Overview

• Most common primary headache disorder; lifetime prevalence ~30–78%
• Often underdiagnosed — many patients self-treat and never present to a physician
• Pathophysiology is incompletely understood — peripheral myofascial mechanisms in episodic form; central sensitization in chronic form

ICHD-3 Diagnostic Criteria

• At least 10 episodes fulfilling below criteria
• Duration: 30 minutes to 7 days
• At least 2 of the following 4 characteristics:
  • Bilateral location
  • Pressing or tightening (non-pulsating) quality
  • Mild or moderate intensity
  • Not aggravated by routine physical activity (walking, climbing stairs)
• Episodic TTH (infrequent or frequent) — both of the following:
  • No nausea or vomiting
  • No more than one of photophobia or phonophobia (not both)
• Chronic TTH — both of the following (ICHD-3):
  • No more than one of photophobia, phonophobia, or mild nausea
  • Neither moderate or severe nausea, nor vomiting

Subtypes

• Infrequent episodic TTH: <1 day/month (<12 days/year)
• Frequent episodic TTH: 1–14 days/month on average for >3 months (12–180 days/year)
• Chronic TTH: ≥15 days/month for >3 months (>180 days/year)
• Each subtype further specified ± pericranial tenderness

Examination Findings

• Pericranial tenderness on manual palpation — most significant abnormal finding
• Increased tenderness in temporalis, masseter, sternocleidomastoid, trapezius, and suboccipital muscles
• Neurologic exam is normal — any focal findings mandate workup for secondary causes

Treatment

Acute Treatment

• Simple analgesics: NSAIDs (ibuprofen 400–800 mg, naproxen 500 mg), acetaminophen 1000 mg
• Aspirin 500–1000 mg is also effective
• Limit use to <15 days/month to avoid medication overuse headache
• Triptans are not indicated for pure TTH

Preventive Treatment (for Chronic TTH)

• Amitriptyline 25–75 mg at bedtime — best-studied preventive; first-line
• Other TCAs: nortriptyline (less sedating)
• Mirtazapine, venlafaxine — second-line options
• Non-pharmacologic: physical therapy, stress management, biofeedback, cognitive behavioral therapy

TTH vs. Migraine

Definition & Key Features

• Daily and unremitting headache from onset (or becoming unremitting within 24 hours of onset)
• The patient can clearly recall the exact date the headache started — this is the hallmark diagnostic feature
• Present for >3 months
• The headache phenotype itself is non-specific — it may resemble either chronic migraine or chronic TTH

ICHD-3 Criteria

• Persistent headache fulfilling criteria B and C
• B: Distinct and clearly remembered onset, with pain becoming continuous and unremitting within 24 hours
• C: Present for >3 months
• Not better accounted for by another ICHD-3 diagnosis

Triggers & Associations

• Viral illness (most common reported trigger — ~30%); often an upper respiratory infection or flu-like illness
• Extracranial surgery
• Stressful life event
• May occur without identifiable precipitant
• Proposed mechanisms: persistent CNS inflammation, glial activation post-infection

Clinical Subtypes

• Self-limiting subtype: resolves spontaneously within months to years without treatment
• Refractory subtype: resistant to aggressive treatment — unfortunately more common

Workup & Differential

• NDPH is a diagnosis of exclusion — must rule out secondary causes of daily headache
• MRI brain with gadolinium: exclude mass, SIH (pachymeningeal enhancement, brain sag), CVT
• MRV: if suspicion for CVT
• LP with opening pressure: exclude elevated ICP (IIH) or low-pressure headache (SIH)
• Medication overuse headache: must exclude — screen for analgesic use ≥10–15 days/month
• Labs: ESR/CRP (giant cell arteritis if ≥50 years old), CBC, metabolic panel

Treatment

• No proven specific therapy; often highly refractory
• Empiric migraine preventives: topiramate, amitriptyline, gabapentin, venlafaxine
• OnabotulinumtoxinA if migraine-like phenotype
• Nerve blocks (greater occipital nerve) — may provide temporary relief
• Doxycycline has been tried based on neuroinflammatory hypothesis

Clinical Features

• Brought on by Valsalva maneuvers: coughing, straining, sneezing, laughing, bending, lifting
• Bilateral, often posterior, sudden onset
• Duration: 1 second to 2 hours (ICHD-3)
• Typically affects patients >40 years old
• No associated autonomic features

Mandatory Workup

• MRI brain (with craniocervical junction views) is mandatory — must exclude Chiari type I malformation
• Secondary cough headache (due to Chiari) is more common than primary cough headache
• Other secondary causes: posterior fossa tumor, CSF leak, platybasia, basilar impression
• Chiari I: cerebellar tonsils ≥5 mm below the foramen magnum

Treatment

• Indomethacin 25–50 mg TID — often effective
• Acetazolamide, topiramate, and lumbar puncture (therapeutic) have been reported helpful
• If secondary to Chiari → posterior fossa decompression is definitive treatment

Clinical Features

• Brought on by sustained strenuous physical exercise (running, weightlifting, rowing)
• Pulsating quality
• Duration: lasting <48 hours (ICHD-3)
• Occurs only during or after exercise
• More common in hot weather or at high altitude

Workup

• First presentation: must exclude SAH (CT ± LP) and arterial dissection (CTA/MRA head and neck)
• Cardiac evaluation if exertional — exclude cardiac cephalgia (rare; headache as anginal equivalent)
• Consider pheochromocytoma if associated with hypertension and diaphoresis

Treatment

• Indomethacin 25–50 mg taken 30–60 minutes before exercise — first-line prophylaxis
• Adequate warm-up before strenuous activity
• Avoid exercising in extreme heat
• Usually self-limited; many patients improve over months to years

ICHD-3 Classification & Clinical Phenotypes

• ICHD-3 4.3 Primary headache associated with sexual activity — single entity. Pre-orgasmic and orgasmic presentations are clinical phenotypes within this single diagnosis, not separate ICHD types (the prior “Type 1/Type 2” split was unified in ICHD-3).
• Pre-orgasmic phenotype:
  • Dull, bilateral, aching head/neck pain that builds gradually with increasing sexual arousal
  • Associated with contraction of head and neck muscles
• Orgasmic phenotype:
  • Explosive, thunderclap-type headache occurring at or just before orgasm
  • Severe intensity, often occipital
  • Duration: minutes to hours (up to 72 hours)

Critical Workup

• Type 2 (orgasmic/thunderclap) on first episode: must exclude SAH, arterial dissection, and RCVS
• CT head → LP if CT negative → CTA/MRA
• RCVS can present with recurrent thunderclap headaches triggered by sexual activity
• Once secondary causes are excluded and a pattern of recurrent episodes is established → primary diagnosis can be made

Treatment

• Indomethacin 25–50 mg taken 30–60 minutes before sexual activity
• Propranolol 40–80 mg as an alternative (taken 1 hour before activity or as daily prophylaxis)
• Triptans taken before activity may be effective in some patients
• Benign and self-limited in most cases

Definition

• Severe headache reaching maximum intensity within 60 seconds (“worst headache of my life”)
• Duration: ≥5 minutes
• Primary thunderclap headache is a diagnosis of exclusion — secondary causes must be ruled out first

Secondary Causes to Exclude

• SAH — most critical to rule out
• RCVS (reversible cerebral vasoconstriction syndrome) — recurrent thunderclap headaches over days to weeks
• Cerebral venous thrombosis
• Cervical artery dissection (carotid or vertebral)
• Pituitary apoplexy — hemorrhage into pituitary adenoma; headache + visual field defect + ophthalmoplegia
• Hypertensive crisis / posterior reversible encephalopathy syndrome (PRES)
• Spontaneous intracranial hypotension — if positional component
• Colloid cyst of the third ventricle — positional thunderclap HA with acute hydrocephalus

Workup Algorithm

• Step 1: Non-contrast CT head — sensitivity approaches ~100% within 6 hours of SAH onset with modern CT (Perry 2011); drops to ~50% at 1 week
• Step 2: If CT is negative → LP (looking for xanthochromia, elevated RBC count that does not clear)
• Step 3: CTA or MRA — evaluate for aneurysm, dissection, RCVS (multifocal segmental vasoconstriction). Initial angiography in RCVS can be normal — if clinical suspicion persists, repeat at 1–3 weeks.
• MRI brain: look for PRES, CVT, pituitary apoplexy, hemorrhagic lesions
• MRV: if CVT suspected

Clinical Features

• “Alarm clock headache” — wakes the patient from sleep at a consistent time each night
• Age of onset: >50 years (mean ~60 years)
• Frequency: ≥10 episodes per month (often nightly)
• Duration: 15 minutes to 4 hours after waking
• Usually bilateral, dull, mild-to-moderate intensity
• No autonomic features (no lacrimation, rhinorrhea, conjunctival injection, ptosis)
• Not side-locked (unlike cluster headache)

Hypnic Headache vs. Cluster Headache

Treatment

• Caffeine 40–60 mg (or a cup of coffee) at bedtime — first-line (safer profile in elderly)
• Lithium 150–600 mg at bedtime — effective but second-line due to narrow therapeutic index in elderly (monitor levels, renal function, thyroid)
• Indomethacin — alternative; less consistently effective than for other primary headaches
• Melatonin 3–5 mg at bedtime — alternative; may help some patients
• Flunarizine has also been used

Clinical Features

• “Ice-pick headache” — spontaneous, ultrabrief stabbing pains
• Duration: seconds (typically ≤3 seconds per stab; single or in series)
• Location: orbito-temporal region (V1 distribution), but can occur anywhere on the head
• May be multifocal and shift locations
• No associated autonomic features
• Often occurs in patients with a history of migraine (~40%)
• Irregular frequency — once to many times per day

Treatment

• Indomethacin 25–50 mg TID — treatment of choice
• COX-2 inhibitors (celecoxib) as an alternative
• Melatonin may be tried in patients who cannot tolerate indomethacin
• Often self-limited; may not require treatment if infrequent

Clinical Features

• Pain localized to a fixed, coin-shaped area of the scalp
• Diameter: typically 2–6 cm, round or elliptical
• May be continuous or intermittent
• Intensity: mild-to-moderate, sometimes with superimposed exacerbations of sharp or stabbing pain
• Trophic changes in the affected area may occur — allodynia, paresthesias, hypoesthesia, or hair loss
• Most commonly affects the parietal region
• The area of pain can be outlined by the patient with precision

Workup

• Consider neuroimaging to exclude underlying skull lesion (metastasis, meningioma, Paget disease) if atypical features present
• Skull radiograph or CT of the skull may reveal bony pathology
• Skin biopsy if dermatologic pathology is suspected

Treatment

• Gabapentin 300–1200 mg/day — first-line
• Topiramate 50–100 mg/day
• Local treatments: lidocaine patches, capsaicin cream, botulinum toxin injection over the affected area
• Tricyclic antidepressants (amitriptyline) may help
• Indomethacin is less reliably effective than for other primary headaches

Definition & ICHD-3 Criteria (3.4)

• Continuous, strictly unilateral headache — no side switching
• Duration >3 months, present without remission
• ≥1 ipsilateral cranial autonomic feature (conjunctival injection, lacrimation, rhinorrhea, nasal congestion, eyelid edema, miosis/ptosis) OR a sense of restlessness/agitation during exacerbations
• Absolute response to indomethacin — ICHD-3 diagnostic criterion D
• Not better accounted for by another ICHD-3 diagnosis

Clinical Subtypes

• Hemicrania continua, remitting (HCRT) — episodes of pain interrupted by pain-free remissions
• Hemicrania continua, unremitting (chronic HC) — continuous pain ≥1 year without remission of ≥24 hours

Diagnostic Indomethacin Trial (“Indotest”)

• INDOTEST: 50–100 mg IM indomethacin → dramatic response within 1–2 hours supports the diagnosis
• Oral diagnostic trial: titrate 25 mg TID → 50 mg TID → 75 mg TID over a few days; complete resolution of pain confirms diagnosis
• Failure to respond at adequate dose excludes hemicrania continua

Maintenance Treatment

• Indomethacin 25–100 mg PO TID (typical maintenance 75–225 mg/day; up to 300 mg/day)
• Use the lowest effective dose; periodic dose-reduction trials are reasonable
• GI protection with a PPI for chronic use
• Alternatives if indomethacin is not tolerated: COX-2 inhibitors (celecoxib), topiramate, melatonin, occipital nerve blocks, onabotulinumtoxinA — all less reliably effective

Mimics & Differential

• Chronic migraine — the key discriminator is that HC responds absolutely to indomethacin; chronic migraine does not
• Cluster headache — episodic, not continuous; HC is continuous with superimposed exacerbations
• Paroxysmal hemicrania — short discrete attacks (2–30 min); HC is continuous
• Cervicogenic headache — usually no autonomic features and not indomethacin-responsive