Migraine Diagnosis and

Pathophysiology
Ward, Thomas N. MD, FAAN, FAHS . CONTINUUM: Lifelong Learning in Neurology.
Volume 18(4) Headache. August 2012: p 753–763.

Abstract
ABSTRACT:
Purpose of Review:
This article describes current knowledge regarding headache, especially migraine, and
includes information on genetics, anatomy, pathophysiology, and pharmacology in order to
demonstrate their relevance to clinical phenomenology.
Recent Findings:
Animal models show that drugs effective in migraine prevention may work by raising the
threshold for initiating cortical spreading depression and may also attenuate the response to
simulation.
Summary:
Great advances have been made in diagnosing and understanding migraine over the past
several decades. Tools such as the International Classification of Headache Disorders assist in
making diagnoses. Although blood vessel changes do occur in migraine, they are not
timelocked to the occurrence of head pain. Cortical spreading depression is at least one
trigger for the events that occur in migraine. Migraine may be due to the interplay of host
susceptibility and various triggers. Nitric oxide and calcitonin gene-related peptide are
important mediators, and estrogen seems to “ramp up” the system.

Key Points
Headache is a symptom with many potential causes, and the International Classification
of Headache Disorders, Second Edition, provides diagnostic criteria, which are useful in
making a precise diagnosis.
Patients with migraines have hyperexcitable brains, and these abnormalities are present
both ictally and interictally. These patients have low brain magnesium levels and do not
accommodate to repetitive stimuli.
Cortical spreading depression appears to be the underlying phenomenon causing auras,
Copyright © 2013, American Academy of Neurology. All rights reserved.
 Cortical spreading depression appears to be the underlying phenomenon causing auras,
although it may occur in silent areas of the brain as well. Imaging studies such as fMRI
and PET have shown this phenomenon.
Estrogen appears to influence nitric oxide (NO) levels and may partially explain why
migraines become more prevalent in women at puberty and even more prevalent by
middle age. Estrogen increases NO synthase activity; women have higher NO levels
that fluctuate with the menstrual cycle and men have lower levels that do not fluctuate.
While blood vessel changes have long been recognized in migraine, they do not and
cannot account for all the clinical phenomenology that occurs in this condition. The
head pain and vessel caliber changes do not occur at the same time, drugs that do not
have vasoconstrictive activity may be effective in migraine, and blood vessel changes
do not explain other features of migraine such as inability to accommodate to repetitive
stimuli.
The trigeminovascular system linking the fifth cranial nerve territory and the upper
cervical region via the trigeminal nucleus caudalis (TNC) explains pain referred
between the face and the neck. Polysynaptic connections between the TNC and the
superior salivatory nucleus in the lower pons explain the occurrence of ipsilateral
autonomic phenomena such as red eye, lacrimation, pupillary inequality, and rhinorrhea
during some headache attacks.
Activation of the trigeminovascular system causes peripheral sensitization of the
first-order neuron innervating dural blood vessels, which explains the pounding pain.
With prolonged duration, second- and third-order neurons become activated, potentially
resulting in central sensitization.
Central sensitization occurs when second-order (trigeminothalamic) and third-order
(thalamocortical) neurons are activated. This process involves glutamate release. Once
this occurs, triptan drugs are less likely to work, although nonsteroidal
anti-inflammatory drugs and dihydroergotamine may still be effective. Central
sensitization is more frequently seen in chronic migraine than episodic migraine.
If animal studies are a valid surrogate, drugs that act to prevent migraines seem to raise
the threshold for initiating cortical spreading depression and, once initiated, attenuate
the response. These drugs seem to be more effective with longer duration of treatment.

Acute and Preventive Treatment of

Migraine
Rizzoli, Paul B. MD, FAAN . CONTINUUM: Lifelong Learning in Neurology. Volume 18(4)
Headache. August 2012: p 764–782.

Abstract
ABSTRACT:
Purpose of Review:
Migraine remains underdiagnosed and undertreated despite advances in the understanding of
its pathophysiology and management. This article focuses on acute and preventive treatment
of migraine, including the mechanisms of action, dosing and side effects of medications, and
Copyright © 2013, American Academy of Neurology. All rights reserved.
of migraine, including the mechanisms of action, dosing and side effects of medications, and
strategies for the most effective care.
Recent Findings:
Best practice suggests that acute migraine treatment should be stratified based on the severity
of the individual event, with a goal of returning the patient to full function within 2 hours of
treatment. Migraine prevention strategies continue to be underused in the United States. More
than 1 in 4 patients with migraines may be candidates for preventive therapy. To obtain the
best results from preventive therapy, slow titration to an adequate dose for an adequate
timeframe with good documentation of the results is recommended.
Summary:
This article reviews several options for managing acute attacks, including information on
expected efficacy, dosing, and adverse effects. Strategies for effective application of acute
therapies are discussed. Prevention can be added to acute therapy depending on headache
characteristics such as frequency, severity, disability, and the presence of comorbid
conditions. The mechanisms of action of preventive medications and strategies for their most
effective use are discussed.

Key Points
Acute migraine treatment by the patient at home should be stratified based on the
severity of the individual event with the goal of returning the patient to full function
within 2 hours of treatment and with no recurrence.
Parenteral sumatriptan should not be overlooked in acute treatment planning because it
is very effective.
Very little evidence links serotonin toxicity and the use of triptans with selective
serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.
More than one in four people with migraine may be candidates for preventive therapy.
Slow titration to an adequate dose for an adequate timeframe with good documentation
of the results is recommended to obtain the best results from migraine preventive
therapy.
Beta-blockers are no longer the most recommended migraine prevention medications
for a variety of reasons and should be considered with some caution in migraine
prophylaxis.
Amitriptyline continues to be widely used in migraine prophylaxis with a good level of
supportive evidence for migraine prevention.
OnabotulinumtoxinA, the first agent to receive US Food and Drug Administration
approval for chronic migraine, is likely safe and well tolerated.

Secondary Headaches
Green, Mark W. MD, FAAN . CONTINUUM: Lifelong Learning in Neurology. Volume
18(4) Headache. August 2012: p 783–795.

Abstract
Copyright © 2013, American Academy of Neurology. All rights reserved.
Abstract
ABSTRACT:
Purpose of Review:
This article identifies the pertinent historical issues that lead to the identification of those
headaches needing additional testing to exclude a serious underlying cause.
Recent Findings:
Recurrences of giant cell arteritis, even after presumed successful treatment, are common.
Postural orthostatic tachycardia syndrome is an often unrecognized cause of headache.
Summary:
Patients with a primary headache disorder are more susceptible to the development of
headache when a secondary cause occurs. Their headaches may be phenotypically similar to
their primary headache disorder. Therefore, a secondary cause should be considered in
patients with preexisting headache disorders who develop a significant increase in the number
and severity of those attacks.

Key Points
Individuals with a preexisting primary headache disorder who develop a secondary
cause commonly experience a change in their preexisting headache type rather than
develop a new headache type.
Headaches associated with brain tumors commonly wake patients from sleep, but this
also occurs frequently with migraines, cluster headaches, and hypnic headaches.
Changes on MRI scans such as empty sellas, flattening of the posterior globes,
protruding optic nerve heads, and vertical tortuosity of optic nerves can strongly
suggest idiopathic intracranial hypertension.
Because primary (benign) cough headache is rare, all patients with cough headache
should be thoroughly evaluated for structural causes.
In an individual with atherosclerotic risk factors, consider a cardiac cause of head pain
when it is triggered by exertion and subsides with rest.
Nearly half of headaches from subarachnoid hemorrhage deviate from the classic
description.
Most patients with AIDS who present with new-onset headache have a secondary
cause.
Inflammatory markers in giant cell arteritis are not always predictive of disease
activity.
As with other causes of secondary headaches, individuals with primary headache
disorders are more likely to develop a secondary headache after head injury, and
treatment is based on the phenotype of that headache.

Nonmedication, Alternative, and

Complementary Treatments for
Copyright © 2013, American Academy of Neurology. All rights reserved.
Complementary Treatments for
Migraine
Mauskop, Alexander MD, FAAN . CONTINUUM: Lifelong Learning in Neurology. Volume
18(4) Headache. August 2012: p 796–806.

Abstract
ABSTRACT:
Purpose of Review:
The efficacy of some nonpharmacologic therapies appears to approach that of most drugs
used for the prevention of migraine and tension-type headaches. These therapies often carry a
very low risk of serious side effects and frequently are much less expensive than
pharmacologic therapies. Considering this combination of efficacy, minimal side effects, and
cost savings, medications should generally not be prescribed alone but rather in combination
with nonpharmacologic therapies.
Recent Findings:
In addition to the established nonpharmacologic therapies, such as biofeedback, relaxation
training, butterbur, riboflavin, magnesium, and coenzyme Q10 (CoQ
10
) supplementation, recent data provide support for the use of aerobic exercise and
acupuncture. Discovery of the high incidence of the C677T mutation of the
methylenetetrahydrofolate reductase gene,
MTHFR
, and attendant elevation of homocysteine levels in patients with migraine with aura led to a
trial of cyanocobalamin, folate, and pyridoxine in these patients. This trial showed that taking
these three supplements resulted in a reduction of homocysteine levels and improvement of
migraines.
Summary:
Therapies proven (to various degrees) to be effective for migraine include aerobic exercise;
biofeedback; other forms of relaxation training; cognitive therapies; acupuncture; and
supplementation with magnesium, CoQ
10
, riboflavin, butterbur, feverfew, and cyanocobalamin with folate and pyridoxine.

Key Points
Forty minutes of aerobic exercise performed 3 times a week is effective for preventing

Copyright © 2013, American Academy of Neurology. All rights reserved.

 headaches.
Frequent isometric neck exercise can relieve cervicogenic headaches and improve
migraine headaches in patients with associated neck pain or muscle spasm.
Caffeine is a major contributor in the transformation of headaches from episodic to
chronic. Daily consumption of as little as two cups of coffee or caffeine drinks plus
analgesic products containing caffeine can worsen headaches.
Reactive hypoglycemia is common in patients with migraine. Adherence to regular
mealtimes, small frequent meals, and avoidance of foods with high glycemic index can
significantly improve migraine headaches.
Serum magnesium levels are unreliable for predicting brain magnesium levels; the
commercially available red blood cell magnesium levels are more indicative of the true
magnesium status but are not entirely accurate. Magnesium levels in the lower half of
the normal range should be considered deficient. Serum levels are helpful only when
they are low.
Clinical symptoms of magnesium deficiency, in addition to headaches, are leg muscle
cramps; feeling cold or having cold extremities; and, in women, premenstrual
syndrome symptoms.
Oral magnesium supplements can cause diarrhea or fail to be absorbed. If magnesium
deficiency is suspected or if serum or red blood cell magnesium levels are low, an IV
infusion of 1 g of magnesium sulfate can be beneficial. Parenteral treatment of migraine
should begin with a magnesium infusion.
Supplementation with 300 mg of CoQ 10 can be effective for preventing migraines in
adults and adolescents. It should be administered in the morning because if taken at
night it can cause insomnia.
Daily intake of 400 mg of riboflavin can prevent migraine headaches, although in some
patients the benefit may appear only after 3 months.
Butterbur and feverfew can be effective for the prevention of migraine headaches in
some patients. Pregnant women, however, should not take these herbal preparations.
Butterbur is associated with several serious potential risks.
Patients with migraine with aura should have their homocysteine level checked. If it is
high, supplementation with folic acid, cyanocobalamin, and pyridoxine may reduce the
homocysteine level and migraine disability.
Acupuncture can be effective for some patients with migraine and tension-type
headaches, although it can be a time-consuming and expensive treatment.

Medication-Overuse Headache
Tepper, Stewart J. MD . CONTINUUM: Lifelong Learning in Neurology. Volume 18(4)
Headache. August 2012: p 807–822.

Abstract
ABSTRACT:
Purpose of Review:
Medication-overuse headache (MOH) is a chronic daily headache in which acute medications
used at high frequency cause transformation to headache occurring 15 or more days per
Copyright © 2013, American Academy of Neurology. All rights reserved.
used at high frequency cause transformation to headache occurring 15 or more days per
month for 4 or more hours per day if left untreated. MOH is a form of US Food and Drug
Administration–defined chronic migraine. This review will describe (1) MOH clinical
features and diagnosis, (2) pathophysiology and structural and functional MOH brain changes,
and (3) prevention and treatment of MOH.
Recent Findings:
MOH causes structural and functional brain changes. Any butalbital or opioid use increases
the risk of transforming episodic into chronic migraine (sometimes referred to as
chronification). The American Migraine Prevalence and Prevention Study demonstrated that
transformation is most likely to occur with 5 days of butalbital use per month, 8 days of
opioid use per month, 10 days of triptan or combination analgesic use per month, and 10 to 15
days of nonsteroidal anti-inflammatory use per month. Acute migraine treatment should be
limited to 2 or fewer days per week, and opioids and butalbital should be avoided.
Treatment of MOH consists of combining prophylaxis, 100% wean of overused acute
medications, and provision of new acute medications, strictly limiting use to 2 or fewer days
per week. Wean can be done slowly in an outpatient setting or it can be done abruptly,
sometimes requiring hospitalization with medicine bridges.
Summary:
MOH development is linked to baseline frequency of headache days per month, acute
medication class ingested, frequency of acute medications ingested, and other risk factors.
Using less effective or nonspecific medication for severe migraine results in inadequate
treatment response, with redosing and attack prolongation, frequently leading to
chronification. Use of any barbiturates or opioids increases the transformation likelihood.
Patients with MOH can usually be effectively treated. The first step is 100% wean, followed
by establishing preventive medications such as onabotulinumtoxinA or daily prophylaxis and
providing acute treatment for severe migraine 2 or fewer days per week. Slow wean or quick
termination of rebound medications can be accomplished for most patients on an outpatient
basis, but some more difficult problems may need referral for multidisciplinary day hospital
or inpatient treatments.

Key Points
The most important predictors for development of chronic migraine and
medication-overuse headache are headache frequency and frequency of acute
medication use.
The ICHD-II defines chronic migraine as a primary chronic daily headache that does
not include medication-overuse headache, which is a secondary daily headache.
The FDA defines chronic migraine as headache occurring 15 days or more per month
with each headache lasting 4 or more hours per day.
When diagnosing chronic migraine, clearly state whether ICHD-IIR criteria are being
used, thus excluding medication-overuse headache (MOH), or whether the FDA
definition is being used, which can include MOH.
The more diagnoses promulgated and the more medications tried and found ineffective,
the more likely the diagnosis of medication-overuse headache.
Consider medication-overuse headache likely in a patient with daily or near-daily

Copyright © 2013, American Academy of Neurology. All rights reserved.

 headache. Rebound should be the default diagnosis; when in doubt, think
medication-overuse headache.
Medication-overuse headache has circadian periodicity, with onset in the morning.
Medication-overuse headache is oftenaccompanied by neck pain and vasomotor
instability; these symptoms generally improve after a wean of rebound medications.
In true high-dose secondary medication-overuse headache, as opposed to primary
ICHD-IIR chronic migraine, remission without wean is unlikely. The adage is, “There
is no spontaneous remission from rebound.”
Medication-overuse headache is associated with both structural and functional brain
imaging changes.
Pro-nociceptive expression of calcitonin gene-related peptide, dynorphin, and glutamate
can manifest in neuronal cell damage and death in medication-overuse headache.
Patients with vascular disease and migraine should receive daily preventive therapy to
reduce frequency, severity, and duration of migraines because acute medication options
are limited, triptans and ergots are contraindicated, and the potential for
medication-overuse headache with overuse of acute medications is high.
Use of nonsteroidal anti-inflammatory drugs, combined analgesics, and triptans should
be limited to 2 or fewer days per week, even when alternated.
Ask the patient to use a headache diary to accurately record the frequency of attacks.
An acute sustained pain-free response (“one and done”) is the best way to prevent
transformation into medication-overuse headache.
If the frequency of headache days reaches 10 days per month or the impact of migraine
is very high, add preventive medication.
Wean is crucial in the treatment of medication-overuse headache.
OnabotulinumtoxinA, at 155 units in a fixed dose/sites protocol, is the only FDA
approved treatment for chronic migraine.
Barbiturate/butalbital withdrawal is potentially fatal.
Patient intake of scheduled medications such as barbiturates, opioids, and
benzodiazepines should be checked against state registries. Ask specifically whether the
patient purchases butalbital off the Internet.
Patients with long durations of medication-overuse headache, significant comorbidities,
high doses of overused medications, narcotic or barbiturate overuse, or those who have
been unsuccessful in previous outpatient programs should be referred to
interdisciplinary headache programs.
Butalbital is generally weaned with a 100-mg butalbital equals 30-mg phenobarbital
conversion.
Because butalbital is often used by patients for anxiolysis, prepare to treat anxiety in
butalbital withdrawal.
Two-thirds of those with chronic migraine in the general population experience
remission by 2 years.

Tension-Type Headache
Kaniecki, Robert G. MD . CONTINUUM: Lifelong Learning in Neurology. Volume 18(4)
Headache. August 2012: p 823–834.

Abstract
Copyright © 2013, American Academy of Neurology. All rights reserved.
ABSTRACT:
Purpose of Review:
This article provides an update on the appropriate diagnosis and evaluation of patients with
tension-type headache, with reviews of the latest concepts regarding pathogenesis and the
evidence-based recommendations for management of this disorder.
Recent Findings:
Pericranial myofascial mechanisms are probably of importance in episodic tension-type
headache, whereas sensitization of central nociceptive pathways and inadequate endogenous
antinociceptive circuitry seem to be more relevant in chronic tension-type headache. While
acute treatment with simple analgesics is generally helpful, recent data attempting to
document the efficacy of preventive therapies are unconvincing.
Summary:
Tension-type headache is the most common form of headache in the general population. It is
characterized by recurrent episodes of headache that are relatively featureless and mild to
moderate in intensity. The diagnosis is based solely on the history and examination. Exclusion
of secondary headaches or forms of migraine is important in the assessment process. Despite
extensive investigation, the underlying pathophysiology remains a matter of speculation, with
peripheral muscular and CNS components both likely involved. Acute management with
simple analgesics, nonsteroidal anti-inflammatory drugs, and caffeine-containing compounds
is typically effective. Preventive therapies include a number of nonpharmacologic
recommendations as well as several antidepressant drugs. Prognosis is generally favorable.

Key Points
Tension-type headache is subclassified by frequency of headache occurrences.
Infrequent episodic tension-type headache occurs less frequently than 1 day per month,
frequent episodic tension-type headache between 1 and 14 days per month, and chronic
tension-type headache 15 days or more per month.
Given the significant symptom overlap, the diagnosis of tension-type headache requires
initial consideration and exclusion of secondary headache disorders and migraine
headache.
Tension-type headache is the most prevalent primary headache condition. In the US
population, the estimated annual prevalence for episodic tension-type headache is
38.3% and for chronic tension-type headache is 2.2%.
Pericranial myofascial mechanisms are probably of importance in episodic tension-type
headache, whereas sensitization of central nociceptive pathways seems to contribute to
the process of chronic tension-type headache.
The approach to the management of tension-type headache involves a combination of
lifestyle, physical, and pharmacologic measures.
Given their superior efficacy in comparative trials, NSAIDs are generally considered
the drugs of choice for acute tension-type headache.
The data for pharmacologic prevention of tension-type headache are most convincing
for amitriptyline, and mirtazapine, extended-release venlafaxine, and tizanidine may be
reasonable alternatives.

Copyright © 2013, American Academy of Neurology. All rights reserved.

 Remission of tension-type headache is positively affected by older age and negatively
impacted by the presence of chronic tension-type headache at baseline, coexisting
migraine or sleep difficulties, and being unmarried.

Migraine in Women
Brandes, Jan Lewis MS, MD, FAAN . CONTINUUM: Lifelong Learning in Neurology.
Volume 18(4) Headache. August 2012: p 835–852.

Abstract
ABSTRACT:
Purpose of Review:
This article discusses hormonal milestones and the influence that hormonal fluctuations make
in the frequency and severity of migraine in women and includes information on acute,
short-term, and preventive strategies for hormonally influenced migraine and the situations in
which hormonal therapies may be offered.
Recent Findings:
Genomic patterns in adolescent girls differentiate between menstrually related migraine and
non–menstrually related migraine. The age at initiation of estrogen replacement therapy
appears to be significant with respect to stroke. No increase in stroke occurred in women on
low-dose (50 µg or less) transdermal estrogen replacement compared to women not using
estrogen replacement. Childhood maltreatment is more common in women with migraine and
depression than in women with migraine alone.
Summary:
Management of hormonally influenced migraine involves a clear identification of the
relationship between migraine and hormone change. A thorough history and detailed diary are
critical in identifying this relationship and in predicting response or following response to
hormonal therapies. The evolution of migraine in an individual may be strongly driven by
hormonal shifts. Although limited, clinical evidence suggests that oral contraceptive use in
young women with episodic migraine may transform their pattern into chronic migraine.
Thus, particular attention to changes in migraine patterns following either endogenous or
exogenous hormonal changes is crucial. Providing reassurance and education that migraine is
a biological disorder and providing an understanding of the role of estrogen in the frequency
and severity of migraine can guide treatment choices. Pharmacologic treatments include acute
therapy, with short-term and standard prevention offered where appropriate. Hormonal
therapies are not first-line therapies but may be important choices for a woman with migraine
whose estrogen fluctuation is continually exacerbating migraine attacks. Given the many
hormonal stages during the life of a woman with migraine, therapies may vary according to
hormonal stage and status. Overall wellness should also be emphasized; regular exercise,
balanced diet, smoking cessation, weight control, and sleep hygiene are important in the
management of migraine.

Copyright © 2013, American Academy of Neurology. All rights reserved.

Key Points
Migraine diaries or calendars are essential for diagnosis of hormonally influenced
migraine.
Take the hormonal history to determine possible influence on migraine.
Ask specifically about hormonal therapies because many women forget to include oral
contraceptives, patches, injections, pellets, intrauterine devices, and creams when
listing their medications.
The presumed triggering mechanism for a menstrual migraine attack is a high estrogen
level followed by a drop in estrogen.
Genomic patterns in adolescent girls can differentiate between menstrual and
nonmenstrual migraine attacks.
Identify “stackable” triggers of menstrual migraine such as sleep deprivation, alcohol,
or attitudinal changes. Determine which are “unstackable” and can reduce severity, or
even risk, of a migraine attack if avoided.
Menstrual migraine attacks seen in clinical practice are longer in duration and more
severe.
Triptans are effective first-line acute therapy for menstrual migraine.
Short-term prevention of menstrual migraine works best in women with predictable
menstrual cycles.
Menstrually related migraine refers to the pattern of having migraine in association
with the menstrual cycle plus additional attacks outside the menstrual window. Pure
menstrual migraine refers to attacks exclusively associated with the menstrual cycle.
Standard prevention should be offered to women with high-frequency menstrually
related migraine attacks.
When choosing a preventive agent, it is important to consider any comorbid disorders
and the impact of the drug on those comorbid conditions, including potential impact on
contraceptive efficacy.
Women of childbearing potential should take 0.4 mg to 0.8 mg of folic acid per day,
whether or not they are on antiepileptic drugs.
Dosage of transdermal estrogen appears important in reducing severity, duration, and
frequency of migraine attacks.
Oral contraceptive pills can have a variable impact on migraine, either inducing
attacks, improving attack frequency, or producing no change in attacks.
Women with a history of thrombosis, ischemic heart disease, stroke, or smoking should
not be offered combined oral contraceptives.
Improvement of migraine during pregnancy occurs in more than 55% of women, but
migraines may be unchanged in 5% to 30%.
Triptans are designated FDA category C for use during pregnancy but are approved for
use during breast-feeding.
Oral clefts associated with topiramate use during pregnancy have prompted a change in
its FDA category from C to D.
Improvement in migraine has been noted in two-thirds of women after spontaneous
menopause. In contrast, worsening is reported in two-thirds of women after surgical
menopause.
Hormone replacement therapy can worsen, improve, or leave unchanged the course of
migraine.
Pharmacologic menopause has shown no clear benefit as a treatment for menstrual

Copyright © 2013, American Academy of Neurology. All rights reserved.

 migraine.
If estrogen replacement therapy exacerbates migraine, the choices include reducing the
estrogen dose, changing the form of estrogen, or stopping the dose. Cyclic estrogen
therapy should be avoided as fluctuation in estrogen often underlies exacerbation.
Migraine is an independent risk factor for stroke and carries twice the risk seen in
patients without migraine.
Women with migraine should not smoke, especially if using oral contraceptives.
Early perimenopause may represent a critical time window during which estrogen
replacement provides beneficial effects on cognition and neuroprotection.
High-dose transdermal and oral high- and low-dose estrogen have been shown to
increase stroke risk compared to women who do not use hormone replacement therapy
(HRT). If offering HRT, use a low-dose transdermal formulation and consider
evaluation for hypercoagulable states before initiating therapy.
The increased ischemic stroke risk in women with any type of migraine occurs only in
women younger than age 45.
Eliciting a history of past or current abuse should be a standard element of the migraine
history.
Childhood maltreatment is more common in women with migraine and depression than
in women with migraine alone.

Headaches in Children
Babineau, Shannon E. MD; Green, Mark W. MD, FAAN . CONTINUUM: Lifelong Learning
in Neurology. Volume 18(4) Headache. August 2012: p 853–868.

Abstract
ABSTRACT:
Purpose of Review:
This article provides an overview of the differences in epidemiology, presentation, and
treatment of pediatric headache compared to adult headache.
New Findings:
New proposals are presented regarding the classification of pediatric migraine and
ophthalmoplegic migraine. The distinction between basilar migraine and migraine with aura
is reconsidered.
Summary:
Pediatric headache is a common but underdiagnosed condition. Primary headache syndromes,
in particular migraine, can present differently in children than in adults. Diagnosis can be
problematic, especially in young children, because standard criteria used for classification are
often incomplete. Treatment focuses on biobehavioral modification and adapted use of
standard adult medication management.

Copyright © 2013, American Academy of Neurology. All rights reserved.

Key Points
Most patients with migraine report onset of headaches in childhood or adolescence, but
often several years pass before the correct diagnosis is made.
Imaging should be considered if there is an abnormal examination, a change in the
nature of the headaches, the recent onset of severe headache, coexistence with seizures
or other signs of neurologic dysfunction, a history of neurocutaneous syndrome, or the
child is younger than 6 years.
Ophthalmoplegic migraine is currently classified as a neuralgia and can be responsive
to corticosteroids.
Headache diagnosis can change over time, with patients diagnosed with migraine later
developing tension-type headache and vice versa.
Pediatric migraine can be bilateral and brief, lasting less than 1 hour. Young children
often have more prominent vomiting and abdominal symptoms, whereas photophobia
and phonophobia often do not appear until the teenage years.
A high rate of sexual, physical, and emotional abuse is found in teenagers with chronic
daily headaches.
Migraine variants are often precursors to migraine headaches and should be noted in
the history. This strengthens the diagnosis of migraine.
Hemiplegic migraine can be either familial or sporadic. The familial form includes
three subtypes based on genetic testing.
Alternating hemiplegia of childhood (AHC) is characterized by eye movement
abnormalities, attacks of hemiparesis or dystonia that can continue for days, baseline
cognitive delay, ataxia, chorea, and epilepsy. While AHC can be associated with
migraine, it is unlikely to be a migraine variant.
Sleep is frequently disturbed in children with migraine, and they have a high prevalence
of sleep-disordered breathing.
Motion sickness, recurrent limb pain, and red ear syndrome occur with higher
prevalence in children with migraine.
About one-third of children with headache will experience remission in the coming
years; however, over one-half of those with migraine will go on to have migraines into
adulthood.
Nonmedication treatment such as sleep and biofeedback can be effective in children.
Nonsteroidal anti-inflammatory drugs and acetaminophen are the mainstays of acute
treatment, although the US Food and Drug Administration has approved almotriptan
for use in patients older than 12 years and rizatriptan for patients older than 6 years.
The standard preventive medications used in adult headache are used in pediatrics,
although scant evidence supports their use.

Facial Pain, Cervical Pain, and

Headache
Graff-Radford, Steven B. DDS . CONTINUUM: Lifelong Learning in Neurology. Volume
18(4) Headache. August 2012: p 869–882.

Copyright © 2013, American Academy of Neurology. All rights reserved.

Abstract
ABSTRACT:
Purpose of Review:
This review discusses the role of musculoskeletal structures of the jaw and neck in
perpetuating or triggering primary headache. Because treatments aimed at these structures
often reduce headache, a better understanding of their role in headache is needed.
Recent Findings:
Central sensitization may result in changes in the afferent pathways, making communication
from cervical and temporomandibular nociceptive neurons to the trigeminal nucleus possible.
This provides the pathophysiologic basis for directing therapy to the neck or
temporomandibular joint to alleviate primary headache.
Summary:
Clinicians should recognize the significant role that musculoskeletal structures of the head
and neck play in the perpetuation of headache and the importance of evaluating every patient
for temporomandibular disorders and cervical abnormalities.

Key Points
Because both headache and temporomandibular disorder are common, they may be
reported as unified or separate entities.
Inflammation within the temporomandibular joint accounts for tempomandibular
disorder pain; the dysfunction is caused by disk-condyle incoordination.
A literature meta-analysis provides no support for occlusion as a factor in headache
etiology.
The right and left temporomandibular joints move as a functional unit and are lined by
a fibrous connective tissue that is more resistant to degenerative change and has a
greater capacity for repair.
Articular disk displacement is the most common temporomandibular arthropathy and is
characterized by an abnormal relationship or misalignment of the articular disk relative
to the condyle.
Asymptomatic clicking does not require treatment.
Frequently pain associated with temporomandibular disorder is muscular in origin.
The potential for cervical dysfunction to manifest as headache is recognized under the
classification of cervicogenic headache. The pain is typically perceived within the
dermatomes of the trigeminal and upper cervical (C2, C3) nerves.
Diseases or dysfunctions of the cervical region may cause pain when the pathology
involves pain-sensitive structures that refer in a physiologically based pattern.
The structures known to cause pain include the facet joints, periosteum, ligaments,
muscles, cervical nerve roots and nerves, and vertebral arteries.
Response to neural blockade does not necessarily exclude the facet joint as a pain
contributor.
Great caution should be exercised in providing mobilization, and in particular
manipulation, because in rare cases stroke and vertebral artery dissection may occur.

Copyright © 2013, American Academy of Neurology. All rights reserved.

 Temporomandibular disorders are self-limiting.

Trigeminal Autonomic Cephalalgias

Goadsby, Peter J. MD, PhD . CONTINUUM: Lifelong Learning in Neurology. Volume 18(4)
Headache. August 2012: p 883–895.

Abstract
ABSTRACT:
Purpose of Review:
This article covers the clinical manifestations and differential diagnosis of the trigeminal
autonomic cephalalgias (TACs).
Recent Findings:
TACs comprise a subgroup of primary headache disorders presenting with lateralized, often
severe, pain accompanied by cranial autonomic features. The key syndromes are cluster
headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with
conjunctival injection and tearing (SUNCT)/short-lasting unilateral neuralgiform headache
attacks with cranial autonomic features (SUNA), and hemicrania continua. Lateralization of
symptoms and signs is the key feature differentiating the TACs and migraine. When
diagnosing a TAC, it is appropriate to consider underlying pituitary or pituitary region
pathology. Cluster headache responds to oxygen and parenteral triptans, with verapamil
having the most success for prevention. Paroxysmal hemicrania responds to indomethacin.
SUNCT/SUNA responds to lamotrigine and topiramate. Hemicrania continua responds to
indomethacin.
Summary:
TACs are a unique group of primary headache syndromes with individual features and
specific responses to treatment that make their identification crucial for optimum management.

Key Points
Photophobia or phonophobia is ipsilateral to the headache in trigeminal autonomic
cephalalgias and remains bilateral in migraine even when the pain is lateralized.
In trigeminal autonomic cephalalgias, cranial autonomic symptoms, such as
lacrimation, conjunctival injection, and nasal congestion, tend to be lateralized to the
side of pain, prominent, and consistent between one attack and another.
In migraine, cranial autonomic symptoms are often bilateral, mild, and do not always
parallel the severity of attacks.
Pituitary gland pathology may accompany trigeminal autonomic cephalalgias.
Verapamil can prolong the PR interval of the ECG. An ECG should be performed 2
weeks after increasing verapamil to check the PR interval.
Oxygen 100% should be given at a rate of 12 L/min to 15 L/min.

Copyright © 2013, American Academy of Neurology. All rights reserved.

 Paroxysmal hemicrania is effectively treated with indomethacin.
SUNCT/SUNA attacks can take three recognized forms: (1) short-lived single stabs, (2)
groups of stabs, and (3) longer attacks with many stabs in which the pain does not
return to baseline.
Hemicrania continua responds absolutely to indomethacin.

Copyright © 2013, American Academy of Neurology. All rights reserved.