with age among both genders,
(La Jolla Donald 2001; Bigal et al. 2006). reaching a maximum at ages 35 to 45 years and
The International Headache Society (IHS) has declining thereafter (Lipton et al. 2007). Aura
an updated classification of headache referred to symptoms may be experienced by 20% to 36%
as the International Classification of Headache of adult migraine patients (Bigal et al. 2006;
Disorders III (ICHD-III). This classification Lipton et al. 2007). Before puberty, migraine is
divides headache into primary and secondary slightly more common in boys, with the highest
headache and, additionally, categorizes painful prevalence between 6 and 10 years of age. In girls,
cranial neuralgias and other facial pain (Society the peak prevalence is between 14 and 19 years of
2013). (Tables 1, 2, 3, and 4). age. Migraine prevalence is inversely related to
Each of the categories is further subdivided income, with low-income groups having the
and provides specific criteria for the diagnoses highest prevalence. Race and geographic region
Headache
Table 1 The International Headache Society Classifica-
tion of Headache Disorders (ICHD) III-Beta
• Part one: the primary headaches (1–4)
• Part two: the secondary headaches (5–12)
• Part three: painful cranial neuropathies, other facial
pains and other headaches (13–14)
• Appendix
Table 2 The ICHD-III classification of primary headache
disorders
1. Migraine
a. Migraine without aura
b. Migraine with aura
c. Chronic migraine
d. Complications of migraine
e. Probable migraine
f. Episodic syndromes that may be associated with
migraine
2. Tension type headaches
a. Infrequent episodic tension type headache
b. Frequent episodic tension type headache
c. Chronic tension type headache
d. Probable tension type headache
3. Trigeminal autonomic cephalgias
a. Cluster headache
b. Paroxysmal hemicrania
c. Short-lasting unilateral neuralgiform headache
attacks
d. Hemicrania continua
e. Probable trigeminal autonomic cephalgias
4. Other primary headache disorders
a. Primary cough headache
b. Primary exercise headache
c. Primary headache associated with sexual activity
d. Primary thunderclap headache
e. Cold-stimulus headache
f. External-pressure headache
g. Primary stabbing headache
h. Nummular headache
i. Hypnic headache
j. New daily persistent headache
are also determining factors. The prevalence of
migraines is highest in North America and
Western Europe and among those of European
descent. Migraine with aura has a stronger genetic
background than migraine without aura. The
American Migraine Study estimates that
23 million US residents have severe headaches.
3
Table 3 The ICHD-III classification of secondary head-
ache disorders
5. Attributed to trauma or injury to the head and/or neck
6. Attributed to cranial or cervical vascular disorder
7. Attributed to nonvascular intracranial disorder
8. Attributed to a substance or its withdrawal
9. Attributed to infection
10. Attributed to disorder of homeostasis
11. HA or facial pain attributed to disorder of cranium,
neck, eyes, ears, nose, sinuses, teeth, mouth, or other
facial or cranial structures
12. Attributed to psychiatric disorder
Table 4 The ICHD-III classification of painful cranial
neuropathies, other facial pains and other headaches
13. Painful cranial neuropathies and other facial pains
14. Other headache disorders
Twenty-five percent of women experience four or
more severe attacks per month, 35% experience one
to three severe attacks per month, and 40% experi-
ence one or less than one per month. The study also
found that more than 85% of women and more than
82% of men with severe migraine have some
migraine-related disability (La Jolla Donald 2001;
Bigal et al. 2006; Lipton et al. 2007).
Trigeminal autonomic cephalgias (TACs) are
relatively rare primary headache disorders.
Prevalence estimates are 1%. Cluster headache
is proposed to have a prevalence between 0.09%
and 0.32% (Sjaastad and Bakketeig 2003). This
particular disorder primarily affects men, with
a male to female ratio of approximately 4:1. In a
population-based sample in Germany, the 1-year
prevalence of cluster headache was estimated to
be 119/100,000. The mean age of onset of cluster
headache is approximately 27 to 31 years of age
which is nearly 10 years later than that of
migraine. Approximately 73% of cluster head-
ache patients are smokers or former smokers and
half note that alcohol can trigger an attack during
a cluster period. There is strong evidence for a
genetic background in cluster headaches, as well.
First-degree relatives of cluster headache patients
are up to 39 times more likely to experience
cluster headaches than the general population,
whereas second-degree relatives are only 8 times
4 S.J. Scrivani et al.
more likely (Manzoni 1999a, b; Ekbom and
Hardebo 2002; Sjaastad and Bakketeig 2003).
Paroxysmal hemicrania (PH) is a rare disorder
and has an estimated prevalence of 0.021% to
0.07%. The female to male ratio is estimated
to be approximately 1.6:1. There is no evidence
for a genetic background on the prevalence of PH.
The average age of onset is usually between
34 and 41 years, with an average duration of
illness of 13 years (Boes and Swanson 2006).
Similar to PH, hemicrania continua (HC) is a
rare headache disorder. Little is known regarding
its true prevalence. Only few hundred cases of HC
have been reported in literature. However, recent
studies indicate that it may be more common than
previously estimated (Peres et al. 2001). HC is
more common in women than in men. The female
to male ratio is estimated to be approximately
2.8:1. There is no evidence of genetics in the
onset or prevalence of the condition. The average
age of onset is similar to that of PH.
Short-lasting unilateral neuralgiform headache
is another rare form of TAC. Epidemiological
investigation suggests an estimated prevalence
and annual incidence of 6.6 and 1.2 per 100,000
(Williams and Broadley 2008). The preponder-
ance of these headaches is more common in men
than in women. The male to female ratio is
approximately 7:1 (Boes and Swanson 2006).
Evaluation of Headache
History
Headache disorders have unique and distinctive
features that typically characterize them. Hence,
in order to accurately diagnose the headache dis-
orders, a careful and thorough analysis of the
headache history is required with special empha-
sis on the description; associated neurological,
gastrointestinal, and systemic symptoms are also
required (Table 5).
It is important to note the location of the
headache and whether it is unilateral or bilateral.
The site where the headache begins and any
radiating pattern of the pain may be important,
along with the timing and duration of the
headache. Additionally, the quality (pressure,
squeezing, throbbing, stabbing) and intensity
(mild, moderate, severe) of the headache should
be documented. Note should also be made of
photophobia, phonophobia, osmophobia, and
any associated autonomic phenomenon (sweat-
ing, redness, swelling, eyelid ptosis, periorbital
edema, conjunctival injection, excessive tearing,
congestion or runny nose, fullness in the ears).
Other important qualities may include restlessness
or a feeling of fatigue and wanting to lie down in a
dark, quiet room, as well as nausea or vomiting.
Some headache disorders are associated with an
aura (a transient neurological event), which may be
visual, sensory, or motor. The more common are
visual auras in the form of visual abnormalities such
as photopsia, fortification spectrum, and scotomas
(Fig. 1). There also may be specific predromal and
postdromal symptoms that may be specific for a
headache type. Additionally, one should inquire
about any triggers (food and drink related, weather
changes, sleep pattern, dietary habits, hydration
status) as well as modifying factors (physical activ-
ity, positional changes, jaw function).
Especially, note any history of trauma to
the head or neck. Identify current and past medica-
tions, relevant family history, and the use of over-
the-counter medications, supplements, and alterna-
tive or complementary therapies. A comprehensive
psychosocial history is imperative for all patients
with headache disorders. Establish the details of any
pending or planned disability claims or litigation.
Note should be made of any unusual or
atypical signs and symptoms (i.e., red flags).
Intracranial and extracranial pathology may cause
headache. The American Headache Society’s mne-
monic tool, “SNOOP” for secondary headache
(Table 6) (Dodick 2003), outlines aspects of a
patient’s symptoms and signs that suggest the
presence of a life-threatening disorder (Table 3).
Physical Examination
The purpose of the physical examination is to
discover any possible cause of the headache.
Therefore, it is important to proceed systemati-
cally. The physical examination should include a
Table 5 History and clinical features of primary headache disorders
Short lasting
Migraine Migraine unilateral
Headache

headache without headache with Tension type Paroxysmal neuralgi form

Parameter aura aura headache Cluster headache hemicrania Hemicrania continua headache attack
Age of onset (yrs) 20–40 20–40 20–40 27–31 34–41 30–40 40–50
Gender ratio (M:F) 1:3 1:3 ? 4:1 1: 1.6 1:2.8 7:1
Clinical features
Pain location Fronto-temporal, Fronto-temporal, Fronto – Temporal, periorbital, Temporal, Fronto – temporal, Temporal,
orbital, and orbital, and temporal, maxillary periorbital, maxillary parietal, occipital periorbital
occipital region occipital region holocephalic
Laterality Unilaterala Unilaterala Bilateral Unilateral Unilateral Unilateral Unilateral
Pain quality Throbbing Throbbing Dull/Aching Boring / sharp / Stabbing / throbbing Pressure / dullness / Sharp / electric /
stabbing / throbbing / boring throbbing stabbing
Pain intensity Moderate – Moderate – Mild – Severe Moderate – severe Moderate Severe
severe severe moderate
Pain duration 4–72 h 4–72 h 30 min to 15 min–180 minc 2 min–30 mind Continuous 1–600 se
days
Additional features • Photophobia • Photophobia • Mild nausea • Ptosis/miosis • Ptosis/miosis • Ptosis/miosis • Ptosis/miosis
• Phonophobia • Phonophobia • Periorbital edema • Periorbital edema • Periorbital edema • Periorbital edema
• Osmophobia • Osmophobia • Facial or forehead • Facial or forehead • Facial or forehead • Facial or forehead
• Nausea • Nausea sweating sweating sweating sweating
• Vomiting • Vomiting • Facial or forehead • Facial or forehead • Facial or forehead • Facial or forehead
• Worsened by • Worsened by redness redness redness redness
exercise exercise • Conjunctival • Conjunctival • Conjunctival • Conjunctival
• Pre-headache injection or tearing injection or tearing injection or tearing injection or
aura symptoms b • Nasal congestion or • Nasal congestion or • Nasal congestion or tearing
rhinorrhea rhinorrhea rhinorrhea • Nasal congestion
• Ear fullness • Ear fullness • Ear fullness or rhinorrhea
• Pacing the floor or • Pacing the floor or • Ear fullness
agitation agitation
• Photophobia • Photophobia
• Phonophobia • Phonophobia
a
Headaches may take place bilaterally as well
b
Visual, sensory, and speech abnormality
c
Once every other day to maximum of 8 attacks per day
d
At least 5 attacks per day more than half of the time
e
5

Single stabs, series of stabs, or in a saw-tooth pattern, at least one headache per day for more than half of the time
6 S.J. Scrivani et al.
Fig. 1 Typical presentation
of visual aura symptoms
associated with the
migraine with aura.
Figure illustrates
scintillating scotoma
(a partial loss of vision or a
blind spot in an otherwise
normal visual field with
crescent of shimmering
zigzags), and digitolingual
paresthesias (abnormal
sensory sensation)
Table 6 SNOOP: Acronym for signs and symptoms of
concern
Systemic symptoms or disease
Fever, weight loss, HIV, systemic cancer
Neurologic signs or symptoms
Confusion, clumsiness, weakness, aphasia, visual
problems
Onset sudden
Thunderclap, progressive, positional
Onset after age 40 years
Vascular (temporal arteritis), tumor, infection
Pattern change
Any new or changed headache pattern or quality or
increase in frequency or intensity
head to toe assessment of the major organ sys-
tems, including a comprehensive neurological
examination, with specific attention to the cranial
nerves, and a complete head and neck examina-
tion. All four principles of physical examination
should be included: inspection, palpation, percus-
sion, and auscultation. The physical examination
should start with taking of the vital signs. This pro-
vides indication of the physiological state of the
patient. Some form of numerical pain rating scale
should be used to register the intensity of the head-
ache present. This indicates the severity of pain and
later aids in the evaluation of management strate-
gies, progression of pain, and outcomes assessment.
The clinician should note facial expression,
general demeanor, dress, posture, gait, and
speech of the patient and assess the mood, cog-
nitive, and physical state. This aids in determin-
ing any neurological signs or symptoms that
might be accompanied with the headache. In
addition, presence of abnormal signs may indi-
cate an underlying organic disorder, warranting
urgent care. Note should also be made of
whether the patient is currently experiencing a
headache during the office visit and the physical
examination.
Examine the head, face, and neck for hyperes-
thesia or allodynia. Inspect the head, face, and
neck for any asymmetry, swelling, redness, dis-
coloration, or skin lesion(s). Presence of such
signs may be suggestive of an underlying pathol-
ogy and necessitate further evaluation. Palpate the
head, occiput, posterior neck, shoulders, and
upper back, as well as the lateral and anterior
neck for muscle tenderness, tender or trigger
points, joint tenderness, or any areas of tactile-
provoked, sharp, shock-like pain. Assess the mas-
ticatory muscles (temporalis, masseter, medial
pterygoid, inferior and superior lateral pterygoid)
and temporalis tendon insertion extraorally and
intraorally for tenderness, pain, and trigger points.
Examine the mandibular range of motion and
assess for any pain or dysfunction associated
Headache 7

with mandibular motion. Examine the temporo-

mandibular joints for swelling or tenderness as
well as for audible noises with jaw movements
(clicking, cracking, popping, or crepitation).
Examine the oral cavity for any evidence of
gross dental decay, gingival inflammation, swell-
ing, and painful and/or mobile teeth. Examine the
oral mucous membranes for lesions and areas of
swelling or discoloration. Examine the floor of the
mouth and palpate and the submandibular glands
for tenderness and masses. Examine the tongue
for lesions, masses, and areas of discoloration.
Examine the hard and soft palate as well as the
posterior and lateral oropharynx. Examine the
parotid glands for enlargements, masses, or areas
of tenderness. Presence of any lesions, masses, or
areas of discoloration in the oral cavity may indi- Fig. 2 Fundal examination of eye demonstrating blurred
cate presence of an underlying disorder, particu- disk margins (arrows). This is indicative of papilledema
larly autoimmune disorders or malignancy. Also
make note of the pattern of the filiform and inflammatory disorders, demyelinating disorders,
fungiform papillae on the tongue. Similarly, alter- or disorders of intracranial pressure.
ation in the distribution of tongue papillae may Perform a comprehensive examination of
indicate presence of a localized oral mucous mem- cranial nerve function, with particular attention
brane disease or a systemic condition. to the trigeminal system. Test for sensory abnor-
Examine the anterior and lateral neck for malities to light touch, sharp touch (pin-prick),
palpable lymphadenopathy or other swellings or pressure, temperature (hot and cold), contact
masses. Palpate the carotid arteries and examine detection (Von Frey filaments), direction sense,
the pulsations as well as auscultate for bruits. and 2-point discrimination. Make note of hyper-
Inspect and palpate the superficial temporal arter- esthesia or allodynia to any of these sensory
ies for nodules, pulsations, or areas of tenderness. modalities. Also, test for motor function strength
Inspect and palpate the thyroid gland for any of the masticatory complex. Look for any alter-
masses, nodules, or areas of tenderness. ation in speech pattern, swallowing, or tongue
Examine the eyes for external structural swell- movements. Examine head and neck movements
ings, lesions, or discolorations. Also, examine the for range of motion and strength. In addition,
eyes for upper lid ptosis, conjunctival injection, perform a thorough sensory and motor examina-
and excessive tearing. Such features are common tion of the rest of the body. Test for coordination
in patients with trigeminal autonomic cephalgias. and balance as well to rule out any underlying
However, they may present secondary to intracra- pathology.
nial pathology as well. Perform an examination of
the full range of motion of the globes looking for
any alteration in extraocular muscle function. Diagnostic Studies
Examine the pupils for size and shape and perform
pupillary light reflexes, examining for direct Contingent upon findings on history and physical
and consensual light reflexes. Additionally, test examination, the clinician should consider addi-
for visual acuity. Lastly, perform a funduscopic tional diagnostic studies. These may include
examination, looking, in particular, for papilledema imaging studies, blood studies, lumbar puncture,
of the optic disc (Fig. 2). This is important to rule out diagnostic injections, electrocardiogram (ECG),
any secondary causes of headaches, particularly electroencephalogram (EEG), polysomnography
8 S.J. Scrivani et al.
(PSG), or electromyography (EMG). The more
common diagnostic studies to perform would
be either computerized tomography (CT) or
magnetic resonance imaging (MRI) of the head.
In addition, MR angiogram (MRA) and MR
venogram (MRV) may be needed. A number of
blood studies may be helpful, including blood
tests such as erythrocyte sedimentation rate
(ESR) to rule giant cell arteritis, lumbar puncture
to rule out pressure induced or infection headache,
complete blood count/full blood count (CBC/FBC)
to rule out anemia and serious blood dyscrasias,
thyroid screen (FT3, FT4, TSH) to rule out thyroid
disease, and a Lyme titer.
Diagnosis and Treatment of Primary
Headache Disorders
The primary headache disorders are:
1. Migraine
2. Tension-type headache
3. Trigeminal autonomic cephalgias
4. Other primary headache disorders
Migraine
Clinical Presentation, Pathophysiology,
and Diagnosis
Migraine is a disorder of the brain and the trigem-
inal system with widespread effects on other
bodily systems. It is divided into multiple sub-
types (Table 7). However, there are two major
subtypes. Migraine without aura is a clinical syn-
drome characterized by headache with specific
features and associated symptoms (IHS 1.1).
Migraine with aura is primarily characterized by
the transient focal neurological symptoms that
usually precede or sometimes accompany the
headache (IHS 1.2) (Fig. 1) (Society 2013).
Furthermore, in some patients there may be a
premonitory phase, occurring hours or days before
the headache, and a headache resolution phase.
Premonitory and resolution symptoms include
hyperactivity, hypoactivity, depression, cravings
for particular foods, repetitive yawning, fatigue,
Table 7 Classification of migraine headache disorders
1.1. Migraine without aura
1.2. Migraine with aura
1.2.1. Migraine with typical aura
1.2.1.1. Typical aura with headache
1.2.1.2. Typical aura without headache
1.2.2. Migraine with brainstem aura
1.2.3. Hemiplegic migraine
1.2.3.1. Familial hemiplegic migraine (FHM)
1.2.3.1.1. Familial hemiplegic migraine type 1
1.2.3.1.2. Familial hemiplegic migraine type 2
1.2.3.1.3. Familial hemiplegic migraine type 3
1.2.3.1.4. Familial hemiplegic migraine, other loci
1.2.3.2. Sporadic hemiplegic migraine
1.2.4. Retinal migraine
1.3. Chronic migraine
1.4. Complications of migraine
1.4.1. Status migrainosus
1.4.2. Persistent aura without infarction
1.4.3. Migrainous infarction
1.4.4. Migraine aura-triggered seizure
1.5. Probable migraine
1.5.1. Probable migraine without aura
1.5.2. Probable migraine with aura
1.6. Episodic syndromes that may be associated with
migraine
1.6.1. Recurrent gastrointestinal disturbance
1.6.1.1. Cyclical vomiting syndrome
1.6.1.2. Abdominal migraine
1.6.2. Benign paroxysmal vertigo
1.6.3. Benign paroxysmal torticollis
difficulty concentrating, emotional changes, diffi-
culty reading or writing, and neck stiffness or
pain. Almost 90% of migraine patients report
triggers or precipitating factors that may initiate
a headache attack. However, exposure to a trigger
or precipitant may not always result in the onset of
a headache attack. Common triggers are stress,
anxiety, foods (such as chocolate, cheese), alco-
holic beverages (such as beer, red wine), menstru-
ation, fatigue, alteration in sleeping pattern,
missed meals, changes in weather, head trauma,
and strong lights or smells.
Migraine headache disorder is considered to be a
neurobiological disorder. The pathophysiology of
migraine involves activation of the trigeminovascular
system. This results in release of vasoactive
Headache
neuropeptides including substance P, calcitonin -
gene-related peptide (CGRP), and neurokinin A
from trigeminal C fibers (Goadsby et al. 1988).
Other mediators considered to play a key role
include 5-hydroxytryptamine, nitric oxide, and
glutamate. When released, the neuropeptides
result in a cascade of events, including mast cell
degranulation, platelet aggregation, vasodilation,
and plasma extravasation, leading to neurogenic
inflammation in the region (Izumi 1999).
Neurogenic inflammation is suggested to be
vital in the prolongation and intensification
of pain associated with migraine. Furthermore,
it may result in peripheral and central sensiti-
zation (phenomena in which neurons become
progressively responsive to nociceptive and
nonnociceptive stimulation). Functional brain imag-
ing suggests that the periaqueductal gray region of
the dorsal raphe nucleus, the dorsal pons, and
locus coeruleus play an important role in the
pathogenesis of migraine headache, probably act-
ing as central generators, or in modulation of pain
associated with migraine.
In migraine with aura, a phenomenon known
as cortical spreading depression of Leão is con-
sidered to play a vital role in the mechanism of
aura symptoms. Cortical spreading depression is a
self-propagating wave of neuronal and glial depo-
larization that spreads across the cerebral cortex
corresponding to the clinically affected region. It
results in oligemia (reduction in blood flow)
followed by hyperemia (increase in blood flow)
(Charles 2009; Leao 1947). In addition to
propagation of aura symptoms, it is suggested to
activate trigeminal nerve afferents and alter blood-
brain barrier permeability (Charles 2009).
Cerebral blood flow imaging studies indicate no
such changes suggestive of cortical spreading
depression during attacks of migraine without
aura. However, blood flow alterations may take
place in brainstem and cortex secondary to pain
activation.
The diagnosis of migraine without aura may
be confirmed when certain IHS criteria are met
and after organic disease is excluded: (80) Patient
needs to have had at least five attacks, each lasting
between 4 and 72 h (untreated or unsuccessfully
treated); (87) headache has at least two of the
9
following four characteristics: unilateral location,
pulsating quality, moderate or severe pain inten-
sity, and aggravation by or causing avoidance of
routine physical activity (e.g., walking or
climbing stairs); (92) and the headache must be
accompanied by nausea or vomiting or photopho-
bia and phonophobia (Society 2013). Migraine
headache in children and adolescents (under
18 years) is most often bilateral, unlike the case
in adults. Similarly, headache attacks in children
may last between 2 and 72 h. Migraine headache
is usually located in the frontotemporal and occip-
ital regions; however, headaches in other areas of
the head have also been described. In the majority
of cases, headaches are unilateral, switching sides.
Some patients may experience bilateral head-
aches. In addition to headaches, some may
develop cutaneous allodynia of the scalp or pain
in the neck and shoulders.
For the diagnosis of migraine with aura, the
patient needs to fulfill the following criteria:
(80) In addition to the criteria for migraine without
aura, the patient needs to have at least two attacks
with aura symptoms; (87) fully reversible aura
symptoms (visual, sensory, speech or language,
motor, brainstem, or retinal); (92) the aura symp-
toms have at least two of the following four fea-
tures: at least one aura symptom spreads gradually
over 5 min and/or two or more symptoms occur
in succession, each individual aura symptom lasts
for 5 to 60 min, at least one aura symptom is
unilateral, and aura is accompanied, or followed
within 60 min, by headache. An aura may also
occur in the absence of a typical migraine head-
ache (IHS 1.2.1.2). It most often takes form of
positive visual phenomena that move across the
visual field over minutes, migrating paresthesia,
or dysphasic speech (Society 2013).
If headache occurs on more than 15 days per
month for at least 3 months, which has the fea-
tures of migraine on at least 8 days per month
and in the absence of medication overuse, it is
called chronic migraine (IHS 1.3) (Society
2013). It is estimated that chronic migraine
(CM) occurs between 2% and 6% of the popula-
tion. Most patients start as having intermittent
headache, characteristic of migraine, and then
transform into CM. The evolution from
10
intermittent headache to chronic headache may
be subtle. Attacks may initially take longer to
recover, with the emergence of a lingering
low-grade headache. The headache “proneness”
increases and even minor perturbations may trig-
ger an attack. In retrospective studies, this tran-
sition may take an average of 10.8 years to
evolve. This progressive shift is considered to
be neurological and is often accompanied by
other central effects, such as depression, anxiety,
insomnia, and other generalized body pains. It is
possible that this is directly due to the pain or due
to the medications taken by the patients to treat
the pain.
If a headache lasts for more than 3 days in
succession, it is called status migrainosus (IHS
1.4.1). Serious complications of migraines are
rare and include persistent aura without infarction
(IHS 1.4.2), migrainous infarction (IHS 1.4.3),
and migraine aura-triggered seizure (IHS 1.4.4).
If migraine without aura is strongly associated
with menstrual onset, it may be pure menstrual
migraine without aura or menstrually related
migraine without aura. In pure menstrual
migraine, women suffer from attacks similar to
migraine without aura, over at least three consec-
utive cycles. The attacks occur exclusively on day
1  2 (i.e., days 2 to +3) of menstruation in at
least two out of three menstrual cycles and at no
other times of the cycle. In contrast, in menstru-
ally related migraine, women experience migraine
attacks without aura, with attacks occurring exclu-
sively on day 1  2 (i.e., days 2 to +3) of
menstruation in at least two out of three menstrual
cycles, as well as at other times of the cycle
(Society 2013).
Treatment
There are numerous potential treatments for
migraine. Treatment may commence with a num-
ber of lifestyle alterations, so-called protective
factors, such as regular sleep and meals, exercise,
smoking cessation, and change in the use of alco-
hol. In addition, elimination of headache triggers,
such as caffeine, dietary supplements (nitrites,
preservatives, and monosodium glutamate), spe-
cific alcoholic beverages, weather factors, bright
lights, loud noises, and irritating smells. In
S.J. Scrivani et al.
addition, there may be certain medications that
may trigger headache, particularly analgesic
agents. Reduction in physical and emotional
stressors may also play an important protective
role. Physical and behavioral medicine therapies
have been shown to be effective preventative
treatments and may also inhibit worsening of
headache. In particular, there is very good evi-
dence to support a variety of behavioral medicine
treatments for migraine (Silberstein et al. 2012).
Pharmacological treatment of migraine may be
abortive or prophylactic. Patients who experience
frequent severe migraine attacks often require
both approaches. The choice of treatment should
be guided by the frequency of the attacks.
Individuals with fewer than 4 headache days per
month and no impairment, or those with no more
than 1 headache day per month regardless of
impairment, can be treated with abortive medica-
tions (Lipton et al. 2007). Individuals with more
frequent attacks, such as those with 6 or more
migraine days per month with normal function-
ing, 4 or more migraine days with some impair-
ment, or 3 or more migraine days with severe
impairment, should be considered for prophylac-
tic treatment (Lipton et al. 2007). If there is a
comorbid illness, a prophylactic agent that can
treat both should be used when possible, and
agents that might aggravate a comorbid illness
should be avoided. Nonpharmacologic methods,
such as biofeedback, relaxation techniques,
acupuncture, and other behavioral interventions,
can be used as adjunct therapy (Holroyd and Drew
2006). Patient preferences should also be
considered.
Several medications are used for acute
migraine treatment, including selective 5-HT
(serotonin)1B/D receptor agonists (ergots, tri-
ptans), analgesics, nonsteroidal anti-inflammatory
drugs (NSAIDs), acetaminophen (APAP)/para-
cetamol, dopamine-antagonistic antiemetics, and
opioids (Table 8). Caution is advised with use of
abortive agents, because overuse of such agents,
especially compounded medications (such as
NSAIDs with caffeine and/or barbiturate), may
enhance the risk of medication-overuse headache
(Silberstein 2000). In general, it is advised that
APAP and NSAIDs should be taken for no more
Headache
Table 8 Classes of migraine abortive agents
Pharmacotherapy
• Triptans
• Dihydroergotamines
• Nonsteroidal anti-inflammatory drugs
• Opioids
• Antiepileptic drugs
• Corticosteroids
Injection therapy
• Neurotoxins (onbotulinumtoxin A)
Supplements
• Vitamins
• Herbs
• Minerals
than 15 days per month, while other abortive and
compound agents are suggested to be taken for
less than 10 days per month (Silberstein 2000).
Drugs with proven benefit, as per the American
Academy of Neurology (Silberstein 2000;
Silberstein et al. 2012), are listed in Table 9.
Prophylactic treatments include a broad range
of medications (Loder et al. 2012; Silberstein
et al. 2012). Beta-blockers (propranolol, timolol,
metoprolol) and anticonvulsants (topiramate,
sodium valproate, divalproex sodium) have rel-
atively the strongest evidence of effectiveness
(Table 10). However, other medications such as
tricyclic antidepressants (amitriptyline) and
serotonin-norepinephrine reuptake inhibitors
(venlafaxine) have also shown to be effective
(Silberstein et al. 2012). These medications are
started at low doses and titrated to the desired
effect to minimize side effects and arrive at the
minimal dose needed. In refractory cases, poly-
pharmacy is often necessary. Similarly, botuli-
num toxin type A (Onabotulinum toxin A) has
been shown to be effective preventive treatment
for chronic migraine (headaches occurring for at
least 4 h per day, 15 or more days per month, for
3 months) (Jackson et al. 2012). For the preven-
tive treatment of menstrually related migraine,
there is strong evidence for the prophylactic
use of long-acting triptans (frovatriptan,
naratriptan). Emerging abortive and preventive
treatments include selective 5-HT1F agonist, cal-
citonin gene-related peptide (CGRP) receptor
antagonist, nitric oxide synthase (NOS)
11
inhibitors, and glutamate receptor antagonist
(Table 11).
There is also some evidence for the use of natural
products, herbal remedies, and supplements for
migraine. The most evidence supports the use of
magnesium, vitamin B2 (riboflavin), coenzyme
Q10, and butterbur (pedasites).
Tension Type Headache
Clinical Presentation, Pathophysiology,
and Diagnosis
Tension type headache (TTH) is described as a
dull ache or nonpulsating pain, lasting from
30 min up to 7 days, mild to moderate in intensity,
often manifesting as tightness, pressure, or sore-
ness in a “band-like” distribution (Society 2013).
The pain location is nonspecific, though it is often
bilateral and may extend into the neck. Temporalis
and masseter muscle involvement may be present,
and mastication may be affected in some patients.
Unlike migraine, TTH is usually not aggravated
by routine physical activity, such as walking or
climbing stairs. It is not associated with nausea or
vomiting and is associated with no more than one
of photophobia and phonophobia. However, in
chronic TTH, headache may be associated with
mild nausea (Society 2013). TTH may be aggra-
vated by a number of factors, such as stress,
anxiety, fatigue, menstruation, alcohol, and sleep
disturbances.
The precise pathophysiology of TTH is
unknown. However, it is considered to be multi-
factorial. Environmental influences such as
peripheral activation of myofascial nociceptors
are considered to play a role in etiology of epi-
sodic TTH, while sensitization of nociceptive
pathways appear to be important for the
development of chronic TTH (Bendtsen 2000).
Functional brain imaging investigations indicate
reduced gray matter density in regions of pons and
cingulate, insular, and orbitofrontal cortices
(Schmidt-Wilcke et al. 2005). These changes cor-
relate with the duration of symptoms in chronic
TTH. Similarly, sensory testing investigations
report reduced pain, thermal, and electrical thresh-
old in chronic TTH, suggestive of alteration in the
12 S.J. Scrivani et al.

Table 9 Recommendation of American Academy of Neurology/American Headache Society for abortive therapy for
migraine headaches
Level A drugs: Established efficacy | 2 RCTs showing efficacy
• Triptans
Almotriptan (12.5 mg – PO)
Eletriptan (20 mg, 40 mg, 80 mg – PO)
Naratriptan (1 mg, 2.5 mg – PO)
Rizatriptan (5 mg, 10 mg – POa)
Sumatriptan (25 mg, 50 mg, 100 mg – PO; 20 mg – IN; 4 mg, 6 mg SC; iontophoretic patch)
Zolmitriptan (2.5 mg, 5 mg – PO; 2.5 mg, 5 mg – IN)
• Ergots
Dihydroergotamine (2 mg – IN; 1 mg – pulmonary inhaler)
• Non-steroidal anti-inflammatory drugs
Aspirin (500 mg – PO)
Diclofenac (50 mg, 100 mg – PO)
Ibuprofen (200 mg, 400 mg – PO)
Naproxyn (500 mg, 550 mg – PO)
Refocoxib (25 mg – PO)
Acetaminophen (1000 mg – PO)
• Opioids
Butrophanol (1 mg – IN)
• Combinations
Sumatriptan/naproxyn (85 mg/500 mg – PO)
Acetaminophen/aspirin/caffeine (500 mg/500 mg/ 130 mg – PO)
Codeine/acetaminophen (25 mg/ 400 mg PO)
Level B drugs: Probably effective | 1 RCT or 2 non-RCT
• Ergots
Ergotamine (1 mg, 2 mg – PO)
Dihydroergotamine (1 mg – IV)
• Opioids
Tramadol (75 mg – PO)
• Non-steroidal anti-inflammatory drugs
Ketoprofen (100 mg – PO)
Ketorolac (30 mg – IV)
• Dopamine antagonists
Prochlorperazine (5 mg, 10 mg – PO; 25 mg – PR)
Chlorpromazine (10 mg, 25 mg – oral; 12.5 mg – IM)
Metoclopramide (10 mg – IV)
• Other agents
Metimizole (1 mg – PO)
Isometheptene (65 mg – PO)
• Supplements
Magnesium (1000 mg, 2000 mg – IV)
Level C drugs: Possibly effective | 1 non-RCT showing efficacy
• Corticosteroids
Dexamethasone (4 mg, 16 mg – PO)
• Antiepileptic drugs
Valproic acid (400 mg, 1000 mg – PO)
• Combination
Butalbital/acetaminophen (50 mg/650 mg – PO)
a
Also available in oral disintegration tablets
PO per oral, SC subcutaneous, IN intranasal spray, IV intravenous
Headache
Table 10 Classes of migraine preventive agents
Pharmacotherapy
• Antiepileptic drugs
• Antidepressant
• Beta-adrenergic blockers
• Calcium channel antagonists
• Serotonin (5-HT) antagonists
• ACE inhibitors/angiotensin II receptor antagonist
Injection therapy
• Neurotoxins (onbotulinumtoxin A)
Supplements
• Vitamins
• Herbs
• Minerals
central pain processing (Bendtsen et al. 1996). On
the contrary, based on similar demographic and
clinical features, response to pharmacotherapy,
and genetic influences it has been suggested that
TTH and migraine headache disorder are part of a
same disorder, but represent opposite ends of a
continuum, varying in severity, intensity, and fre-
quency of symptoms (Vargas 2008).
The IHS primarily classifies TTH based on the
frequency of headache occurrences (Table 12). It
is classified as Infrequent episodic TTH (IHS 2.1)
if headache occurs on 1 day or more per month
(less than 12 days per year), and Frequent epi-
sodic TTH (IHS 2.2) if they occur on less than
1 day per month but less than 15 days per month
for at least 3 months. Chronic TTH evolves from
episodic TTH and is diagnosed when the head-
aches occur more often than 15 days per month for
at least 3 months. The categories are typically
subdivided according to the presence or absence
of pericranial tenderness as assessed by manual
palpation.
Treatment
Patients with TTH tend to self-medicate with
over-the-counter analgesics and caffeine. Rarely
do they consult their physicians for relief unless
the frequency or intensity of the headaches
increases. Treatment of TTH may also include
behavioral methods, such as relaxation training,
biofeedback techniques, and physical therapy.
Pharmacotherapy may be needed, but the patient
should be aware of the potential complications.
13
Recent practice guidelines based on very limited
published and controlled data recommend
NSAIDs and acetaminophen for acute care,
while the drugs of choice for the prevention of
TTH are amitriptyline (first choice); mirtazapine
or venlafaxine (second choice); and clomipra-
mine, maprotiline, and mianserin (third choice)
(Bendtsen et al. 2010). For acute as well as pre-
ventive care, side effects associated with these
drugs may limit their tolerability. No preventive
drugs are FDA approved for this indication
(Bendtsen et al. 2010; Jackson et al. 2012).
Trigeminal Autonomic Cephalgia
Cluster Headache
Clinical Presentation, Pathophysiology, and
Diagnosis
Cluster headache (CH) is an episodic headache
disorder associated with severe pain and major
autonomic activation. The headache is considered
the most severe pain that humans can endure.
The pain is typically unilateral stabbing,
throbbing, located in the eye or temple and side-
locked from attack to attack (Society 2013).
Approximately 15% of patients will experience a
side shift between cluster periods. Attacks are
relatively brief, varying from 15 to 180 min,
with a mean of less than 1 h. They may occur
daily or near daily, with up to 8 attacks per day,
often occurring at the same time each day, partic-
ularly during sleep. The attacks occur during
“cluster periods” lasting from 2 weeks to a few
months, and these periods will often reoccur on an
annual or biannual basis during the same seasons.
Cluster attacks are associated with autonomic fea-
tures ipsilateral to the pain and with a sense of
restlessness or agitation. The autonomic features
consist of at least one of the following: conjuncti-
val injection or lacrimation; nasal congestion or
rhinorrhea; eyelid edema; forehead and facial
sweating; forehead and facial flushing; sensation
of fullness in the ear; and miosis or ptosis. In
certain patients, cluster headache attacks may be
associated with photophobia or phonophobia,
which may complicate the assessment and result
14 S.J. Scrivani et al.

Table 11 Recommendation of American Academy of Neurology/American Headache Society for preventive therapy for
migraine headaches
Level A drugs: Established efficacy | 2 RCTs showing efficacy
• Beta-blockers
Metoprolol (50–150 mg per day)
Propranolol (80–240 mg per day)a
Timolol
• Antiepileptic drugs
Topiramate (25–150 mg per day) a
Divalproex (250–1500 mg per day)
Sodium valproate
• Triptans
Frovatriptanb
• Supplements
Butterburc
Level B drugs: Probably effective | 1 RCT or 2 non-RCT
• Antidepressants
Amitriptyline (10–150 mg per day)
Venlafaxine (37.5–150 mg per day)
• Beta-blockers
Atenolol (50–100 mg per day)
Nadolol
• Triptans
Naratriptanb
Zolmitriptanb
• Non-steroidal anti-inflammatory drugs
• Supplements
Riboflavin (vitamin B2)
Feverfew
Level C drugs: Possibly effective | 1 non-RCT showing efficacy
• ACE inhibitors
Lisinopril
• Angiotensin receptor blockers
Candesartan
• α-Agonist
Clonidine
Guanfacine
• Antiepileptic drugs
Carbamazepine
• Beta-blockers
Nebivolol
Pindolol
• Antihistamines
Cyproheptadine (2–8 mg per day)
• Supplements
Coenzyme Q10
Level U drugs: Inadequate or conflicting data to support or refute medication use | Methodological shortcomings
or conflicting data
• Antidepressants
Fluvoxamine
(continued)
Headache 15

Table 11 (continued)
Fluoxetine
Protriptyline
• Antithrombotics
Acenocoumarol
Warfarin
Picotamide
• Beta-blockers
Bisoprolol
• Calcium channel blockers
Nicardipine
Nifedipine
Nimodipine
Verapamil (180–480 mg per day)
• Antiepileptics
Gabapentin (300–1800 mg per day)
• Direct vascular smooth muscle relaxants
Cyclandelate
Other drugs: Medications that are established as possibly or probably ineffective
• Antiepileptics
Lamotrigined
Oxcarbazepinee
• Antidepressants
Clomipraminef
• Antihypertension
Acebutolole
Telmisartane
• Other medications
Clonazepame
Nabumetonee
Montelukast
a
FDA indication
b
Short-term prophylaxis of menstrually related migraine
c
Some developing safety concerns
d
Established as not effective
e
Possibly not effective
f
Probably not effective

in diagnostic delay. Cluster headache attacks may
be provoked by alcohol, histamine, or nitroglyc-
erin. They are often associated with premonitory
and prodromal symptoms. These may occur
minutes to days before the onset of headache.
Local prodrome includes autonomic symptoms,
mild pain, and nonspecific symptoms such as
pressure, tingling, heaviness, and pulsating.
Some may also describe sensitivity to smell, nau-
sea, vomiting, tiredness, irritability, hunger, dry
mouth, metallic taste, and feeling of tightness in
the teeth (Boes and Swanson 2006).
The pathophysiology of CH is complex. The
clinical presentation of circannual and circadian
periodicity, the neuroendocrine alterations,
and functional brain imaging investigation
findings indicate that posterior region of hypo-
thalamus plays an important role in the patho-
genesis of CH (May et al. 1998; May and
Goadsby 1998; Leone and Bussone 2009). Sim-
ilarly, the clinical distribution of pain in the
ophthalmic division and changes in the concen-
tration of neuropeptides are suggestive of acti-
vation of trigeminovascular system during the
16
Table 12 Classification of tension-type headache disorder
2. Tension type headache
2.1. Infrequent episodic tension-type headache
2.1.1. Infrequent episodic tension-type headache
associated with pericranial tenderness
2.1.2. Infrequent episodic tension-type headache not
associated with pericranial tenderness
2.2. Frequent episodic tension-type headache
2.2.1. Frequent episodic tension-type headache
associated with pericranial tenderness
2.2.2. Frequent episodic tension-type headache not
associated with pericranial tenderness
2.3. Chronic tension-type headache
2.3.1. Chronic tension-type headache associated
with pericranial tenderness
2.3.2. Chronic tension-type headache not associated
with pericranial tenderness
2.4. Probable tension-type headache
2.4.1. Probable infrequent episodic tension-type
headache
2.4.2. Probable frequent episodic tension-type
headache
2.4.3. Probable chronic tension-type headache
period of CH (May et al. 1998; Leone and
Bussone 2009).
It has been postulated that metabolic activity in
the hypothalamic region can consequently result
in activation of the trigeminal nucleus, using the
anatomical pathways present between hypotha-
lamic nuclei and the trigeminal nucleus
(trigemino-thalamic pathways) (Leone and
Bussone 2009). In addition, trigeminovascular
stimulation can result in reflex activation of the
parasympathetic outflow from the superior
salivatory nucleus (SSN). Likewise, stimulation
of the trigeminovascular system leads to vasodi-
lation of the peripheral blood vessels, which can
cause neuropraxic injury to the perivascular sym-
pathetic plexus, resulting in sympathetic dysfunc-
tion. This explains the strong autonomic
component of these headache attacks (May and
Goadsby 1998; Leone and Bussone 2009).
Cluster headache can be episodic or chronic.
The IHS classifies cluster headache as episodic if
there is greater than 1 month of headache-free
days per year. For cluster headaches to be consid-
ered chronic, the headache attacks occur for more
than 1 year without remission or with remission
S.J. Scrivani et al.
periods lasting less than 1 month. Between 80%
and 90% of cluster headache patients have the
episodic form, but 13% of them will progress to
chronic. Approximately one third of chronic clus-
ter headache patients will spontaneously remit to
an episodic form.
Treatment
The treatment of cluster headache is essentially
pharmacologic. The goal is to shorten and allevi-
ate the cluster headache attacks, as well as to
shorten and prevent the period of attacks. The
pharmacotherapy can be divided into abortive
and prophylactic. Due to the intensity of the head-
ache attacks, the abortive therapy has to be rapid
in onset. Acute agents that are most effective are
oxygen and the serotonin1B/D receptor agonists
(triptans). Pure 100% oxygen is delivered via
non-rebreathing mask at rates from 12 to 15 L
per minute for approximately 15 to 20 min. For
rapid relief of symptoms, sumatriptan has been
FDA approved and can be delivered subcutane-
ously (Pascual et al. 2007). Headaches refractory
to pharmacotherapy agents may require interven-
tional procedures, such as sphenopalatine
ganglion or occipital nerve block.
Prophylactic therapies should be initiated as
soon as a cluster period begins. However, the
FDA has approved none of the pharmacother-
apies for this indication. Verapamil appears to
have the strongest evidence of effectiveness.
Other medications include lithium, divalproex
sodium, and topiramate. Corticosteroids can
also be beneficial in the management of cluster
headache. However, the use is limited as initia-
tion or bridging therapy for short periods of time
(Pascual et al. 2007). The prophylactic medica-
tions are often continued for 1 month after the
last cluster attack and then discontinued until the
next cluster period begins. Due to chronicity of
the attacks (annual or biannual) patients may
start prophylactic therapy 1 month before the
usual time period of onset of headache attacks.
Headaches refractory to preventive therapy may
require surgical intervention. Gamma-knife radi-
ation, occipital nerve stimulation, and deep brain
stimulation of the hypothalamus in patients with
intractable chronic cluster headache have yielded
Headache
promising results (Ford et al. 1998; Burns et al.
2007; Leone et al. 2010).
Paroxysmal Hemicrania
Clinical Presentation, Pathophysiology,
and Diagnosis
Paroxysmal hemicrania (PH) is a headache disor-
der with clinical characteristics similar to those of
cluster headache. However, it is characterized by
relatively short duration attacks (2 to 30 min),
more frequent (at least 5 attacks per day more
than half of the time), and has an absolute
response to indomethacin therapy. Furthermore,
unlike cluster headache, paroxysmal hemicrania
is more common in women than in men (Society
2013). The headache attacks are strictly unilateral,
predominantly limited to the periorbital region.
Like cluster headache, the diagnosis is confirmed
when the headache is accompanied by at least one
ipsilateral autonomic sign (lacrimation, conjunc-
tival injection, rhinorrhea, nasal congestion, fore-
head and facial sweating, forehead and facial
flushing, miosis, ptosis, fullness in the ear, and
eyelid edema) (Boes and Swanson 2006, Society
2013).
The pathophysiology of PH is similar to that of
cluster headache. It is suggested that there is met-
abolic activation of the posterior portion of the
hypothalamus, with concurrent activation of the
trigeminovascular system, resulting in subsequent
parasympathetic activation and sympathetic dys-
function (May and Goadsby 1998; Leone and
Bussone 2009).
Attacks occurring in periods lasting 7 days to
1 year separated by pain-free periods lasting for
1 month or more are classified as episodic parox-
ysmal hemicrania and attacks occurring more
than 1 year without remissions or with remission
lasting less than 1 month are classified as chronic
paroxysmal hemicrania (Society 2013).
Treatment
Paroxysmal hemicrania has an absolute response
to indomethacin therapy. Oral indomethacin
should be used, initially in a dose of at least
150 mg daily and increased if necessary up to
225 mg daily. The dose by injection is 100 to
17
200 mg. There are reports in the literature of
cases refractory to indomethacin. However,
based on the current IHS guidelines, in order for
a headache to be classified as paroxysmal
hemicrania, it has to have an absolute response
to indomethacin (Society 2013). Nevertheless,
some reports have suggested mild to moderate
relief with sumatriptan or topiramate (Pascual
and Quijano 1998; Boes and Swanson 2006;
Camarda et al. 2008).
Hemicrania Continua
Clinical Presentation, Pathophysiology,
and Diagnosis
Hemicrania continua (HC) is a rare persistent
headache disorder. Headache is strictly unilateral
and is often associated with the presence of ipsi-
lateral autonomic symptoms, such as conjunctival
injection or lacrimation, nasal congestion or
rhinorrhea, eyelid edema, forehead and facial
swelling, forehead and facial flushing, sensation
of fullness in the ear, or miosis or ptosis (Society
2013). In certain individuals, there may be sense
of restlessness or agitation associated with the
headache, which may be aggravated by move-
ment or there may be the presence of ipsilateral
photophobia and phonophobia. Another charac-
teristic feature of this particular headache disorder
is that it has an absolute response to therapeutic
doses of indomethacin. The headache is com-
monly located in the frontal, temporal, and peri-
orbital region. The headache is described as a
sensation of pressure, dullness, or throbbing. It is
of mild to moderate intensity; however, there may
be periods of severe pain during which headache
may become stabbing in quality. Furthermore,
during periods of exacerbation it may be associ-
ated with a feeling of sand particles in the eyes.
These periods of severe exacerbated pain usually
take place at night and may awake the patient from
sleep. Similar to other headache disorders,
hemicrania continua may be worse with physical
activity, menses, strong smells, and stress (Boes
and Swanson 2006).
The pathophysiology of HC is similar in mech-
anism to that of other trigeminal autonomic
cephalgias. Functional brain imaging suggests
18
activity in the posterior hypothalamus, dorsal ros-
tral pons, and ventrolateral midbrain. This corre-
sponds to the clinical presentation of HC, which is
similar to other trigeminal autonomic cephalgias
and migraine headaches (Matharu and Goadsby
2005).
Posterior hypothalamic activation is observed
in other trigeminal autonomic cephalgias. It is
proposed that presence of autonomic symptoms
and distribution of pain in the trigeminal region
is due to posterior hypothalamic activity, with
secondary activation of trigeminovascular
response and trigemino-autonomic reflex. The
role of activation in the dorsal rostral pons and
ventrolateral midbrain is unclear. However, as
indicated earlier in this chapter, these regions
are activated during migraine headaches and
may play a role in disinhibition of the trigeminal
nociceptive pathways, as well as explain clinical
features of HC that it shares with migraine head-
ache (May et al. 1998; Matharu and Goadsby
2005).
The IHS further classifies hemicrania
continua into two subcategories, remitting sub-
type (IHS 3.4.1) and unremitting subtype (HIS
3.4.2) (Society 2013). The remitting subtype is
characterized by headache that is not daily or
continuous but is interrupted by remission periods
of at least 1 day without treatment. Correspond-
ingly, the unremitting subtype is characterized by
headache that is daily and is continuous for at least
1 year without remission periods of 1 day or more
(Boes and Swanson 2006; Society 2013).
Treatment
Hemicrania continua have an absolute response to
indomethacin. The therapeutic dosage is 150 to
225 mg daily for oral indomethacin and 100 to
200 mg daily for injectable indomethacin (Society
2013). The results are dramatic with a rapid onset
of relief occurring within hours. However in some
cases, it may require up to 1 to 2 days. The
maintenance dosage of indomethacin is usually
less than the initial therapeutic dosage. Other
NSAIDs, in particular aspirin, ibuprofen,
piroxicam, diclofenac, or selective COX-2 inhib-
itors, have shown to be less effective in providing
absolute relief (Boes and Swanson 2006).
S.J. Scrivani et al.
Short-Lasting Unilateral Neuralgiform
Headache Attacks
Clinical Presentation, Pathophysiology,
and Diagnosis
Short-lasting unilateral neuralgiform headache
attacks are a primary headache disorder with clin-
ical features resembling cluster headache, parox-
ysmal hemicrania, and trigeminal neuralgia. It is
characterized by headache attacks that are moder-
ate to severe in intensity, strictly unilateral, short
duration (lasting from 1 to 600 s), and occurring as
single stabs, series of stabs, or in a saw-tooth
pattern. The headache has a frequency of at least
one per day for more than half of the time when
the disorder is active. The location of the pain is
often orbital, supraorbital, or temporal. However,
it may involve or be limited to other areas of
the trigeminal distribution. The attacks are accom-
panied by ipsilateral autonomic symptoms (lacri-
mation, conjunctival injection, rhinorrhea, nasal
congestion, forehead and facial sweating, fore-
head and facial flushing, miosis, ptosis,
fullness in the ear, and eyelid edema). Based on
the type of ipsilateral autonomic features, it is
further subclassified into short-lasting unilateral
neuralgiform headache attacks with conjunctival
injection and tearing (SUNCT) and short-lasting
unilateral neuralgiform headache attacks with
autonomic symptoms (SUNA) (Boes and Swanson
2006; Society 2013).
The pathophysiology of short-lasting neuralgi-
form headache attacks is similar to that of other
trigeminal autonomic cephalgias. Clinical fea-
tures, functional brain imaging, and neuroendo-
crine investigations suggest activation in the
posterior hypothalamic region (Bussone and
Usai 2004). It is hypothesized that presence of
autonomic symptoms in short-lasting neuralgiform
headache attacks is secondary to signal generation in
the hypothalamic region, with secondary activation
of the trigeminovascular response and trigemino-
autonomic reflex (Bussone and Usai 2004;
Goadsby et al. 2010).
The differential diagnosis of SUNCT and
SUNA prominently includes trigeminal neuralgia
(TN). Compared to TN, SUNCT, and SUNA
attacks are more likely to be located in the
Headache
Table 13 Important types of secondary headache
disorders
1. Headache attributed to ischemic stroke or transient
ischemic attack
2. Headache attributed to trauma or injury to the head
and/or neck
3. Headache attributed to nontraumatic intracranial
hemorrhage
4. Headache attributed to giant cell arteritis
5. Headache attributed to increased cerebrospinal fluid
pressure
6. Headache attributed to low cerebrospinal fluid pressure
7. Headache attributed to intracranial neoplasia
ophthalmic division of the trigeminal nerve.
While both TN and SUNCT and SUNA may be
triggered by cutaneous stimuli, SUNCT and
SUNA are less likely to demonstrate a refractory
period immediately after an attack. Attacks occur-
ring in periods lasting 7 days to 1 year separated
by pain-free periods lasting for 1 month or more
are classified as episodic. Attacks occurring for
more than 1 year without remission, or with remis-
sion lasting less than 1 month, are classified as
chronic (Society 2013).
Treatment
Short-lasting unilateral neuralgiform headache is
typically treated with anticonvulsant agents, such
as lamotrigine, topiramate, or gabapentin,
although no data from large-scale, controled trials
are available. It is not responsive to indomethacin
(as compared to paroxysmal hemicrania) or to
high-flow oxygen or subcutaneous sumatriptan
(by contrast to cluster headache) (Boes and
Swanson 2006; Goadsby et al. 2010).
Diagnosis and Treatment of Important
Secondary Headache Disorders
Secondary headache disorders are defined as
headaches that occur in close temporal relation
to another disorder that is known to cause head-
ache or fulfills criteria for causation by that disor-
der (Society 2013). The IHS classification divides
the secondary headache disorders into the follow-
ing categories:
19
1. Headaches attributed to trauma or injury to the
head and/or neck
2. Headaches attributed to cranial or cervical vas-
cular disorder
3. Headaches attributed to nonvascular intracra-
nial disorder
4. Headache attributed to a substance or its
withdrawal
5. Headache attributed to infection
6. Headache attributed to disorder of
homoeostasis
7. Headache or facial pain attributed to disorder
of the cranium, neck, eyes, ears, nose, sinuses,
teeth, mouth, or facial or cervical structure
8. Headache attributed to psychiatric disorder
It is not within the scope of this chapter to
discuss all of these disorders. However, the impor-
tant and relatively prevalent disorders are listed in
Table 13 and outlined briefly below.
Headache Attributed to Ischemic
Stroke or Transient Ischemic Attack
Headache associated with acute ischemic cere-
brovascular disease is well recognized but poorly
understood. Although the pain is usually mild to
moderate in intensity, there is nothing pathogno-
monic about the quality of the pain, its intensity,
or location. This diagnosis should be considered
based on the accompanying neurologic deficits
that present in an acute fashion, often in a person
older than 50 years. It seems temporally related
to the head pain that will typically be of a differ-
ent type than previously experienced by the
patient. Posterior circulation dysfunction (in the
vertebral and basilar artery distribution) is more
likely to cause headache than carotid artery dys-
function. Neurologic deficits include visual
obscurations, diplopia, weakness, numbness,
altered cognition, dysarthria, aphasia, and ataxia.
Transient ischemic attacks present with neuro-
logic deficits that might be seen in an acute
ischemic stroke, most commonly amaurosis
fugax, and weakness or numbness on one side.
These deficits resolve, by definition, within 24 h
and usually within 20 min. Symptoms or signs
20
consistent with cerebral ischemia warrant
emergent care.
This cause of headache typically affects older
individuals with vascular risk factors (such as
diabetes, coronary disease, hypertension, hyper-
cholesterolemia, and tobacco use). However,
stroke can occur at any age. A head CT may be
sufficient for the diagnosis, especially if there is a
question of acute bleeding, but MRI will have a
much higher sensitivity and specificity. The dif-
ferential diagnosis for a patient with headache and
neurologic symptoms must include migraine. An
older migraineur who develops a headache with
new neurologic symptoms or signs should be
considered to be vascularly compromised until
proven otherwise. Treatment for the headache
must be individualized and typically this pain
lasts for a few days at most. Vasoactive drugs are
contraindicated.
Headache Attributed to Trauma or
Injury to the Head and/or Neck
Headaches secondary to traumatic intracranial
hematoma may be due to an epidural or subdural
hematoma (Fig. 3). Headache secondary to
Fig. 3 Images of intracranial head computed tomography.
(a) Demonstrates right side frontal traumatic subarachnoid
S.J. Scrivani et al.
nontraumatic intracranial hematoma may be due
to an intracerebral hemorrhage or subarachnoid
hemorrhage (SAH) (Society 2013). Like pain
associated with ischemia, pain stemming from
hemorrhage is best diagnosed according to its
accompanying symptoms.
An epidural hematoma is most often caused by
severe blunt trauma to the skull, causing fracture
and subsequent rupture of the middle meningeal
artery. The patient may experience a so-called
lucid interval, which refers to a period of time
during which the patient apparently recovers for
the most part after head trauma only to become
somnolent and then comatose in short order
(Lobato et al. 1988). Lucid interval is, however,
more the exception than the rule; more frequently,
patients will continue to have severe pain
followed by a change in cognition. Rapid surgical
drainage of the epidural hematoma is necessary to
prevent mortality.
A subdural hematoma may present acutely,
subacutely, or even with chronic symptoms. The
subdural space fills with blood after a bridging
vein ruptures, usually from a fall or other type of
head trauma. Older patients are at greater risk
because they are more likely to have gait instabil-
ity and their bridging veins are stretched. Often
hemorrhage (arrow). (b) Demonstrates right side epidural
hematoma following head injury (arrow)
Headache
Fig. 4 Intracranial magnetic resonance angiography illus-
trating an intracranial aneurysm
there is a history of minimal head trauma, with
neurologic symptoms beginning several hours or
even days later. Patients on anticoagulation ther-
apy and those taking frequent aspirin or (NSAIDs)
are particularly at risk. Pain is not always the chief
complaint. Symptoms may include any neuro-
logic deficit, such as gait disturbance, personality
change, somnolence, visual disturbances, or
focal changes such as hemiparesis, hemisensory
changes, and visual field defects. Surgical evacu-
ation of the hematoma is sometimes necessary,
while in other cases careful observation of a
small subdural hematoma without brain shift or
pressure can be an effective treatment.
Headache due to a subarachnoid hemorrhage
(SAH) is fairly characteristic. Patients with an
SAH typically present with a very sudden-onset,
“thunder clap” headache. This pattern of headache
reaches its maximal intensity in less than 1 min,
often within seconds. It is commonly associated
with nausea and vomiting, a stiff neck, or, fre-
quently, rapid loss of consciousness. A ruptured
saccular aneurysm is the most common cause of
spontaneous SAH. Whenever an SAH is
suspected, the patient should be sent to an emer-
gency room by an ambulance, where a head CT
can be performed. If the suspicion of SAH is high
and the head CT is unremarkable, the patient
21
should undergo a lumbar puncture for blood or
xanthochromia (which takes several days to
develop). A head MRI should also be considered,
as it may show an aneurysm or arteriovenous
malformation (Fig. 4). Management includes,
maintaining hemodynamic stability and neurosur-
gical consultation for either aneurysmal clipping
or endovascular coiling, and treatment of
vasospasm (Bousser et al. 2001).
Headache Attributed to NonTraumatic
Intracranial Hemorrhage
Head pain associated with nontraumatic intrace-
rebral hemorrhage (Society 2013) most typically
presents with acute neurologic deficits. Intracere-
bral hematoma may be due to several etiologies
(hypertension, neoplasm, arteriovenous malfor-
mation). If large enough, it can extend into a
ventricle. An intracerebral hematoma may result
in coma or death, contingent upon the cause and
volume of the bleed, causing destruction of cere-
bral tissue and mass effect.
Headache Attributed to Giant Cell
Arteritis
Giant cell arteritis (GCA) is a disease in which
there is inflammation of cranial arteries (Society
2013), resulting in occlusion of blood vessels. In
temporal arteritis, the superficial temporal artery
is affected. Other arteries commonly affected by
GCA include the maxillary, ophthalmic, and pos-
terior ciliary arteries. The involved artery may be
enlarged and tender to palpation. Patients often
complain of intense or deep headache that
worsens upon lying flat and of malaise, weakness,
and weight loss. Jaw claudication is a common
finding, which can impersonate the much more
common temporomandibular disorders. Further-
more, patients may complain of pain on combing
their hair because of allodynia. Patient with GCA
may have polymyalgia rheumatica, causing pain,
stiffness, and weakness in the proximal arms and
legs. Occlusion of the optic artery may result in
blindness. On examination, there may be presence
22
Fig. 5 Enlargement of temporal artery (arrows)
of an enlarged, tender temporal artery or abnormal
funduscopy (Fig. 5). Women over the age of
50 years are most commonly affected (Levine
and Hellmann 2002).
Laboratory studies reveal an elevated (ESR)
and C-reactive protein (CRP). Temporal artery
biopsy is required for a definitive diagnosis.
GCA results in skipped lesions along the vessel
walls. Due to this, a sample of at least 2 to 2.5 cm
of blood vessel is suggested with thin sectioning
for microscopic examination. Treatment with
high-dose corticosteroid (e.g., prednisone 40 to
60 mg per day) should begin immediately,
followed by referral for biopsy and long-term
management. A delay in treatment may result in
blindness, which is irreversible. GCA is usually
self-limited but relapse can occur (Levine and
Hellmann 2002).
Headache Attributed to Increased
Cerebrospinal Fluid Pressure
Increased intracranial pressure may yield a non-
specific headache involving the entire head. The
patient may have a mass that exerts pressure or
have a process often wise that impairs the normal
circulation and egress of cerebrospinal fluid
(CSF). This headache typically worsens with
Valsalva maneuver or recumbency and may be
associated with nausea or vomiting, visual prob-
lems, and neurological deficits. The examiner
should watch for extraocular eye movement
abnormalities, especially diplopia, and evidence
S.J. Scrivani et al.
of papilledema (Fig. 2). Idiopathic intracranial
hypertension (previously referred to as pseudo-
tumor cerebri) occurs most often in young,
obese, females. Hormonal contraceptives and cer-
tain other medications, such as tetracycline, may
also be risk factors. Typically, this condition pro-
duces a generalized daily headache with intermit-
tent visual disturbances and possibly pulsatile
tinnitus. Neuroimaging should be unremarkable,
except for slit-like ventricles and sometimes ste-
nosis of both transverse sinuses, especially appar-
ent on MRV. Examination may reveal
papilledema (Fig. 2) and abducens (sixth cranial
nerve) palsy. Increased opening pressure on
lumbar puncture, usually higher than 200 to
250 mm H2O, with a normal head MRI, confirms
the diagnosis. If left untreated, blindness may
ensue (La Jolla Donald 2001). After proper
referral, treatment consists of risk factor
modification (weight loss) and with acetazol-
amide, which decreases the production of CSF,
or corticosteroids (La Jolla Donald 2001;
Chaaban et al. 2013). Some patients may require
multiple lumbar punctures to lower the pressure,
optic nerve sheath fenestration for relief of
papilledema, or lumboperitoneal shunting to
reduce headaches and prevent visual loss
(La Jolla Donald 2001).
Headache Attributed to Low
Cerebrospinal Fluid Pressure
Headache due to low CSF pressure is worsened
within few minutes of standing and relieved by
recumbency. It may be accompanied by neck
stiffness or pain, tinnitus, hypoacusis, paraesthe-
sia of the neck and arms, photophobia, or nausea.
Low CSF pressure may be iatrogenic after lumbar
puncture or occur postoperatively or spontane-
ously. The latter may be associated with rupture
of meningeal diverticula, or weakened dura mater,
as a result of connective tissue disease, such as
Marfan syndrome (Marcelis and Silberstein 1990;
Mokri 2003). The positional component of the
headache becomes less evident over time. The
headache is produced by traction by the sagging
when standing on the dura mater and its pain-
Headache
sensitive vasculature. Head MRI typically reveals
postcontrast pachymeningeal enhancement of the
dura and perhaps descent of the cerebellar tonsils,
with flattening of the prepontine cistern and dis-
tortion of the brainstem. The headache may
resolve spontaneously or within 48 to 72 h of
treatment. Treatment may involve complete bed
rest without head elevation for 2 or 3 days, mild
analgesics, caffeine or theophylline, or an epidural
blood patch. The blood patch has a pain relief
success rate of over 90% (Marcelis and Silberstein
1990; Mokri 2003).
Headache Attributed to Intracranial
Neoplasia
Intracranial neoplasm is accompanied by head-
ache in approximately 50% and is one of the
primary presenting symptoms in approximately
20%. However, patients usually presents with
focal neurologic symptoms or seizure. Headache
may be attributed to increased intracranial pres-
sure or hydrocephalus caused by the neoplasm, to
the pressure from the neoplasm itself or to carci-
nomatous meningitis (Society 2013). Other asso-
ciated symptoms include morning headaches,
weight loss, personality changes, seizure, or neu-
rologic deficits, such as focal weakness or numb-
ness, trouble walking, or visual disturbances.
Headache brought on acutely by coughing or
Valsalva maneuver is usually indicative of a
benign condition. However, in rare cases, it can
be due to a tumor causing increased intracranial
pressure. This takes place if a neoplastic process
intermittently occludes normal CSF flow,
producing a ball-valve mechanism that manifests
as posture-dependent headache (Vázquez-
Barquero et al. 1994; Pfund et al. 1999).
Headaches Attributed to Cervicogenic
Disorders
The prevalence of cervicogenic headaches is esti-
mated to be 0.4% to 2.5% in the general popula-
tion, and 15% to 20% in patients with chronic
headache (Haldeman and Dagenais 2001). It is
23
more prevalent in females, with a female to male
ratio of 4:1. The mean age of onset is around
40 years.
The pain is mostly unilateral in location; how-
ever, bilateral headaches can also occur. The pain
is distributed over the occipital region, and it tends
to radiate anteriorly toward the frontal region.
Pain can be continuous or intermittent, of
nonthrobbing quality, and aggravates with
cervical functional and parafunctional
movements. In addition, there is a positive history
of cervical disorders. There have been reports
of accompanying signs of associated nausea,
vomiting, phonophobia, photophobia, and
periorbital edema or flushing (Haldeman and
Dagenais 2001).
The pathophysiology of cervicogenic head-
aches is associated with presence of trigemino-
cervicogenic complex that provides an anatomical
connection between trigeminal and cervical struc-
tures (Haldeman and Dagenais 2001).
The ICHD-III diagnostic criteria for cervico-
genic headaches requires that there be clinical,
laboratory, and/or imaging evidence of a disorder
or lesion within the cervical spine or soft tissues of
the neck that is known to cause a headache. In
addition, the guidelines suggest that there should
be evidence of at least two of the following: head-
ache developed in temporal relation to the onset of
the cervical disorder or appearance of the lesion;
headache has significantly improved or resolved
with improvement or resolution of the cervical
disorder or lesion; cervical range of motion is
reduced and headache worsen with provocative
maneuvers; and headache is eliminated after diag-
nostic blockage of the sensory innervation of the
cervical structures. Furthermore, ICHD-III guide-
lines report that in addition for a patient to be
diagnosed with cervicogenic headache disorder
they need to meet criteria for tension type head-
ache (Society 2013).
Headaches Associated with Disorders
of Nose and Paranasal Sinuses
Headache associated with infectious, inflamma-
tory, or other disorders of the paranasal sinuses
24
are often described as pressure-like or dull ache
that are distributed bilaterally around the peri-
orbital region. However, they have been described
as unilateral and along the frontal and temporal
regions. Characteristically, these headaches are
associated with symptoms associated with sinus
disease, such as nasal congestion or obstruction,
nasal purulence, postnasal drip, alternation in the
sense of smell, cough, fever, fatigue, lethargy,
halitosis, pharyngitis, and otalgia (Lanza and
Kennedy 1997).
The ICHD-III guidelines for headaches
attributed to acute rhinosinusitis suggest that
there should be either clinical or investigational
(nasal endoscopic or imaging) evidence of acute
rhinosinusitis. Moreover, it requires evidence
of causation, i.e., temporal relation between
headaches and onset of the rhinosinusitis;
alteration of headaches with modification of
the rhinosinusitis; headache is worsened by
application of pressure over the sinus region;
and that if headaches are unilateral they are ipsi-
lateral to the location of rhinosinusitis (ICHD-III)
(Society 2013).
The ICHD-III guidelines for headaches
attributed to chronic rhinosinusitis require clini-
cal, nasal endoscopic, and/or imaging evidence of
present or past infection or inflammatory process
within the paranasal sinuses. Similarly, it requires
evidence of causation demonstrated by presence
of at least two of the following: headache has
developed in temporal relation to chronic
rhinosinusitis; headache severity parallels the
severity of nasal and/or sinus symptoms associ-
ated with rhinosinusitis; headache exacerbates by
palpation of paranasal sinuses; and if symptoms
are unilateral, headache and rhinosinusitis symp-
toms are ipsilateral to each other (ICHD-III)
(Society 2013).
The location, quality of pain, and associated
symptoms of headaches associated with disorders
of nose or paranasal sinuses are similar to those of
migraine and tension type headaches. However,
there are distinct differentiations present between
these respective headache disorders (Tarabichi
2000; Meltzer et al. 2004). Furthermore, the
ICHD-III guidelines for headaches associated
with rhinosinusitis require headaches to be
S.J. Scrivani et al.
not better accounted for by another ICHD-III
diagnosis (Society 2013).
Medication Overuse Headache
Headaches that occur on 15 or more days per
month, in a patient with preexisting headache
disorder, after more than 3 months of regular
overuse of abortive and/or symptomatic agents
for headache is known as medication overuse
headache (MOH). The prevalence of MOH ranges
from 1% to 2%, with a female-to-male ratio of 3:1
(Kristoffersen and Lundqvist 2014). Migraine and
TTH are the most common type of primary head-
ache disorders associated with MOH. The clinical
symptoms of MOH vary and depend on the pre-
existing headache disorder and the drug being
overused. Medication associated with MOH are
short-acting ergotamine, triptan, opioid barbitu-
rate, simple analgesics (NSAID and acetamino-
phen), and/or combinations (Silberstein 2000).
The pathophysiology of MOH is poorly under-
stood. However, it is considered to have genetic
predisposition. The headache usually resolves
after the overuse is stopped (Silberstein 2000).
Temporomandibular Disorders
and Headache
Temporomandibular disorder (TMD) encompass
a group of musculoskeletal and neuromuscular
conditions that involve the temporomandibular
joint(s) (TMJ), the masticatory muscles, and asso-
ciated tissues (Greene 2010). The prevalence of
pain-related TMD such as masticatory myalgia,
masticatory myofascial pain, spasm, tendonitis,
and TMJ arthralgia has been reported to be
between 2.5% and 10% in the general adult pop-
ulation (LeResche 1997; Slade et al. 2011;
Schiffman et al. 2014). However, the prevalence
of at least one sign of TMD, pain-related or non-
painful, is reported to be as high as 40% to 75%,
making it the second most common musculoskel-
etal condition after chronic back pain, resulting in
pain and disability. TMD is most commonly
reported in young to middle-aged adults (age
Headache
20 to 50 years). The female-to-male ratio of
patients seeking care has been reported to range
from 3:1 to as high as 9:1 (LeResche 1997; Slade
et al. 2011). Common manifestations of TMD
consist of pain of a persistent, recurring, or
chronic nature; alteration in the range of mandib-
ular motion; and joint noises. TMD can affect the
individual’s daily activities, psychosocial
functioning, and quality of life (Greene 2010;
Slade et al. 2013). It has been estimated that
the annual TMD management cost in the
United States, excluding diagnostic imaging,
in the last decade was approximately $4 billion.
Furthermore, in the United States, it is estimated that
for every 100 million working adults, pain-related
TMD contributes to 17.8 million lost workdays
annually.
TMD and headache (migraine, TTH) are asso-
ciated with each other. Headache is more preva-
lent in TMD (in particular in the pain-related
subgroup), compared to controls, and symptoms
and signs of TMD are more intense and frequent
in headache patients. For example, muscle tender-
ness is common in migraine and TTH patients,
with a distribution that is similar to that of TMD
(Fernandes et al. 2013; Franco et al. 2014).
The temporomandibular joints (TMJ) and their
associated musculature are innervated by the tri-
geminal nerve. Similarly, headaches are also
mediated through the trigeminal system. Presence
of either disorder will result in activation of com-
mon central pathways, such as the trigeminal
nucleus caudalis. This explains the comorbidity,
which therefore would be bidirectional (pain in
the trigeminal distribution predisposes to other
forms of facial pain or headache). Similarly, pain
associated with TMD may be perceived as head-
ache or headache may result in sensitization and
pain of the masticatory system. Pain from TMD
may start out as a peripheral phenomenon, but
with repeated afferent barrages of pain, central
sensitization may occur. This sensitization can
result in expansion of the area of pain or referred
pain to a distant location, which may confuse the
diagnosis. It has therapeutic importance, as one,
for example, migraine may contribute to refracto-
riness to treatment of the second, for
example, TMD.
25
There is a considerable overlap in the treatment
of masticatory myofascial pain and tension-type
headache. Both involve using medications or
behavioral techniques to enhance central inhibi-
tion while simultaneously reducing peripheral
input through physical therapy. The latter, which
includes specific stretching exercises, is to
improve body posture and mechanics. Trigger
point injections and spray and stretch are useful
techniques as well. Medications such as NSAIDs,
muscle relaxants, antidepressants, and benzodiaz-
epines are used in the management of TMD.
NSAIDs are often of value in the acute stage.
Initial treatment is usually administered for 10 to
14 days, at which time the patient should be
reevaluated. Chronic opioid analgesic use should
be avoided. Muscle relaxants are frequently used
for the acute episode but have not been proven
efficacious in chronic TMD. Antidepressants have
a long history of effectiveness for the treatment of
chronic pain. Their use is often indicated when
pain and dysfunction are part of generalized mus-
cle pain with symptoms and signs and of depres-
sion. They are the most widely used in a bedtime-
only schedule of 10 to 50 milligrams of nortripty-
line, desipramine, or doxepin, which can be
expected to alleviate symptoms in 2 to 4 weeks.
Treatment, if successful, is maintained for 2 to
4 months and then tapered to a low maintenance
dose. Serotonin selective reuptake inhibitors
(SSRIs) have also been employed. However,
some of them (fluoxetine and paroxetine) have
been implicated in producing increased
masticatory muscle activity (bruxism) especially
during sleep and are generally not recommended.
The tricyclic antidepressants and selective
norepinephrine reuptake inhibitor antidepressants
(SNRIs), such as duloxetine, can be recom-
mended and show some efficacy.
Anxiolytic agents, such as the benzodiazepines,
are also commonly used. Short-term use (a few
weeks) of a long-acting benzodiazepine in a low
dose, typically at night, is recommended (diaze-
pam 2.5 to 5 mg, clonazepam 0.5 mg). It is impor-
tant that the benzodiazepine use is limited and
patients are followed frequently because of the
potential for dependency (Dionne 1997; Singer
and Dionne 1997; Herman et al. 2002; List et al.
26
2003; Crider et al. 2005; Furto et al. 2006;
McNeely et al. 2006; Schiffman et al. 2007;
Scrivani et al. 2008; Nilsson et al. 2009).
Similarly, use of oral appliances has shown to be
effective in management of TMD and tension-
type headaches in patients with masticatory mus-
cle disorders. Multiple types of oral appliances
exist, and their multiplicity indicates that the opti-
mal design has yet to be discovered. The most
common type of device is flat hard
consistency stabilization appliance. It has shown
to be equally if not superior to other types of
devices such as anterior repositioning device,
anterior bite appliance, and soft consistency sta-
bilization appliance (Scrivani et al. 2008;
Truelove et al. 2006; Ekberg and Milner 2006).
Conclusion and Future Directions
Headache disorders are very common and can
be significantly debilitating pain conditions.
Unique and distinctive features characterize each
of the headache disorders. The International
Headache Society (IHS) has an updated classifi-
cation of headache referred to as the International
Classification of Headache Disorders III (ICHD-
III). This classification divides headache into pri-
mary and secondary headache and, additionally,
categorizes painful cranial neuralgias and other
facial pain conditions. In order to accurately diag-
nose headache disorders, a careful and thorough
analysis of the headache history is required with
special emphasis on the description and associ-
ated neurological, gastrointestinal, and systemic
symptoms. In addition, a thorough and compre-
hensive physical examination is necessary to rule
out any underlying pathology. Similarly, contin-
gent upon findings on history and physical exam-
ination, the clinician should consider additional
diagnostic studies. The understanding of head-
ache disorders has evolved significantly in the
last few years. There are many new and improved
treatments for headache disorders that can be
helpful and a vast array of clinical studies with
good efficacy data for many of these treatments,
both pharmacological and nonpharmacological.
In the future, it is hoped that there may be
S.J. Scrivani et al.
advanced, specific genetic testing, biomarkers of
disease, and functional imaging studies to clarify
the mechanisms for headache, particularly
migraine, and guide more specific and targeted
treatments.
Dedication This chapter is dedicated to the memory of
Dr. Steven B. Graff-Radford, a dear friend, colleague and
leader in the field of headache medicine and orofacial pain.
His knowledge, teaching and guidance will be missed. His
friendship with me will also be missed.
Steven J. Scrivani
Cross-References
▶ Arthritic Conditions Affecting the Temporo-
mandibular Joint
▶ Classification of Orofacial Pain
▶ Clinical Evaluation of Oral Disease
▶ Clinical Evaluation of Orofacial Pain
▶ Diagnostic Imaging Principles and Applica-
tions in Head and Neck Pathology
▶ Internal Derangements of the Temporomandib-
ular Joint
▶ Laboratory Medicine and Diagnostic Pathology
▶ Masticatory Muscle Pain
▶ Neurophysiology of Orofacial Pain
▶ Neurovascular Orofacial Pain
▶ Sleep Medicine
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