Response to prophylactic treatment of benign headache in children

INTRODUCTION: Common childhood headaches seldom require prophylactic treatment which, nevertheless, is quite often unsatisfactory. OBJECTIVE: To study drug and non-drug related factors that may influence the therapeutic response. MATERIAL AND METHODS: A four-month follow-up study of all patients attended during a year at the neuropediatric, outpatient hospital-based clinic, with > or = 2 monthly migraine without aura attacks, > or = 10 tension-type headaches, or both types of headaches. Patients were randomized to be treated on an open basis, placebo controlled, with flunarizine or piracetam. Headache frequency was evaluated according to treatment and patients' basal characteristics. RESULTS: 98 patients studied (56 migraine without aura, 24 tension-type headache, 18 mixed). 33% dropped out; they were school underachievers more frequently than those that completed the protocol. Of those completing the protocol and treated with placebo as the first choice of therapy, 27% reported total remission of symptomatology; those not remitting with placebo were high achievers at school significatively more frequently. At the end of the trial, 43% of the initially randomized patients still complained of headaches, regardless of treatment, showing a seasonal relationship. CONCLUSIONS: Prophylaxis of benign childhood headaches is needed in less than half of those reporting a high headache frequency; school achievement should be taken into consideration as another clue to compliance and headache persistence. On a short-term basis only the seasonal influence and the placebo effect can be held responsible for amelioration of symptomatology.     

Histamine inhalation is a specific but insensitive laboratory test for migraine

Migraine is a subjective complaint and no laboratory test has until now been of value. The aim of the present study is to evaluate whether histamine inhalation may be used as a diagnostic test for migraine. In a double-blind study design, 15 migraineurs and 15 control subjects scored headache intensity and characteristics before, during, and in the subsequent 12 h after inhalation of increasing doses of histamine (0, 2, 4, 8, 16, 32 and 64 mg/ml). During the histamine inhalations, headaches increased dose-dependently in both groups. Eleven of the migraineurs and eight of the healthy controls experienced headaches after the inhalations. These headaches fulfilled the IHS criteria for migraine without aura in six of the migraineurs, but in none of the control subjects. Using this as a test parameter, the specificity of the test was 1, but the sensitivity was only 0.4. Our results indicate that histamine inhalation is a specific but insensitive laboratory test for migraine. Migraineurs should be informed about the risk of a migraine attack being provoked before histamine inhalation in pulmonary laboratories.     

Sumatriptan. An updated review of its use in migraine

Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5-HT1B/1D subtypes. It is an effective treatment for acute migraine attacks and the injectable form has also shown efficacy in the treatment of cluster headaches. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing resolution or reduction of other symptoms associated with migraine, including nausea, photophobia and phonophobia. Improvements in clinical disability were also significantly greater after sumatriptan than after placebo. Headache recurred in 21 to 57% of patients who received oral or subcutaneous sumatriptan, but most patients responded to a second dose of the drug. Results of comparative trials showed that subcutaneous sumatriptan 6 mg was significantly more effective than either patients' usual antimigraine treatments or intranasal dihydroergotamine mesylate 1 mg in relieving migraine headache. Subcutaneous sumatriptan 6 mg and subcutaneous dihydroergotamine mesylate 1 mg provided similarly effective migraine relief, but the headache recurrence rate was significantly higher after sumatriptan than after this formulation of dihydroergotamine mesylate. Response rates achieved after oral sumatriptan were similar to those reported after treatment with oral naratriptan, rizatriptan or lysine acetylsalicylate plus metoclopramide. Treatment of acute migraine attacks with oral or subcutaneous sumatriptan leads to less loss of workplace productivity than other antimigraine therapies. Several pharmacoeconomic analyses showed that gains in workplace productivity in sumatriptan recipients ranged from 12.1 to 89.8 hours per patient per year. Significant improvements from baseline in overall health-related quality-of-life scores were also experienced by sumatriptan recipients. Sumatriptan is generally well tolerated. Nausea, vomiting, malaise and fatigue are the most common adverse events with oral sumatriptan. Injection site reactions occur in 10 to 40% of patients receiving the drug subcutaneously. A bitter taste at the back of the mouth occurs frequently after intranasal administration. Serious adverse events occur in about 0.14% of patients with migraine treated with sumatriptan. As the drug is associated with the rare development of cardiovascular effects, it is contraindicated in patients with a history of cardiovascular disease. CONCLUSIONS: Despite its relatively high acquisition cost, reductions in lost workplace productivity experienced by patients treated with sumatriptan may result in savings in the overall cost of migraine to society. Thus, sumatriptan is a useful first- or second-line treatment option for patients with moderate or severe migraine.     

Psychophysiological treatment of migraine and tension headaches: A 12-month follow-up.

Conducted a 12-mo follow-up of the present authors' (1983) study population of chronic headache sufferers by telephone interviewing 31 chronic migraine and 25 chronic tension headache patients (aged 18–61 yrs) who had been treated with EMG, muscle relaxation, and fingertip temperature training to test a hypothesis of biofeedback placebo effects. A previous 3-mo follow-up had revealed that all treatments had produced significant improvement, and relaxation was not as good as the biofeedback devices for obtaining a reduction in monthly headache hours. At 12-mo follow-up, the 3-mo improvement was sustained overall, but migraineurs as a group appeared to regress slightly, while tension patients improved significantly in the interim. On the basis of a 50% reduction in symptomatology, biofeedback treatment was significantly superior to relaxation for tension headaches, although this had not been true at the 3-mo assessment. Temperature training was at least as effective as EMG for both headache groups. In view of these results, biofeedback treatment is viewed less as placebo administration and more as a secondary reinforcer of a specific but unknown physiological response. (11 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treating headaches. A conceptual framework

BACKGROUND: Similar medications are effective in migraine and muscle contraction headache therefore the term recurrent headache is used to cover the spectrum of classic migraine and muscle contraction headache. OBJECTIVE: The concept of a threshold to headache triggers is proposed. Treatment for chronic headaches is directed at raising the threshold or removing triggers. DISCUSSION: The most important factors that lower the threshold to headaches are hormones, mood and sleep disturbance. Therapeutic strategies for raising the threshold and treatment of the acute headache are discussed.     

Management of primary headache in emergency services of Santos and surrounding towns

OBJECTIVES: Primary headaches are often seen by Clinicians on duty at Emergency Services. We have investigated the treatment of such patients by 43 medical doctors who have been working at Emergency Services in the city of Santos and surrounding towns for many years. RESULTS: We confirmed the high prevalence of primary headaches in Emergency Services. There seem to be diagnosis difficulties concerning differentiating attacks of migraine and tension type headache. We also observed that IV dipirone was the most frequently prescribed treatment for patients with primary headaches in this study. There is no protocol in the literature which recommends IV dipirone for the treatment of migraine attacks or other primary headaches. CONCLUSION: It would be advisable to perform controlled double blind studies in order to verify the advantages of IV dipirone in the treatment of intense attacks primary headaches. We concluded that headache management recycling programs could be of interest for doctors who regularly work at Emergency Services.     

Transformed migraine, analgesic rebound, and other chronic daily headaches

Although the International Headache Society's classification of headache has greatly enhanced the diagnosis of migraine and cluster headache, its application in chronic headache has been less than satisfactory. Based on a review of the literature and the author's experience, this article demonstrates the need for an expanded and modified classification and broader understanding of chronic headaches. The author proposes new categories, including transformed migraine. Analgesic rebound is described as a major cause of chronic headaches. The comorbidity of chronic headache disorders is also discussed. The article concludes with a suggestion for management of chronic headaches.     

Headache and cortisol responses to m-chlorophenylpiperazine are highly correlated

The serotonin receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin, and induces migraine-like headaches. We have studied the neuroendocrine and headache responses to m-CPP in 8 subjects with migraine and 10 normal subjects. Each subject underwent two challenge tests, one with 0.25 mg/kg PO of m-CPP and the other with placebo, administered in a double-blind crossover format. Serial measurements of serum cortisol, prolactin, and m-CPP levels were made at 30-min intervals for 210 min following ingestion of the medication. The incidence and severity of headache was assessed by a structured telephone interview after each test. We confirmed that m-CPP stimulates the release of cortisol and prolactin, and may induce headache, in both migraine subjects and normal controls. The cortisol response as well as ratings of headache severity and duration directly correlated with plasma levels of m-CPP. There were highly significant associations between the cortisol response and both headache severity and duration, independent of m-CPP plasma levels. We did not find statistically significant differences between the migraine and normal subjects in terms of their neuroendocrine or headache responses to m-CPP.     

Bacterial causes of bovine mastitis in Wondogenet, Ethiopia

This community study on headache in Malaysia was based on IHS diagnostic criteria and showed the last-year prevalence of migraine was 9.0%. Migraine with aura accounted for only 10.6% of the migrainous population. The last-year prevalence of tension headache was 26.5% (94.4% episodic, 5.6% chronic) and 28.2% for other types of headache. No case of cluster headache was found. Almost two thirds of the migraine subjects graded their headaches as severe, while almost 60% of the tension headache subjects and almost 70% of the other headache subjects graded their headaches as mild. Overall, there was higher prevalence in females for migraine and tension headache, and in males for the other types of headache. The prevalence of headache was lower among those younger than 15 and older than 65 years of age. No significant differences were found in the prevalence of headache among the different racial groups nor among the urban versus the rural population. All the headache types shared the same triggering factors suggesting that different physiological characteristics are responsible for the type of pain suffered. In the location of this community with its tropical climate, headache was attributed to sun exposure in 51.9% of the migraine subjects, 55.7% of the tension headache subjects, and 36.6% of the group with other headaches.     

A double-blind provocative study of chocolate as a trigger of headache

A provocative double-blind study of headache was performed using chocolate as the active agent and carob as the placebo. The chocolate and carob samples were formulated to duplicate products used in an earlier study (1) in which strong differential effects between the ability of chocolate and carob to trigger headache in migraine were shown. Sixty-three women with chronic headache (50% migraine, 37.5% tension-type, 12.5% combined migraine and tension-type) participated in the study. After 2 weeks of following a diet that restricted vasoactive amine-rich foods, each subject underwent double-blinded provocative trials with two samples of chocolate and two of carob presented in random order. Diaries were maintained by the subjects throughout the study, monitoring diet and headache. The results demonstrated that chocolate was not more likely to provoke headache than was carob in any of the headache diagnostic groups (chi2(2)=0.36, p=0.83). Interestingly, these results were independent of subjects' beliefs regarding the role of chocolate in the instigation of headache (chi2(1)=0.73, p=0.39). Headache diagnosis and the concomitant use of additional vasoactive amine-containing foods were also not associated with chocolate acting as a headache trigger. Thus, contrary to the commonly held belief of patients and physicians, chocolate does not appear to play a significant role in triggering headaches in typical migraine, tension-type, or combined headache sufferers.     

Side-locked unilaterality and pain localization in long-lasting headaches: migraine, tension-type headache, and cervicogenic headache

Side-locked unilaterality and specific localization of pain are not as well-defined clinical characteristics in long-lasting headaches (duration more than 4 hours) as they are in short-lasting forms. We examined side-locked unilaterality and pain distribution at onset and at peak headache in 74 patients with different forms of long-lasting headache: migraine and tension-type headache (IHS) and cervicogenic headache (according to Sjaastad et al). Side-locked unilaterality of pain was found in all forms, but to differing extents - 20.8% in migraine, 12.5% in tension-type headache, while it was a mandatory criterion for cervicogenic headache. The pain tended to localize anteriorly, particularly at onset, in migraine; was more diffuse in tension-type headache; and always began in the occipitonuchal region in cervicogenic headache. Our results may contribute to a better clinical definition of long-lasting headaches.     

Headache during pregnancy

A questionnaire was submitted to 430 women 3 days after delivery, asking mainly about features of headache before and during pregnancy, and their possible modification or recurrence; moreover, delivery modalities and the condition of the newborn were evaluated. One-hundred-and-twenty-six (29.3%) were found to be primary headache sufferers (IHS criteria, 1988), 81 of whom had migraine without aura (MO), 12 migraine with aura (MA), and 33 tension-type headache (TH). In all three groups, about 80% showed complete remission or a higher than 50% decrease in the number of attacks. The improvement was more evident after the end of the first trimester; this trend was common to the three primary headaches considered. In our series of primary headaches, there was only one case (MO) which began during pregnancy. In a subgroup of pluripara, headache maintained the improvement presented in the first pregnancy also during the following gravidic periods in about 50% of cases, whereas in the remaining 50% a worsening in parallel with successive pregnancies was found. Primary headaches "per se" do not seem to increase the pregnancy or delivery risks, nor the vitality of the newborn. During pregnancy, drug use was very much reduced and was restricted to a limited number of compounds.     

Assessment of International Headache Society diagnostic criteria: a reliability study

In 1988 the International Headache Society (IHS) introduced new diagnostic criteria for headaches and craniofacial pain. Since headaches can be diagnosed solely on the basis of information provided by the patient, it is essential that the criteria are reproducible and consistent. Two neurologists evaluated the clinical records of 100 consecutive outpatients and transferred the data on headache and associated phenomena to a form designed to reflect the IHS criteria. Interobserver concordance (kappa statistics) in the application of the diagnostic criteria of primary headaches was: (i) "perfect" to "substantial" for the first IHS digit, being kappa = 1.0 for cluster headache and paroxysmal hemicrania; kappa = 0.88 for migraine; kappa = 0.75 for tension-type headache; (ii) "almost perfect" to "substantial" for the second digit (kappa = 0.94 for cluster headache; kappa = 0.90 for migraine with aura; kappa = 0.81 for episodic tension-type headache; kappa = 0.78 for migraine without aura; kappa = 0.71 for chronic tension-type headache; kappa = 0.66 for cluster headache-like disorder not fulfilling the criteria; (iii) "moderate" for migrainous disorder (kappa = 0.48) and headache of the tension-type (kappa = 0.43) not fulfilling the criteria. These results show that the IHS diagnostic criteria are satisfactorily applicable to high quality medical records abstracted by experienced neurologists.     

Biofeedback and relaxation training with three kinds of headache: Treatment effects and their prediction.

After a 4-wk baseline period during which daily ratings of headache activity were made and all participants took several psychological tests, 91 18–68 yr old patients with chronic headache (tension, migraine, and combined tension and migraine) were given a 10-session relaxation-training regimen. Ss who did not show substantial reductions in headache activity from the relaxation therapy were given a 12-session regimen of biofeedback (thermal biofeedback for vascular headaches and frontal EMG biofeedback for tension headaches). Relaxation therapy alone led to significant improvement for all groups, with a trend for the tension headache group to respond the most favorably. Biofeedback therapy led to further significant reduction in headache activity for all who received it, with a trend for combined migraine and tension headache patients to respond the most favorably. Multiple regression analyses revealed that approximately 32% of the variance in end-of-treatment headache diary scores could be predicted after relaxation and that 44% of the variance after biofeedback could be predicted using standard psychological tests. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical research designs for emerging treatments for Alzheimer disease: moving beyond placebo-controlled trials

The design of clinical trials must evolve as new therapies become available. The demonstrated efficacy and clinical use of donepezil and vitamin E for Alzheimer disease (AD) has shifted the options for AD research design. There is now a compelling case for alternatives to trials that include a treatment arm with no active therapy (ie, a placebo control). With an existing therapy, such as donepezil or vitamin E, new drugs that are clearly superior to those drugs should be sought. Combination therapy is a likely strategy for the future, implying that clinical trials, if possible, should replicate actual practice. The long duration of future AD trials also will make placebo-controlled trials more difficult to justify and more difficult to recruit for. Add-on or active-control designs represent the alternative approaches. We believe that definitive clinical trials of new AD drugs that use one or the other of these designs would be more likely to bring about therapeutic advances than would comparisons with inactive treatments. Our argument is not a general rejection of placebo-control designs. Our recommendations apply only to the circumstances in which the field of AD drug therapy now finds itself.     

Investigations into the role of nitric oxide and the large intracranial arteries in migraine headache

Previous studies suggest that nitric oxide (NO) is involved in headaches induced by i.v. infusion of the vasodilator and NO donor glyceryl trinitrate (GTN) in healthy subjects. Extending these studies to sufferers of migraine without aura, it was found that migraineurs experienced a stronger headache than non-migraineurs. In addition, most migraineurs experienced a delayed migraine attack at variable times (mean 5.5 h) after GTN provocation. This biphasic headache response in migraineurs may be linked to hypersensitivity in the NO-cGMP pathway. Thus, compared to controls, migraineurs were found to be more sensitive to GTN-induced intracranial arterial dilatation, which is known to be mediated via liberation of NO and subsequent synthesis of cGMP Furthermore, histamine infusions in migraineurs induced headache responses and intracranial arterial responses resembling those induced by GTN in migraineurs. Histamine is known to liberate NO from the endothelium via stimulation of the H1 receptor, which is present in the large intracranial arteries in man. Because both immediate histamine-induced headache and intracranial arterial dilatation and delayed histamine-induced migraine are blocked by H1-receptor blockade, a likely common pathway for GTN and histamine-induced headaches/migraines and intracranial arterial responses may be via activation of the NO-cGMP pathway. The delay in the development of these experimental migraines may reflect activation of multiple physiological processes. The intracranial arteries of migraineurs were found supersensitive to the vasodilating effect of GTN (exogenous NO). This relates to clinical findings suggesting dilatation of the large intracranial arteries on the headache side during spontaneous migraine attacks. The function of arterial regulatory mechanisms involving NO in migraine was therefore studied. In peripheral arteries, no endothelial dysfunction of NO was found and cardiovascular and intracranial arterial sympathetic function was normal. A mild parasympathetic dysfunction may be involved and may, via denervation supersensitivity, be responsible for the observed supersensitivity to NO. Another possibility is that NO initiates a perivascular neurogenic inflammation with liberation of vasoactive peptides. NO also mediates a variety of other physiological phenomena. One of these, the pain-modulating effect observed in animals, was evaluated in a human study using GTN infusion and measurements of pain thresholds. No definite effects of GTN were demonstrated. The precise mechanisms involved in NO-triggered migraines and which part of the NO-activated cascade that is involved remain to be determined. The possibilities for pharmacological stimulation and/or inhibition of several steps of the NO-activated cascade increase rapidly and soon may be available for human studies.     

Childhood headaches: discrete entities or continuum?

The aims of this study were to investigate the signs and symptoms of recurrent headaches in children and to identify if there are any discrete groups of children whose headaches corresponded to the World Federation of Neurology (1969) definition of migraine. One-hundred and fifty children recruited from the neurology clinics at Royal Manchester, Booth Hall, and Birmingham Children's Hospitals were interviewed to complete a standardized questionnaire. The data were examined using cluster analysis followed by comparative analysis of the headache signs and symptoms in the different groups identified. No stable groups were identified (i.e., no group was reliably identified by different methods of cluster analysis) which corresponded to the World Federation of Neurology definition of migraine. This would suggest that this definition is not appropriate for the sample investigated. Three groups of children evolved after cluster analysis. None of these groups was in agreement with the International Headache Society classification of headaches. The groups were neither 'stable' clusters nor 'useful' in predicting prognosis. This outcome supports the continuum theory of headache syndromes.     

A comparison of various estimators of a treatment difference for a multi-centre clinical trial

When a clinical trial is conducted at more than one centre it is likely that the true treatment effect will not be identical at each centre. In other words there will be some degree of treatment-by-centre interaction. A number of alternative approaches for dealing with this have been suggested in the literature. These include frequentist approaches with a fixed or random effects model for the observed data and Bayesian approaches. In the fixed effects model, there are two common competing estimators of the treatment difference, based on weighted or unweighted estimates from individual centres. Which one of these should be used is the subject of some controversy and we do not intend to take a particular methodological position in this paper. Our intention is to provide some insight into the relative merits of the indicated range of possible estimators of the treatment effect. For the fixed effects model, we also look at the merits of using a preliminary test for interaction assuming a 10 per cent significance level for the test. In order to make comparisons we have simulated a 'typical' trial which compares an active drug with a placebo in the treatment of hypertension, using systolic blood pressure as the primary variable. As well as allowing the treatment effect to vary between centres, we have concentrated on the particular case where one centre is out of line with the others in terms of its true treatment difference. The various estimators that result from the different approaches are compared in terms of mean squared error and power to reject the null hypothesis of no treatment difference. Overall, the approach that uses the fixed effects weighted estimator of overall treatment difference is recommended as one that has much to offer.     

Treatment of childhood migraine using autogenic feedback training.

Assigned 28 7–16 yr olds who suffered from migraine headaches to 1 of 2 conditions (treatment group or waiting-list control group). All Ss recorded at breakfast, lunch, dinner, and bedtime whether they had a headache and its intensity. The records of headache index, frequency, duration, intensity, average intensity, and medication generated weekly scores. Analysis showed that Ss in the treatment condition were significantly improved at the end of treatment (7 wks) and at 1-mo follow-up. No improvement was found for control Ss. 93% of Ss in the autogenic feedback condition were clinically improved, using a criterion of 50% reduction of headache activity. Six months after treatment, Ss were asked to complete headache recordings. 13 Ss responded (8 Ss from the treatment groups and 5 from the control group). Treated Ss maintained significant improvement. Findings are important in light of the need for effective nonpharmacological treatment procedures for childhood migraine. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)