What is the cause of hemicrania paroxysmal headaches?

Causes of Paroxysmal Hemicrania Headaches

Paroxysmal hemicrania is a rare primary headache disorder characterized by strictly unilateral, severe, short-lasting pain attacks with accompanying cranial autonomic features, and an absolute response to indomethacin.

Clinical Features and Pathophysiology

Paroxysmal hemicrania (PH) belongs to the trigeminal autonomic cephalalgias (TACs) group and has these distinctive characteristics:

• Attack duration: Relatively short attacks averaging 17 minutes 1
• Attack frequency: High frequency with a mean of 11 attacks per day 1
• Pain distribution: Primarily orbital and temporal (77%), retro-orbital (61%), frontal (55%), and occipital (42%) 1
• Autonomic features: Lacrimation (87%), conjunctival injection (68%), rhinorrhea (58%), nasal congestion (54%), ptosis, and facial flushing 1
• Behavioral response: Most patients (80%) are agitated or restless during attacks 1

Cause of Paroxysmal Hemicrania

The exact cause of paroxysmal hemicrania remains unclear, but current evidence points to:

1. Abnormal brain function: Dysfunction in the hypothalamus and trigeminal-autonomic reflex pathways 2

2. Neurovascular mechanisms: Similar to other TACs, involving activation of the trigeminovascular system and parasympathetic pathways

3. Unique indomethacin response: The hallmark diagnostic feature is the absolute response to indomethacin, suggesting a distinct underlying pathophysiology compared to other headache disorders 1, 2

Primary vs. Secondary Paroxysmal Hemicrania

Most cases are primary (idiopathic), but secondary causes should be considered:

• Demyelinating diseases: Multiple sclerosis, particularly relapsing-remitting MS, is the most common cause of secondary PH 3
• Cerebrovascular diseases: Including aneurysms and vascular malformations
• Structural lesions: Affecting the thalamus, lenticular nucleus, globus pallidus, or internal capsule 3
• Basal ganglia calcification: Both idiopathic and secondary to metabolic disorders 3

Diagnostic Considerations

Diagnosis requires:

1. Clinical pattern recognition: Strictly unilateral, severe, short-lasting attacks with autonomic features
2. Indomethacin response: A positive response to indomethacin (100-200 mg) is considered the sine qua non for diagnosis 1
3. Exclusion of secondary causes: Brain imaging to rule out structural lesions

Differential Diagnosis

Important differential diagnoses include:

• Cluster headache: Longer attack duration (15-180 minutes) and less frequent attacks
• Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT): Shorter attacks and no response to indomethacin
• Migraine: Longer duration and different treatment response
• Hemicrania continua: Continuous pain with fluctuations rather than discrete attacks 2

Clinical Pitfalls and Caveats

1. Misdiagnosis is common: PH is often misdiagnosed as migraine, cluster headache, or trigeminal neuralgia due to its rarity

2. Indomethacin side effects: Long-term use can cause gastrointestinal, renal, and cardiovascular complications 4

3. Treatment challenges during pregnancy: Indomethacin is contraindicated in pregnancy, creating management challenges 5

4. Limited alternative treatments: Alternative treatments like peripheral nerve blocks have shown inconsistent results 5

5. Secondary PH: Higher indomethacin dose requirements were initially thought to indicate secondary causes, but this has not been consistently demonstrated 2

The diagnosis of paroxysmal hemicrania should be considered in any patient with strictly unilateral, severe headaches occurring in short-lasting attacks with autonomic features, and confirmation requires a therapeutic trial of indomethacin.