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Biomedical subjects

J Olesen

Publications and source records attributed to J Olesen.

At least 37 records · Page 2Linked to original sources
PubMed2005

The effect of circulating adenosine on cerebral haemodynamics and headache generation in healthy subjects.

Adenosine is an endogenous neurotransmitter that is released from the brain during hypoxia and relaxes isolated human cerebral arteries. Many cerebral artery dilators cause migraine attacks. However, the effect of intravenous adenosine on headache and cerebral artery diameter has not previously been investigated in man and reports regarding the effect of intravenous adenosine on cerebral blood flow are conflicting. Twelve healthy participants received adenosine 80, 120 microg kg(-1) min(-1) and placebo intravenously for 20 min, in a double-blind, three-way, crossover, randomized design. Headache was rated on a verbal scale (0-10). Regional cerebral blood flow (rCBF) with 133Xe inhalation and single-photon emission computed tomography (SPECT) and MCA flow velocity (V(MCA)) with transcranial Doppler, were measured in direct sequence. Six participants developed headache during 80 microg kg(-1) min(-1) and six during 120 microg kg(-1) min(-1) compared with none on placebo (P = 0.006). The headache was very mild and predominantly described as a pressing sensation. When correcting data for adenosine-induced hyperventilation, no significant changes in rCBF (P = 0.22) or V(MCA) (P = 0.16) were found between treatments. A significant dilation of the superficial temporal artery (STA) was seen (P < 0.001). These results show that circulating adenosine has no effect on rCBF or V(MCA), while it dilates the STA and causes very mild headache.

Adenosine↗
PubMed2005

Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigated in vitro and in vivo.

Calcitonin gene-related peptide (CGRP) and related peptides may be involved in migraine pathogenesis. To understand their vasomotor role in the cerebral circulation, we performed two studies, a pressurized arteriography study of the middle cerebral artery (MCA) and a genuine closed cranial window (gCCW) in vivo study. Using the pressurized arteriography model rat MCAs were mounted on micropipettes, pressurized to 85 mmHg and luminally perfused. The diameter responses to luminally and abluminally applied rat-alphaCGRP, rat-betaCGRP, amylin and adrenomedullin were compared with the resting diameter. Only abluminally applied CGRP induced dilation of the cerebral arteries; E(max) for alphaCGRP and betaCGRP were 35 +/- 0.5% and 10.8 +/- 0.2%. These responses were blocked by CGRP(8-37). The gCCW model allowed videomicroscopic visualization of the pial vessels in anaesthetized rats. Changes in vessel diameter to intravenously administered alphaCGRP and betaCGRP were compared with pre-infusion baseline. Intravenous infusion of alphaCGRP and betaCGRP in the highest dose induced dilation of the cerebral cortical pial arteries/arterioles of 40.3 +/- 7.5% and 49.1 +/- 8.4%, respectively. However, this was probably secondary to a decrease in blood pressure of 44.8 +/- 3.3 mmHg and 49.2 +/- 3.3 mmHg. Our results suggest that CGRP receptors are probably functional on the smooth muscle cells and not on the endothelium of rat cerebral arteries.

Adrenomedullin↗
PubMed2005

The Visual Aura Rating Scale (VARS) for migraine aura diagnosis.

To supplement the traditional ICHD-2 diagnosis for migraine with aura (MA) we developed a diagnostic scale for migraine aura that quantifies the importance of the cardinal characteristics of MA. Since more than 99% of MA patients have visual aura, we developed for simplicity a Visual Aura Rating Scale (VARS). In total 427 patients with MA (ICHD-2) or nonaura visual disturbances were diagnosed in a validated semistructured interview by a trained physician. The patients were separated into a derivation sample and a validation sample. By regression analysis we identified the visual aura characteristics associated with MA in the derivation sample. Based on the identified characteristics we developed VARS and derived a predictive VARS score which was tested in the validation sample. The VARS score is the weighted sum of the presence of five visual symptom characteristics: duration 5-60 min (3 points), develops gradually > or = 5 min (2 points), scotoma (2 points), zig-zag lines (2 points), and unilateral (1 point). The maximum score is 10 points. A VARS score of 5 or more diagnosed MA with a sensitivity of 96% (95% CI 92-99%) and a specificity of 98%(95% CI 95-100%) in the derivation sample, and a sensitivity of 91% (95% CI 86-95%) and a specificity of 96% (95% CI 91-100%) in the validation sample. VARS adds evidence based weights to a number of clearly specified characteristics; it is easy to learn, apply and teach and may therefore be a valuable addition to traditional ICHD-2 diagnosis.

Adolescent↗
PubMed2005

Efficacy of multidisciplinary treatment in a tertiary referral headache centre.

Despite the high prevalence of headaches, multidisciplinary headache clinics are few and their efficacy still needs validation. We set out to describe the procedures, characterize the patients and evaluate the treatment results in Danish Headache Centre. All clinical records for patients discharged in 2002 were systematically reviewed. Diagnoses were classified in accordance with ICHD-II. Outcome results were analysed with respect to headache diagnoses, frequency, intensity, absence from work and medication use. Five hundred and five patients were included and 336 were eligible for the study. Mean age was 46 years and male/female ratio 1:2.4. For patients without medication overuse headache (MOH) a reduction in headache frequency (P<0.01) and intensity (P<0.05) was seen for frequent episodic and chronic tension-type headache (TTH), migraine, cluster and other headaches. No reduction was seen in post-traumatic headache. Absence from work decreased significantly for migraine (P<0.001) and frequent episodic TTH (P<0.05). For patients with MOH a reduction in headache frequency was seen for TTH and migraine (P<0.001). A specialized headache centre is valuable in treatment of patients with complex headache disorders.

Adult↗
PubMed2005

Sensitivity and specificity of the new international diagnostic criteria for migraine with aura.

OBJECTIVES: Since 1998, migraine with aura (MA) has been diagnosed according to the operational diagnostic criteria of the International Headache Society (ICHD-1). Here we present the data underlying the new criteria for MA in the ICHD-2 classification. METHODS: Sensitivity of the new criteria was tested in patients with MA and specificity in patients with reversible non-aura visual disturbances. The diagnoses in both groups of patients were made in a validated semistructured physician-conducted interview. We tested five sets of criteria for sensitivity and specificity comparing with the diagnosis according to the ICHD-1 in 200 patients and the selected set of criteria in 274 additional patients. RESULTS: Four sets of criteria had sensitivity/specificity of 46%/100%, 71%/100%, 62%/95%, and 99%/76%. Sensitivity of the selected set of criteria was 84% (95% CI 79% to 90%) and specificity 97% (95% CI 95% to 99%). According to these criteria at least two of the following should be fulfilled: homonymous visual or unilateral sensory symptoms; at least one aura symptom develops gradually over > or =5 minutes and/or different symptoms occur in succession over > or =5 minutes; each symptom lasts > or =5 and < or =60 minutes. In the additional sample sensitivity of the selected criteria was 90% (95% CI 86% to 94%) and specificity 96% (95% CI 91% to 100%). CONCLUSIONS: The diagnostic criteria for MA selected for ICHD-2 had high sensitivity and specificity. The ICHD-2 criteria are more operational and probably delineate a more homogeneous sample of patients than the ICHD-1. The ICHD-2 for MA is intended equally for research and clinical practice and can be used at different levels of specialisation.

Adolescent↗
PubMed2004

Classification of primary headaches.

Given the range of disorders that produce headache, a systematic approach to classification and diagnosis is an essential prelude to clinical management. For the last 15 years, the diagnostic criteria of the International Headache Society (IHS) have been the accepted standard. The second edition of The International Classification of Headache Disorders (January 2004) reflects our improved understanding of some disorders and the identification of new disorders. Neurologists who treat headache should become familiar with the revised criteria. Like its predecessor, the second edition of the IHS classification separates headache into primary and secondary disorders. The four categories of primary headaches include migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalalgias, and other primary headaches. There are eight categories of secondary headache. Important changes in the second edition include a restructuring of these criteria for migraine, a new subclassification of tension-type headache, introduction of the concept of trigeminal autonomic cephalalgias, and addition of previously unclassified primary headaches. Several disorders were eliminated or reclassified. In this article, the authors present an overview of the revised IHS classification, highlighting the primary headache disorders and their diagnostic criteria. They conclude by presenting an approach to headache diagnosis based upon these criteria.

Adult↗
PubMed2004

New international classification of migraine with aura (ICHD-2) applied to 362 migraine patients.

The International Classification of Headache Disorders 2nd edition (ICHD-2) subdivides migraine with aura (MA) differently from the ICHD-1 and includes new diagnostic criteria. The aim of the present study was to evaluate how the new classification works in practice and in comparison with the ICHD-1. The patients were recruited from a screen of the Danish National Patient Registry and from Danish neurologists. We included 362 patients diagnosed with MA according to the ICHD-1 in a validated semistructured physician-conducted interview. According to the ICHD-2, 89% (322 of 362) had MA and 11% (40 of 362) had probable MA. The MA patients had one or more ICHD-2 subtype of MA: 54% (173 of 322) had typical aura with migraine headache (MA-MH), 40% (129 of 322) had typical aura with non-migraine headache (MA-NMH), 37% (120 of 322) had aura without headache (MA-WOH), and 7% (26 of 322) had basilar-type migraine (MA-B). Of patients with MA-MH 34% (59 of 173) had co-occurrence of MA-WOH, 9% (16 of 173) had co-occurrence of MA-B and 5% (8 of 173) had co-occurrence of both MA-WOH and MA-B. Of patients with MA-NMH 27% (35 of 129) had co-occurrence of MA-WOH. Only 6% (18 of 322) of the MA patients had exclusively MA-WOH and <1% (2 of 322) had exclusively MA-B. Patients with MA-MH had an earlier age at onset (P = 0.044), an increased lifetime number of MA attacks (P = 0.054) and a higher co-occurrence of migraine without aura (P = 0.002) than patients with MA-NMH. Patients with MA-B tended to have an earlier age at onset and more severe attacks and patients with MA-WOH had a higher age at onset and less severe attacks than patients with MA-MH. The variations between ICHD-2 subtypes of MA indicate that patients with similar subtype of MA share phenotype and very likely have similar underlying aetiology.

Adolescent↗
PubMed2004

No effect of eletriptan administration during the aura phase of migraine.

Migraine aura is a warning sign readily recognized by patients. From the onset of aura it takes 30-60 min before the headache phase starts. Administration of acute medication during aura should provide sufficient time to achieve therapeutic plasma levels, counteracting the headache. To test this hypothesis we evaluated the efficacy of eletriptan 80 mg taken during aura. Patients met International Headache Society diagnostic criteria for migraine with aura, with an attack frequency of at least one per month and with aura occurring in > 50% of recent attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind, one attack, during the aura phase before headache, dose of either eletriptan 80 mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean age, 40 years). The primary outcome measure was the proportion of patients not developing moderate-to-severe headache within 6 h post-dose. There was no significant difference in the proportion of patients developing moderate-to-severe headache on eletriptan (61%) versus placebo (46%). Eletriptan was well tolerated and did not prolong the aura phase. Typical transient triptan adverse events were observed; most were mild-to-moderate in intensity. This study confirms the findings of two studies showing that triptans are ineffective but safe when given during the migraine aura phrase.

Adult↗
PubMed2004

Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache.

Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce headache and migraine, no significant differences in plasma levels of CGRP, cGMP and cAMP were detected after sildenafil compared with placebo. In conclusion, plasma levels of CGRP, cGMP and cAMP remain normal during sildenafil-induced headache or migraine. However, since previous studies indicate an important role of these signalling molecules, the present study questions whether cAMP and cGMP in peripheral blood can be used for monitoring pathophysiological events in headache and migraine mechanisms.

Adult↗
PubMed2004

Clinical characteristics of 362 patients with familial migraine with aura.

The objectives of the present study were to describe the clinical characteristics of patients with severe familial non-hemiplegic migraine with aura (NHMA) and to compare these data to those from cases in previous population-based Danish studies using the same methodology. NHMA families were recruited from the Danish patient registry and from Danish neurology practices. A total of 362 NHMA patients were diagnosed according to the 1988 International Headache Society criteria using a validated semistructured physician-conducted interview. Visual aura occurred in almost every NHMA attack. In aura without headache visual aura occurred primarily in isolation. Aura without headache was most common in older, male patients. Several clinical characteristics of familial NHMA differed from migraine with aura in the general population: firstly, the age at onset was lower, secondly, the age at cessation was higher, thirdly, aura symptoms were more severe and finally, the co-occurrence of migraine without aura was higher in familial NHMA. There seems to be a correlation between more severe symptoms and familial aggregation. These results have both clinical and scientific implications.

Adolescent↗
PubMed2004

The prophylactic effect of valproate on glyceryltrinitrate induced migraine.

In this study the human glyceryltrinitrate (GTN) model of migraine was for the first time used to test the effect of a prophylactic drug. We chose to test valproate due to its well documented effect as a migraine prophylactic drug. Efficacy of this compound would support the usefulness of the model in prophylactic antimigraine drug development. Twelve patients with migraine without aura were included in a randomized double blind crossover study. Valproate 1000 mg or placebo was given daily, each for a minimum of 13 days. On the last treatment day of each arm a 20 min intravenous infusion of GTN (0.25 microg/kg/min) was given. Headache was registered for 12 h after the infusion and headache intensity was scored on a scale from 0 to 10. Fulfillment of IHS criteria was recorded for 24 h. The middle cerebral arteries were evaluated by transcranial Doppler and the diameter of the superficial temporal and radial arteries were measured with high frequency ultrasound. GTN evoked migraine fulfilling IHS criteria 1.1 in 6 patients after placebo and in 2 patients after valproate (P = 0.125). Including additionally 3 patients on placebo and 1 patient on valproate who felt they had suffered a migraine attack, but who had as associated symptoms only photophobia or phonophobia, a significant reduction in the number of patients with induced migraine after valproate was seen (P = 0.031). Median peak headache intensity was 1 (range 0-9) after valproate compared to 4.5 (range 0-8) after placebo (P = 0.120). Pretreatment with valproate as compared to placebo reduced the velocity in both middle cerebral arteries after GTN (left P = 0.021, right P = 0.031). No effect of valproate was seen in the diameter of the superficial temporal artery (P = 0.781) or the radial artery (P = 0.367) before or after GTN. The study indicates that a prophylactic effect of valproate may be demonstrated using the GTN human migraine model. Although, all headache parameters were reduced after valproate compared to placebo, only one parameter was statistically significantly reduced probably because of the small number of patients. The size of the effect was similar to that of valproate in clinical trials. The GTN model may therefore be a valid tool for testing new prophylactic antimigraine drugs.

Adult↗
PubMed2004

Physiotherapy for tension-type headache: a controlled study.

The role of non-pharmacological therapies in the preventive treatment of tension-type headache (TTH) is still an object of debate. The primary aim of this study was therefore to investigate the therapeutic effect of physiotherapy in properly classified patients with TTH in a controlled trial. Fifty patients with TTH, 26 with episodic, frequent (ETTH) and 24 with chronic TTH (CTTH) fulfilling the International Headache Society classification criteria were included in the study. After a 4-week run-in period, they were randomized to either an 8-week period of standardized physiotherapy (group 1) or to an 8-week observation period followed by an identical course of physiotherapy (group 2); after the physiotherapy all patients were followed for a 12-week follow-up period. We then evaluated the number of days with headache, severity and duration of the headache attacks, and drug consumption for symptomatic treatment before and after the course of physiotherapy. Forty-eight patients completed the study. The average number of days with headache per 4-week period was reduced from 16.3 days at baseline to 12.3 days in the last 4 weeks of treatment [from 14.5 days to 10.5 days (P < 0.001) in group 1 and from 18.1 days to 14.1 days (P < 0.001) in group 2]. Severity and duration of headache as well as drug consumption were unchanged throughout the study. Analysing the response to treatment separately in the various subgroups, we found that the number of responders was significantly higher among patients with CTTH vs. patients with ETTH (P < 0.002) and in females vs. males (P < 0.02). No differences were found between patients with and without disorder of pericranial muscles. We conclude that a standardized physiotherapy programme has a good therapeutic effect, albeit on a restricted group of patients.

Adult↗
PubMed2004

Possible mechanisms of pain perception in patients with episodic tension-type headache. A new experimental model of myofascial pain.

A new experimental human model of myofascial pain using intramuscular infusion of a combination of bradykinin, serotonin (5-hydroxytryptamine), histamine, and prostaglandin E2 was applied to patients with episodic tension-type headache (ETTH) in order to examine pain perception. Fifteen patients with ETTH and 15 healthy controls completed the randomized, balanced, double-blinded, placebo-controlled study. Pain intensity, punctate hyperalgesia and allodynia, and pain quality were recorded. The combination induced a moderate and prolonged pain in both patients (median 51 min) (P = 0.001) and controls (median 22 min) (P = 0.001). Patients reported more pain than controls both after the combination (P = 0.045) and after placebo (P < 0.001). The McGill pain score [PRI(R)] was significantly higher in patients (P = 0.002) and in controls (P = 0.001), whereas pain quality and hyperalgesia were similar after the combination compared with placebo in the two groups. Due to side-effects nine subjects did not complete the study. The increased pain response, but similar qualitative pain perception, in ETTH patients may be explained by sensitization of peripheral nociceptors even though central mechanisms may also be involved.

Adult↗
PubMed2004

A double-blind study of SB-220453 (Tonerbasat) in the glyceryltrinitrate (GTN) model of migraine.

The need for experimental migraine models increases as therapeutic options widen. In the present study, we investigated SB-220453 for efficacy in the glyceryltrinitrate (GTN) human experimental migraine model. SB-220453 is a novel benzopyran compound, which in animal models inhibits neurogenic inflammation, blocks propagation of spreading depression and inhibits trigeminal nerve ganglion stimulation-induced carotid vasodilatation. We included 15 patients with migraine without aura in a randomized double-blind crossover study. SB-220453 40 mg or placebo was followed by a 20-min GTN infusion. Headache, scored 0-10, was registered for 12 h, and fulfillment of International Headache Society (IHS) criteria was recorded until 24 h. Four subjects had a hypotensive episode after SB-220453 plus GTN but none after GTN alone. The reaction was unexpected, since animal models and previous human studies had shown no vascular or sympaticolytic activity with SB-220453. The study was terminated prematurely due to this interaction. GTN was consistent in producing headache and migraine that resembled the patients' usual spontaneous migraine. Nine patients had GTN on both study days. Peak headache score showed a trend towards reduction after SB-220453 compared with placebo (median 4 vs. 7, P = 0.15). However, no reduction was seen in the number of subjects experiencing delayed headache (8 vs. 8), number of subjects reporting migraine (6 vs. 8), migraine attacks fulfilling IHS criteria 1.1 or 1.7 (6 vs. 7) or IHS 1.1 alone (4 vs. 5). SB-220453 had no significant pre-emptive anti-migraine activity compared with placebo in this human model of migraine. Interaction between SB-220453 and GTN was discovered. This is important for the future development of the compound and underlines the usefulness of experimental migraine models.

Adult↗