Cluster headache

Cluster headache (CH) is a type of primary headache that mostly affects adult men. Patients present with recurrent attacks of agonizing, strictly unilateral headaches in the periorbital and forehead region (areas innervated by the trigeminal nerve) that last from fifteen minutes up to three hours. These attacks are associated with ipsilateral symptoms of increased cranial autonomic activity, e.g., lacrimation, conjunctival injection, rhinorrhea, or partial Horner syndrome. Cluster headaches tend to occur in episodic patterns (called cluster periods or cluster bouts) followed by months of remission; they are considered chronic if remission between bouts lasts less than three months. Diagnosis is based on the patient's history, in particular on the exact description and timing of the headaches. In patients with red flag symptoms for headache, secondary headache should be ruled out using an MRI. Acute episodes are treated with 100% oxygen and/or triptans, and verapamil is most commonly used as prophylaxis.

• Sex: : ♂ > ♀ (3:1) ^[1]
• Peak incidence: 20–40 years ^[2]
• Prevalence: rare, ∼ 0.1% of general population ^[1]

Epidemiological data refers to the US, unless otherwise specified.

The etiology of cluster headache is not entirely understood but is thought to involve a genetic component.

• Risk factor: : tobacco use ^[1][3]
• Triggers of cluster headache
  • Alcohol ^[1]
  • Histamine
  • Seasonal fluctuations
  • Nitroglycerine
  • Volatile substances (solvents, oil-based paint) ^[4]

• Headache characteristics
  • Agonizing pain
  • Strictly unilateral, periorbital, and/or temporal
  • Quickly developing (within minutes), short, recurring attacks; that usually occur in a cyclical pattern (“cluster periods”)
    • May become chronic (less common), with interruptions of less than three months between cluster bouts ^[2]
    • Attacks often wake patients up during sleep.
• Ipsilateral autonomic symptoms
  • Conjunctival injections and/or lacrimation
  • Rhinorrhea and nasal congestion
  • Partial Horner syndrome: ptosis and miosis, but no anhidrosis
• Restlessness and agitation

While patients with migraine headaches tend to rest motionlessly in a quiet, dark room, individuals with cluster headache pace around restlessly in excruciating pain!

References:^{[2][5][6][7][8]}

Approach ^[1][9]

• Clinical diagnosis
  • Perform a diagnostic workup for headache.
  • Rule out red flag symptoms for headache.
• Apply diagnostic criteria for cluster headaches.
• Subclassify into episodic CH or chronic CH, based on the characteristics of cluster periods.
• Consider obtaining an initial MRI head to rule out secondary headaches. ^[1][10]
• Consider screening for depressive disorders at diagnosis.

In patients with high-risk headaches, obtain further diagnostics to rule out life-threatening secondary headaches (e.g., SAH, meningitis).

Diagnostic criteria ^[2]

Diagnostic criteria for cluster headache

A diagnosis of cluster headache can be established in the presence of ≥ 5 attacks that fulfill criteria 1–4.

1. Severe unilateral, orbital, supraorbital, and/or temporal pain for a duration of 15–180 minutes (if untreated)
2. At least one of the following:
   • Sense of restlessness or agitation
   • Any of the following signs ipsilateral to the headache:
     • Conjunctival injection and/or lacrimation
     • Forehead and facial sweating
     • Eyelid edema
     • Nasal congestion and/or rhinorrhea
     • Miosis and/or ptosis (partial Horner syndrome)
3. Frequency: from 1 every other day to 8 per day
4. Not better explained by another diagnosis

Subclassification

• Episodic cluster headache
  • ≥ 2 cluster periods lasting 7 days to 1 year
  • Remission periods (i.e., pain-free periods) of ≥ 3 months
• Chronic cluster headache
  • Cluster periods for ≥ 1 year
  • Remission periods of < 3 months, or no remission

See the article on “Headache” for more information regarding differential diagnoses.

Paroxysmal hemicrania

• Epidemiology
  • Rare; the exact prevalence is unknown
  • Equal gender distribution: ♀ = ♂ ^[11]
• Clinical features
  • Severe unilateral attacks of periorbital pain that recur several times per day
  • Cranial autonomic dysfunction (e.g., lacrimation, conjunctival injection)
  • Attacks are generally more frequent (usually ≥ 5 per day) and shorter (2–45 min) than cluster headaches and may occur at any time of the day.
• Treatment: no established treatment for acute attacks
• Prevention: indomethacin

Short-lasting unilateral neuralgiform headache attacks

• Definition: a form of trigeminal autonomic cephalgia characterized by unilateral throbbing pain and autonomic symptoms (i.e., conjunctival injection and/or tearing)
• Subtypes
  • Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)
  • Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA)
• Clinical features
  • Unilateral throbbing, piercing, and/or burning head pain with temporal, orbital, or supraorbital distribution
  • Attacks are frequent
    • At least 1 per day
    • Last between 1 second and 10 minutes as single stabs, a series of stabs, or in a saw-tooth pattern
  • At least one cranial autonomic symptom is usually present
    • Conjunctival injection and/or lacrimation (tearing)
    • Eyelid edema
    • Facial and forehead sweating
    • Miosis and/or ptosis
    • Nasal congestion and/or rhinorrhea
  • Attacks can be triggered without a refractory period
• Diagnosis: mainly clinical following a history of at least 20 attacks; CT or MRI may be used to rule out other causes (e.g., tumor)
  • SUNCT is diagnosed if both conjunctival injection AND lacrimation are present ipsilateral to the pain
  • SUNA is diagnosed if not > 1 of conjunctival injection or lacrimation occurs ipsilateral to the pain
• Treatment: no abortive treatment
  • Acute attacks: IV lidocaine decreases the frequency of attacks.
  • Prevention: antiepileptic drugs (e.g., lamotrigine, topiramate, or gabapentin)

References: ^{[2][12][13][14][15]}

The differential diagnoses listed here are not exhaustive.

Approach ^[9][16]

• Treat acute attacks using oxygen therapy and/or triptans.
• Initiate prophylactic treatment (e.g., verapamil) to reduce the frequency of attacks.
• Avoid cluster headache triggers.
• Neuromodulation therapy may be considered for patients with refractory symptoms.

Acute treatment ^[1][16][17]

• First-line
  • Oxygen therapy with F_iO₂ 100%: usually the first choice if available ^{[1][9][16][18]}
  • Triptans
    • Subcutaneous sumatriptan
    • Or intranasal zolmitriptan (off label) ^[9][16][17]
• Second-line: if first-line treatment is insufficient or not tolerated
  • Consider either:
    • Intranasal sumatriptan (off label) ^[9][16]
    • Oral zolmitriptan (off label) ^[16][17]
  • Other options : e.g., ergotamine, intranasal lidocaine, or subcutaneous octreotide ^[16]

Standard analgesics (e.g., acetaminophen, NSAIDs, opioids) are not recommended because they are ineffective and may lead to medication overuse headache if used frequently. ^[19]

To improve absorption, apply nasal sprays in the nostril unaffected by congestion.

Prophylactic treatment ^{[9][16][20][21]}

• Prophylactic agents
  • Verapamil (off-label) : usually the first choice despite mixed evidence ^[9][16][21]
  • If verapamil is ineffective or not tolerated, consider either of the following :
    • Lithium
    • Melatonin
    • Emerging therapies: e.g., galcanezumab , civamide ^[9][16]
  • May be stopped after the episodic CH period has ceased, or continued long-term for chronic CH.
• Transitional treatment options: Consider as a bridge therapy until prophylactic agents become effective. ^[1][9][16]
  • Suboccipital steroid injections
  • Short-term glucocorticoids : e.g., prednisone (off-label) or methylprednisolone (off-label) ^[9]

Transitional therapy with shorter onset latencies may be necessary until prophylactic treatment takes effect.

Neuromodulation ^[1][9][16]

Neuromodulation is usually reserved for cluster headache refractory to multiple medical treatments.

• Noninvasive neurostimulation: noninvasive vagus nerve stimulation ^[9]
• Invasive neurostimulation: e.g., sphenopalatine ganglion stimulation and occipital nerve stimulation ^[1][16]
  • Disadvantages: uncertain benefits, potential for serious adverse effects
  • Advantages: possible acute and prophylactic effects

• Evaluate for red flags for headache, including sudden onset and neurological deficits.
• Consider MRI brain to rule out secondary headache in patients with a new diagnosis of cluster headache or any red flags.
• Initiate oxygen therapy with 100% F_iO₂ through a nonrebreather mask at 6–12 L/min.
• If oxygen is not available or ineffective, treat with subcutaneous sumatriptan or intranasal zolmitriptan.
• Start concurrent prophylactic therapy (e.g., verapamil) with or without transitional therapy (e.g., glucocorticoids).
• Consider admission to neurology in patients with a first episode of cluster headache, suicidal ideation, or refractory pain.