Abstract
Migraine is reported to vary in accordance with a number of internal and external factors such as menstruation, variation in sleep duration and intake of certain or alcohol (1). Exposure to light may be irritating for some patients with migraine and in some cases provoke new attacks. There is a special interest in how the burden of migraine may be influenced by the large seasonal variation in light conditions in an arctic area. The literature suggesting that light sensitivity may be related to hypothalamic dysfunction in patients with migraine, while pathophysiological mechanisms in patients with chronic paroxysmal hemicrania (CPH) are less known. In Troms⊘ (North Norway), an arctic area north of the polar circle, we regularly see migraine patients reporting more severe headache during the light season. Since the focus on seasonal variation of headache in certain primary headache syndromes is limited in the literature, we present two patients with migraine, with and without aura, one fulfilling the criteria of CPH, all reporting more headache ailments during the bright arctic summer with the presence of the midnight sun.
Although the understanding of migraine pathophysiology is incomplete, there are some evidence that the hypothalamus may play a role in the production of symptoms. Before menarche, the frequency of the disease is similar in boys and girls, while the gender difference in adults may be due to cyclic hormonal changes in women. Migraine is related to menstruation in many women (2, 3), especially in those with aura (4). How migraine is initiated is not known, but a transient dysfunction in the hypothalamus may possibly explain migraine symptoms in menstruation migraine (5). Less is known about how seasonal variation may trigger headache in CPH. The aim of this work was to present three patients, two with migraine and one with CPH, who all reported more severe headache in the arctic light season, and thereby indicate a direction for further studies.
Case reports
Case 1
A 32-year-old woman working as a nurse in the community was referred to our neurological department because of migraine. She had already tried two different triptans (sumatriptan and rizatriptan) prescribed by a general practitioner with limited effect. Her menstruation cycle was irregular at the time of examination. Except from birth delivery 3 years earlier and previous tonsillectomy, she reported no previous or concomitant disorders. She had suffered from migraine for as long as she could remember with a frequency of two to three attacks per month, frequently related to menstruation. Usually the attacks appeared half a day before menstruation and typically started on the right side of the head, shifting to the left side the next day. The headache was precipitated by visual aura in more than half of the migraine attacks. A number of factors including alcohol, variation of sleep duration, menstruation, dusty bedroom, tension headache and pain in the neck and stressful situations commonly triggered migraine attacks. The duration of headache was 1–2 days and the pain, which she perceived as severe, became worse while performing daily activities during the attack. Nausea commonly accompanied the headache. In the light season from March until September, she also became hypersensitive to light. Both intensive light and prolonged exposure to light frequently triggered attacks, but the migraine features were otherwise the same regardless of season. Between the attacks she also experienced light hypersensitivity and therefore had to wear sunglasses while performing out-door activities during the light season. Clinical neurological examination was normal and the patients was treated with another triptan (eletriptan) and recommended a β-blocker as prophylactic treatment during the light arctic ‘midnight-sun’ season. The attacks were both less severe and less frequent during the β-blocker course at the 1-year follow-up consultation.
Case 2
A woman aged 35 years had been treated for narcolepsy and migraine for many years. In 2003 she moved from southern to northern Norway (60° north) to settle down in Finnmark (72° north), the northernmost county in Norway. Previously her migraine attacks had occurred almost exclusively at the time of menstruation, but after she moved to Finnmark the headache frequency increased. A few months later, she was hospitalized due to daily pulsating and throbbing headache. No aura or autonomic symptoms were reported in the medical notes, but she reported nausea and light intolerance along with the headache. Attacks started typically with mild pain in the neck. Gradually she developed a severe and pulsating headache on both sides of the head frequently triggered by stress, sleep deprivation, strong smells, sexual activity and alcohol or food intake. Suspecting a condition of mixed migraine and medication overuse headache, sumatriptan was withdrawn for a period of time. Three months later, she was readmitted to hospital for chronic daily headache which had not improved significantly. She then started prophylactic treatment for migraine with an angiotensin II receptor antagonist (kandersartan) with a daily dose of 8 mg. Two months later she visited the clinic for control. The migraine headache had worsened markedly after moving to North Norway. In contrast to when living in southern Norway, the migraine attacks increased in frequency during the light season compared with winter, with a long period without appearance of the sun. Additionally, exposure to light became the most troublesome trigger factor for her migraine headache. She had to use sunglasses almost always when outside in order to avoid migraine attacks. After being recommended not to use daily analgesic drugs she became aware of the seasonal variation of her migraine. The situation improved and she needed no further neurological assistance the next 12 months.
Case 3
A 35-year-old woman living in the northernmost county in Norway (Finnmark) had episodic headaches with a duration of 3 years. She had previously been treated for anorexia. She worked in the community as a specially trained pedagogue. There was no history of headache among first-degree relatives. She had been treated for migraine before referral and used a triptan (sumatriptan) at the time of consultation. β-Blocker had recently been withdrawn due to a possible side-effect (weight gain). Regularly the migraine started with visual aura and was followed by unilateral, pulsating, severe headache along with nausea and photophobia. The other headache was short-lasting, with a duration of about 2 min and occurred periodically five to six times per day and was always located on the right side. She had conjunctival injection ipsilaterally during the attacks. The period of attacks started in the light season and gradually decreased after summer time, while the migraine attacks continued as before. Later the same year, she had a new short period with episodic headache. The frequency of attacks increased from about April the year thereafter. She was then treated with indometacin (25 mg × 3) daily, whereupon the CPH symptoms disappeared abruptly. The migraine symptoms was also less severe in this period. On a revisit 1 year later, the symptoms were still under control. When she tried to cease indomethacin on her own, the headache appeared exactly as in recent years. The neurologist recommended her to use indometacin more regularly, especially during the light arctic season, i.e. from April to September.
Discussion
In North Norway (67° to 72° north), an area with extreme variations in light exposure, it is a common clinical experience that patients with migraine suffer more from headache in the light season. The sun is completely absent from about 20 November to 20 January depending on location, while the midnight sun is present from mid May until mid July. It is well known that migraine may be triggered by weather conditions as well as many other stimuli. Obviously, case reports are biased and can never be representative. The reported patients, all fulfilling the criteria for well-known headache disorders (migraine and CPH) set by the International Headache Society (IHS) (6), illustrate some interesting features of migraine that may point to new scientific hypotheses.
In the first case, the burden of migraine decreased after trying prophylactic treatment limited to a certain interval during the light season, demonstrating a co-occurrence of circadian variability and advent of migraine headache indicating a possible connection between circadian and biological rhythms. A second patient with migraine living in the southern part of Norway who moved to an area north of the arctic circle reported that the headache for the first time started to vary with the seasons, being worse in the northern light summer. She also became more sensitive to light between attacks and used sunglasses frequently when she performed outdoor activities. The migraine changed in character, with the consequence that she developed chronic daily headache, probably related to excessive use of analgesic medication. The third case, involving an increase in the number of headache episodes, as seen in migraine patients, was also a patient with CPH. This has not previously been reported in the medical literature, at least not in patients living in an arctic area. Although we cannot conclude that CPH and migraine share common biological features based on these observations alone, it is an interesting finding that exposure to light in an arctic area increases the burden of headache.
In a previous questionnaire study of about 1000 patients referred for headache, migraine patients reported more headache ailments during the light than the dark season (7). In a follow-up study, we found that close to 50% of patients with aura, but less than 20% of patients without aura, reported more frequent attacks during the bright arctic season (8). The mechanism behind seasonal variation of migraine is not known. There is evidence that exposure to light and darkness may be related to hypothalamic functions. Others have shown that light exposure suppresses melatonin more markedly in migraineurs compared th controls in symptom-free intervals (9). Migraine is frequently associated with menstruation, especially in migraine without aura (3). The complex interplay between the hypothalamic–pituitary axis and ovarian function seems to play a role in migraine related to menstruation (5). The effects may be mediated via the suprachiasmatic nucleus and melatonin production (9). CPH is a primary headache disorder classified as one of the trigeminal autonomic cephalalgias (10). The headache is strictly unilateral and is accompanied by autonomic symptoms (5). Cluster headache, a related paroxysmal severe headache syndrome, may follow a seasonal rhythm (11) and many patients wake up at night with attacks (12). Most authorities now regard the hypothalamus as the primary site of dysfunction in cluster headache, but how the hypothalamic functions are related to CPH is less known. The notion of an association between migraine with aura and cortical depression has been reported for several decades. Recently, several reports using advanced methods such as functional magnetic resonance imaging have revealed sequential cortical events during a migraine attack starting with an initial hyperaemia followed by cortical spreading, mild hypoperfusion and recovery in the area where the migraine-related findings started (13). There is evidence in the literature supporting the notion that hyperexcitability of the occipital cortex in migraine patients may explain the seasonal periodicity with more migraine attacks in the light season, especially in those with aura (14, 15). Whether circadian and biological rhythms, such as menstruation, may covary and thereby produce symptoms in migraine as well as in other episodic headache disorders is an interesting question. A further question is how the light and dark changes may be related to biological rhythms. Light may alter biological systems by its intensity, length of exposure, change between extreme light and darkness or a combination of these factors.