What is the pathophysiology and management of hemicrania?

Pathophysiology and Management of Hemicrania

Hemicrania is a trigeminal autonomic cephalalgia characterized by unilateral headache with ipsilateral autonomic features, with pathophysiology involving activation of the trigeminovascular system and hypothalamus, and indomethacin is the definitive treatment for both chronic paroxysmal hemicrania and hemicrania continua. 1, 2

Pathophysiology

Hemicrania belongs to the trigeminal autonomic cephalalgias (TACs) group, with two main subtypes:

1. Chronic Paroxysmal Hemicrania (CPH):

   • Characterized by multiple, brief, severe unilateral headache attacks with ipsilateral autonomic features
   • Episodes last 2-30 minutes with high frequency (>5 per day)

2. Hemicrania Continua (HC):

   • Continuous unilateral background headache with superimposed severe exacerbations
   • Previously classified as a TAC but now categorized under "other primary headaches"

Neuroanatomical Basis

• Trigeminovascular System Activation: Primary mechanism involving activation of the trigeminal nerve and its connections to cerebral blood vessels 1
• Hypothalamic Involvement: Neuroimaging studies show hypothalamic activation during attacks, suggesting its role in attack initiation and central facilitation 1
• Pain Matrix Activation: Involves brain regions associated with nociception
• Autonomic Nervous System Dysfunction: Manifests as ipsilateral cranial autonomic symptoms (lacrimation, conjunctival injection, rhinorrhea)

Clinical Presentation

Diagnostic Features

• Pain Characteristics:

  • Strictly unilateral pain in trigeminal distribution
  • Moderate to excruciating intensity
  • Continuous in HC with superimposed exacerbations
  • Brief, severe attacks in CPH (2-30 minutes)

• Autonomic Features (ipsilateral to pain):

  • Conjunctival injection
  • Lacrimation
  • Nasal congestion/rhinorrhea
  • Ptosis/miosis
  • Eyelid edema

• Behavioral Response:

  • Agitation during severe exacerbations

Diagnostic Challenges

• Delayed Diagnosis: Average delay of 8.0 ± 7.2 years 2
• Misdiagnosis: Often mistaken for migraine (up to 70% of HC patients fulfill migraine criteria during exacerbations) 2
• Key Diagnostic Error: Focusing only on exacerbations while ignoring continuous background headache in HC

Management

First-Line Treatment

• Indomethacin: Absolute response to indomethacin is pathognomonic and a diagnostic criterion 3, 2
  • Dosing: Start at 25mg three times daily, titrate up to 75-225mg daily
  • Response typically occurs within 24-48 hours
  • Must be continued long-term in most cases

Alternative Treatments (for indomethacin-intolerant patients)

• Topiramate: Effective in some cases of both CPH and HC 3

  • Starting dose: 25mg daily, gradually titrated to effective dose
  • Particularly useful when indomethacin causes adverse effects

• Other Medications with Variable Efficacy:

  • Verapamil (calcium channel blocker)
  • Gabapentin
  • Lamotrigine (especially for SUNCT, another TAC)

Management of Special Situations

• Posttraumatic Hemicrania: Cases temporally linked to head trauma still respond to indomethacin 4

• Hemicrania-Tic Syndrome: Coexistence of hemicrania with trigeminal neuralgia

  • Requires combination therapy with indomethacin and carbamazepine 5

Monitoring and Follow-up

• Regular monitoring for indomethacin side effects (gastrointestinal complications occur in ~25% of patients) 3
• Consider gastroprotective agents for long-term indomethacin use
• Periodic attempts at dose reduction to find minimum effective dose

Treatment Algorithm

1. Confirm diagnosis through detailed history focusing on:

   • Headache location (strictly unilateral)
   • Temporal pattern (continuous with exacerbations vs. paroxysmal)
   • Autonomic features
   • Response to indomethacin (therapeutic trial)

2. Initiate indomethacin:

   • Start 25mg TID
   • If no response in 48 hours, increase to 50mg TID
   • Maximum dose: 75mg TID (225mg daily)

3. If indomethacin is effective but poorly tolerated:

   • Add gastroprotective agent OR
   • Try topiramate starting at 25mg daily, gradually increasing

4. For refractory cases:

   • Consider surgical interventions (occipital nerve stimulation)
   • Explore combination therapy based on individual response

Pitfalls to Avoid

• Misdiagnosis: Don't mistake for migraine, cluster headache, or trigeminal neuralgia
• Incomplete Assessment: Always evaluate for both continuous pain and exacerbations
• Inadequate Trial: Ensure adequate dosage and duration of indomethacin before declaring treatment failure
• Overlooking Side Effects: Monitor for gastrointestinal complications with long-term indomethacin use
• Stopping Treatment Prematurely: Most patients require continuous therapy

By understanding the pathophysiology and following this structured approach to management, clinicians can effectively diagnose and treat hemicrania, significantly improving patient quality of life and reducing morbidity associated with this often misdiagnosed condition.