Episodic Paroxysmal Hemicrania
Episodic paroxysmal hemicrania (EPH) is a rare primary headache disorder characterized by frequent, daily attacks of severe unilateral headache lasting 2-30 minutes with ipsilateral cranial autonomic features, occurring in bouts separated by remission periods, and showing absolute response to indomethacin. 1, 2
Clinical Characteristics
Attack Features
Pain is strictly unilateral, side-locked, and primarily affects the ophthalmic division (V1) of the trigeminal nerve, presenting as moderate to excruciating intensity requiring pharmacological treatment 1, 3
Attack duration ranges from 2 to 30 minutes (mean <20 minutes), which is significantly shorter than cluster headache attacks 1, 2
Attack frequency is remarkably high, typically 5 or more attacks per day, distinguishing it from cluster headache which usually has 1-8 attacks daily 4, 2
Patients remain fully conscious during attacks without any alteration in awareness 1
Autonomic Features
Ipsilateral cranial autonomic symptoms accompany the pain and include: lacrimation, conjunctival injection, nasal congestion, rhinorrhea, eyelid edema, facial sweating, miosis, and ptosis 4, 1
Restlessness or agitation during attacks is now recognized as part of the diagnostic criteria 2
Temporal Pattern
EPH occurs in attack periods (bouts) lasting weeks to months, separated by remission intervals lasting months to years 5
Some patients demonstrate seasonal variation, with bouts occurring predictably during specific months of the year (e.g., first months of the year) 5
A chronic form exists (chronic paroxysmal hemicrania) where attacks occur for more than one year without remission periods or with remissions lasting less than 3 months 4, 6
Pathophysiology
Trigeminal afferents generate the pain, while the trigeminal-autonomic reflex explains the accompanying autonomic features 2
Functional imaging studies reveal posterior hypothalamic activation, similar to other trigeminal autonomic cephalalgias, suggesting a "permissive" central role of the hypothalamus 1, 2
The mechanism underlying the dramatic response to indomethacin remains poorly understood despite being the hallmark of the disorder 3
Diagnostic Approach
Key Distinguishing Features
EPH must be differentiated from cluster headache based on: shorter attack duration (<30 minutes vs 15-180 minutes), higher attack frequency (>5 daily vs 1-8 daily), and absolute indomethacin response 1, 2
Distinguish from SUNCT/SUNA by longer attack duration (minutes vs seconds) and presence of indomethacin response 2
Differentiate from migraine by the strictly unilateral, side-locked nature, short duration, high frequency, and dramatic indomethacin response not seen in migraine 3
Diagnostic Confirmation
Complete response to therapeutic doses of indomethacin (typically 75-150 mg daily) is required for diagnosis and represents one of the current diagnostic criteria 6, 5
Neuroimaging should be obtained in new-onset cases to exclude secondary causes, though the syndrome and treatment response are similar whether primary or secondary 3
Look for atypical features that may suggest secondary causes: higher indomethacin dose requirements (though this does not reliably predict secondary pathology), new neurological signs, or progressive symptoms 3
Treatment
First-Line Therapy
Indomethacin 75-150 mg daily is the definitive treatment, providing complete pain relief in true EPH 6, 5
Patients may need maintenance therapy for several months before attempting dose reduction 1
The disorder has a tendency toward chronicity, requiring long-term management planning 1
Alternative Options for Indomethacin Intolerance
In approximately 25% of patients who develop adverse events (mostly gastrointestinal) from indomethacin, alternative treatments must be considered 6
Other COX-2 inhibitors including newer selective agents have shown efficacy in some patients 3, 2
Topiramate has demonstrated remarkable response in case reports of patients intolerant to indomethacin 6
Calcium-channel blockers and epicranial nerve blocks have shown benefit in select patients 2
Prednisone may provide relief in cases where indomethacin fails or becomes ineffective over time 5
Hypothalamic deep brain stimulation has been used in treatment-refractory cases 2
Common Pitfalls
Missing the diagnosis by treating as migraine due to presence of nausea, photophobia, phonophobia, or even aura, which can occur in EPH despite being typically associated with migraine 3
Failing to recognize EPH when cranial autonomic symptoms are absent or subtle, as these features may not always be prominent 3
Overlooking the diagnosis in patients with prior episodic patterns (often days at a time) and analgesic overuse, which deflects attention from the true diagnosis 3
Not attempting indomethacin trial when the clinical picture suggests EPH, as there is little therapeutic overlap with other headache disorders and limited effective alternatives 3
Assuming higher indomethacin dose requirements indicate secondary pathology, as this does not reliably predict underlying structural causes 3