Rheumatology Advance Access originally published online on December 20, 2005
Rheumatology 2006 45(5):621-623; doi:10.1093/rheumatology/kei255
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The prevalence of headache in Behçet's syndrome
Department of Clinical Neurosciences, Royal Free Hospital and RFC/UCL School of Medicine, Pond Street, London NW3 2QG, UK.
Correspondence to: D. Kidd. E-mail: d.kidd{at}medsch.ucl.ac.uk
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Objectives. Behçet's syndrome is an uncommon systemic disorder that involves the nervous system in 5% of cases. Headache may arise in conjunction with such complications but also appears to occur independently. We sought to define the prevalence of headache in an unselected group of patients with Behçet's syndrome, to characterize the headache syndromes and to identify what treatments are being used.
Methods. A questionnaire was sent to an unselected group of patients through their support group newsletter.
Results. The results showed a prevalence of recurrent headache in 82.5% of responders; the majority exhibited symptoms that fulfilled the International Headache Society criteria for migraine, with a higher than normal prevalence of visual or sensory aura of 52%. Using the Migraine Disability Assessment (MIDAS) score for disability in migraine, 62% of responders showed moderate or severe disability. Headache treatment was poor, the majority of sufferers resorting to over-the-counter remedies; preventative treatments had rarely been prescribed.
Conclusions. Recurrent headache is very common in Behçet's syndrome, is poorly treated and is associated with disablement.
KEY WORDS: Behçet's syndrome, Neurological complications, Headache
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Behçet's syndrome is a multisystem disorder of unknown aetiology in which orogenital ulceration, skin lesions and uveitis are common. The disorder may also affect the joints, gut, lungs and the nervous system. For the most part the pathophysiology of the disorder has a vasculitic basis, although this is not seen within the nervous system. Neurological complications involve an inflammatory infiltration or arise as a manifestation of vascular complications [1]. Neurological involvement is seen in around 5% of all cases of Behçet's syndrome [2], inflammatory and parenchymal involvement being more common than vascular complications.
Headache is a frequent accompaniment of meningoencephalitis and meningitis, in which an escalating, often throbbing, headache develops and worsens over several days. Photophobia, neck stiffness and focal neurological signs often, but not always, follow, and as the syndrome resolves the headache disappears. However, many patients find that headache is a frequent and troublesome symptom in Behçet's syndrome, including those with no clinical evidence for neurological involvement. MRI studies of patients with Behçet's syndrome have shown that in patients with headache as the sole neurological symptom, around half had normal MRI scans and the remainder showed small white-matter lesions within the hemispheres [3, 4]. This implies that not all patients with headaches who have Behçet's syndrome also have neurological involvement by means of perivascular inflammatory cell infiltration or by venous occlusion. Another study [5] of 20 patients without neurological signs (the symptom of headache was not noted in the paper) who underwent non-activated SPECT scanning showed decreased or asymmetric HMPAO uptake or both in 35% of cases. Hence there may be a proportion of patients without neurological involvement who may have abnormal cerebral blood flow; whether or not this may be associated with headache or inflammatory neurological disorders is not clear.
The purpose of this study was to define the prevalence of headache in an unselected group of patients with Behçet's syndrome, to characterize the headache syndromes and to identify what treatments are being used.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Members of the Behçet's Syndrome Society in the UK were approached and invited to fill out a questionnaire. The approach was made as an advertisement in the quarterly newsletter sent to all members of the society. In the questionnaire they were asked to note whether or not they had ever suffered a series of neurological symptoms, including headache, loss of balance, double vision, numbness or tingling, vestibular symptoms and others. They ticked boxes and sent it in by post. A further questionnaire was sent to those who had responded, which asked them to note the characteristics of any headache that they had suffered, its frequency and duration, the presence of additional symptoms (Table 1), and whether or not there was an aura. For those with recurrent headaches, the treatment the patient chose to use and its usual effect were also noted, and a severity score that has been validated in migraine, the MIDAS (Migraine Disability Assessment) instrument [6], was used to assess headache-related disability. Ethical approval for the study to be performed was granted by the London Multicentre Research Ethics Committee.
|
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The initial questionnaire was returned by 327 members; of these, 270 (82.5%) had noted headache as a recurrent symptom. Two hundred and twenty-three returned the second questionnaire, of whom 201 (90.0%) had noted headache. None had had neurological complications other than headache.
Headache was common and recurrent (Table 2) and often lasted for days. The presence of throbbing, a unilateral onset, photophobia and phonophobia were taken to indicate a neurovascular type headache; the absence of these symptoms with a description of a dull, constant, occipitovertical ache was taken to indicate a tension-type headache. Any aura was described in words or diagrammatically. The MIDAS score was calculated based on the information provided. A score of 0–5 indicates little or no disability (grade I), 6–10 mild disability (grade II), 11–20 moderate disability (grade III) and greater than 21 severe disability (grade IV) [6]. Fifty (24.5%) patients had grade I, 28 (13.8%) grade II, 31 (15.2%) grade III and 95 (46.5%) grade IV disability.
|
The majority of patients was inadequately treated; data were acquired from 193 respondents; most (84%) used over-the-counter medicines and only 5% were using treatments specifically for neurovascular headaches. Even fewer patients were using a migraine preventative such as pizotifen or a ß-blocker (Table 3).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In this cohort of patients the prevalence of headache was high at 82.5%; clearly there may be bias in the second group in that the questionnaire was focused on headache alone, and it is not, thus, surprising that the prevalence of headache rose in this group. There may be further bias; not all patients with Behçet's syndrome are members of the Behçet's Syndrome Society, and it is conceivable that those who are members are more severely affected than those who are not and that those who responded are more severely affected by neurological symptoms. Others, previously diagnosed who no longer have disease activity, may not have responded, feeling that their headaches were unrelated. The prevalence of Behçet's syndrome in Hertfordshire was 5 x 105 in 2002 [7], suggesting that there would be 1500 patients in the UK were the prevalence to be the same throughout the country; hence, the survey cannot claim to represent the experiences of all patients in the UK. However, previous studies of selected groups of patients attending Behçet's syndrome clinics have also shown high prevalence of headaches [8–10]. The majority of patients in this cohort described headaches that fulfil the International Headache Society criteria for migraine [11]. Only 2% had headache characteristics in keeping with tension-type headache. Of the remainder, a surprisingly high percentage (52.7%) experienced visual aura during most of their headaches. The prevalence of migraine in the general population is 8–17% and the prevalence of aura is only 2–30% [12, 13]; hence, in this population both headache and migraine aura are over-represented. Why might this be? Clearly there are inadequacies in the method used in this study; non-responders were not approached in order to define whether or not the results are skewed in favour of those with more severe and frequent headache symptoms, and the data were not acquired prospectively; rather, the responder was asked to give an impression of headache frequency and severity, which may not therefore be accurate. Nonetheless, it is clear from this and other studies that vascular headache is a common symptom in this disorder.
Migraine is a neurovascular headache in which dysfunction of nociceptive afferent pathways within the brainstem and diencephalic nuclei occurs, leading to excessive discharges from the spinal nucleus of the trigeminal nerve, so causing the appreciation of pain. Dilatation of blood vessels occurs as a secondary phenomenon, leading to further pain. Migraine aura arises as result of cortical hyperaemia immediately followed by oligaemia, which is due to a ‘spreading depression’ of depressed cortical function [14]. Why some patients have aura and others do not is not understood.
In Behçet's syndrome vasculitis may arise, but perhaps not in the brain [15]; venous thrombosis, including that of the venous sinuses, may arise and, more rarely, aneurysm formation. There is accumulating evidence that factor V Leiden mutations contribute to the vascular complications of uveitis [16] and to venous thrombosis [17]. The prevalence of these abnormalities in headache has not yet been established. Vascular endothelial cell abnormalities also exist, and studies of brachial artery flow-mediated dilatation show impairments in patients with Behçet's syndrome which were absent in normal controls and which were reversed by the administration of vitamin C, an antioxidant that removes superoxide anion radicals [18]. This study suggested that reduced endothelial cell function in Behçet's syndrome may be related to increased oxidative stress. Nitric oxide levels are reduced in Behçet's syndrome, which would be inclined to induce vasoconstriction since nitric oxide is a potent vasodilator, and yet vasodilators such as GTN are used to induce migraines in susceptible patients for studies. It is not clear, therefore, how an underlying vascular abnormality in Behçet's syndrome may contribute to this. Studies of vascular reactivity in migraine show an increased response to exercise, stress and carbon dioxide, which again is the opposite to that seen in Behçet's syndrome.
Another association to consider would be a linked genetic predisposition; inherited forms of migraine have been linked to the 
1 subunit of the P/Q-type voltage-gated calcium channel on chromosome 19 [19]. No genetic association between Behçet's syndrome and this gene has been found, however, and a recent study in which the genome was screened has shown evidence for linkage on chromosomes 6 and 12 [20].
Vascular headaches are said to be prevalent in systemic lupus erythematosus [21] and Sjögren's syndrome [22], but again the pathogenesis is not understood. Moreover, a recent meta-analysis of previously published studies of headache in lupus has failed to prove that a true relationship exists between the two disorders [23].
Epidemiological studies of migraine have shown that most patients are undertreated, many having given up on physician advice and resorting to over-the-counter preparations for migraine relief [12]. Such appears also to be the case for this cohort of patients. In the author's experience, many patients simply presume that frequent headache is part of the difficulty of having Behçet's syndrome and accept that nothing may be done successfully to alleviate the problem. However, it is also the author's experience that these patients respond well to standard antimigraine preparations, such as propranolol and pizotifen. No formal trial of the effectiveness of these drugs in the treatment of headache in Behçet's syndrome has yet been undertaken.
In summary, this study has revealed a very high prevalence of headache in an unselected population of patients with Behçet's syndrome. The majority of headaches is of neurovascular type and the prevalence of visual or sensory aura is higher than that seen in the general population of migraine sufferers. In general, patients are inadequately treated. Neurovascular headache occurs in patients with and without clinical evidence for inflammatory or vascular neurological complications of the disorder. The reason for the high prevalence of headache in this population is not currently understood and a formal class 1 prospective epidemiological study is currently underway that will investigate this further.
|
Acknowledgments |
|---|
Professor Peter Goadsby gave advice on the structure of the headache questionnaire and the use of the MIDAS instrument. He also made comments on the first draft of the manuscript. The author is extremely grateful for this.
The authors have declared no conflicts of interest.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Kidd D, Steuer A, Denman AM, Rudge P. Neurological complications of Behçet's syndrome. Brain 1999;122:2183–94.
[Abstract/Free Full Text] - Kidd D. The prevalence of Behçet's syndrome in Hertfordshire, UK. In: Zouboulis C, ed. Adamantiades-Behçet's disease. Adv Exp Med Biol 2003;528:95–7.[Medline]
- Jager HR, Albrecht T, Curati-Alasonatti WL, Williams EJ, Haskard DO. MRI in neuro-Behçet's syndrome: comparison of conventional spin-echo and FLAIR pulse sequences. Neuroradiology 1999;41:750–8.[CrossRef][Medline]
- Tali ET, Atilla S, Keskin T, Simonson T, Isik S, Yuh WTC. MRI in neuro-Behçet's disease. Neuroradiology 1997;39:2–6.[CrossRef][Web of Science][Medline]
- Avci O, Kutluay E, Argon M, Erdem S, Gunes AT. Subclinical cerebral involvement in Behçet's disease: a SPECT study. Eur J Neurol 1998;5:49–53.[Medline]
- Stewart WF, Lipton RB, Kolodner K, Liberman J, Sawyer J. Reliability of the Migraine Disability Assessment score in a population-based sample of headache sufferers. Cephalalgia 1999;19:107–14.[CrossRef][Web of Science][Medline]
- Kidd D. The prevalence of Behçet's syndrome and its neurological complications in Hertfordshire, UK. Adv Exp Med Biol 2003;528:95–7.[Medline]
- Serdaroglu P, Yazici H, Ozdemir C, Yurdakul S, Bahar S, Atkin E. Neurologic involvement in Behçet's syndrome. A prospective study. Arch Neurol 1989;46:265–9.
[Abstract/Free Full Text] - Wechsler B, Dell’Isola B, Vidailhet M, Dormont D, Piette JC, Bletry O, Godeau P. MRU in 31 patients with Behçet's disease and neurological involvement: prospective study with clinical correlation. J Neurol Neurosurg Psychiatry 1993;56:793–8.
[Abstract/Free Full Text] - Monastero R, Mannino M, Lopez G et al. Prevalence of headache in patients with Behçet's disease without overt neurological involvement. Cephalalgia 2003;23:105–8.[Medline]
- Headache classification committee of the International Headache Society. The international classification of headache disorders. Cephalalgia 2004;24:1–160.
- Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States. Epidemiology and patterns of health care use. Neurology 2002;58:885–94.
[Abstract/Free Full Text] - Steiner TJ, Scher AI, Stewart WF, Kolodner K, Liberman J, Lipton RB. The prevalence and disability burden of adult migraine in England and their relationship to age, gender and ethnicity. Cephalalgia 2003;23:519–27.[CrossRef][Web of Science][Medline]
- Goadsby PJ, Lipton RB, Ferrari MD. Migraine – current understanding and treatment. N Engl J Med 2002;346:257–70.
[Free Full Text] - Hadfield MG, Aydin F, Lippman HR, Kubal WS, Sanders KM. Neuro-Behçet's disease. Clin Neuropathol 1996;15:249–55.[Web of Science][Medline]
- Verity DH, Vaughan RW, Madanat W et al. Factor V Leiden mutation is associated with ocular involvement in Behçet disease. Am J Ophthalmol 1999;128:352–6.[CrossRef][Web of Science][Medline]
- Gurgey A, Balta G, Boyvat A. Factor V Leiden mutation and PAI-1 gene 4G/5G genotype in thrombotic patients with Behçet's disease. Blood Coagul Fibrinolysis 2003;14:121–4.[Medline]
- Chambers JC, Haskard DO, Kooner JS. Vascular endothelial function and oxidative stress mechanisms in patients with Behçet's syndrome. Am J Cardiol 2001;37:517–20.
[Abstract/Free Full Text] - Ophoff RA, Terwindt GM, Vergouwe MN et al. Familial hemiplegic migraine and episodic ataxia type 2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996;87:543–52.[CrossRef][Web of Science][Medline]
- Gul A, Hajeer AH, Worthington J, Ollier WE, Silman AJ. Linkage mapping of a novel susceptibility locus for Behçet's disease to chromosome 6p22-23. Arthritis Rheum 2001;44:239–40.[CrossRef][Medline]
- Glanz BI, Venkatesan A, Schur PH, Lew RA, Khoshbin S. Prevalence of migraine in patients with systemic lupus erythematosus. Headache 2001;41:285–9.[CrossRef][Web of Science][Medline]
- Pal B, Gibson C, Passmore J, Griffiths ID, Dick WC. A study of headaches and migraine in Sjogren's syndrome and other rheumatic disorders. Ann Rheum Dis 1989;48:312–6.
[Abstract/Free Full Text] - Mitsikostas DD, Sfikakis PP, Goadsby PJ. A meta-analysis of headache in systemic lupus erythematosus: the evidence and the myth. Brain 2004;127:1200–9.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||