Tolerability and safety of galcanezumab in patients with chronic cluster headache with up to 15 months of galcanezumab treatment.

OBJECTIVE: The objective of the study was to assess the tolerability and safety of galcanezumab in patients with chronic cluster headache (CH) with up to 15 months of treatment. BACKGROUND: Chronic CH is a highly debilitating disease with a substantial and unmet medical need. METHODS: Patients were randomized to receive placebo or galcanezumab (300 mg) monthly for 12 weeks, followed by an optional 52-week open-label extension and 16-week posttreatment follow-up (washout). This is a secondary analysis and long-term follow-up of a previously conducted clinical trial. The safety analysis included patients who received galcanezumab at any time during the study. Outcomes included adverse events (AEs), discontinuations, laboratory values, vital signs, electrocardiograms (ECGs), and suicidality ratings. RESULTS: A total of 233 patients received at least one galcanezumab dose. The mean exposure was 341 days. Galcanezumab-treated patients were mostly male (n = 169/233; 72.5%) with a mean age of 44.9 (±10.9) years. Treatment-emergent adverse events (TEAEs) were reported by 185 patients (n = 185/233; 79.4%), 23 patients (n = 23/233; 9.9%) reported serious adverse events (SAEs), and 18 patients (n = 18/233; 7.7%) discontinued due to AEs. The SAE CH was reported by three patients. The most common TEAEs (>10%) were nasopharyngitis (n = 41/233; 17.6%) and injection site pain (n = 33/233; 14.2%). 27.5% of patients (n = 64/233) had TEAEs related to injection sites. Likely hypersensitivity events, including injection site rash, injection site urticaria, and injection site hypersensitivity were reported (n = 14/233; 6.0%). There were past histories of suicidal ideation (n = 55/237; 23.2%) and suicidal behavior (n = 9/236; 3.8%). During the study, 15 patients (n = 15/230; 6.5%), seven with previous history, reported suicidal ideation. One patient had a nonfatal suicide attempt during the open-label extension and an aborted attempt during the washout. There were no new safety findings compared with the placebo-controlled treatment period in laboratory values, vital signs, or ECGs. CONCLUSIONS: Galcanezumab 300 mg monthly had a favorable tolerability and safety profile in patients with chronic CH with up to 15 months of treatment.

Clinical Subtypes of Medication Overuse Headache - Findings From a Large Cohort.

BACKGROUND: The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population. METHOD: This descriptive cross-sectional observational study included 660 patients with MOH referred to headache centers in Europe and Latin America as a part of the COMOESTAS project. Information about clinical features was collected with structured patient interviews and with self-administered questionnaires for measuring disability, anxiety, and depression. RESULTS: Female/male ratio, body mass index, marital status, and level of education were similar among in subjects enrolled in the 5 centers. The mean age was higher among subjects overusing triptans (T-MOH) with respect to subjects overusing simple analgesic (A-MOH). Duration of headache before chronification was longer in T-MOH (19.2 ± 11.9 years) and in subjects overusing ergotamines (E-MOH, 17.8 ± 11.7 years) with respect to the A-MOH group (13.1 ± 10.9; P < .001 and P = .017, respectively) and in T-MOH with respect multiple drug classes (M-MOH, 14.9 ± 11.7; P = .030). Migraine Disability Assessment (MIDAS) score was significantly lower in E-MOH group (33.6 ± 41.6), while T-MOH group (56.8 ± 40.6) had a significant lower MIDAS score with respect to M-MOH (67.2 ± 62.5; P = .016 and P = .037, respectively). Prevalence of depression and anxiety was lower in patients overusing T with respect to other groups of patients (χ2  = 10.953, P = .027 and χ2  = 25.725, P < .001, respectively). CONCLUSION: In this study on a large and very well characterized population of MOH, we describe the distinctive clinical characteristics of MOH subtypes. These findings contribute to more clearly define the clinical picture of a poorly delineated headache disorder. They also provide some insights in the possible trajectories leading to this highly disabling chronic headache, that is classified as a secondary form, but whose occurrence is entirely dependent on an underlying primary headache.

Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies.

BACKGROUND: Maintenance of effect following treatment with galcanezumab compared to placebo in adult patients with episodic or chronic migraine was evaluated. METHODS: In 2 similarly designed studies of patients with episodic migraine (6 months) and 1 study of patients with chronic migraine (3 months), patients randomized in a 1:1:2 ratio received a subcutaneous injection of galcanezumab 120 mg/month (after an initial loading dose of 240 mg) or 240 mg/month or placebo. Maintenance of effect during the double-blind phase was evaluated based on a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of 30, 50, 75, and 100% response (defined as ≥30, ≥50, ≥75, and 100% reduction from baseline in monthly migraine headache days [MHD]) at an individual patient level. Logistic regression analyses were used for between treatment comparisons. RESULTS: A total of 1773 adult patients with episodic migraine (n = 444 for galcanezumab 120 mg; n = 435 for galcanezumab 240 mg; n = 894 for placebo for 2 studies pooled) and 1113 patients with chronic migraine (n = 278 for galcanezumab 120 mg; n = 277 for galcanezumab 240 mg; n = 558 for placebo) were evaluated. In patients with episodic migraine, ≥50% response was maintained in 41.5 and 41.1% of galcanezumab-treated patients (120 mg and 240 mg, respectively) for ≥3 consecutive months (until patient's endpoint) and 19.0 and 20.5%, respectively, for 6 consecutive months and was significantly greater than the 21.4 and 8.0% of placebo-treated patients at ≥3 and 6 months consecutively (P < 0.001). Approximately 6% of galcanezumab-treated patients maintained ≥75% response all 6 months versus 2% of placebo-treated patients. Few galcanezumab-treated patients maintained 100% response. In patients with chronic migraine, 29% of galcanezumab-treated patients maintained ≥30% response all 3 months compared to 16% of placebo patients while ≥50% response was maintained in 16.8 and 14.6% of galcanezumab-treated patients (120 mg and 240 mg) and was greater than placebo (6.3%; p < 0.001). Few patients maintained ≥75% response. CONCLUSIONS: Treatment with galcanezumab 120 mg or 240 mg demonstrated statistically significant and clinically meaningful persistence of effect in patients with episodic migraine (≥3 and 6 consecutive months) and in patients with chronic migraine (for 3 months). STUDY IDENTIFICATION AND TRIAL REGISTRATION: Study Identification: EVOLVE-1 (I5Q-MC-CGAG); EVOLVE-2 (I5Q-MC-CGAH); REGAIN (I5Q-MC-CGAI) TRIAL REGISTRATION: ClinicalTrials.gov ; NCT02614183 (EVOLVE-1); NCT02614196 (EVOLVE-2); NCT02614261 (REGAIN).

Noninvasive neuromodulation in cluster headache.

PURPOSE OF REVIEW: Neuromodulation is an alternative in the management of medically intractable cluster headache patients. Most of the techniques are invasive, but in the last 2 years, some studies using a noninvasive device have been presented. The objective of this article is to review the data using this approach. RECENT FINDINGS: Techniques as occipital nerve stimulation or sphenopalatine ganglion stimulation are recommended as first-line therapy in refractory cluster patients, but they are invasive and maybe associated with complications. Noninvasive vagal nerve stimulation with an external device has been tried in cluster patients. Results from clinical practice and a single randomized clinical trial have been presented showing a reduction of the number of cluster attacks/week in the patients treated with the device. The rate of adverse events was low and most of them were mild. SUMMARY: In the last decade, invasive neuromodulation treatments have demonstrated good efficacy in cluster refractory patients. Noninvasive approaches such as the noninvasive vagal nerve stimulation have shown efficacy in one trial and could be an easier alternative in the management of this debilitating headache. We need to replicate these results with further controlled studies and conduct basic research in order to clarify the mechanism of action.

Stimulation of the sphenopalatine ganglion in intractable cluster headache: expert consensus on patient selection and standards of care.

CONTEXT AND OVERVIEW: Chronic cluster headache (CCH) is a debilitating headache disorder with a significant impairment of the patients' lives. Within the past decade, various invasive neuromodulatory approaches have been proposed for the treatment of CCH refractory to standard preventive drug, but only very few randomized controlled studies exist in the field of neuromodulation for the treatment of drug-refractory headaches. Based on the prominent role of the cranial parasympathetic system in acute cluster headache attacks, high-frequency sphenopalatine ganglion (SPG) stimulation has been shown to abort ongoing attacks in some patients in a first small study. As preventive effects of SPG-stimulation have been suggested and the rate of long-term side effects was moderate, SPG stimulation appears to be a promising new treatment strategy. AIMS AND CONCLUSION: As SPG stimulation is effective in some patients and the first commercially available CE-marked SPG neurostimulator system has been introduced for cluster headache, patient selection and care should be standardized to ensure maximal efficacy and safety. As only limited data have been published on SPG stimulation, standards of care based on expert consensus are proposed to ensure homogeneous patient selection and treatment across international headache centres. Given that SPG stimulation is still a novel approach, all expert-based consensus on patient selection and standards of care should be re-reviewed when more long-term data are available.

Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study.

BACKGROUND: The pain and autonomic symptoms of cluster headache (CH) result from activation of the trigeminal parasympathetic reflex, mediated through the sphenopalatine ganglion (SPG). We investigated the safety and efficacy of on-demand SPG stimulation for chronic CH (CCH). METHODS: A multicenter, multiple CH attack study of an implantable on-demand SPG neurostimulator was conducted in patients suffering from refractory CCH. Each CH attack was randomly treated with full, sub-perception, or sham stimulation. Pain relief at 15 minutes following SPG stimulation and device- or procedure-related serious adverse events (SAEs) were evaluated. FINDINGS: Thirty-two patients were enrolled and 28 completed the randomized experimental period. Pain relief was achieved in 67.1% of full stimulation-treated attacks compared to 7.4% of sham-treated and 7.3% of sub-perception-treated attacks ( P < 0.0001). Nineteen of 28 (68%) patients experienced a clinically significant improvement: seven (25%) achieved pain relief in ≥50% of treated attacks, 10 (36%), a ≥50% reduction in attack frequency, and two (7%), both. Five SAEs occurred and most patients (81%) experienced transient, mild/moderate loss of sensation within distinct maxillary nerve regions; 65% of events resolved within three months. INTERPRETATION: On-demand SPG stimulation using the ATI Neurostimulation System is an effective novel therapy for CCH sufferers, with dual beneficial effects, acute pain relief and observed attack prevention, and has an acceptable safety profile compared to similar surgical procedures.

Headache after trauma: physiological considerations.

Posttraumatic headache (PTH) is one of the most controversial disorders in secondary headaches. It is the most common symptom of postconcussion syndrome. There are many unresolved issues around PTH despite the efforts by the International Headache Society to classify and clarify this entity. This article reviews the classification, pathophysiology, and treatment of PTH, as well as best management of patients with psychiatric comorbidities. Due to the complexity of PTH, the different forms of appearance, its pathophysiology, and the implications of psychological factors, a multidisciplinary team to cover all aspects appears as the best way to approach management and treatment.

Treatment options for subjective tinnitus: self reports from a sample of general practitioners and ENT physicians within Europe and the USA.

BACKGROUND: Tinnitus affects about 10-15% of the general population and risks for developing tinnitus are rising through increased exposure to leisure noise through listening to personal music players at high volume. The disorder has a considerable heterogeneity and so no single mechanism is likely to explain the presence of tinnitus in all those affected. As such there is no standardized management pathway nor singly effective treatment for the condition. Choice of clinical intervention is a multi-factorial decision based on many factors, including assessment of patient needs and the healthcare context. The present research surveyed clinicians working in six Westernized countries with the aims: a) to establish the range of referral pathways, b) to evaluate the typical treatment options for categories of subjective tinnitus defined as acute or chronic, and c) to seek clinical opinion about levels of satisfaction with current standards of practice. METHODS: A structured online questionnaire was conducted with 712 physicians who reported seeing at least one tinnitus patients in the previous three months. They were 370 general practitioners (GPs) and 365 ear-nose-throat specialists (ENTs) from the US, Germany, UK, France, Italy and Spain. RESULTS: Our international comparison of health systems for tinnitus revealed that although the characteristics of tinnitus appeared broadly similar across countries, the patient's experience of clinical services differed widely. GPs and ENTs were always involved in referral and management to some degree, but multi-disciplinary teams engaged either neurology (Germany, Italy and Spain) or audiology (UK and US) professionals. For acute subjective tinnitus, pharmacological prescriptions were common, while audiological and psychological approaches were more typical for chronic subjective tinnitus; with several specific treatment options being highly country specific. All therapy options were associated with low levels of satisfaction. CONCLUSIONS: Despite a large variety of treatment options, the low success rates of tinnitus therapy lead to frustration of physicians and patients alike. For subjective tinnitus in particular, effective therapeutic options with guidelines about key diagnostic criteria are urgently needed.

Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial.

BACKGROUND: Many patients who require migraine preventive treatment have not been able to tolerate or have not responded to multiple previous preventive medications. We aimed to assess the safety and efficacy of galcanezumab, an antibody to calcitonin gene-related peptide, in patients with migraine who had not benefited from preventive medications from two to four categories. METHODS: CONQUER was a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial done at 64 sites (hospitals, clinics, or research centres) in 12 countries (Belgium, Canada, Czech Republic, France, Germany, Hungary, Japan, the Netherlands, South Korea, Spain, the UK, and the USA). Patients were 18-75 years of age, with episodic or chronic migraine, with migraine onset before the age of 50 years, who had a documented failure of preventive medications from two to four drug categories in the past 10 years owing to lack of efficacy or tolerability, or both. Patients were randomised 1:1 to receive subcutaneous placebo or galcanezumab 120 mg per month (with a 240 mg loading dose administered as two 120 mg injections) for 3 months. For masking purposes, patients receiving placebo also received two injections during the first dosing visit. Randomisation was done by a computer-generated random sequence by means of an interactive web-response system stratified by country and migraine frequency (low frequency episodic migraine, four to fewer than eight migraine headache days per month; high frequency episodic migraine, eight to 14 migraine headache days per month and fewer than 15 headache days per month; chronic migraine, at least eight migraine headache days per month and at least 15 headache days per month). The primary endpoint was the overall mean change from baseline in number of monthly migraine headache days during the 3-month treatment period in all patients who were randomly assigned and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03559257, and is now completed. FINDINGS: Between Sept 10, 2018, and March 21, 2019, 462 participants with episodic (269 [58%]) or chronic (193 [42%]) migraine were randomly assigned and received at least one injection with placebo (n=230) or galcanezumab (n=232). Galcanezumab-treated patients had significantly greater reduction in migraine headache days versus placebo across months 1-3. The galcanezumab group had on average 4·1 fewer monthly migraine headache days compared with baseline (13·4), while the placebo group had on average 1·0 fewer than at baseline (13·0; between-group difference -3·1 [95% CI -3·9 to -2·3]; p<0·0001; effect size=0·72). Types and number of treatment-emergent adverse events were similar between galcanezumab and placebo. Treatment-emergent adverse events were reported in 122 (53%) of 230 patients in the placebo group and 119 (51%) of 232 patients in the galcanezumab group. There were four serious adverse events during the study, two (1%) reported in the placebo group and two (1%) reported in the galcanezumab group. INTERPRETATION: Galcanezumab was superior to placebo in the preventive treatment of migraine and was safe and well tolerated in patients for whom multiple previous standard-of-care preventive treatments had failed. Galcanezumab might represent an important treatment option for patients who have not benefited from or tolerated previous standard-of-care treatments. FUNDING: Eli Lilly.

Anterior lumbosacral polyradiculopathy after intrathecal administration of methotrexate.

Transient paraparesis has been reported with intrathecal chemotherapy agents and the most common cause is an incomplete inflammatory myelopathy. We report a case of a 30-year-old man diagnosed with acute lymphoblastic leukaemia who developed subacute anterior lumbosacral polyradiculopathy following intrathecal methotrexate, an unusual complication of intrathecal chemotherapy in adults. Spinal magnetic resonance discarded myelopathy. Cerebrospinal fluid exam showed elevation of protein, mononuclear pleocytosis and immunoglobulin synthesis. Electrodiagnostic study showed alterations of sensory and motor conductions only in lower limbs, consistent with multilevel radiculopathy. Differential diagnosis included toxic and neoplastic polyradiculopathy, and axonal variant of acute inflammatory demyelinating polyradiculoneuropathy. The authors review possible pathogenic mechanisms and propose several therapeutic and preventive options.

Botulinum toxin for the treatment of somatic tinnitus.

Subjective tinnitus is an auditory sensation experienced in the absence of external or internal acoustic stimuli. It causes significant morbidity and can progress to a chronic debilitating condition. Somatic tinnitus is tinnitus that can be modulated by stimulation of the somatic sensory system. It occurs because of interactions between the auditory and the somatosensory system that may occur at several levels of the central nervous system. In the present chapter, we discuss how botulinum toxin can improve tinnitus and discuss the mechanism of its action, and how it relates to its effects on chronic pain.

Topiramate in migraine prophylaxis--results from a placebo-controlled trial with propranolol as an active control.

Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo-controlled, dose-ranging trials. We conducted a randomised, double-blind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine with and without aura were randomised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double-blind treatment phase. Five hundred and seventy-five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles.

The impact of a worksite migraine intervention program on work productivity, productivity costs, and non-workplace impairment among Spanish postal service employees from an employer perspective.

BACKGROUND: Migraine is associated with a significant productivity loss to employers, who may benefit from making a migraine intervention available to their employees. OBJECTIVE: To evaluate changes in migraine-related productivity and non-workplace impairment associated with a migraine intervention program from the employer perspective. METHODS: This was a pre-test post-test study of Spanish Postal Service employees with migraine. The intervention consisted of counseling from occupational health physicians and rizatriptan 10 mg for symptomatic treatment of two subsequent migraine headaches. Physicians also prescribed additional medications for migraine prophylaxis, treatment of tension headaches, and rescue medications. Migraine-related work loss and non-workplace impairment (interference with daily and social activities) were self-reported at baseline (pre-intervention) and separately following each migraine headache (post-intervention) with the aid of a diary. Migraine-related work loss was reported as work loss due to absenteeism, reduced productivity while at work, and the sum of the two (total lost work day equivalents [LWDE]). An employer perspective was taken for the cost analysis, and thus productivity costs were the only costs considered. RESULTS: A total of 436 patients comprised the population for analysis. The number of migraine-related LWDE per migraine attack were 0.48 days per migraine headache in the month before the intervention, decreasing to 0.20 days and 0.07 days per migraine headache during the first and second migraine headaches following the intervention (p < 0.0001 vs. baseline). Total migraine-related productivity costs per migraine headache were 34 euros/patient before the intervention, decreasing to 14 euros/patient and 5 euros/patient during the first and second headaches following the intervention (p < 0.0001). Non-workplace activity impairment was also significantly reduced (p < 0.0001) following the intervention. The main limitations of the study were the lack of a parallel control group and the potential for differential recall bias between the usual care and the intervention periods. In addition, the results may not be generalizable to other employers or other countries. CONCLUSION: This study documents the value of a workplace migraine intervention program, which focused on migraine prevention and rizatriptan-based symptomatic treatment. It also highlights the important role occupational health clinics can play in helping employers and employees reduce the burden of migraine.

Sphenopalatine ganglion stimulation for the treatment of cluster headache.

Cluster headache is a severe, debilitating disorder with pain that ranks among the most severe known to humans. Patients with cluster headaches have few therapeutic options and further, 10-20% develop drug-resistant attacks. The often brief duration of cluster attacks makes abortive therapy a challenge, and preventive medications are almost always provided to patients, but the side effects of these preventive medications can be significant. The sphenopalatine ganglion (SPG) is believed to play a role in headache pain and cranial autonomic symptoms associated with cluster headache, which is a result of activation of the trigeminal-autonomic reflex. For over 100 years, the SPG has been a clinical target to treat primary headache disorders using pharmacologic and nonpharmacologic methods. Radiofrequency lesioning and nerve-resection therapies, while initially beneficial, are irreversible procedures, and the use of neurostimulation provides one method of interfacing with the neural pathways without causing permanent damage to neural tissue. SPG neurostimulation is both reversible and adjustable, and has recently been tested in both proof-of-concept work and in a randomized, sham-controlled trial for the treatment of cluster headache. A randomized, sham-controlled study of 32 patients was performed to evaluate further the use of SPG stimulation for the acute treatment of chronic cluster headache. Of the 32 patients, 28 completed the randomized experimental period. Overall, 68% of patients experienced an acute response, a frequency response, or both. In this study the majority of adverse events were related to the implantation procedure, which typically resolved or remained mild in nature at 3 months following the implant procedure. This and other studies highlight the promise of using SPG stimulation to treat the pain-associated cluster headache. SPG stimulation could be a safe and effective option for chronic cluster headache.

The effect of migraine prophylaxis on migraine-related resource use and productivity.

In the US, it is estimated that up to 10% of men and 25% of women, particularly those aged 25-55 years, experience debilitating migraines, such that the condition presents an enormous economic burden for patients, health systems, employers and society. Migraine headache is a particularly prevalent condition associated with major reductions in patients' quality of life. From a payer perspective, the implementation of relevant programmes of migraine prophylaxis is highly desirable. Consistent evidence exists, from several randomized, controlled studies, of the efficacy of amitriptyline, divalproex sodium, propranolol, timolol and topiramate in migraine prophylaxis. Considering resource utilization, various studies suggest that migraine prophylaxis with antiepileptics, antidepressants, beta-blockers or calcium channel antagonists markedly reduces triptan use and visits to physician offices and emergency departments (EDs), without compromising quality of care or treatment outcomes. Over recent years, the effects of topiramate in reducing resource utilization in patients with migraine have been relatively widely studied. In US claims database analyses involving >4000 patients with migraine, topiramate significantly reduced triptan use by up to 20% in the 12-month period after starting treatment. Reductions were also noted in the numbers of ED visits, diagnostic procedures, hospital admissions and migraine-related hospitalization days. These long-term benefits of topiramate manifested without any increase in overall headache-related costs. Furthermore, in detailed modelling analyses based on UK and US data, topiramate-induced savings in acute medical services were estimated to offset about one-quarter of the monthly per patient cost of the topiramate regimen, which was shown to be a dominant cost-effective intervention relative to no preventive therapy: cost-effectiveness ratios were calculated as pound 5728 per quality-adjusted life-year (QALY) [2005 costings] and $US10 888 per QALY (2002 costings), respectively. Overall, there is a need to improve quality of care in migraine, and prophylactic therapy appears to be an effective option, particularly with respect to decreasing resource use and improving productivity. For both health-plan payers and employers, topiramate appears to be a cost-effective intervention for preventing migraine.

Labor productivity in migraine patients: primary care contribution to occupational medicine.

OBJECTIVE: To estimate the impact of migraine on labor productivity and health resources utilization in an active population attending Primary Care settings in Spain. METHODS: An observational, cross-sectional, and multicenter study was designed. Productivity, loss workdays equivalents and previous 3-months health resources utilization were calculated. RESULTS: Four thousand four hundred twenty six patients were evaluated. The migraine group showed the lowest productivity, highest loss workdays equivalents and health resources utilization compared with non-migraine headaches and subjects without headaches (P < 0.05 in all cases). Within the migraine group, lower productivity values were observed in female patients compared to male (64.04 vs 59.69; P < 0.05), while emergency room visits were more frequent for male patients (0.71 vs 076; P < 0.05). CONCLUSIONS: Subjects with migraine showed higher impact on health resources utilization and productivity when evaluated at Primary care level.

Almotriptan: meeting today's needs in acute migraine treatment.

Migraine is a common disorder associated with considerable individual and economic burden. Triptans are recommended for the treatment of migraine of any severity in patients who have failed to gain adequate relief with nonspecific medication; early transition to triptans avoids prolonged morbidity in patients failing to respond to nonspecific medications. There is evidence that early intervention therapy with oral formulations in migraine, soon after the onset of an attack and when pain is still mild, improves efficacy. Seven different triptans are currently marketed, with differing pharmacologic, efficacy and tolerability profiles. Almotriptan has many positive features, which include rigorously demonstrated efficacy in sumatriptan nonresponders, as early therapy and in menstrual migraine. In addition, almotriptan has a favorable pharmacologic profile with a lack of clinically relevant pharmacokinetic interventions with other drugs, adverse reactions rate similar to placebo, superior cost-effectiveness and excellent performance on composite clinical outcome measures that incorporate features of greatest importance to patients. Although effective in both triptan-naive and -experienced patients, and as both early and standard therapy, almotriptan shows greater efficacy in triptan-naive patients and as early treatment, and is consistently one of the preferred triptans in multiattribute decision-making analyses incorporating attributes of significance for patients and physicians. Therefore, almotriptan has many features that make it an ideal choice for a triptan-naive patient moving from nonspecific medication, a patient switching from another triptan owing to inefficacy or tolerability issues and patients being advised to take a triptan early in the course of a migraine attack.

Predictive model for the Migraine-ACT questionnaire in primary care.

BACKGROUND: Migraine is frequently under-treated. The 4-item Migraine Assessment of Current Therapy (Migraine-ACT) questionnaire is a simple, patient-friendly tool to identify patients requiring change in acute migraine treatment. OBJECTIVE: To establish a predictive model for the Migraine-ACT questionnaire in primary care. RESEARCH DESIGN AND METHODS: This open-label, prospective, two-visit study at 1100 primary care sites enrolled patients reporting migraine for > 1 year and > or = 1 migraine attack/month. Predictive validity of the Migraine-ACT questionnaire was evaluated using a logistic regression model adjusted for baseline disability, diagnosis, sex, age, attack frequency, attack duration, baseline treatment change, treatment(s) for the study period and baseline Migraine-ACT score. RESULTS: A total of 3272 patients, 78% female, entered the study and 2877 patients (88%) returned at 3 months. Investigators changed baseline migraine treatment for 72% of returning patients. Percentages of patients who were completely or very satisfied with migraine therapy increased from 15% at baseline to 49% at 3 months. The adjusted logistics regression model yielded sensitivity of 86% and specificity of 85% to detect > or = 1-point change in Migraine-ACT score at 3 months (p < 0.001). The model yielded 77% sensitivity and 95% specificity to detect > or = 1-point improvement in patient satisfaction at 3 months among patients who improved > or = 1 point in the Migraine-ACT score (adjusted odds ratio, 2.63; 95% confidence interval, 1.97-3.51; p < 0.001). CONCLUSIONS: The Migraine-ACT questionnaire is a simple but sensitive and specific tool to predict improvements at 3 months resulting from changes in migraine treatment and can be used to detect patients with suboptimal migraine management and to monitor treatment effectiveness.

Antiepileptic drugs for the treatment of chronic and episodic cluster headache: a review.

Cluster headache needs to be rapidly diagnosed and effectively managed, as the individual headache attacks that are characteristic of this disorder are excruciatingly painful and debilitating. Preventive therapies are necessary to reduce the frequency of attacks during the cluster period. However, preventive therapy for this disorder is limited by a lack of controlled evidence of efficacy and the potential for systemic toxicity. Recent progress has been made in understanding both the pathophysiological mechanisms underlying cluster headache and the mechanisms of action of the antiepileptic drug class for the treatment of primary headache syndromes. Newly available preliminary clinical trial data evaluating antiepileptic drugs for the prevention of cluster headache suggest that these agents may be effective and that further evaluation in randomized, placebo-controlled trials is warranted.

Perfusion-weighted magnetic resonance imaging in acute intracerebral hemorrhage at baseline and during the 1st and 2nd week: a longitudinal study.

BACKGROUND AND PURPOSE: Ischemic penumbra has been suggested as a contributing mechanism to secondary neuronal injury in intracerebral hemorrhage (ICH). Preliminary data suggest the presence of perihematomal hypoperfusion within the first hours after acute ICH. Our objective was to elucidate perfusion changes in the perihematomal region over time using magnetic resonance imaging (MRI). METHODS: Two perfusion-weighted MRIs were studied prospectively in 18 ICH patients. All patients had an acute perfusion-weighted MRI within 24 h of the onset of symptoms (time 0); 11 patients had a follow-up study on day 7 (time 1), and 7 patients on days 10-14 (time 2). The region of interest (ROI) was placed over the penumbral area, on high-intensity FLAIR and perfusion overlapping map imaging. Clinical data were assessed at baseline (National Institutes of Health Stroke Scale) and on day 90 (Canadian Scale, modified Rankin Scale). RESULTS: The average hematoma volume was 56 (9-140) ml; 10 were located deeply, and 8 were lobar. When we compared the perfusion changes (mean transit time prolongation) in the perihematomal area (lesion ROI) relative to itself over time, we found significant differences only between times 0 and 2 (p = 0.05). There were also significant differences in mean transit time between the lesion ROI and the contralateral mirror ROI in the baseline study (p = 0.001), with a trend to significance for time 1. CONCLUSIONS: Our data confirm the presence of hypoperfusion around an acute ICH and demonstrate that this change disappears completely after the first week. These data suggest that further evaluation of this feature of acute ICH is warranted, as its confirmation may lead to modifications in the current therapeutic approach.