HEADACHE
Cranial autonomic symptoms
GENERAL PRINCIPLES
Primary headaches
- Headache and its associated features are the
disorders in itself
- Often results in considerable disability and a de
crease in the patient’s quality of life
Secondary headaches
- Caused by exogenous disorders
NOTE: Migraine and other primary headache types are not
New-onset and severe headache
ANATOMY AND PHYSIOLOGY OF HEADACHE
Mechanisms of headache
1. Pain occurs when peripheral nociceptors are
stimulated to tissue injury, visceral distension, or
other factors
2. Pain result when pain-producing pathways of
the peripheral or central nervous system are dam
aged or activated inappropriately
Pain-producing cranial structures
- Scalp, middle meningeal artery, dural sinuses, falx
cerebri, and proximal segments of the large pial
arteries
Non-pain-producing cranial structures
- Ventricular ependymal, choroid plexus, pial veins,
and much of the brain parenchyma
Recurrent headache disorders
Key structures involved in primary headache
1. Large intracranial vessels and dura mater and
the peripheral terminals of the trigeminal nerve
that innervate these structures
- Trigeminovascular system
2. Caudal portion of the trigeminal nucleus
- Extends into the dorsal horns of the upper cerv
ical spinal cord
- Receives input from the first and second cervical
nerve roots (trigeminocervical complex)
3. Rostral pain-processing regions
- E.g. Ventroposteromedial thalamus and cortex
4. Pain-modulatory systems in the brain
- Modulate input from the trigeminal receptors at
all levels of the pain-processing pathways
- Influence vegetative function, such as hypothala
mus and brainstem structures
- Lacrimation, conjunctival injection, nasal conges
tion, rhinorrhea, periorbital swelling, aural fullness,
and ptosis
- Prominent in the trigeminal autonomic cephalgi
as and in migraine
- Causes similar vascular changes as seen
in functional imaging studies
- Reflect activation of cranial parasympathetic
pathway
- Often mistaken for S/Sx of cranial sinus inflamma
tion
“vascular headaches”
CLINICAL EVALUATION
- Greater probability of finding a potentially serious
case than in recurrent headache
- DDx: Meningitis, subarachnoid hemorrhage, epi
dural or subdural hematoma, glaucoma, tumor,
and purulent sinusitis
- Evaluation
1. Careful neurologic examination
2. CT or MRI: Equally sensitive
3. Lumbar puncture, unless etiology is benign
- General evaluation
- Cranial arteries by palpation
- Cervical spine by the effect of passive
movement of the head and by imaging
- Investigation of cardiovascular ad renal
status by blood pressure monitoring and
urine examination
- Eyes by funduscopy, intraocular pressure
measurement, and refraction
- Psychological status
- Relationship exists between head pain
and depression
- To identify comorbidity rather than pro
vide an explanation for the headache,
because troublesome headache is sel
dom simply caused by mood change
- Activated by pain that follows otologic or endo
dontic surgical procedures
- Pain about the head as the result of diseased
tissue or trauma may reawaken an otherwise qui
escent migraine syndrome
- Treatment directed to the primary problem
- DDx: Brain tumor
- Majority with benign cause
 HEADACHE

D. Temporal Arteritis

- Inflammatory disorder of arteries that frequently involves

the extracranial carotid circulation
- Epidemiology
- Common disease of elderly
- Annual incidence: 77/100,000 for >50 y/o
- Average onset: 70 y/o
- Women: 65% of the cases
- Associated s/sx
- Headache, polymyalgiarheumatica, jaw claudi
cation, fever, and weight loss
- Headache
- Dominant symptom
- Often appears in association with malaise and
muscle aches
- May be unilateral or bilateral
- Located temporally (50%); May involve any and
all aspects of the cranium
- Usually appears gradually over a few hours be
fore peak intensity is reached; Occasionally explo
sive in onset
- Only seldom throbbing; Almost invariably dull and
boring, with superimposed episodic stabbing pains
similar to the sharp pains in migraine
- Origin mostly superficial, external to the skull, ra
ther than originating deep within the cranium (vs.
migraine)
- Scalp tenderness: Brushing of hair or resting the
SECONDARY HEADACHE head on a pillow may be impossible
- Usually worse at night and often aggravated by
A. Meningitis exposure to cold
- Acute, severe headache with stiff neck and fever - Additional findings
- Associated s/sx: Striking accentuation of pain with eye - Reddened, tender nodules or red-streaking of the
movement skin overlying the temporal arteries, and tender
- Diagnosis: Lumbar puncture ness of the temporal, or less commonly, the occipi
- DDx: Migraine tal arteries
(+) Pounding headache, photophobia, nausea, - Blindness
and vomiting - D/t involvement of the ophthalmic artery and its
branches
B. Intracranial hemorrhage - Major cause of rapidly developing bilateral blind
- Acute, severe headache with stiff neck but without fever ness in patients >60 y/o
- Possible causes: Ruptured aneurysm, arteriovenous mal- - Diagnosis
formation, or intraparenchymal hemorrhage - ESR: Often, although not always, elevated
- Diagnosis - Temporal artery biopsy
- Head CT scan: Normal if the hemorrhage is small - Treatment: Glucocorticoids
or below the foramen magnum - Immediately following biopsy
- LP: Definitive diagnosis - Prednisone: 80mg/d for the first 4-6 weeks

C. Brain tumor E. Glaucoma

- Headache: CC in 30% of patients
- Characteristics: Usually nondescript; Intermittent deep, - Prostating headache associated with nausea and vomit-
dull aching of moderate intensity, which may worsen with ing
exertion or change in position and may be associated with - Headache often starts with eye pain
nausea and vomiting - PE: Eye is often red with fixed, moderately dilated pupil
- Disturbs sleep (10%)
- DDx
- Posterior fossa brain tumors: Vomiting preceding
headaches
- Prolactin-secreting pituitary adenoma (or PCOS):
With hx of amenorrhea or galactorrhea
- Cerebral metastases or carcinomatous meningi
tis, or both: Headache arising de novo in a patient
with known malignancy
- Posterior fossa mass, Chiari malformation, or low
CSF volume: Head pain appearing abruptly after
bending, lifting, or coughing
 HEADACHE
PRIMARY HEADACHE DISORDERS
A. Chronic Daily Headache
- Headache >15 days per month
- Encompasses a number of different headache syn-
dromes, primary or secondary
- Epidemiology: ~4% of adults with daily or near-daily head-
ache
Management
- Diagnose any secondary headache and treat
the problem
- Preventive treatments: Tricyclics, either amitripty
line or nortriptyline, doses up to 1mg/kg for mi
graine and tension-type headache or whenever a
secondary cause has activated the underlying
primary headache
- Tricyclics: Started in low doses (10-25 mg) daily
and may be given 12h before the expected time
of awakening in order to avoid excess morning
sleepiness
- Anticonvulsants: Topiramte, valproate, flunarizine,
and candesartan
Managament of Medically Intractable Disabling
Primary Chronic Daily Headache
- Neuromodulatory approaches
1. Occipital nerve stimulation: Modulate thalamic
processing in migraine, chronic cluster head
ache, short-lasting unilateral neuralgiform head
ache attacks with cranial autonomic symptoms
(SUNA), short-lasting unilateral neuralgiform head
ache attacks with conjunctival injection and tear
ing (SUNCT) and hemicontinua
2. Single-pulse transcranial stimulation
Medication-overuse Headache
- Overuse of analgesics for headache
- Aggravate headache frequency
- Markedly impair the effect of preventive
medicines
- Induce a refractory state daily or near-
daily headache
- Residual symptoms after regular use of opioids or
barbiturates
- Probably represent the underlying prima
ry headache disorder
- Patients are commonly prone to mi
graine
A. Outpatients
- Analgesics can be reduced and eliminated
1. Reduce the medication dose by 10%
every 1-2 months
2. Immediate cessation of analgesic use,
provided there is no contraindication
- Facilitated by a use of medication diary main
tained during the month or two before cessation
- Small dose NSAID, e.g. naproxen, 500 mg bid:
Relieve residual pain as analgesic use is reduced
- NSAID overuse: Prevented by use of NSAID with
longer half-life; Avoid use of frequent dosing
schedule or shorter-acting NSAIDS
- PREVENTIVES DO NOT WORK IN THE PRESENCE OF
ANALGESIC OVERUSE
- Most common cause of unresponsive
ness to treatment
B. Inpatients
- Hospitalization for detoxification
- Acute medications are withdrawn completely on
the first day of hospitalization, in the absence of
contraindication
- Administer antiemetics and fluids; clonidine for
residual symptoms
- Acute intolerable pain
- During waking hours: Aspirin, 1g IV
- At night: IM chlorpromazine
- Administer IV dihydroergotamine (DHE) 3 to 5
days after admission, every 8 h for 5 consecutive
days for significant remission
- Administer 5-HT3 antagonists, e.g. ondansetron or
granisetron, or the neurokinin receptor antagonist,
aprepitant, and domperidone orally or by suppose
tory, with DHE to prevent significant nausea
- Avoid sedating or otherwise side-effect prone
emetics
B. New Daily Persistent Headache
Clinical Presentation
- Headache begins abruptly, but onset may be
more gradual, with evolution more that 3 days
- Does not remit
- IMPORTANT: Distinguish between a primary and
secondary cause
- Subarachnoid hemorrhage: Most serious second
ary cause
Secondary NDPH
 HEADACHE
1. Low CSF Volume Headache
- Head pain is positional, begins when the patient
sits or stands upright, and resolves uponreclining
- Occipitofrontal pain, usually dull but may be
throbbing
- Typically present with hx of headache from one
day to the next that is generally not present on
waking but worsens during the day
- Most common cause: CSF leak following LP
- Begins within 48h but may be delayed for
up to 12 days
- Incidence: 10-30%
- Relieved by beverages containing caf
feine
- Index events: Epidural injection or a vig
orous Valsalva maneuver, e.g. in lifting,
straining, coughing, clearing the Eusta
chian tubes in an airplane, or multiple or
gasms
- As time passes from the index event, the
postural nature may become less appar
ent
- Sx are d/t low volume rather than low
pressure: Typically 0-50 mmH20m, but may
be as high 140mmH20
- DDx: Postural orthostatic tachycardia syndrome
- Evaluation
- MRI with gadolinium: Study of choice
(+) Diffuse meningeal enhance
ment
(+) Chiari malformations: Surgery
to decompress the posterior fossa
- Spinal MRI with T2 weighing
(+) Leak, spinal meningeal cysts
- Identification of the source of leak
- MRI with appropriate sequences
- CT or MR myelography
- 111 In-DTPA CSF studies
- Management
- Initial tx: Bed rest
- Persistent pain: IV caffeine (500 mg in 500
mL of saline administered over 2h
- ECG: To screen for arrhythmia
before caffeine administration
- Administer at least 2 infusions of
caffeine before additional tests
- If unsuccessful, use an abdominal binder
- Autologous blood patch: For
identified source and post-LP
headache
- Location = Site of LP
- Intractable pain: Oral theophylline
2. Raised CSF Pressure Headache
- Brain imaging can reveal the cause, e.g. space-
occupying lesion
- Possible causes
- Idiopathic intracranial HPN(pseudomotor
cerebri) without visual problems, particu
larly with normal fundi
- Headache on rising in the morning or at
night: Obstructive sleep apnea or poorly
controlled HPN
- Can trigger chronic migraine, if persistent
- Typically present with hx of generalized
headache present on waking and im
proves as the day goes on
- Generally worse on recumbency
- (+) Visual obscurations: Perform formal
visual field testing
- Evaluation
- Brain imaging: MRI including MR veno
gram
- Perform LP if there is no contraindication
- Done if pt is symptomatic
- Remove 20-30 mL of CSF
- Diagnostic if (+) elevated open
ing pressure and improvement of
headache following CSF removal
- Management
- Initial tx: Acetazolamide, 250-500 mg bid
- If ineffective, administer topiramate
- Carbonic anhydrase inhibition,
weight loss, and neuronal mem
brane stabilization
- If unresponsive to medical tx: Intracranial
pressure monitoring and shunting
3. Post-traumatic Headache
- Possible causes
- D/t injury to the head; infectious episode,
typically viral meningitis, a flu-like illness, or
a parasitic infection
- After carotid dissection and SAH and
after intracranial surgery
- Associated s/sx: Dizziness, vertigo, impaired
memory
- Evaluation
- Neurologic examination: Normal
- CT or MR: Unrevealing results
- DDx: Chronic subdural hematoma
4. Other causes
- Transient, flu-like illness
- (+) Fever, neck stiffness, photophobia,
marked malaise
- Evaluation: No apparent cause for head
ache
- Patients undergoing LP during the acute illness:
Consider iatrogenic low CSF volume headache
NDPH Treatment
- Largely empirical
- Tricyclic antidepressants: Amitriptyline
- Anticonvulsants: Topiramate, valproate,
gabapentin
- Monoamine oxidase inhibitor: Phenelzine
- Headache usually resolves within 3-5 years, but it
can be quite disabling.
 HEADACHE

PRIMARY CARE AND HEADACHE MANAGEMENT

- Investigation should focus on identifying worrisome caus-

es of headache or on gaining confidence if no primary
headache diagnosis can be made.
- Follow-up care is essential to identify whether progress has
been made against the headache complaint
- Primary headache disorder: ~90% will have migraine
- Patients without clear diagnosis, with primary headache
disorder other than migraine or tension-type headache, or
unresponsive to two or more standard therapies for the
considered headache type should be considered for refer-
ral to a specialist.

Reference:
Harrison’s Principles of Internal Medicine, 19th ed.