Genetics of migraine and pharmacogenomics: some considerations

Migraine is a complex disorder caused by a combination of genetic and environmental factors

Proinflammatory mediators and migraine pathogenesis: Moving towards CGRP as a target for a novel therapeutic class

Migraine is a complex neurological disorder in which genetic and environmental factors interact. At present, frontline therapies in migraine's acute treatment include the use of NSAIDS and triptans. Restrictions in the use of frontline drugs for migraine treatment and evidence concerning CGRP's key role led research towards new pathways involved in migraine pathophysiology. CGRP is a strong vasodilatory neuropeptide released from activated trigeminal sensory nerves. The development of CGRP antagonists has also been driven by the fact that triptans are vasoconstrictive and cannot be used in patients with vascular risk factors. BIBN4096 (olcegepant) is the first CGRP antagonist for the treatment of migraine which has been tested in clinical trials, but its principal limitation is that BIBN4096 presents low oral bioavailability and has only been tested through intravenous formulation. The first oral nonpeptide CGRP antagonist, MK-0974 (telcagepant), has recently been shown to be highly effective in the treatment of migraine attacks. This development can be considered the most important pharmacological breakthrough for migraine treatment since the introduction of sumatriptan in the early 1990s. These results are important since they confirm the current pathophysiological concept of migraine. The future introduction of CGRP antagonists in clinical practice could represent a progress for migraine therapy. © 2008 Expert Reviews Ltd

Rehabilitating chronic migraine complicated by medication overuse headaches: how can we prevent migraine relapse?

Headache is among the most common neurological symptoms in clinical practice. In some cases of episodic migraine, the headache intensifies into a chronic form, defined as chronic migraine (CM) and such a condition encompasses a headache frequency of 15 days/month, with features similar to those of migraine attacks. The assessment of CM in the US general population ranges around 1.3-2%. Migraine progression from an episodic into a chronic form is realized through a period of time involving several months or years, during which an increase attack frequency occurs. Both Topiramate and Onabotulinum toxin A can be considered to be safe as well as effective medications, therefore, representing a treatment choice. Regarding drug abusers, the initial relief step always consists of drug interruption. Only after detoxification can a new prophylaxis therapy be commenced, which otherwise would be useless from the start. The feasible diagnostic setting for the tailored treatment of CM based on the application of pharmacogenomics will allow us in predetermining the efficacy of a single old and new drugs by avoiding abuse due to non-responsivity of the abused drug

Role of NSAIDs in acute treatment of headache

Headache is one of the most common neurological disorders worldwide. Tension-type headache (TTH) represents the most frequent headache form, involving 82% of sufferers. Of this population, 14% are affected by migraine and 4% by a chronic form of headache (chronic daily headache [CDH]). Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most used acute therapy for TTH and migraine because of issues with coxibs safety. NSAIDs play a minor role is the treatment in trigeminal-autonomic cephalgias (TACs); if excluding indomethacin in the acute management of paroxysmal hemicrania (PH). Despite limitations in their utilization, NSAIDs still constitute drugs of primary importance, being effective and being well tolerated in the treatment of acute episodes. © 2007 Wiley-Liss, Inc

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31â127 anaesthetic procedures in 30â874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0â5·5) with an incidence of respiratory critical events of 3·1% (2·9â3·3). Cardiovascular instability occurred in 1·9% (1·7â2·1), with an immediate poor outcome in 5·4% (3·7â7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10â000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86â0·90; p<0·0001), medical history, and physical condition (1·60, 1·40â1·82; p<0·0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0·99, 0·981â0·997; p<0·0048 for respiratory critical events, and 0·98, 0·97â0·99; p=0·0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia. Funding European Society of Anaesthesiology

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6.35 years (SD 4.50) were included. The incidence of perioperative severe critical events was 5.2% (95% CI 5.0-5.5) with an incidence of respiratory critical events of 3.1% (2.9-3.3). Cardiovascular instability occurred in 1.9% (1.7-2.1), with an immediate poor outcome in 5.4% (3.7-7.5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0.88, 95% CI 0.86-0.90; p<0.0001), medical history, and physical condition (1.60, 1.40-1.82; p<0.0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0.99, 0.981-0.997; p<0.0048 for respiratory critical events, and 0.98, 0.97-0.99; p=0.0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia