Abstract
Our objective was to compare the presence of self-reported unilateral photophobia or phonophobia, or both, during headache attacks comparing patients with trigeminal autonomic cephalalgias (TACs)—including cluster headache, shortlasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and paroxysmal hemicrania—or hemicrania continua, and other headache types. We conducted a prospective study in patients attending a referral out-patient clinic over 5 months and those admitted for an intramuscular indomethacin test. Two hundred and six patients were included. In episodic migraine patients, two of 54 (4%) reported unilateral photophobia or phonophobia, or both. In chronic migraine patients, six of 48 (13%) complained of unilateral photophobia or phonophobia, or both, whereas none of the 24 patients with medication-overuse headache reported these unilateral symptoms, although these patients all had clinical symptoms suggesting the diagnosis of migraine. Only three of 22 patients (14%) suffering from new daily persistent headache (NDPH) experienced unilateral photophobia or phonophobia. In chronic cluster headache 10 of 21 patients (48%) had unilateral photophobia or phonophobia, or both, and this symptom appeared in four of five patients (80%) with episodic cluster headache. Unilateral photophobia or phonophobia, or both, were reported by six of 11 patients (55%) with hemicrania continua, five of nine (56%) with SUNCT, and four of six (67%) with chronic paroxysmal hemicrania. Unilateral phonophobia or photophobia, or both, are more frequent in TACs and hemicrania continua than in migraine and NDPH. The presence of these unilateral symptoms may be clinically useful in the differential diagnosis of primary headaches.
Keywords
Introduction
Photophobia and phonophobia are reported in some three-quarters of migraine patients and form part of the core characteristics employed in the International Headache Society definition (1). Phonophobia and particularly photophobia are reported in patients with cluster headache (2–4), paroxysmal hemicrania (5), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) (6) and hemicrania continua (5), although this has never been systematically studied. The trigeminal autonomic cephalalgias (TACs: cluster headache, paroxysmal hemicrania and SUNCT), as well as hemicrania continua, leave a clinical impression that thesensory sensitivity to light and sound, photophobia and phonophobia, is unilateral and ipsilateral to the pain (7).
The aim of this study was to assess systematically the laterality of hypersensitivity to light and sound in patients with primary headache, including patients presenting with medication overuse, attending a headache referral clinic. We wished to address whether there was lateralization of photophobia and phonophobia with the pain, and whether this had any clinical value in the differential diagnosis of TACs, hemicrania continua and migraine.
Methods
Patients from our headache out-patient clinic, or patients admitted for an intramuscular indomethacin test (8, 9) as part of their routine clinical work-up in the differential diagnosis of TACs and hemicrania continua, were questioned. Having observed a possible excess of lateralized photophobia and phonophobia in routine practice, and introduced this question into our routine clinical evaluation, we considered this investigation in the nature of clinical audit by current UK definitions. Ethical approval is not required for audit.
The patients were routinely asked during a clinical interview about the presence of photophobia and phonophobia with questions such as ‘Does light or sound bother you during a headache attack’ and by questions regarding their behaviour during the attack such as ‘During a headache attack, would you prefer to be in a dark and quiet room?’. Unilateral phonophobia and photophobia was diagnosed when these symptoms were one-sided. The patients were also asked about laterality of the pain and the light and sound sensitivity.
We prospectively recorded information from October 2004 until February 2005 by proforma, and had one physician verify all the clinical data (P.I.). Patients with TACs and hemicrania continua and patients with episodic migraine or chronic migraine and new daily persistent headache (NDPH) (10) were considered as a contrasting population. Medication overuse patients (11) were included since they are a very important part of the neurologist's headache case load.
As is standard, all patients had a comprehensive headache history, general neurological and medical history and neurological examination with investigations as indicated.
Patients were diagnosed according to the International Headache Society criteria (1), except for those with medication overuse, who represent cases fulfilling overuse but not necessarily withdrawal characteristics, since we wished to explore clinical features useful at presentation. NDPH was diagnosed syndromically as we have described (10).
Analysis
Data are presented as tabulated summary measures. We tested the hypotheses that unilateral photophobia or phonophobia is more common in episodic TACs vs. episodic migraine and that it is more common in chronic TACs and hemicrania than in migraine, medication overuse and NDPH. A χ2 test was used with a level of significance of P < 0.05.
Results
We screened 242 patients, 88 men and 154 women, aged 18–86 years (mean 43 years). A total of 36 subjects with secondary headaches, other than medication-overuse headache, auditory or visual disorders and those in whom the diagnostic studies were not completed, were excluded.
Pain
Unilateral pain in most of the attacks was experienced by 38 of 54 patients with episodic migraine with and without aura (70%) and in 33 of 48 patients with chronic migraine (69%). Patients with medication overuse (11) usually reported bilateral pain, with superimposed hemicranial migraine attacks in 18 of 24 patients (75%). In all patients with TACs and hemicrania continua the pain was strictly unilateral during an individual attack.
Unilateral photophobia or phonophobia
Unilateral photophobia or phonophobia was reported by two of 54 patients with episodic migraine, and six of 48 with chronic migraine. In contrast, 51 episodic and 47 chronic migraine patients reported bilateral photophobia or phonophobia. No patient with medication overuse had unilateral photophobia or phonophobia. Only three of 22 patients with NDPH experienced unilateral photophobia or phonophobia.
Among patients with chronic cluster headache, 18 (85%) reported photophobia or phonophobia. In this group, 10 patients (48%) had unilateral symptoms, eight (38%) had bilateral symptoms and two experienced neither photophobia nor phonophobia. Unilateral photophobia or phonophobia was reported by four patients of five with episodic cluster headache and five of nine with SUNCT. Only one patient with episodic cluster and two patients with SUNCT did not have photophobia or phonophobia. In all patients with chronic paroxysmal hemicrania, hemicrania continua and probable TAC the pain was accompanied by photophobia or phonophobia. Unilateral symptoms were referred by four of nine with chronic paroxysmal hemicrania, six of 11 with hemicrania continua and five of six with probable TACs.
Comparing the episodic primary headaches, unilateral photophobia or phonophobia was more common in TACs than migraine (χ2 3 = 84.9, P < 0.0001). Furthermore, comparing chronic primary headaches, unilateral photophobia or phonophobia was more common in chronic cluster headache, chronic paroxysmal hemicrania and hemicrania continua than chronic migraine, patients with medication overuse or NDPH (χ2 5 = 117.3, P < 0.0001).
Lateralization
Patients with episodic and chronic cluster headache, chronic paroxysmal hemicrania, SUNCT syndrome or hemicrania continua reported photophobia or phonophobia ipsilateral to the side of pain in > 50% of the cases on average (Table 1).
Unilateral photophobia or phonophobia homolateral to pain for the different headache types
SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; NDPH, new daily persistent headache; TAC, trigeminal autonomic cephalalgia.
Discussion
Prospective recording of the relationship between lateralization of photophobia and phonophobia to the side of pain suggests this is a prominent feature in TACs and hemicrania continua (> 50%), and an uncommon feature of migraine (< 10%) and NDPH. The differential diagnosis between TACs, hemicrania continua and migraine may be difficult in some patients. Given there are no findings on physical examination, conventional structural neuroimaging or biomarkers, such as blood tests, for the primary headaches, clinical clues to the differential diagnosis are important. Lateralization of photophobia or phonophobia with pain is a simple symptom that can be helpful and has no disadvantages in clinical practice. Its presence seems to favour markedly TACs or hemicrania continua over migraine.
Unilateral pain and presence of cranial autonomic symptoms are features common to migraine (12) and TACs (1). In practice, differentiation of migraine from paroxysmal hemicrania and SUNCT is not particularly troublesome. The latter two conditions are distinguished by very short attacks of unilateral pain with prominent cranial autonomic features. Cluster headache can be distinguished from migraine by the circadian rhythmicity of attacks and the presence of cluster periods in the episodic form (13). Furthermore, the attacks of cluster headache are usually shorter and associated very often with a sense of restlessness or agitation (3). However, migraine is common, and thus sometimes presents with complex symptomatology. Cranial autonomic features, such as lacrimation or conjunctival injection, so typical of cluster headache, occur in migraine (12, 14), as would be predicted by the physiology of the trigeminal-autonomic connections in the brainstem (15). Some cluster headache patients have interparoxysmal pain, sometimes in association with medication overuse (16), and more so in chronic cluster headache. Although not always necessary, having an added clinical pointer can be helpful when dissecting apart TACs and migraine with unilateral pain.
The differentiation between hemicrania continua and unilateral chronic migraine is particularly troublesome, so much so that some consider the two conditions ends of a spectrum. Differential findings on functional brain imaging with dorsolateral brainstem activation in migraine (17) and, in addition, posterior hypothalamic and ventral midbrain activation in hemicrania continua (8) suggest a plausible basis for considering the conditions as distinct. The indomethacin effect of hemicrania continua is rapid, reproducible and can be easily differentiated from placebo (8). Indomethacin can be problematic in medium-term use, with some patients developing upper gastrointestinal symptoms and indeed peptic ulcer disease. Unilateral photophobia or phonophobia, or both, ipsilateral to the pain, is about three times more common in our hemicrania continua patients compared with chronic migraine sufferers with unilateral pain. Our findings might be particularly helpful in distinguishing hemicrania continua and chronic migraine in those migraineurs who present with unilateral pain in the majority of the attacks. In our migraine patients with unilateral pain, and in the patients with medication overuse, who were mostly migraineurs, phonophobia and photophobia were usually bilateral. This finding is consistent with the clinical outcome from a previous study (2), although Drummond (18) has reported greater photophobia on the painful side. The difference may relate to the methods employed. Our study was clinical, which is a limitation in some respects, and a strength in others, since clinicians are usually limited to history when making their assessment.
A limitation of our study, as with any clinical study of this type, is reliance on patient reporting and issues of recall. We were impressed by the clarity of the symptom of unilateral photophobia or phonophobia when it was present. Over time we have not noted patients to change their account often, perhaps because for TACs they have had to endure so many attacks that experience has reinforced the perception. Although this limitation cannot be avoided, it is also present when one uses this information in practice.
Another potential limitation of the study was the lack of a structured questionnaire with detailed and close-ended questions regarding the presence of photophobia and phonophobia and laterality of the symptoms. Although we can not eliminate completely an interviewer bias, the data were obtained in a clinical interview, almost all patients were questioned by the same physician, and all the physicians involved in this study were trained in headache diagnosis and used similar questions.
Unilateral photophobia or phonophobia as a single clinical symptom does not offer a diagnosis, but is a useful pointer. A comprehensive history is the most important tool for accurate headache diagnosis. When clinicians consider a differential diagnosis that includes migraine, TACs and hemicrania continua, certain clinical features, such as the presence of unilateral photophobia or phonophobia, may be helpful.