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Peter J Goadsby

Publications and source records attributed to Peter J Goadsby.

At least 55 records · Page 3Linked to original sources
PubMed2004

Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine.

BACKGROUND: Calcitonin gene-related peptide (CGRP) may have a causative role in migraine. We therefore hypothesized that a CGRP-receptor antagonist might be effective in the treatment of migraine attacks. METHODS: In an international, multicenter, double-blind, randomized clinical trial of BIBN 4096 BS, a highly specific and potent nonpeptide CGRP-receptor antagonist, 126 patients with migraine received one of the following: placebo or 0.25, 0.5, 1, 2.5, 5, or 10 mg of BIBN 4096 BS intravenously over a period of 10 minutes. A group-sequential adaptive treatment-assignment design was used to minimize the number of patients exposed. RESULTS: The 2.5-mg dose was selected, with a response rate of 66 percent, as compared with 27 percent for placebo (P=0.001). The BIBN 4096 BS group as a whole had a response rate of 60 percent. Significant superiority over placebo was also observed with respect to most secondary end points: the pain-free rate at 2 hours; the rate of sustained response over a period of 24 hours; the rate of recurrence of headache; improvement in nausea, photophobia, phonophobia, and functional capacity; and the time to meaningful relief. An effect was apparent after 30 minutes and increased over the next few hours. The overall rate of adverse events was 25 percent after the 2.5-mg dose of the drug and 20 percent for the BIBN 4096 BS group as a whole, as compared with 12 percent for placebo. The most frequent side effect was paresthesia. There were no serious adverse events. CONCLUSIONS: The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine.

Acute Disease↗
PubMed2004

Migraine aura: a knockin mouse with a knockout message.

Migraine aura is a sometimes disabling disorder of the brain that involves significant neurological symptoms in about 30% of patients. In this issue of Neuron, van den Maagdenberg et al. characterize a mouse with a knockin mutation known to cause familial hemiplegic migraine and provide evidence that a lowered threshold to the triggering of CSD may account for the devastating phenotype of familial hemiplegic migraine.

Animals↗
PubMed2004

Pituitary volume and headache: size is not everything.

BACKGROUND: Pituitary tumors are commonly associated with disabling headache. The accepted mechanisms for headache are dural stretch and cavernous sinus invasion. OBJECTIVE: To determine if there is a relationship between pituitary tumor size and the report of headache. DESIGN: We prospectively studied 63 patients who were initially seen with pituitary tumors. Clinical headache scores, pituitary tumor volume, and the extent of cavernous sinus invasion were obtained for each patient. RESULTS: The prevalence of headache was 70%. There was no positive correlation the between clinical headache score and pituitary volume (r = -0.32, P =.01, Spearman rank correlation). There was also no association between cavernous sinus invasion and headache. There was a strong association between pituitary-associated headache and a family history of headache (chi(2) = 8.36, P =.004). CONCLUSIONS: These data suggest that a pituitary tumor-associated headache may not simply be a structural problem. Other factors such as family history of headache, and the endocrine activity of the tumor may be equally important determinants of headache. Elucidating these mechanisms will aid in the treatment of these patients and further our understanding of other headache syndromes.

Cavernous Sinus↗
PubMed2004

Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study.

Current practical evidence-based acute treatments of cluster headache are limited to subcutaneous and intranasal formulations of sumatriptan, and oxygen. Two small randomized, double-blind trials suggested efficacy of somatostatin in cluster headache. We sought to determine whether octreotide, a somatostatin analog, is effective in the abortive treatment of acute cluster headache. Patients with episodic and chronic cluster headache, as defined by the International Headache Society, were recruited to a double-blind placebo-controlled crossover study. Patients were instructed to treat two attacks of at least moderate pain severity, with at least a 24-hour break, using subcutaneous octreotide microg or matching placebo. The primary end point was the headache response defined as very severe, severe, or moderate pain becomes mild or nil, at 30 minutes. The primary end point was examined using a multilevel analysis approach. A total of 57 patients were recruited of whom 46 provided efficacy data on attacks treated with octreotide and 45 with placebo. The headache response rate with subcutaneous octreotide was 52%, whereas that with placebo was 36%. Modeling the treatment outcome as a binomial where response was determined by treatment, using the patient as the level 2 variable, and considering period effect, sex, and cluster headache type as other variables of interest, we found that the effect of subcutaneous octreotide 100 microg was significantly superior to placebo (p < 0.01). Subcutaneous octreotide 100 microg is effective in the acute treatment of cluster headache when compared with placebo. Nonvasconstrictor treatment of acute cluster headache is possible.

Adolescent↗
PubMed2004

Functional neuroimaging of primary headache disorders.

Until recently, primary headache disorders such as migraine and cluster headache were considered to be vascular in origin. However, advances in neuroimaging techniques, such as positron emission tomography, single photon emission computerized tomography, and functional magnetic resonance imaging, have augmented the growing clinical evidence that these headaches are primarily driven from the brain. This review covers functional imaging studies in migraine, cluster headache, rarer headache syndromes, and experimental head pain. Together with newer techniques, such as voxel-based morphometry and magnetic resonance spectrometry, functional imaging continues to play a role in elucidating and targeting the neural substrates in each of the primary headache syndromes.

Cerebrovascular Circulation↗
PubMed2004

Prioritizing treatment attributes and their impact on selecting an oral triptan: results from the TRIPSTAR Project.

Seven oral triptans, which differ on a range of attributes important for treatment selection, are now available for treating migraine. US neurologists were surveyed to assess the relative importance of treatment attributes, prespecified by clinical relevance and availability of controlled study data, for selecting among oral triptans. Using a multiattribute decision model, we combined these data on the importance of treatment attributes with information on the relative performance of the oral triptans derived from a recent meta-analysis of controlled clinical trials.

Animals↗
PubMed2004

Post-triptan era for the treatment of acute migraine.

There now is one realized and several attractive targets for the treatment of acute attacks of migraine that will follow and augment the use of serotonin 5-HT1B/1D receptor agonists, the triptans. Calcitonin gene-related peptide (CGRP) receptor blockade recently has been shown to be an effective acute antimigraine strategy; therefore, blockade of CGRP release by inhibition of trigeminal nerves would seem a logical approach. A number of targets are reviewed in this article including serotonin 5-HT1F and 5-HT1D receptors, adenosine A1 receptors, nociceptin, vanilloid TRPV1 receptors, and anandamide CB1 receptors. Development of one or more such compound offers the exciting prospect of new non-vasoconstrictor treatments for migraine and cluster headache.

Acute Disease↗
PubMed2004

Priorities for triptan treatment attributes and the implications for selecting an oral triptan for acute migraine: a study of US primary care physicians (the TRIPSTAR Project).

BACKGROUND: Physicians treating patients with migraine can now choose from among 7 triptans, which differ on a range of attributes that may be important for treatment selection. OBJECTIVE: The aims of this study were to determine the relative importance of treatment attributes of the available triptans and assess their impact on deciding the most appropriate treatment for a particular patient with migraine. METHODS: As part of the TRIPSTAR project, US primary care physicians were surveyed to elicit their views on the relative importance of a prespecified set of treatment attributes for making treatment choices in clinical practice. The treatment attributes assessed were those for which data from controlled clinical trials were available for subsequent comparison. The resulting attribute-importance weights were then combined with data on the performance of individual triptans across these attributes in a multiattribute decision model to assist selection of an oral triptan. RESULTS: Efficacy attributes were considered more important than tolerability or consistency of effect in selecting an oral triptan. For triptan-naive but not triptan-experienced patients, tolerability was considered significantly more important than consistency (30% [95% CI, 27%-34%] vs 21% [19%-24%]). Sustained pain-free status and freedom from cardiovascular (chest) adverse events were the most important efficacy and tolerability attributes for both patient categories. When the relative importance of the treatment attributes was combined in a multiattribute decision model with meta-analysis data from controlled trials, almotriptan, eletriptan, and rizatriptan were significantly closer to the hypothetical ideal triptan than the reference product, sumatriptan 100 mg. CONCLUSION: Multiattribute decision-making models (such as that used in the TRIPSTAR project) that determine and apply the relative importance of treatment attributes to drug selection have considerable potential value as a decision support tool in the treatment of acute migraine.

Acute Disease↗
PubMed2004

Hypothalamic activation after stimulation of the superior sagittal sinus in the cat: a Fos study.

Clinical observations, particularly of the premonitory phase of migraine, suggest the involvement of the hypothalamus in the earliest phases of an attack. Stimulation of the superior sagittal sinus (SSS) in humans produces head pain and permits study of the activated trigeminovascular system in experimental settings. The distribution of neurons expressing the protein product (Fos) of the c-fos immediate early gene was examined in the hypothalamus of anaesthetised (alpha-chloralose) cats. Animals were studied after either 2-h stimulation of the SSS or sham stimulation. Fos protein was detected using immunohistochemistry, and positive neurons were plotted onto standardised templates and counted by a blinded observer. In response to electrical stimulation of the superior sagittal sinus, we found significant activation of the supra-optic nucleus (SON) rising from 3 (0-13) (median, 95% confidence interval) to 53 (31-78; P = 0.005) fos-positive cells. In the posterior hypothalamic area (Hp), fos-positive cells rose from 4 (0-14) to 35 (17-45; P = 0.015) Taken together with other physiological studies, the data are consistent with a role for hypothalamic structures in the modulation of trigeminovascular nociceptive afferent information, and thus for a role in headache.

Animals↗
PubMed2004

Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in the acute treatment of migraine.

BACKGROUND: Health care providers frequently cite concerns about cardiovascular safety of the triptans as a barrier to their use. In 2002, the American Headache Society convened the Triptan Cardiovascular Safety Expert Panel to evaluate the evidence on triptan-associated cardiovascular risk and to formulate consensus recommendations for making informed decisions for their use in patients with migraine. OBJECTIVE: To summarize the evidence reviewed by the Triptan Cardiovascular Safety Expert Panel and their recommendations for the use of triptans in clinical practice. PARTICIPANTS: The Triptan Cardiovascular Safety Expert Panel was composed of a multidisciplinary group of experts in neurology, primary care, cardiology, pharmacology, women's health, and epidemiology. EVIDENCE AND CONSENSUS PROCESS: An exhaustive search of the relevant published literature was reviewed by each panel member in preparation for an open roundtable meeting. Pertinent issues (eg, cardiovascular pharmacology of triptans, epidemiology of cardiovascular disease, cardiovascular risk assessment, migraine) were presented as a prelude to group discussion and formulation of consensus conclusions and recommendations. Follow-up meetings were held by telephone. CONCLUSIONS: (1) Most of the data on triptans are derived from patients without known coronary artery disease. (2) Chest symptoms occurring during use of triptans are generally nonserious and are not explained by ischemia. (3) The incidence of serious cardiovascular events with triptans in both clinical trials and clinical practice appears to be extremely low. (4) The cardiovascular risk-benefit profile of triptans favors their use in the absence of contraindications.

Acute Disease↗
PubMed2004

Posterior hypothalamic and brainstem activation in hemicrania continua.

OBJECTIVE: To determine the brain structures involved in mediating the pain of hemicrania continua using positron emission tomography. BACKGROUND: Hemicrania continua is a strictly unilateral, continuous headache of moderate intensity, with superimposed exacerbations of severe intensity that are accompanied by trigeminal autonomic features and migrainous symptoms. The syndrome is exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that of the trigeminal autonomic headaches and migraine in which the hypothalamus and the brainstem, respectively, have been postulated to play central pathophysiologic roles. We hypothesized, based on the clinical phenotype, that hemicrania continua may involve activations in the hypothalamus, or dorsal rostral pons, or both. METHODS: Seven patients with hemicrania continua were studied in two sessions each. In one session, the patients were scanned during baseline pain and when rendered completely pain free after being administered indomethacin 100 mg intramuscularly. In the other session, the patients were scanned during baseline pain and when still in pain after being administered placebo intramuscularly. Seven age- and sex-matched nonheadache subjects acted as the control group. The scan images were processed and analyzed using SPM99. RESULTS: There was a significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua. In addition, there was activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus and the substantia nigra, and bilateral pontomedullary junction. No intracranial vessel dilatation was obvious. CONCLUSIONS: This study demonstrated activations of various subcortical structures, in particular the posterior hypothalamus and the dorsal rostral pons. If posterior hypothalamic and brainstem activation are considered as markers of trigeminal autonomic headaches and migrainous syndromes, respectively, then the activation pattern demonstrated in hemicrania continua mirrors the clinical phenotype, with its overlap with trigeminal autonomic headaches and migraine.

Adult↗
PubMed2004

Cluster headache: focus on emerging therapies.

Cluster headache is a strictly unilateral headache that occurs in association with cranial autonomic features. It is an excruciating syndrome and is probably one of the most painful conditions known to mankind with female patients describing each attack as being worse than childbirth. In most patients, it has a striking circannual and circadian periodicity. This disorder has a highly stereotyped clinical phenotype and responds to specific therapies, thereby underlying the importance of distinguishing it from other primary headache syndromes. In this review, the clinical manifestations, differential diagnosis, diagnostic workup and treatment options for this syndrome have been outlined.

Analgesics↗
PubMed2003

Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study.

Electrical stimulation of primary sensory afferents is known to have an antinociceptive effect. Animal and functional imaging studies suggest a role for supraspinal structures in this response. Eight patients with chronic migraine (> or =15 days per month of attacks of migraine without aura), who had shown a marked beneficial response to implanted bilateral suboccipital stimulators, were studied. Stimulation evoked local paraesthesia, the presence of which was a criterion of pain relief. On stimulation, the headache began to improve instantaneously and was completely suppressed within 30 min. On switching off the stimulation, the headache recurred instantly and peaked within 20 min. PET scans were performed using regional cerebral blood flow (rCBF) as a marker of neuronal activity. Each patient was scanned in the following three states: (1) stimulator at optimum settings: patient pain-free but with paraesthesia; (2) stimulator off: patient in pain and no paraesthesia; (3) stimulator partially activated: patient with intermediate levels of pain and paraesthesia. All scans were processed and analysed using Statistical Parametric Mapping (SPM) 99. There were significant changes in rCBF in the dorsal rostral pons, anterior cingulate cortex (ACC) and cuneus, correlated to pain scores, and in the ACC and left pulvinar, correlated to stimulation-induced paraesthesia scores. The activation pattern in the dorsal rostral pons is highly suggestive of a role for this structure in the pathophysiology of chronic migraine. The localization and persistence of activity during stimulation is exactly consistent with a region activated in episodic migraine, and with the persistence of activation of that area after successful treatment. The dorsal rostral pons may be a locus of neuromodulation by suboccipital stimulation. In addition, suboccipital stimulation modulated activity in the left pulvinar.

Adult↗
PubMed2003

Prostaglandin E2 injected into the posterior hypothalamus has no effect on trigeminal nociception in the rat.

Craniovascular prostaglandin E2 (PGE2) release is elevated in the headache phase of migraine and in experimental models of headache. PGE2 synthesised in the brain may be involved in modulating trigeminal nociception. We examined whether PGE2 injected into the posterior hypothalamus could modulate trigeminovascular nociception. In seven rats, electrophysiological recordings were made from trigeminal nucleus caudalis neurons responsive to noxious middle meningeal artery stimulation and inhibited by bicuculline activation of the posterior hypothalamus. Microinjection into the posterior hypothalamus of a non-pyrogenic dose of PGE2 (2.5 microg/ml) produced no effect on nociceptive trigeminal nucleus caudalis neurons compared with saline injection (P=0.29). The mean response to PGE2 injection was 97% of baseline. We conclude that PGE2 in the posterior hypothalamus is unlikely to play a significant role in modulating trigeminal nociception.

Animals↗
PubMed2003

Herbal medicine.

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Humans↗