Migraine Headache Attacks Research Articles

The Quest for the Anti-Migraine Principle(s) of Feverfew, Tanacetum parthenium (L.) Schultz Bip.

Feverfew (Tanacetum parthenium) has had a traditional reputation for treating fever, headache, and women's ailments. Only in the 1970s did feverfew gain popularity as a migraine prophylactic. The effectiveness of feverfew in reducing the incidence and severity of migraine headache attacks, along with alleviating associated nausea and vomiting, has been established in randomized controlled clinical trials, primarily using whole feverfew leaf, whereas more recently a supercritical carbon dioxide fluid extract has been shown successful, although only in a small subset of subjects who experienced at least four migraine attacks monthly. The demise of the formerly widely touted anti-migraine mechanism involving the sesquiterpene lactone parthenolide has focused attention on other feverfew constituents as potential candidates for the mantle of active principle.

127. Migraine – Changing Views Over 50 Years

Fifty years ago migraine was regarded as a vascular headache, the result of the pioneering work of Harold G Wolff and his colleagues in New York. Acute treatment relied on ergotamine and preventive therapy on “Bellergal”, a mixture of ergotamine, phenobarbitone and belladonna alkaloids. Federigo Sicuteri in Florence started the serotonin story when he reported that an ergot derivative, methysergide, a so-called serotonin antagonist, was an effective prophylactic agent. Our laboratory in Sydney followed this lead, showing that serotonin was discharged from blood platelets at the onset of migraine headache and confirming an American report that the intravenous injection of serotonin eased the headache, at the expense of severe side effects.

Are Cortical Spreading Depression and Headache in Migraine Causally Linked?

During the past few decades, much controversy has surrounded the pathophysiology of migraine. Cortical spreading depression (CSD) is widely accepted as the neuronal process underlying visual auras. It has been proposed that CSD can also cause the headaches, at least in migraine with aura. We describe three patients, each fulfilling the International Headache Society criteria for migraine with aura, who suffered from headaches 6-10 days per month. Two patients were treated with flunarizine and the third patient with topiramate for the duration of 4 months. All patients reported that aura symptoms resolved completely, whereas the migraine headache attacks persisted or even increased. These observations question the theory that CSD (silent or not) is a prerequisite for migraine headaches.

Recent Advancements in Anti-Migraine Drug Research: Focus on Attempts to Decrease Neuronal Hyperexcitability

Migraine is a painful, sometimes debilitating disorder, which is frequently associated with various neurological symptoms. Its prevalence in the population is higher than that of any other neurological disorders, thus the burden of this disease on society is considerable. Although the introduction of triptans nearly two decades ago revolutionized the treatment of the disease there is still a huge unmet need regarding drugs with better properties. Formerly, migraine therapy primarily aimed at treating the pathological alterations of meningeal blood vessels that are thought to directly initiate a migraine headache attack. By now, it has been increasingly recognized by drug companies that abnormal neural function may be more important in the development of the disease and also in triggering an attack. Migraine is associated with an increased neuronal excitability and episodes of cortical spreading depression. Understanding the molecular mechanisms underlying the abnormal functioning of over-activated neuronal circuits may help to identify novel anti-migraine drug targets. Besides a general description of the pathophysiology and pharmacotherapy of migraine this review paper aims at discussing the possible drug targets through which migraine-related hyperexcitability and over-excitation can be attenuated. It will be shown how these new ideas appear in the recent patent literature.

Does Early Migraine Treatment Shorten Time to Headache Peak and Reduce Its Severity?

To explore whether early treatment would shorten the duration of headache from headache onset to its peak and reduce headache severity at peak. Prior clinical studies almost exclusively focused on headache relief after dosing. No data are available on whether early intervention affects the duration from headache onset to peak and headache severity at peak. Adult migraineurs were enrolled in this observational study from multi-site headache clinics. Patients recorded their migraine experiences via an electronic diary over 1 month. Patients reported the time and pain severity at onset, dosing, and peak. We used a linear mixed model to evaluate the impact of the timing of treatment and to adjust for covariates and correlation of observations within subjects. A total of 182 patients reported 970 migraine episodes, 620 of which were treated before headaches progressed to peak. Mean time from headache onset to peak varied from 1.9 hours to 8.9 hours for patients treated within 15 minutes of onset and those who waited for 4 or more hours, respectively. However, early intervention was not associated with reduced headache severity at peak. In multivariate analysis, early treatment, use of triptans, and mild migraine headache in the past 3 months were significantly associated with shorter time from onset to headache peak. A separate model indicated that the timing of medication was not associated with the duration between dosing and headache peak, but use of triptans shortened the time from dosing to headache peak. Early treatment and use of triptans may lead to shorter duration from migraine headache onset to its peak but did not alleviate headache severity at peak. This could result in decreased migraine burden by reducing total migraine headache duration.

Effect of Early Intervention With Almotriptan vs Placebo on Migraine‐Associated Functional Disability: Results From the AEGIS Trial

To investigate the effect of early acute migraine intervention with almotriptan vs placebo on functional disability and health-related quality of life (HRQoL) indicators. In this multicenter, double-blind, parallel-group trial, adults with international classification of headache disorders-defined migraine, with or without aura, were randomized 1:1 to treat 3 consecutive headaches with either almotriptan 12.5 mg or placebo. Patients were instructed to take their study medication at the first sign of migraine headache pain of any intensity, within 1 hour of onset. Patients recorded level of functional disability (normal, disturbed, bed rest required, emergency room [ER]/hospitalization required) at baseline (pretreatment), 0.5, 1, 2, 4, and 24 hours posttreatment and at time of pain-free. Patients completed the Migraine Disability Assessment Scale (MIDAS) at randomization and completed the Migraine Quality-of-Life Questionnaire (MQoL) at 24 hours after each attack. Results are presented for 315 patients (160 almotriptan, 155 placebo) in the evaluable for efficacy population. At 2 hours posttreatment of Attack 1, 54.4%, 32.5%, 13.1%, and 0%, respectively, of almotriptan-treated patients reported normal function, disturbed function, bed rest required, and ER/hospitalization required compared with 38.1%, 45.2%, 16.1%, and 0.6%, respectively, of placebo-treated patients. The differences in level of functional disability between the 2 treatment groups were statistically significant at 2 hours (P = .007; Cochran-Mantel-Haenszel, stratified by center) and at 4 hours (P < .001). Resolution of pain was associated with a normal level of function; at 2 hours posttreatment, 91.7% of patients in the total population who achieved pain-free reported normal function compared with 44.8%, 8.0%, and 0% of patients with mild, moderate, and severe pain, respectively. The absence compared with the presence of photophobia, phonophobia, and nausea at 2 hours also was associated with less disability (P < .0001 for each symptom). Treatment with almotriptan compared with placebo resulted in consistently better 24-hour MQoL scores with significant results for all 3 migraine headache attacks in the social function and feelings/concern domains. A logistic regression model determined that pretreatment functional level (P = .0117), pretreatment pain intensity (P = .0089), and pretreatment MIDAS score (P = .0152) were significant covariates of the proportion of patients who achieved normal function at 2 hours posttreatment. Early treatment with almotriptan within 1 hour of migraine pain onset significantly reduced levels of functional disability at 2 and 4 hours posttreatment compared with placebo. Consistency in improvement of HRQoL indicators was observed across 3 headaches treated.

Incidence, Timing, and Predictive Factors of New-Onset Migraine Headache Attack After Transcatheter Closure of Atrial Septal Defect or Patent Foramen Ovale

The objectives of this study were to evaluate the incidence, predictive factors, and duration of migraine headache attack (MHA) after transcatheter atrial septal defect (ASD) or patent foramen ovale (PFO) closure. A total of 260 consecutive patients who underwent ASD or PFO closure in our center answered a structured headache questionnaire focused in 3 period times, including (1) at baseline (just before closure), (2) within the 3 months after ASD-PFO closure, and (3) at the last (median 27 months, range 6 to 80 months) follow-up. All questionnaires were evaluated by a neurologist who established the diagnosis of MHA with or without aura, according to International Headache Society criteria. The Amplatzer ASD or PFO device was used in 95% of the patients, and aspirin, for at least 6 months, was the antithrombotic treatment in 91% of the cases. A total of 185 patients (71%) had no history of MHA before ASD-PFO closure, and these constituted the study population (mean age 39 +/- 21 years). MHA occurred in 13 patients (7%) after ASD-PFO closure, with aura in 9 of them. MHA appeared after a median of 10 days (range 0.3 to 30 days) after the procedure and were still present at the last follow-up (23 +/- 17 months) in 9 patients (69%). The median number of MHA within the 3 months after the procedure was 4 per month (interquartile range 1 to 23), and decreased to 1 per month (interquartile range 0.3 to 1) at the latest follow-up (p = 0.03). Compared with the patients who did not develop MHA, patients with MHA after ASD-PFO closure were younger (26 +/- 16 vs 39 +/- 21 years; p = 0.02) and were more likely to have undergone ASD closure (100% vs 58%; p = 0.001). In the multivariate analysis, ASD closure was the only predictor of MHA occurrence after the procedure (odds ratio 7.7; 95% confidence interval 1.5 to 22; p = 0.01). In conclusion, MHA, mostly with aura, occurred in 7% of patients after transcatheter ASD-PFO closure and persisted in most of them after a mean follow-up of 2 years. ASD closure was the only independent predictor of MHA occurrence after the procedure. These results suggest that mechanisms other than device composition are involved in the occurrence of MHA in these cases.

Association Between Stress at Work and Primary Headache Among Nursing Staff in Taiwan

Stress, one of the most commonly identified triggers for primary headache in the workplace, usually leads to inefficient work during attacks. Stress-related primary headaches in the nursing staff of hospitals have received little attention. To realize the association between stress and headache, and the means of coping with this kind of headache. A cross-sectional, hospital-based study using a semi-structured questionnaire was administered to 900 nursing staffers in a tertiary medical center in southern Taiwan. Thirty-two items, including basic information, headache- and stress-related questions, work satisfaction, and coping strategies were measured. Headache sufferers with either migraine or episodic tension headache (attacks <15 days per month) based on International Headache Society (IHS) criteria were enrolled for analysis. The Student's t-test, one-way analysis of variance (ANOVA), and chi-square test were used for statistical analysis. Three hundred eighty-six out of 779 responders (49.6%) had experienced primary headaches in the previous year, and 374 (48.1%) had had episodic-type headaches (<15 days/month). A careful neurological interview of the latter group revealed that 222 (28.5%) had migraine, 104 (13.4%) had tension headache, 37 (4.8%) had mixed migraine and tension headache, and 11 (1.4%) had other causes of headache. There were no demographic differences between the sufferers and nonsufferers, although a statistically significant difference was noted in self-reported sources of stress (individual P values ranged from .021 to < .001). Headache sufferers had more stress at work than non-headache sufferers (P < .001). The youngest and least experienced of the nursing staff, the unmarried, and those with a lower level of education had a higher level of stress. The methods used to deal with headaches were sleep, taking medicine, taking a rest, visiting the doctor, and seeking psychological help. Nurses commonly used acetaminophen (panadol--500 mg) to relieve their pain. These results indicate that stress at work is associated with primary headaches among nursing staff, and that nurses rarely seek help in the beginning. Therefore, nursing staff education aimed at ameliorating the stress and coping with the headaches, thus allowing the nurses to provide better patient care, may be warranted.

Botulinum Toxin—A Treatment for Migraine? A Systematic Review

Scalp injection of botulinum toxin type A (BT-A) into the superficial musculature has evoked interest in the management of migraine headache. In clinical trials, prevention of migraine attacks for 3 months or more has been seen in some patients following BT-A scalp injections. In the majority of pain syndromes where BT-A is effective, inhibition of muscle spasms appears to be an important component of its activity. A direct or independent and prolonged analgesic action unrelated to skeletal muscle relaxation is believed to underlie the prophylactic efficacy of BT-A in migraine; peripheral and central modulation of pain impulses by BT-A has also been proposed. A direct peripheral antinociceptive effect was not seen in three controlled studies of BT-A in normal human volunteers. Experimental evidence for BT-A-induced analgesia in rats is suggestive but dose-dependent and lasts only 2 weeks. In migraine patients, a consistent or dose-dependent response to BT-A treatment has not been seen. Peak responses to BT-A in migraine patients are seen at 8-12 weeks, whereas BT-A-affected nerve endings in mice fully recover function between 63 and 91 days; the difference in species limits the interpretation of this dissonance. As BT-A does not normally cross the intact blood-brain barrier, meningeal nociceptors appear unlikely to be influenced by scalp injections of BT-A; the possibility of antidromic transfer of BT-A in the trigeminovascular system should be considered. The extended period for which migraine prophylaxis might be required, the antigenic and headache-provoking potential of BT-A, the inability of BT-A to affect central neuronal processes significantly, including the aura of migraine, the possible placebo effect of needling, and purely subjective outcome measures in headache studies are additional concerns in evaluating this treatment strategy. The clinical utility of BT-A has not been compared against established migraine prophylactic agents. The efficacy of BT-A in preventing migraine headache attacks remains controversial and the underlying scientific rationale is debatable.

Trigger factors of migraine and tension-type headache

tating factors for both migraine and tension-type headache attacks has identified several potential triggers with percentages differing widely among studies [1–5]. They include menstrual cycle, particularly in women affected by migraine; environmental factors, especially changes in weather conditions and temperature; afferent stimulation, physical activity and psychological factors, mainly stress or relaxation from stress; sleep disturbances; frequent travelling; oral contraceptives; and finally eating habits, and some food items. According to some authors, lifetime migraineurs experienced headache attacks preceded by triggering factors more frequently than tension-type headache sufferers [5]. Moreover, certain endogenous and exogenous factors seem to differentiate migraine from tension-type headache and it is of interest to note in this regard that three of the precipitating factors considered more migraine-specific (i.e., weather, smell and smoke) involve the nose/sinus system, suggesting a greater significance of this system in migraine than is generally believed [4]. The aim of the Wober et al. [6] study was to investigate the consistency of the recurrence of precipitating factors in migraineurs and tension-type headache patients enrolled from a clinical outpatient setting and from a sample, although not conspicuous, of the general population. The authors found that the majority of trigger factors precipitate migraine and tension-type headache only occasionally and not consistently in almost the majority of cases. In contrast to previous experiences, no differences emerged in this study in the percentages of factors referred as attack precipitants between the two patient groups. The occasional occurrence of some precipitating factors in some but not all migraine and tension-type headache attacks supports the view that they can surely play a role, although not exclusively, in influencing the pathophysiological substrate underlying the threshold for attacks in both headache forms. This predisposed substrate can be, from time to time, influenced by different inner and outer stimuli. Mechanisms involved in the potentiality of different factors in precipitating attacks by activating strategic brain areas involved in the generation and abnormal processing of painful information from the head remain to be established. New imaging techniques and particular experimental settings could be helpful in clarifying this important issue, at least for some attack precipitants, as recent experiences have found [7]. J Headache Pain (2006) 7:172–173 DOI 10.1007/s10194-006-0304-4

Metoclopramide aborts cough-induced headache and ameliorates cough - a pilot study

Metoclopramide (MTCL) can abort attacks of migraine headache. I report swift resolution of cough-induced headache as well as suppression of cough in six male patients following parenteral administration of MTCL. A similar unexpected rapid antitussive action of MTCL was also observed in 12 of 14 other patients (13 male and 1 female) with severe paroxysmal cough without headache. Use of MTCL primarily for analgesia is reviewed, and the pharmacological basis for its antinociceptive action is proposed. As a nonopiate agent with potential to stimulate endogenous opiate-mediated mechanisms, MTCL appears to have additional valuable roles in clinical practice. This is the first report of an antitussive action of MTCL. Further controlled studies are required to confirm the therapeutic role of MTCL in cough-induced headache as well as its potential antitussive and general analgesic actions.

Clinical data on the CGRP antagonist BIBN4096BS for treatment of migraine attacks.

Basal studies have shown that calcitonin gene-related peptide (CGRP) is a major sensory neuronal messenger in the trigeminovascular system, the pathway conveying intracranial pain. In migraine and cluster headache attacks, CGRP is released in parallel with the pain and successful treatment of the attacks abort both the associated pain and the CGRP release. The search for a potent small molecule CGRP antagonist has been successful and such an agent has been tested in preclinical and clinical studies. The aim of the present study was to examine current knowledge on the clinical pharmacology of systemic BIBN4096BS, which has been shown in man to abort acute migraine attacks as well or better than oral sumatriptan. BIBN4096BS is a specific and potent CGRP receptor antagonist in humans. In safety and tolerability studies the substance is well tolerated with no or only mild side effects. In acute migraine attacks the overall response was 66% with the drug and 27% with placebo. A difference as compared to placebo was seen at 30 min; the response was still rising at 4 h suggesting a long duration of action. At 24 h the pain-free rate was better than that with triptans, suggesting a lower grade of rebound and perhaps even a prophylactic possibility.

Open‐Label Trial of Cinnarizine in Migraine Prophylaxis

To assess the effectiveness and safety of cinnarizine as a migraine-preventive therapy. Sixty patients with more than 2 migraine headache attacks during a 4-week baseline entered the study and received a 25-mg tablet cinnarizine twice daily for the first 3 days and then 3 times daily. They were assessed on weeks 2, 6, 10, and 14. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Reduction in migraine attacks duration and severity was also evaluated. The mean reduction in 4-week migraine headache rate was 4.6 +/- 2.2 from the baseline of 6.2 +/- 2.2 after 14 weeks of treatment, which was statistically significant (P < 0.001). Percent reduction in 4-week migraine frequency was 35% after 2 weeks, 74% after 6 weeks, 74% after 10 weeks, and 75% after 14 weeks of treatment. Significant reduction in attack duration (P < 0.001) and severity (P < 0.001) was also noted. No serious adverse events were observed in this series of patient. Cinnarizine is an efficacious and well-tolerated prophylactic antimigraine medication, which has early onset effectiveness.

Subcutaneous Sumatriptan Provides Symptomatic Relief at any Pain Intensity or Time During the Migraine Attack

Over the years the paradigm of treating early during the migraine attack has become well established in clinical practice. It is also recommended that the 5-HT(1B/1D) agonists be administered early during the migraine attack for efficacy. This is because it has been proposed that most migraineurs are less responsive to delayed treatment, owing to the development of central sensitization of the pain transmission. The main objective of this prospective, cross-over study at a specialist clinic was to evaluate if these recommendations should also apply to the subcutaneous formulation of sumatriptan. Results are based on 20 adult International Headache Society migraineurs. Two attacks (n=40) were treated with 6 mg subcutaneous sumatriptan as early as possible after the onset of migraine headache and two attacks (n=40) as late as the patients could bear. The median intra-individual difference between the two strategies in time from first occurrence of pain to injection was 5.7 h and the median intra-individual difference in pain intensity at the time of injection was 29 visual analogue units. No significant differences were found in time to freedom from pain, pain severity at 1 and 2 h, area under the curves from injection to pain free or in headache recurrence after injection. At the end of the study, most of the patients claimed that their medication was as effective when given early as when given late in the course of the attack. The discrepancy between our present findings and retrospective analyses of trials on oral triptans probably has more to do with the less disturbed pharmacokinetics early during the migraine attack than with central sensitization. Consequently, we recommend nonoral formulations of triptans, which do not necessarily have to be administered early during the migraine attack to provide efficacy. In conclusion, it is reassuring for migraineurs that it is worthwhile taking their medication in an appropriate formulation even if they have not been able to do so early in the course of the attack.

Disability Associated With Headaches Occurring Inside and Outside the Menstrual Period in Those With Migraine: A General Practice Study

This study investigated the disability of females who have migraine and other headache attacks occurring during and outside the menstrual period. One thousand four hundred and thirty-four of 3470 female patients (41.3%) aged 14 to 50 years registered at a UK general practice completed two questionnaires. The first questionnaire assessed the prevalence of headache, depression, and bodily pain in the total population. The second questionnaire assessed the disability of all headaches over a 2-month period (to capture a complete menstrual cycle) for patients reporting migraine who were still menstruating. Disability was assessed as the time lost and time spent at less than 50% productivity in normal activities due to headache, and analyzed as rank sums using the Mann-Whitney U-test. The first part of the study showed that the prevalence of headache (66.1%), depression (55.4%), and bodily pain (40.6%) were high in this population of women. Thirty migraine patients who were still menstruating reported 89 migraine and 114 nonmigraine headache episodes in the second part of the study. For migraine, the rank order of time at less than 50% productivity was greater for attacks taking place inside the menstrual period than for those occurring outside the menstrual period. The comparison was significant for time at less than 50% productivity (P=.01). For nonmigraine headaches, the rank order of time lost was greater for attacks taking place outside the menstrual period than for those occurring inside the menstrual period. The comparison was not significant for time lost (P= .06). For those with migraine, migraine attacks that took place during the menstrual period tended to be slightly more disabling than those taking place outside the menstrual period, but the opposite was true for nonmigraine headache.

The contribution of functional neuroimaging to primary headaches

Functional imaging techniques have begun to provide considerable insight into the pathophysiology of primary headache syndromes. PET and f-MRI have allowed to to monitor the physiological cortical reaction and nociceptor transmission of head-pain, but more importantly have identified pathophysiological abnormalities and even the "motor" in migraine and cluster headache attacks. This has even prompted new treatment options such as DBS in cluster headache and will undoubtly change the way we see headache. Innovative techniques such as voxel- and deformation-based morphometry have just started to unravel the structural consequences of chronic pain. Functional imaging will undoubtedly provide further opportunities to study and compare metabolic, haemodynamic and structural parameters in headache sufferers' brains.

French guidelines for the diagnosis and management of migraine in adults and children

BackgroundThe French Recommendations for Clinical Practice: Diagnosis and Therapy of Migraine are guidelines concerning the overall management of patients with migraine, including diagnostic and therapeutic strategies and assessment of disability. ObjectiveThis article summarizes the guidelines as they apply to adults and children, and proposes future direction for steps toward optimal treatment of migraine in patients in France. MethodsThe recommendations were categorized into 3 levels of proof (A—C) according to the National Agency for Accreditation and Evaluation in Health (ANAES) methodology and were based on a professional consensus reached among members of the Working Group and the Guidelines Review Group of the ANAES. ResultsThe International Headache Society diagnostic criteria for migraine should be used in routine clinical practice. Recommended agents for the treatment of migraine in adults include nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) monotherapy or in combination with metoclopramide, acetaminophen monotherapy, triptans, ergotamine tartrate, and dihydroergotamine mesylate. Patients should use the medication as early as possible after the onset of migraine headache. For migraine prophylaxis in adults, the following can be used: propranolol, metoprolol, oxetorone, or amitriptyline as first-line treatment, and pizotifen, flunarizine, valproate sodium, or topiramate as second-line treatment. Migraine in children can be distinguished from that in adults by shorter duration (2–48 hours in children aged <15 years), more frequent bilateral localization, frequent predominant gastrointestinal disturbances, and frequent pallor hailing the onset of the attack. The following drugs are recommended in children and adolescents: ibuprofen in children aged >6 months, diclofenac in children weighing >16 kg, naproxen in children aged >6 years or weighing >25 kg, ASA alone or in combination with metoclopramide, acetaminophen alone or in combination with metoclopramide, and ergotamine tartrate in children aged >10 years. ConclusionsThese guidelines are intended to help general practitioners to manage migraine patients according to the rules of evidence-based medicine.

Botulinum toxin in migraine prophylaxis

Migraine is a chronic headache disorder manifesting in attacks lasting 4-72 hours. Characteristics of headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea, photophobia and phonophobia. The migraine aura is a complex of neurological symptoms, which occurs just before or at the onset of migraine headache. Botulinum toxin A represents a completely new option for patients with chronic pain conditions. Numerous retrospective open-label chart reviews and 4 double-blind, placebo-controlled studies have demonstrated that botulinum toxin type A is significantly effective in migraine prophylaxis and reduces the frequency, severity, and disability associated with migraine headaches. Studies have generally reported a good and consistent efficacy. The differential therapeutic use of botulinum toxin appears to be worth attempting in migraine patients with the following characteristic features: (1) Muscular stress as migraine trigger, e. g., in craniocervical dystonia, pericranial painful muscular trigger points or tender points, oromandibular dysfunction, (2) concurrent chronic tension-type headache with the aggravating factors of muscular stress or oromandibular dysfunction, (3) chronic migraine with frequent migraine attacks on more than 15 days per month for longer than 3 months and if other therapeutic options have been either ineffective or have not been tolerated. The use of the agent does not cause CNS side effects. Migraine patients in particular, often suffer greatly, as a result of the adverse effects of the drugs used, from fatigue, dizziness, reduced concentration, loss of appetite, weight gain, hair loss and changes in libido. These side effects are not known in association with botulinum toxin A. To date, neither organic damage nor allergic complications have been reported. Thus, both the tolerability and the safety of this therapeutic measure are high. The mode of action by which botulinum toxin is effective in migraine prophylaxis is not fully understood and is under investigation. Currently, a number of other randomized, placebo-controlled, clinical trials are being conducted to evaluate the efficacy, optimal dosing, and side-effect profile of botulinum toxin type A in the prophylaxis of migraine and other headache entities.

The association between tension-type headache and psychosocial factors in Japanese patients

The purpose of this retrospective multicenter study was to evaluate the use and the self-perceived efficacy and tolerability of pharmacological and non-pharmacological treatments in children and adolescents with primary headaches.Study of a cohort of children and adolescents diagnosed with primary headache, consecutively referred to 13 juvenile Italian Headache Centers. An ad hoc questionnaire was used for clinical data collection.Among 706 patients with primary headaches included in the study, 637 cases with a single type of headache (migraine 76% – with and without aura in 10% and 67% respectively; tension-type headache 24%) were selected (mean age at clinical interview: 12 years). Acetaminophen and non-steroidal anti-inflammatory drugs (in particular ibuprofen) were commonly used to treat attacks, by 76% and 46% of cases respectively. Triptans were used overall by 6% of migraineurs and by 13% of adolescents with migraine, with better efficacy than acetaminophen and non-steroidal anti-inflammatory drugs.Preventive drugs were used by 19% of migraineurs and by 3% of subjects with tension-type headache. In migraineurs, flunarizine was the most frequently used drug (18%), followed by antiepileptic drugs (7%) and pizotifen (6%), while cyproheptadine, propanolol and amitriptyline were rarely used. Pizotifen showed the best perceived efficacy and tolerability. Melatonin and nutraceuticals were used by 10% and 32% of subjects, respectively, both for migraine and tension-type headache, with good results in terms of perceived efficacy and tolerability.Non-pharmacological preventive treatments (i.e. relaxation techniques, biofeedback, cognitive-behavioral therapy, acupuncture) were used only by 10% of cases (migraine 9%, tension-type headache 15%).Non-steroidal anti-inflammatory drugs, especially ibuprofen, should be preferred to acetaminophen for acute attacks of migraine or tension-type headache, because they were usually more effective and well tolerated.Triptans could be used more frequently as first or almost second choice for treating migraine attack in adolescents.Non-pharmacological preventive treatments are recommended by some pediatric guidelines as first-line interventions for primary headaches and their use should be implemented in clinical practice.Prospective multicenter studies based on larger series are warranted to better understand the best treatment strategies for young people with primary headaches.

Ergotamine‐induced anorectal strictures: report of five cases.

Dis Colon Rectum. 2002 Feb;45(2):271‐2Purpose: Ergotamine tartrate suppositories are used for treatment of migraine headache attacks. Chronic abuse may lead to severe anorectal complications such as ulceration, stricture, and rectovaginal fistula. These complications are rare, and only sporadic reports may be found. Nevertheless, awareness of this entity on the part of prescribing physicians and treating colorectal surgeons is essential for a successful outcome, because withdrawal of this medication is an inherent part of treatment. Patients: Five female patients were referred for treatment of symptomatic strictures of the anal canal and lower rectum. All of these patients admitted prolonged, nearly daily use of three to seven ergotamine tartrate suppositories.Results: Three patients with severe stenosis of the anal verge and anal canal were treated by Y‐V anoplasty, and two patients with circular stricture of the lower third of the rectum had balloon dilatations. In all patients the use of ergotamine suppositories was stopped, and alternative medication was instituted. Long‐term follow‐up (3‐12 years) showed complete resolution of symptoms.Conclusion: In view of the availability of new effective drugs for treatment of migraine headache (serotonin agonists) and considering the potentially severe complications of chronic use of ergotamine, the use of this medication should be abandoned.Comment: Ergotamine users beware of the sting in the tail! DSM.