| 1. |
- Edvinsson, Lars
(author)
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Blockade of CGRP receptors in the intracranial vasculature: a new target in the treatment of headache.
- 2004
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 24:8, s. 611-622
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Research review (peer-reviewed)abstract
- In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP) but not with any of the other neuronal messengers. The purpose of this review is to describe the role of CGRP in the intracranial circulation and to elucidate a possible role for a specific CGRP receptor antagonist in the treatment of primary headaches. Acute treatment with a 5-HT1B/1D agonist (triptan) results in alleviation of the headache and normalization of the cranial venous CGRP levels, in part due to a presynaptic inhibitory effect on sensory nerves. The central role of CGRP in migraine and cluster headache pathophysiology has led to the search for small molecule CGRP antagonists with few cardiovascular side-effects. The initial pharmacological profile of such a group of compounds has recently been disclosed. One of these compounds has been found to be efficacious in the relief of acute attacks of migraine.
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| 2. |
- Smith, D, et al.
(author)
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An immunocytochemical investigation of human trigeminal nucleus caudalis: CGRP, substance P and 5-HT1D-receptor immunoreactivities are expressed by trigeminal sensory fibres
- 2002
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 22:6, s. 424-431
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Journal article (peer-reviewed)abstract
- 5-HT1D (but not 5-HT1B )-receptor immunoreactivity (i.r.) can be detected on trigeminal fibres within the spinal trigeminal tract of the human brainstem. The present study used immunohistochemical and morphometric techniques to determine the proportions of trigeminal fibres expressing substance P, CGRP or 5-HT1D -receptor immunoreactivities. Co-localization studies between 5-HT1D -receptor and substance P- or CGRP-i.r. were also performed. Brainstem material was obtained with consent (four donors) and the total number of immunoreactive fibres within the trigeminal tract was estimated using random field sampling. A greater proportion of fibres (>1 mum diameter) expressed CGRP-i.r. (80 +/- 6%) compared with substance P-i.r. (46 +/- 7%) or 5-HT1D -receptor-i.r. (25 +/- 1%). 5-HT1D -receptor-i.r. was co-localized on some CGRP- or substance P-i.r. fibres. This suggests that 5-HT1D -receptors can regulate the release of CGRP and substance P and may be relevant to the clinical effectiveness of 5-HT1B/1D -receptor agonists in the treatment of migraine and other cranial pain syndromes.
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| 3. |
- Uddman, Rolf, et al.
(author)
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Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2.
- 2002
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 22:2, s. 112-116
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Journal article (peer-reviewed)abstract
- In migraine and other primary headaches there is a strong vascular component. Besides the trigeminovascular components some of the associated symptoms point to the involvement of brain stem regions. The central limb of the trigeminal vascular pathway is its projection to the trigeminal nucleus caudalis (TNC) and to the C1-C2 levels of the spinal cord. The aim of the present study was to demonstrate the occurrence of some neurotransmitters in these regions in man. In both the TNC and in the Rexed's laminae I and II of the dorsal horns at the C1 and C2 levels there were numerous substance P immunoreactive fibres. Fibres containing calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) were moderately dense in number. Fibres containing vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) were not seen in the TNC or at the C1 and C2 levels of the spinal cord.
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| 4. |
- Ekbom, K, et al.
(author)
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Age at onset and sex ratio in cluster headache: observations over three decades
- 2002
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 22:2, s. 94-100
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Journal article (peer-reviewed)abstract
- Five hundred and fifty-four patients with episodic cluster headache (ECH) and chronic cluster headache (CCH) were examined between 1963 and 1997. Mean age at onset was significantly higher in women with CCH compared with women with ECH and in men with ECH or CCH. In women with CCH age at onset was evenly distributed from 10 to 69 years, whereas in men with CCH and in both sexes with ECH, there was a peak when they were in their 20s. In women with ECH a second peak of onset occurred in their 50s. Although not statistically significant, primary CCH started later in women (mean 50.8 years) than secondary CCH (mean 35.5 years). There was a significant variation in the male : female ratio with respect to age at onset, being largest between 30 and 49 years of age (ECH 7.2 : 1; CCH 11.0 : 1) and lowest after 50 (ECH 2.3 : 1; CCH 0.6 : 1). During the observation period of more than 30 years there was a trend towards a decreasing male preponderance; the male: female ratio was significantly higher among patients with onset before rather than after 1970. The proportion of episodic vs. chronic CH did not change during the study period. The nature of the sex- and age-related pattern of cluster headache onset remains to be elucidated but mechanisms associated with sex hormone regulation, perhaps of hypothalamic origin, may be involved, as well as environmental factors related to lifestyle.
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| 5. |
- Ekbom, K, et al.
(author)
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Periods of cluster headache induced by nitrate therapy and spontaneous remission of angina pectoris during active clusters
- 2004
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 24:2, s. 92-98
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Journal article (peer-reviewed)abstract
- Glyceryl trinitrate (GTN) is known to induce single extra attacks of cluster headache (CH) during active cluster periods, most probably via actions of nitric oxide (NO). Induction of whole periods of CH by organic nitrates has, however, attracted little attention in the literature. We report on eight patients with episodic CH and coexistent effort-induced angina pectoris. Cases 1-6 had been free of their headaches for many years but got recurrence of CH within a few weeks after the administration of long-acting organic nitrates (isosorbide-dinitrate, isosorbide-5-mononitrate or slow-release GTN) aimed at treating their chest pains. These nitrate-induced headache periods were more severe and had a longer duration than the previous spontaneous ones. Furthermore, one of the subjects and two additional cases experienced a marked reduction of their anginal attacks during successive CH periods. Exercise time to effort-induced angina was increased in all three patients and one of them revealed a markedly elevated threshold for eliciting ischaemic cardiac symptoms by standardized physical exercise on a cycle ergometer. We hypothesize whether extra CH periods elicited by sustained nitrate therapy and remission of angina pectoris during active clusters are caused by central mechanisms involving inhibition of sympathetic tone and effects on both cranial vessels and cardiac functions.
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| 6. |
- Ekbom, T, et al.
(author)
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Did Franz Kafka suffer from cluster headache?
- 2004
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 24:4, s. 309-311
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Journal article (other academic/artistic)
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| 7. |
- Landtblom, Anne-Marie, 1953-, et al.
(author)
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Sudden onset headache : a prospective study of features, incidence and causes
- 2002
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 22:5, s. 354-360
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Journal article (peer-reviewed)abstract
- Sudden onset headache is a common condition that sometimes indicates a life- threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache = TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants > 18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.
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| 8. |
- Laurell, Katarina, et al.
(author)
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Headache in schoolchildren : agreement between different sources of information
- 2003
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In: Cephalalgia. - : Blackwell Publishing. - 0333-1024 .- 1468-2982. ; 23:6, s. 420-428
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Journal article (peer-reviewed)abstract
- The level of agreement between different sources of information, i.e. questionnaires, interviews and diaries, was evaluated in a sample of 129 schoolchildren, 69 girls and 60 boys, ranging in age from 7 to 17 years. Headache diagnoses and headache features showed high agreement between questionnaires and subsequent interviews. The concordance between questionnaires and interviews for headache diagnoses increased, and the number of unclassified headaches decreased, when the International Headache Society (IHS) duration criterion was excluded. When comparing headache frequency reported in questionnaires and interviews with diary recordings, the agreement was low and the frequency higher in the diaries. Overall, the agreement between questionnaires, interviews and diaries was not related to age or gender. The questionnaire may serve as a valid source of information in studies of headache in schoolchildren. Prospective recordings in diaries provide additional information, in particular of low-intensity headache. In children, the IHS duration criterion should be modified or excluded.
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| 9. |
- Laurell, Katarina, et al.
(author)
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Prevalence of headache in Swedish schoolchildren, with a focus on tension-type headache
- 2004
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In: Cephalalgia. - : Blackwell Publishing. - 0333-1024 .- 1468-2982. ; 24:5, s. 380-388
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Journal article (peer-reviewed)abstract
- To estimate the prevalence of tension-type headache, migraine and other headaches, 1850 schoolchildren, age 7-15 years, from the city of Uppsala, were invited to complete a questionnaire. The response rate was 74.1%. To validate the information from the questionnaires, 131 children and their parents were interviewed. Using the criteria of the International Headache Society, the 1-year prevalence of tension-type headache and migraine was 9.8 and 11.0%, respectively. However, these prevalence rates increased considerably, to 23.0 and 17.0%, respectively, when excluding the criteria defining the number of earlier episodes and duration of headache. The prevalence of headache increased with age, similarly in girls and boys up to 11 years, and thereafter only in girls. The preponderance in teenage girls was even more pronounced for tension-type headache than for migraine. Our results indicate an increase over time in headache prevalence when compared with findings in a study conducted in the same city in 1955.
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| 10. |
- Linde, Mattias, 1966, et al.
(author)
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Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.
- 2004
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 24:12, s. 1057-66
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Journal article (peer-reviewed)abstract
- Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.
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| 11. |
- Remahl, AIMN, et al.
(author)
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Hyperbaric oxygen treatment of active cluster headache: a double-blind placebo-controlled cross-over study
- 2002
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 22:9, s. 730-739
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Journal article (peer-reviewed)abstract
- Sixteen patients, 12 with episodic and four with chronic cluster headache (CH) according to the International Headache Society criteria (1), participated in the study. They were randomly selected to start with one out of two different hyperbaric treatments in a double-blind, placebo-controlled, cross-over study design. Both gases were administered by mask inside a multiplace hyperbaric chamber for 70 min at 250 kPa (2.5 ATA) in two sessions 24 h apart. Active treatment was 100% oxygen (HBO treatment), while placebo treatment was 10% oxygen in nitrogen (hyperbaric normoxic placebo = sham treatment) corresponding to breathing air at sea level. All patients were decompressed on air. The patients documented the number of headache attacks and their degree of severity according to a modified VAS scale (level 0-4, where level 0 = no headache and level 4 = very severe headache). A headache index (HI = sum of (number of attacks times degree of severity)) was calculated for the run-in week prior to and the week after each separate treatment. A treatment was regarded as effective if it reduced the HI by > 50%. Blood samples were taken from the external jugular vein before and during hyperbaric treatment (after 30 and 70 min), 1 day and 1 week after each treatment for analyses of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) and in a few patients also endotheline and nitrate. No difference between HBO and sham treatment on the HI or the prophylactic effect was observed in our study. However, 83% of the episodic CH patients and 25% of the chronic ones responded to either of the two treatments with at least 50% reduction of HI or remission for shorter or longer periods. This response rate exceeds an expected high placebo response due to the study procedure. Two episodic CH patients still experienced remission on follow-up 1 year after sham treatment. Five patients reported mild or moderate CH attacks during the sham treatment, and none during the HBO treatment. Changes in neuropeptides, endotheline and nitrate levels did not differ systematically when comparing the two different hyperbaric treatments or with respect to responders and non-responders. We conclude that two HBO sessions were not more effective than two sham treatments in reducing the HI and interrupting the CH period when given in a well-established cluster period or in chronic CH. The hyperbaric condition itself seems effective in reducing the HI, at least in patients with episodic CH, although a powerful placebo response can not be ruled out.
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| 12. |
- Remahl, AIMN, et al.
(author)
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Placebo response in cluster headache trials: a review
- 2003
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 23:7, s. 504-510
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Journal article (peer-reviewed)abstract
- Probably because of its relative rarity as primary headache, there are few well-controlled clinical trials on cluster headache (CH) patients. Due to the severity of the pain, the placebo response in CH has been considered to be small. During the eighties the first double-blind, placebo-controlled trials were reported, and placebo responses demonstrated. Here we review the placebo response in CH trials in order to assess its magnitude and consider how future studies can be optimized. Six trials were identified with a double-blind, placebo-controlled, cross-over design testing treatments of acute CH. For those with a primary endpoint set to no or mild headache the placebo responses varied from 7 to 42%. In five of seven prophylactic trials, using a double-blind, placebo-controlled, parallel-group design, the placebo was merely used to set a baseline for comparison. The placebo responses were reported in only two trials. Here the response varies from 14 to 43%, the lowest value was reported using the strict endpoint; cessation of headache attacks. We conclude that a placebo response exists in trials of drugs on CH patients. Furthermore, this placebo response is of the same magnitude as that seen in migraine studies. We recommend the use of IHS guidelines when designing new trials. The possibility of a genuine biological mechanism responsible for the placebo response is discussed.
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| 13. |
- Sjostrand, C, et al.
(author)
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Analysis of nitric oxide synthase genes in cluster headache
- 2002
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 22:9, s. 758-764
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Journal article (peer-reviewed)abstract
- The aetiology of cluster headache is still not yet completely understood, but the potential relevance of genetic factors has been recognized during recent years. Nitric oxide (NO) plays a critical role in the regulation of vasodilation, neurotransmission, inflammation and many other events throughout the body. NO also appears to be an important mediator of vascular headache pathophysiology. In this study we have performed an association analysis of five polymorphic micro-satellite markers in the three different NO synthase (NOS) genes; nNOS (NOS1), iNOS (NOS2A) and eNOS (NOS3). Ninety-one cluster headache patients diagnosed according to International Headache Society criteria and 111 matched controls were studied. Phenotype and allele frequencies were similarly distributed in patients and controls except for an iNOS (NOS2A) pentanucleotide repeat allele which was significantly more common in controls. We observed a higher phenotype frequency of this allele in our control group compared with rates in control groups of other studies, whereas the frequency in our patients was similar to that in controls from previous reports. Thus, we conclude that it is unlikely that genetic variations within the NOS genes contribute greatly to cluster headache susceptibility.
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| 14. |
- Sjostrand, C, et al.
(author)
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CACNA1A gene polymorphisms in cluster headache
- 2001
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 21:10, s. 953-958
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Journal article (peer-reviewed)abstract
- Cluster headache (CH) is a primary headache disorder where the aetiological and pathophysiological mechanisms still are largely unknown. An increased risk of CH in first- and second-degree relatives suggests the importance of genetic factors. Mutations of the P/Q type calcium channel alpha 1 subunit (CACNA1A) gene on chromosome 19p13 have been shown to cause several neurological disorders with a wide clinical spectrum, mainly episodic diseases. Missence mutations of the gene cause familial hemiplegic migraine (FHM) and it is also likely to be involved in the more common forms of migraine. The CACNA1A gene is thus a promising candidate gene for CH. In this study we performed an association analysis of an intragenic polymorphic (CA)n-repeat with marker D19S1150 and a (CAG)n-repeat in the 3′UTR region, in 75 patients with CH according to IHS criteria and 108 matched controls. Genotypes and allele frequencies were similarly distributed in patients and controls. Linkage disequilibrium between the two markers was similar in patients and controls. We conclude that an importance of the CACNA1A gene in sporadic CH is unlikely.
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| 15. |
- Svensson, DA, et al.
(author)
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A note on cluster headache in a population-based twin register
- 2003
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 23:5, s. 376-380
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Journal article (peer-reviewed)abstract
- Evidence of a familial risk factor in cluster headache is accumulating and studies of twin concordance may resolve family resemblance into genetic and environmental influences. The past literature on cluster headache in twins comprises a few case reports of concordant monozygotic pairs. Swedish twin pairs with a diagnosis of cluster headache were selected through a cross-match of national registers of twin births and hospitalizations. Seventeen discordant twin pairs were found, in which it was possible to verify cluster headache status in 11 complete pairs (two monozygotic, four dizygotic, and five unlike-sexed pairs). In both members of a female monozygotic pair, migraine without aura developed after birth of the first child and remitted by menopause, whereas post-menopausal development of chronic cluster headache occurred in only one of them. The importance of individual specific factors for cluster headache was demonstrated. However, to explain familial aggregation a larger sample of affected twin pairs is necessary.
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