What is Chronic Paroxysmal Hemicrania (CPH)?

Chronic Paroxysmal Hemicrania (CPH)

Chronic Paroxysmal Hemicrania is a rare primary headache syndrome characterized by short-lasting (2-30 minutes), severe, unilateral headaches occurring multiple times daily (>5/day) with autonomic features and an absolute response to indomethacin.

Clinical Features

• Pain characteristics:

  • Strictly unilateral (93% of cases) 1
  • Moderate to excruciating intensity 2
  • Fronto-orbital-temporal location 3
  • Short duration (average 26 minutes per attack) 1
  • High frequency (average 6 attacks per day) 1
  • Daily occurrence in most patients (78%) 1

• Autonomic symptoms (present in 96% of cases) 1:

  • Lacrimation
  • Rhinorrhea
  • Conjunctival injection
  • Ptosis
  • Eyelid edema

• Other features:

  • Some patients may experience aura before attacks
  • Attacks may be triggered by stress in some cases 4

Pathophysiology

CPH is classified as a Trigeminal Autonomic Cephalgia (TAC), sharing pathophysiological mechanisms with cluster headache. Evidence shows:

• Elevated levels of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) in the cranial circulation during attacks 5
• These neuropeptide changes normalize with successful indomethacin treatment 5
• Suggests trigemino-parasympathetic activation as the underlying mechanism 5

Diagnosis

Diagnosis is based on clinical features and response to indomethacin. Key diagnostic criteria include:

1. At least 20 attacks fulfilling criteria 2-4
2. Severe unilateral orbital, supraorbital or temporal pain lasting 2-30 minutes
3. Headache accompanied by at least one of the following ipsilateral autonomic symptoms:
   • Conjunctival injection and/or lacrimation
   • Nasal congestion and/or rhinorrhea
   • Eyelid edema
   • Forehead and facial sweating
   • Miosis and/or ptosis
4. Attacks occurring more than 5 times daily for more than half the time
5. Attacks completely prevented by therapeutic doses of indomethacin

Differential Diagnosis

CPH must be distinguished from:

• Cluster headache (longer attack duration, lower frequency)
• Hemicrania continua (continuous pain with fluctuations)
• SUNCT (shorter attacks, higher frequency)
• Secondary headache disorders (intracranial pathology)

Treatment

First-line Treatment

• Indomethacin: Absolute response is a diagnostic criterion
  • 75% of patients show consistent response 1
  • Typical dosage: 25-50 mg three times daily, can be increased if needed
  • Some patients (9/13 in one study) may eventually discontinue indomethacin without headache recurrence 1

Alternative Treatments (for indomethacin-intolerant patients)

• Topiramate: Effective in some indomethacin-intolerant patients 2
• Oxygen: Beneficial in some cases (3 patients in one study) 1

Special Considerations

• Pediatric presentation: Rare but documented in children as young as 6-7 years 3, 4
• Secondary CPH: Always consider underlying pathology, as 3 surgically treatable cases were identified in a series of 74 patients 1
• Monitoring: About 25% of patients may develop side effects from indomethacin, primarily gastrointestinal 2
• Treatment challenges: Some clinically typical cases do not respond to indomethacin, and tachyphylaxis may develop in some patients 1

Red Flags Warranting Further Investigation

• Atypical clinical features
• Poor response to indomethacin
• Abnormal neurological examination
• New onset in older adults
• Progressive worsening of symptoms

CPH significantly impacts quality of life due to the severe pain and high frequency of attacks, making prompt diagnosis and effective treatment essential for reducing morbidity and improving patient outcomes.