An Unusual Indomethacin-Sensitive Headache: A Case of Bilateral Episodic Paroxysmal Hemicrania without Autonomic Symptoms?

Episodic paroxysmal hemicrania (EPH) is a very rare variant of the trigeminal autonomic cephalalgias. Following the revised International Headache Society (IHS) classification (1), paroxysmal hemicrania (PH) presents with bouts of short-lasting (1–30 min), frequent (up to 30 times daily) attacks of severe, unilateral throbbing or stabbing headache, with accompanying autonomic features such as conjunctival injection, eye tearing with nasal congestion and rhinorrhoea. Heart rate changes, increased sweating or salivation are not common in PH, but all have been reported (2). A response to indomethacin is characteristic of this condition. The first reported cases of PH were of continuous nature and were categorized as chronic paroxysmal hemicrania (CPH) (3, 4). Recently an episodic form (EPH) has been recognized, in which periods of frequent attacks are separated by relatively long remissions lasting weeks or months in a pattern similar to cluster headache. At least 17 cases of EPH have been reported in the literature so far (5–17), which led to the acknowledgement of the episodic type in the revised IHS classification (1). To our knowledge all cases of EPH in the literature up to date have been unilateral and coincided with autonomic symptoms. We have recently evaluated a patient with a temporal headache profile/pattern highly characteristic of EPH and a significant response to indomethacin. However, the pain was symmetrically bilateral localized and instead of autonomic symptoms she experienced migrainous features such as sensitivity to light and sound and allodynia of the affected skin area.

Case report

A 50-year-old Caucasion female with a 34-year history of headache was referred to us by her gynaecologist. Family history was positive for migraine-type headaches in her mother. Prior to the age of 16 she never experienced headaches but at 16 she started to experience cycles of head pain lasting from 1 to 6 weeks. In these headache episodes she suffered from daily attacks of short severe headaches occurring on an almost hourly basis. The frequency of these episodes, however, has gradually increased over the years with initially about two cycles to the current four episodes a year. In addition, the duration of these headache episodes has increased from initially 1 week to up to 6 weeks today, but no circannual rhythm could be detected. Interestingly, the only time in which these episodes subsided was during her two pregnancies 1978 and 1979 and during breast-feeding. Several months after the second birth the episodes recurred in typical manner. Birth-control measures such as the birth-control pill and the contraceptive coil as well as peri- and postmenopausal hormone replacement therapy did not influence the occurrence of her headache episodes.

Today she recognizes the onset of a new headache episode by a subtle frontotemporal pressure. Over several days this constant pressure changes into actual short-lived painful attacks. In these, pain intensity gradually increases over 2–3 min until it reaches a maximum, stays constant (plateau) for about 5 min and then rapidly decreases to no pain for about 45 min until the next attack begins. These attacks occur hourly (up to 24 attacks/day) without predilection for any time of day. Pain intensity and frequency of the single episodes increase slowly over the first few days of an episode until they reach a plateau, when attacks occur hourly and visual analogue scale (VAS; 0 = no pain, 10 = worst pain ever experienced) of the single attack is reported to be between 8 and 9. At this stage attacks wake her up from sleep.

Pain is located bifronto-temporally without side-dominance, at times the pain involves occipital areas. At the very beginning of a headache attack, pain is described as crackling and then builds to a throbbing, pulsating sensation. The headache is associated with severe photo- and phonophobia, and the affected skin feels pathologically sensitive (allodynia). The allodynia is located bilaterally upon the forehead, temples and at times in the parietal scalp area. It is only present during acute pain attacks (the 5–10 min), not between attacks. It is evoked by various types of stimuli including touch, prick and temperature sensation.

The headache is not associated with autonomic symptoms. During the attacks she prefers to hold still; however, this does not alleviate the pain. After the headache attack she reports a sensation of feeling cold, which lasts only briefly. The isolated attacks cannot be triggered, and non-steroidal antiphlogistics and ergotamine are ineffective to alleviate the pain. She was never exposed to triptans. At the end of an episode both parameters (intensity and frequency) decrease over a short time until well-being is re-established.

Medical history

She had prior orthopaedic, neurological, homeopathic, chiropractic and ophthalmological evaluations and tried several courses of acupuncture, anticonvulsants and antidepressants (imipramine) without effect. Previous medical work-up has included blood tests and EEG and cranial computed tomography (CCT), which were reported to be normal. Apart from the headache episodes, her medical history is completely unremarkable.

Work-up and process

The patient consulted us during the beginning of the last headache episode in June 2003. Our work-up included all the investigations suggested to identify acknowledged underlying symptomatic causes of CPH (18): blood count, ESR, and other laboratory tests screening for vasculitis (ANA, pANCA, cANCA, dsDNA, ENA, anti-cardiolipin and anti-phospholipid antibodies) and as well as brain imaging procedure [CCT with contrast and magnetic resonance imaging (MRI)] to look for an intracranial tumour such as a lesion at the sella turcica, all of which were normal. Since occipital pain also was part of the picture an MRI of the cervical spine was performed and showed no abnormalities. The ECG was normal with no bundle brunch block or atrial fibrillation. Lumbar puncture was normal and excluded intracranial hypertension responsive to indomethacin. We started her on indomethacin 25 mg three times daily in combination with an antacid (omeprazole). The morning following the first dose she was completely headache free and stayed so. After 4 weeks the patient, who was on holiday at that time, assumed that the natural course of the episode might have been over and stopped the medication. However, 36 h after stopping the medication the headache recurred, so that she started the medication again, and again the headache stopped in the next 12 h. Another 2 weeks later probationary stopping of the medication did not result in headache recurrence. In the next headache phase, which occurred 4 months after initial presentation in our headache clinic, we began the indomethacin at a 25-mg dose daily, but a dose of only 50 mg daily was sufficient to stop the headaches.

Discussion

This case resembles a headache syndrome sharing the typical symptoms of EPH, with attack frequency and duration of individual attacks and the complete response to indomethacin being the most striking feature. However, several aspects of this condition are interesting.

First, to our knowledge no case of bilateral EPH has been reported so far. It has been described that pain may cross the midline and also affect the other side, but no perfectly symmetric bilateral pain has been reported for EPH before. However, bilateral pain has been reported in at least three cases of CPH (19–21) and also in other trigemino-autonomic syndromes, such as cluster headache and hemicrania continua. Another interesting aspect is the lack of any autonomic symptoms, despite extensive interviewing of the patient and her husband. EPH, like other trigemino-autonomic syndromes, is typically accompanied by a number of usually ipsilateral autonomic phenomena. Our patient described photo- and phonophobia as well as allodynia of the facial skin. However, according to the Mayo Clinic series migrainous symptoms are not rare in CPH (20). Finally, the presumed hormonal influence is noteworthy. Interestingly, even though the patient experienced consistently three to four headache episodes annually, she did not experience a single headache episode through either her pregnancy or breast-feeding.

In conclusion, we describe a patient with a headache condition, in which the time course and the temporal dynamics are sufficient to lead to the diagnosis of EPH, even though several aspects of this condition are unusual for ‘classical EPH’. These aspects include the bilateral location of pain, photo- and phonophobia and the lack of autonomic symptoms and the hormonal influence.