Informed consent for image-guided procedures: a nationwide survey of perceptions and current practices.

AIM: To characterise the current landscape of informed consent practices for image-guided procedures, including location of consent, guideline availability, and utility of decision-aid resources. MATERIALS AND METHODS: A survey of 159 interventional radiologists was conducted from April through June 2022. The survey evaluated participant demographics (gender, practice type, and level of training) and consent practices. Fifteen questions investigated discussion of benefits, risks, and alternatives, who obtained consent, location of consent conversations, how decision-making capacity is assessed, availability of formal guidance on consent discussions, and if and how decision-aids are used. RESULTS: Most respondents (93.7%) were "extremely" or "very" comfortable discussing the benefits and risks of image-guided procedures during informed consent. Most respondents were "very" comfortable discussing alternative treatments within radiology (86.8%) while fewer felt confident regarding alternatives outside radiology (46.5%). Most respondents indicated obtaining consent in a pre-procedure area (89.9%), while 12.7% of respondents obtained consent in the procedure room. Of the respondents, 66.7% did not have formal education or documented guidance on what providers should disclose during consent. Ninety-two respondents (57.9%) reported using decision aids. The type of decision aid varied, with most reporting using illustrations or drawings (46.6%). Decision aid utility was more prevalent in non-teaching/academic (71.4%) versus academic (61%) institutions (p=0.02). CONCLUSION: Regardless of demographics, interventionalists are confident in discussing benefits, risks, and alternative image-guided therapies, but are less confident discussing alternative treatment options outside of radiology. Formal education on informed consent is less common, and the use of decision aids varies between teaching and non-teaching institutions.

Single-item migraine screening tests, self-reported bothersome headache or stripe pattern hypersensitivity?

BACKGROUND: A simple screening tool may potentially help the migraine diagnosis in a primary care setting. The use of single-item tests, such as stripe pattern hypersensitivity test and self-reported bothersome headache (HA) question, as migraine screening tools have not been fully explored. METHODS: Two hundred and fifty-four subjects (patients and companions) were randomly enrolled from an OB/GYN clinic (men 82, women 172; age 38 ± 14). They were instructed to rate the stripe sensitivity level (0-4) and to report any bothersome HA (yes/no). A brief structured HA interview was conducted to describe the HA characteristics and for migraine diagnosis based on the ICHD-IIIß criteria. RESULTS: In a multivariate model, bothersome HA question and stripe pattern hypersensitivity test were both significantly associated with EM+PM+CM (odds ratio: 24.0, P < 0.01 vs 2.6, P = 0.01) or EM (odds ratio: 16.2, P < 0.01 vs 3.0, P < 0.01). Bothersome HA question had a greater screening power than stripe pattern hypersensitivity for screening EM+PM+CM (area under the ROC curve: 0.84 [95% CI 0.78-0.89] vs 0.62 [95% CI 0.55-0.69]) or EM (area under the ROC curve: 0.80 [95% CI 0.73-0.86] vs 0.64 [95% CI 0.56-0.72]). CONCLUSION: When performed in an OB/GYN clinic, self-reported bothersome HA question seemed more powerful than visual stripe pattern test in screening migraine thus could potentially be used as a single-item screening test.

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability.

Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.

OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program.

OBJECTIVE: Chronic migraine (CM) is a prevalent and disabling neurological disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX(®)) for prophylaxis of headaches in adults with CM. This secondary analysis assessed patients who received all five treatment cycles and completed the study. MATERIALS AND METHODS: PREEMPT (two phase III studies: 24-week double-blind, placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (≥15 days/month with headache lasting ≥4 h a day). Patients were randomized (1:1) to onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by onabotulinumtoxinA for three cycles. Multiple headache symptom measures were evaluated. Results for the completer (five cycles) subgroup of patients are reported. RESULTS: Of 1384 total PREEMPT patients, 1005 received all five treatment cycles (513 received onabotulinumtoxinA only [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA (P/O)]). Demographics were similar between treatment groups. At Week 56, after all patients were treated with onabotulinumtoxinA, there continued to be significant between-group differences favoring the O/O vs P/O group for the following headache symptom measures: LS mean change from baseline in frequencies of headache days (-12.0 O/O, -11.1 P/O; P = 0.035), migraine days (-11.6 O/O, -10.7 P/O; P = 0.038), and moderate/severe headache days (-11.0 O/O, -10.1 P/O; P = 0.042). For other measures (cumulative hours of headache on headache days, frequency of headache episodes, and percentage with severe Headache Impact Test (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life Questionnaire scores), there were also large mean improvements from baseline. The percent of patients with a ≥50% reduction from baseline in frequency of headache days was significantly greater for the onabotulinumtoxinA-only group at Week 56 (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was 28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for patients treated with onabotulinumtoxinA for all five cycles throughout the 56-week trials. CONCLUSIONS: This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.

Occipital nerve stimulation for primary headaches.

Occipital nerve stimulation may be effective for primary headache disorders. Four studies, including two double-blind show, stimulation-controlled studies that were performed for chronic migraine showed evidence of benefit. A separate study suggested a benefit for combined supraorbital and greater occipital nerve stimulation. Anecdotal evidence suggests benefit in hemicrania continua. In chronic cluster headache, several case series have shown improvement, which, combined with the safety of occipital nerve stimulation relative to deep brain stimulation, have led to published reports supporting this as the preferred surgical technique for chronic cluster headache. A few case reports suggest a possible benefit in short-lasting unilateral neuralgiform headache attacks with conjunctival injection tearing and short-lasting unilateral neuralgiform headache.

Integrated headache care.

Patients with chronic or difficult to treat headaches are generally under the care of general practictioners or neurologists in private practice. Some are referred to a headache specialist for evaluation and advice. Treatment is often provided by the referring physician. An alternative is a multidisciplinary headache centre, where care is provided by different disciplines (neurology, behavioural psychology, psychiatry, psychosomatic medicine, physical therapy, sport therapy) across sectors of the healthcare system involving out- and inpatient care and treatment. This is called integrated headache care. This review summarizes experiences in integrated headache care settings in Europe and the USA, describes these settings, and reports outcome data.

Time-dependent soft and hard x-ray measurements using streak and x-ray diode array diagnostic systems.

High-temperature, high-density experiments require a simultaneous understanding of temporal and spectral regions. The spectral x-ray streak camera (SXSC) is a new high-temporal-resolution spectral x-ray diagnostic system that allows researchers to differentiate between soft and hard x-ray regions. The diagnostic offers three spectral channels with a wide spectral range, one direct channel that includes a filter and two indirect channels that include both mirrors and filters. The opto-mechanical design positions the filtered radiation at three different locations along the streak photo-cathode (PC) slit to provide time-dependent spectral channels with pico-second temporal resolution. A moderate spatial resolution (150-700 µm) is achieved using slits perpendicular to the PC slit, while the slit width is optimized according to the central channel wavelength (for each channel). The diagnostic system covers a spectral range of 30-500 eV for the mirror channels and >1300 eV for the direct channel. The temporal and spatial axes of the streak camera are calibrated with respect to a sequence of x-ray pulses. The SXSC diagnostic system is tested and analyzed using Marshak-wave emission from an SiO2 foam that was heated by a laser-beam irradiated halfraum. The SXSC results are compared to measurements from an x-ray diode array with similar spectral channels.

1st Post-European Headache Federation Meeting: a review of the latest developments presented at the 2020 European Headache Federation Congress. / I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.

INTRODUCTION: After the European Headache Federation (EHF) Congress, renowned Spanish neurologists specialised in migraine presented the most significant latest developments in research in this field at the Post-EHF Meeting. DEVELOPMENT: The main data presented concerning the treatment of chronic and episodic migraine were addressed, with attention paid more specifically to those related to preventive treatments and real-life experience in the management of the disease. An important review was carried out of the new therapeutic targets and the possibilities they offer in terms of understanding the pathophysiology of migraine and its treatment. An update was also presented of the latest developments in the treatment of migraine with fremanezumab, a monoclonal antibody recently authorised by the European Medicines Agency. Participants were also given an update on the latest developments in basic research on the pathology, as well as an overview of the symptoms of migraine and COVID-19. Finally, the repercussions of migraine in terms of its burden on the care and economic resources of the health system were addressed, along with its impact on society. CONCLUSIONS: The meeting summarised the content presented at the 14th EHF Congress, which took place in late June/early July 2020.

TITLE: I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.Introducción. Tras la celebración del congreso de la European Headache Federation (EHF), reconocidos neurólogos españoles expertos en el tratamiento de la migraña expusieron en la Reunión Post-EHF las principales novedades presentadas en el congreso y relacionadas con ese ámbito. Desarrollo. Se abordan los principales datos presentados relacionados con el tratamiento de la migraña crónica y episódica; concretamente, los relacionados con los tratamientos preventivos y la experiencia en vida real en el manejo de la enfermedad. Se hizo una importante revisión de las nuevas dianas terapéuticas y las posibilidades que ofrecen en cuanto al conocimiento de la fisiopatología de la migraña y su tratamiento. Asimismo, se hizo una actualización de las novedades presentadas en el tratamiento de la migraña con fremanezumab, anticuerpo monoclonal recientemente autorizado por la Agencia Europea de Medicamentos. Se hizo una actualización de las novedades en investigación básica en la patología, así como una relación de los síntomas de migraña y COVID-19. Finalmente, se abordaron las implicaciones de la migraña en la carga sanitaria asistencial y económica, y su impacto en la sociedad. Conclusiones. En la reunión se hizo un resumen del contenido presentado en el 14 Congreso de la EHF, que tuvo lugar a finales de junio y principios de julio de 2020.

Right-to-left shunt is common in chronic migraine.

Our aim was to determine the prevalence of right-to-left shunt (RtLS) in patients with chronic migraine (CM), and to correlate the presence and grade of RtLS with aura and neurological symptoms, and duration and severity of disease. The prevalence of RtLS in migraine without aura is similar to that of the general population (between 20 and 35%). In migraine with aura, the prevalence is much higher (approximately 50%). The prevalence in CM, with or without aura, is unknown. Consecutive patients between the ages of 18 and 60 years with CM attending a tertiary care specialty headache clinic over an 8-week period were eligible. There were 131 patients in the study. A structured diagnostic interview was performed. Bubble transcranial Doppler with Valsalva manoeuvre determined RtLS presence and grade. Sixty-six percent (86/131) of patients had RtLS, a statistically significantly greater rate than those reported in the general population and in migraine with or without aura (P < 0.001). There was no difference in RtLS rate or grade between those with and those without aura. Specific headache features and the presence of neurological symptoms were similar between those with and those without RtLS. Compared with both the general population and the episodic migraine population (with and without aura), patients with CM, with or without aura, are more likely to have RtLS. The clinical implications of our findings need to be determined.

OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial.

OBJECTIVES: This is the second of a pair of studies designed to evaluate the efficacy and safety of onabotulinumtoxinA (BOTOX) for prophylaxis of headaches in adults with chronic migraine. METHODS: PREEMPT 2 was a phase 3 study, with a 24-week, double-blind, placebo-controlled phase, followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections of onabotulinumtoxinA (155U-195U; n = 347) or placebo (n = 358) every 12 weeks for two cycles. The primary efficacy endpoint was mean change in headache days per 28 days from baseline to weeks 21-24 post-treatment. RESULTS: OnabotulinumtoxinA was statistically significantly superior to placebo for the primary endpoint, frequency of headache days per 28 days relative to baseline (-9.0 onabotulinumtoxinA/-6.7 placebo, p < .001). OnabotulinumtoxinA was significantly favoured in all secondary endpoint comparisons. OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few patients (3.5% onabotulinumtoxinA/1.4% placebo) discontinued due to adverse events. CONCLUSIONS: The results of PREEMPT 2 demonstrate that onabotulinumtoxinA is effective for prophylaxis of headache in adults with chronic migraine. Repeated onabotulinumtoxinA treatments were safe and well tolerated.

OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial.

OBJECTIVES: This is the first of a pair of studies designed to assess efficacy, safety and tolerability of onabotulinumtoxinA (BOTOX) as headache prophylaxis in adults with chronic migraine. METHODS: The Phase III REsearch Evaluating Migraine Prophylaxis Therapy 1 (PREEMPT 1) is a phase 3 study, with a 24-week, double-blind, parallel-group, placebo-controlled phase followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections every 12 weeks of onabotulinumtoxinA (155 U-195 U; n = 341) or placebo (n = 338) (two cycles). The primary endpoint was mean change from baseline in headache episode frequency at week 24. RESULTS: No significant between-group difference for onabotulinumtoxinA versus placebo was observed for the primary endpoint, headache episodes (-5.2 vs. -5.3; p = 0.344). Large within-group decreases from baseline were observed for all efficacy variables. Significant between-group differences for onabotulinumtoxinA were observed for the secondary endpoints, headache days (p = .006) and migraine days (p = 0.002). OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. CONCLUSIONS: There was no between-group difference for the primary endpoint, headache episodes. However, significant reductions from baseline were observed for onabotulinumtoxinA for headache and migraine days, cumulative hours of headache on headache days and frequency of moderate/severe headache days, which in turn reduced the burden of illness in adults with disabling chronic migraine.

Amygdaloid pERK1/2 in corticotropin-releasing hormone overexpressing mice under basal and acute stress conditions.

Corticotropin-releasing hormone (CRH) coordinates neuroendocrine and behavioral adaptations to stress. Acute CRH administration in vivo activates extracellular signal-regulated kinase 1/2 (ERK1/2) in limbic brain areas, acting through the CRH receptor type 1 (CRH-R1). In the present study, we used CRH-COE-Cam mice that overexpress CRH in limbic-restricted areas, to analyze the effect of chronic CRH overexpression on ERK1/2 activation. By immunohistochemistry and confocal microscopy analysis we found that pERK1/2 levels in the basolateral amygdala (BLA) were similar in control and CRH overexpressing mice under basal conditions. Acute stress caused comparably increased levels of corticosterone in both control (CRH-COEcon-Cam) and CRH overexpressing (CRH-COEhom-Cam) animals. CRH-COEhom-Cam mice after stress showed reduced pERK1/2 immunoreactivity in the BLA compared to CRH-COEhom-Cam animals under basal conditions. Radioligand binding and in situ hybridization revealed higher density of CRH-R1 in the amygdala of CRH-COEhom mice under basal conditions compared to control littermates. A significant reduction of the receptor levels was observed in this area after acute stress, suggesting that stress may trigger CRH-R1 internalization/downregulation in these CRH overexpressing mice. Chronic CRH overexpression leads to reduced ERK1/2 activation in response to acute stress in the BLA.

The essential OST2 gene encodes the 16-kD subunit of the yeast oligosaccharyltransferase, a highly conserved protein expressed in diverse eukaryotic organisms.

Oligosaccharyltransferase catalyzes the transfer of a preassembled high mannose oligosaccharide from a dolichol-oligosaccharide donor to consensus glycosylation acceptor sites in newly synthesized proteins in the lumen of the rough endoplasmic reticulum. The Saccharomyces cerevisiae oligosaccharyltransferase is an oligomeric complex composed of six non-identical subunits (alpha-zeta). The alpha, beta, gamma, and delta subunits of the oligosaccharyltransferase are encoded by the OST1, WBP1, OST3, and SWP1 genes, respectively. Here we describe the functional characterization of the OST2 gene that encodes the epsilon-subunit of the oligosaccharyltransferase. Genomic disruption of the OST2 locus was lethal in haploid yeast showing that expression of the Ost2 protein is essential for viability. Overexpression of the Ost2 protein suppresses the temperature-sensitive phenotype of the wbp1-2 allele and increases in vivo and in vitro oligosaccharyltransferase activity in a wbp1-2 strain. An analysis of a series of conditional ost2 mutants demonstrated that defects in the Ost2 protein cause pleiotropic underglycosylation of soluble and membrane-bound glycoproteins. Microsomal membranes isolated from ost2 mutant yeast show marked reductions in the in vitro transfer of high mannose oligosaccharide from exogenous lipid-linked oligosaccharide to a glycosylation site acceptor tripeptide. Surprisingly, the Ost2 protein was found to be 40% identical to the DAD1 protein (defender against apoptotic cell death), a highly conserved protein initially identified in vertebrate organisms. The protein sequence of ost2 mutant alleles revealed mutations at highly conserved residues in the Ost2p/DAD1 protein sequence.

A role for the DnaJ homologue Scj1p in protein folding in the yeast endoplasmic reticulum.

Members of the eukaryotic heat shock protein 70 family (Hsp70s) are regulated by protein cofactors that contain domains homologous to bacterial DnaJ. Of the three DnaJ homologues in the yeast rough endoplasmic reticulum (RER; Scj1p, Sec63p, and Jem1p), Scj1p is most closely related to DnaJ, hence it is a probable cofactor for Kar2p, the major Hsp70 in the yeast RER. However, the physiological role of Scj1p has remained obscure due to the lack of an obvious defect in Kar2p-mediated pathways in scj1 null mutants. Here, we show that the Deltascj1 mutant is hypersensitive to tunicamycin or mutations that reduce N-linked glycosylation of proteins. Although maturation of glycosylated carboxypeptidase Y occurs with wild-type kinetics in Deltascj1 cells, the transport rate for an unglycosylated mutant carboxypeptidase Y (CPY) is markedly reduced. Loss of Scj1p induces the unfolded protein response pathway, and results in a cell wall defect when combined with an oligosaccharyltransferase mutation. The combined loss of both Scj1p and Jem1p exaggerates the sensitivity to hypoglycosylation stress, leads to further induction of the unfolded protein response pathway, and drastically delays maturation of an unglycosylated reporter protein in the RER. We propose that the major role for Scj1p is to cooperate with Kar2p to mediate maturation of proteins in the RER lumen.

The alpha subunit of the Saccharomyces cerevisiae oligosaccharyltransferase complex is essential for vegetative growth of yeast and is homologous to mammalian ribophorin I.

Oligosaccharyltransferase mediates the transfer of a preassembled high mannose oligosaccharide from a lipid-linked oligosaccharide donor to consensus glycosylation acceptor sites in newly synthesized proteins in the lumen of the rough endoplasmic reticulum. The Saccharomyces cerevisiae oligosaccharyltransferase is an oligomeric complex composed of six nonidentical subunits (alpha-zeta), two of which are glycoproteins (alpha and beta). The beta and delta subunits of the oligosaccharyltransferase are encoded by the WBP1 and SWP1 genes. Here we describe the functional characterization of the OST1 gene that encodes the alpha subunit of the oligosaccharyltransferase. Protein sequence analysis revealed a significant sequence identity between the Saccharomyces cerevisiae Ost1 protein and ribophorin I, a previously identified subunit of the mammalian oligosaccharyltransferase. A disruption of the OST1 locus was not tolerated in haploid yeast showing that expression of the Ost1 protein is essential for vegetative growth of yeast. An analysis of a series of conditional ost1 mutants demonstrated that defects in the Ost1 protein cause pleiotropic underglycosylation of soluble and membrane-bound glycoproteins at both the permissive and restrictive growth temperatures. Microsomal membranes isolated from ost1 mutant yeast showed marked reductions in the in vitro transfer of high mannose oligosaccharide from exogenous lipid-linked oligosaccharide to a glycosylation site acceptor tripeptide. Microsomal membranes isolated from the ost1 mutants contained elevated amounts of the Kar2 stress-response protein.

Marihuana: studies on the disposition and metabolism of delta-9-tetrahydrocannabinol in man.

Delta(9)-Tetrahydrocannabinol (the major active component of marihuana) administered intravenously to normal human volunteers persists in plasma for more than 3 days (t(1/2) = 56 hours). Its metabolites appear in plasma within 10 minutes after administration and persist along with the precursor compound. Delta(9)-Tetrahydrocannabinol is completely metabolized in man, and the radioactive metabolites are excreted in urine and feces for more than 8 days.

Coal conversion technologies: some health and environmental effects.

Several technologies to convert coal to liquid and gaseous fuels are being developed in the United States, some with support from the Department of Energy. Substitution of these technologies for those currently being used will produce different health and environmental hazards. In this article, selected health and environmental effects of four coal conversion and four existing technologies are compared. For each technology, the emission estimates for complete fuel cycles, including all steps in fuel use from extraction to the end use of space and water heating by electricity or direct combustion, were prepared by means of the Brookhaven Energy System Network Simulator model. Quantitative occupational health and safety estimates are presented for the extraction, transportation, distribution, processing, and conversion activities associated with each technology; also included are some public health damage estimates arising from fuel transportation and air pollution impacts. Qualitative estimates of health damage due to polycyclic organic matter and reduced sulfur are discussed. In general, energy inefficiencies, environmental residuals, and hence implied environmental effects and health damage increase in the order: (i) direct combustion of natural gas and oil, (ii) direct combustion of synthetic gas and oil, (iii) central-station electric power produced from synthetic gas, (iv) central-station electric power produced from coal, and (v) central-station electric power produced by the combustion of synthetic liquid fuels. The compliance and conflict of these technologies with the amendments of the Clean Air Act and other legislation are discussed.

Tonabersat, a novel gap-junction modulator for the prevention of migraine.

Migraine is a common, recurrent, primary headache disorder associated with significant morbidity as well as high direct and indirect costs. Despite its impact, only a proportion of migraineurs who meet criteria for prophylactic treatment take preventive medication. Antiepileptic drugs and beta-blockers are among the most used preventive therapies, but their exact mechanisms of action in migraine prophylaxis are unknown. Recent research has pointed to the role of cortical spreading depression in the genesis of migraine aura and pain, with neuronal-glial gap junctions playing a prominent part in cortical spreading depression. Tonabersat is a unique compound with demonstrated activity as a gap-junction inhibitor in animal studies. In preclinical and clinical trials, tonabersat was well tolerated, with no cardiovascular effects; the pharmacokinetic profile suggested its usefulness in the prophylaxis of migraine.

Hemicrania continua: who responds to indomethacin?

Hemicrania continua (HC) is a primary headache disorder characterized by a continuous, moderate to severe, unilateral headache and defined by its absolute responsiveness to indomethacin. However, some patients with the clinical phenotype of HC do not respond to indomethacin. We reviewed the records of 192 patients with the putative diagnosis of HC and divided them into groups based on their headaches' response to indomethacin. They were compared for age, gender, presence or absence of specific autonomic symptoms, medication overuse, rapidity of headache onset, and whether or not the headaches met criteria for migraine when severe. Forty-three patients had an absolute response and 122 patients did not respond to adequate doses of indomethacin. The two groups did not differ significantly in terms of age, sex, presence of rapid-onset headache, or medication overuse. Autonomic symptoms, based on a questionnaire, did not predict response. Eighteen patients could not complete a trial of indomethacin due to adverse events. Nine patients could not be included in the HC group despite improvement with indomethacin: one patient probably had primary cough headache, another paroxysmal hemicrania; three patients improved but it was uncertain if they were absolutely pain free, and four patients dramatically improved but still had a baseline headache. We found no statistically significant differences between patients who did and did not respond to indomethacin. All patients with continuous, unilateral headache should receive an adequate trial of indomethacin. Most patients with unilateral headache suggestive of HC did not respond to indomethacin.

Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine.

Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of tonabersat to relieve the symptoms of moderate to severe migraine was evaluated in 859 migraineurs enrolled in two dose-ranging, double-blind, randomized, placebo-controlled, parallel-group trials, one international and the other North American. In the international study, significantly more patients given tonabersat than given placebo experienced relief of headache pain at 2 h (15 mg, 36.8%; 40 mg, 40.7%), the principal efficacy variable, and at 4 h (40 mg, 63.0%) and complete abolition of headache at 4 h (40 mg, 34.3%). None of the primary or secondary efficacy variables indicated significant differences between tonabersat and placebo in the North American study. Tonabersat was generally well tolerated, with dizziness and nausea the most common side-effects. Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events. These results suggest a possible interplay between tonabersat pharmacokinetics (the relatively long time required to reach maximum plasma concentrations) and patient characteristics (previous triptan exposure) in the management of acute migraine attacks. Based on the pharmacokinetics and actions on cortical spreading depression, tonabersat may have potential value in migraine prophylaxis.