Facial paroxysmal hemicrania associated with the menstrual cycle

Abstract

Paroxysmal hemicrania (PH) is a rare trigeminal autonomic cephalalgia (TAC) which is usually not associated with the menstrual cycle and usually affects the first trigeminal branch. We present a 47-year-old female patient with a facial variant of PH. For over 11 years, the patient had suffered from 8 to 12 typical PH attacks per day localized in the left maxilla in bouts of 4–9 days solely during her menstruation and ovulation. Single dosages of indomethacin 25 mg showed good efficacy in the prevention of the attacks for several hours. However, the intake of indomethacin had to be ceased due to severe psychiatric side effects. Ibuprofen 400 mg also reliably reduces the attack frequency with the same effectiveness as indomethacin. Attacks of PH can occur solely in the facial region and can be associated with the menstrual cycle which can prove to be a diagnostic challenge. Also, the intake of indomethacin can be limited by psychiatric side effects but can be adequately substituted by ibuprofen.

Background

Paroxysmal hemicrania (PH) is a trigeminal autonomic headache characterized by severe, strictly unilateral head pain attacks lasting only minutes, often accompanied by autonomic symptoms, which responds absolutely to indomethacin. ^1,2 It was first described in the 1970s by Sjaastad and Dale ^3,4 and is considered part of the trigeminal autonomic cephalalgia (TAC). ^5,6 The International Classification of Headache Disorder, 3rd edition (ICHD-3), separates episodic PH from chronic PH, in which attacks occur for more than 1 year or with remission periods of less than 3 months. ¹ PH is a rare headache syndrome. The incidence rate was found to be 0.1 (95% confidence interval: 0.0–0.5) per 100,000 person years in a 2009 study. ⁷ The prevalence is unknown but estimated to be about 1 in 50,000. ^8,9 Women were initially reported to be affected more often by PH than men with a ratio of 2.36:1, ⁸ while later studies could not confirm a significant female predominance. ² Facial involvement is rare. ¹⁰

Unlike migraine, where an association to menstruation is rather frequent, leading to a comment and separate list in the appendix of ICHD-3 (A1.1.1 Pure menstrual migraine without aura, A1.1.2 Menstrually related migraine without aura, A1.2.0.1 Pure menstrual migraine with, aura, and A1.2.0.2 Menstrually related migraine with aura), ¹ an association with the menstrual cycle is certainly rare in nearly all other primary headaches.

To the best of our knowledge only one case report of a patient with PH associated to menstruation has been published to this date by Maggioni et al. first in 2007. ^11,12 The 43-year-old patient “suffered from menstrual related migraine without aura and later developed a typical PH strictly time-related to her menses.” ¹¹ Another study reported of one female patient who experienced worsening of her PH during the menstruation, without giving further details. ¹³ In 1991, a case report was published, reporting about a woman with attacks lasting seconds to 1 min accompanied by trigeminal autonomic features always occurring during her ovulation. ¹⁴ The authors discussed this syndrome as being related to episodic PH at the time of publishing. However, by current classification standards, this would rather account for a disease of the SUNCT/SUNA spectrum. ¹

In the following, we describe a female patient who suffered from menstrual-related migraine with and without aura and later developed attacks fitting the ICHD-3 criteria for 3.2.2 Chronic paroxysmal hemicrania, ¹ which only occurred in the face and were strictly associated to her menstruation and ovulation.

Case presentation

Written informed consent was obtained from the patient for publication of this case report. The 47-year-old female patient presented herself first in July 2018 with attacks of strictly one-sided facial pain in her left maxilla, precisely the premolars 24 and 25 (according to the World Dental Federation notation ¹⁵ ). These attacks first appeared 11 years prior to the first consultation, and the clinical manifestation had never changed. The pain was described as nagging and to be of extreme intensity (8–10/10 in the Numeric Rating Scale). During the attacks, the patient experiences ipsilateral lacrimation and conjunctival injection. Additionally, she reported subtle nausea during the attacks. She usually “freezes” during attacks and tries to refrain from any movements. The attacks appear spontaneously, and the patient cannot name any triggers for the attacks. She denied being able to worsen or alleviate the pain.

Without medication these painful attacks last around 15–20 min (never longer or shorter) and arise usually between 8 and 12 times per day with approximately 2–3 h gap between attacks. The attacks occur during the whole 24 h including at night without any circadian rhythm. In between attacks, the patient is basically pain-free and describes only a subtle ache in her teeth, nuchal region, and shoulder.

Since the attacks first appeared in 2007, they had always followed the same pattern and from 2013 onward until today the patient kept an electronic diary of the attacks. For the utmost part, they had been strictly associated to her menstruation and the calculated ovulation, and during the last 11 years, the patient does not recall a menstruation without these typical attacks. Her current menstrual cycle lasts about 24–26 days and the attacks arise in bouts of 4–9 days (mean around 6 days) and can start from day −2 to +2 of the menstrual cycle and then again on day 9–12 of her menstrual cycle slightly before or during her calculated ovulation.

The typical bouts got longer over the years and from 2013 until today the amount of pain days has risen to 4–6 days during menstruation and again 2–3 days at ovulation.

Clinically unrelated, the patient suffered additionally since the age of 12 from a menstrual-related migraine with and without aura. The migraine attacks were accompanied by typical migraine-associated phenomena and lasted between 1 and 2 days. They usually occur on day 2 and 3 of the menstrual cycle, but in the past may have happened additionally independent from the menstruation. However, they became fewer and less intense over the last years. In the last 6 months, the patient only suffered from two migraine attacks which were not treated since they were rather mild. Migraine attacks and attacks of PH were never present at the same time.

The clinical–neurological examination was normal and magnetic resonance imaging showed no abnormalities. The patient suffered from symptoms of anxiety and a panic disorder in the past but is otherwise healthy.

Unsuccessful therapy strategies for PH included intake of zolmitriptan, nasal application of lidocaine, neural therapy, acupuncture, hypnosis, and pain-specific psychotherapy. The best efficacy was experienced with ibuprofen 400 mg retard or 600 mg which can reliably suppress attacks for 6–8 h. The attack frequency can be reduced from approximately 10 to approximately 4 per day. A subsequently consulted neurologist diagnosed a PH and proposed indomethacin. Indomethacin was taken irregularly between October 2013 and April 2014. Single dosages of indomethacin 25 mg could reliably prevent attacks for about 6–8 h. However, the patient suffered from pronounced adverse psychiatric side effects including tangible suicidal ideation during the intake of indomethacin, which was consequently stopped. Ibuprofen has since been taken in a dosage of 400 mg 2–3 times per day during the active bouts and dependably reduces the frequency to approximately four attacks per day.

Discussion

The patient suffers from facial pain attacks strictly associated with her menstrual cycle. Despite the occurrence in the second trigeminal branch, we diagnosed a variant of PH only occurring in the face due to the strict unilaterality of attacks with a defined length of 10–20 min, multiple attacks per day, slight autonomic symptoms associated with the attacks, inability to trigger attacks with alcohol and efficacy of nonsteroidal anti-inflammatory drugs (NSAID) but not triptans. An exclusive facial presentation of PH is infrequent, but not uncommon. ^2,16 Indomethacin was effective but lead to the rare side effect of psychiatric symptoms, whereas ibuprofen did not but is also effective. This unusual good response of PH to ibuprofen may be owed to the menstrual pattern of the disease.

The strict association of facial PH attacks with the menstrual cycle makes this case additionally remarkable. Only one other patient with menstrual PH (albeit headache attacks) has been described so far. ¹¹ Like that patient, our patient also suffered from migraine. The frequency and intensity of migraine however declined over the years, and it does not have a relevant impact on the patient’s well-being anymore. Over time, a “shift” of migraine pain into the facial region is a phenomenon seen in few, predominantly female patients. ¹⁶ However, this does not seem to play a role in this case, as the patient clearly described the emergence of a second, phenotypically different syndrome.

Another peculiarity of this case is the fact that psychiatric side effects limited the further use of indomethacin. In rare cases, indomethacin can possibly aggravate the symptomology of preexisting psychiatric disorders as mentioned by the summary of product characteristics, ¹⁷ and there are several case series describing adverse psychiatric events during the intake of NSAID, especially indomethacin and selective cyclooxygenase (COX)-2 inhibitors. ¹⁸ Considering the widespread use of NSAID, these adverse psychiatric side effects might be rare; however, this rather extreme case, including suicidal ideation, shows that they can be the limiting factor of an otherwise successful therapy. Another, often neglected side effect of indomethacin is headache. ¹⁹ It is the authors’ experience that in such cases COX-2 inhibitors may be useful with a higher efficacy than usual NSAID and that gabapentin is certainly the method of second choice. ^20,21

Clinical implications

– A strict association of PH to the menstrual cycle is extremely rare.

– Attacks of PH can occur solely in the facial region.

– The intake of indomethacin can be limited by psychiatric side effects.

– The efficacy of ibuprofen for the treatment of PH can be comparable to indomethacin in some patients.