EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force.

BACKGROUND: Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life. OBJECTIVES: To give evidence-based or expert recommendations for the different drug treatment procedures in the particular migraine syndromes based on a literature search and the consensus of an expert panel. METHODS: All available medical reference systems were screened for the range of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies (EFNS) resulting in level A, B, or C recommendations and good practice points. RECOMMENDATIONS: For the acute treatment of migraine attacks, oral non-steroidal antiinflammatory drug (NSAID) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAID and triptans, oral metoclopramide or domperidone is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. Status migrainosus can be treated by cortoicosteroids, although this is not universally held to be helpful, or dihydroergotamine. For the prophylaxis of migraine, betablockers (propranolol and metoprolol) flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis include amitriptyline, naproxen, petasites, and bisoprolol.

Placebo efficacy in childhood and adolescence migraine: an analysis of double-blind and placebo-controlled studies.

Studies on the treatment of migraine in children and adolescents are rare and difficult to design. In particular, the high placebo response in some trials makes it difficult to prove efficacy of a verum drug. We analysed all available placebo-controlled trials on acute and on prophylactic migraine treatment in children and adolescents with respect to different placebo rates (pain free and pain relief at 2 h; rate of responders with >or= 50% attack frequency decrease). We identified eight crossover and 11 parallel group trials on acute treatment. The placebo response rates were considerably lower in crossover trials than in parallel group trials (19.2% vs. 27.1% for pain free after 2 h and 39.4% vs. 56.9% for pain relief after 2 h). In the 10 prophylactic trials included in this analysis, only a small trend towards a lower placebo rate in crossover trials could be observed. Further significant factors associated with a lower placebo rate in childhood and adolescence trials on the acute treatment of migraine were single-centre (vs. multicentre) trials and small sample size. Age and sex were not associated with the placebo response. Our study suggests that parallel group trials on the acute treatment of migraine in children and adolescents show a very low therapeutic gain due to a high placebo rate. The verum response rates, however, are very similar to those seen in adulthood trials. In conclusion, trial designs on the acute and prophylactic treatment of migraine in children and adolescents should consider the specific findings of this analysis in order to exhibit a higher probability of showing significant differences between placebo and verum drug.

Biological markers of cervicogenic headache.

Upper cervical pain is frequent in different primary headaches and not sufficient evidence for cervicogenic headache (CH). Biological markers should help to differentiate CH from other headache disorders. In most cases, imaging techniques of the cervical spine are not helpful for the diagnosis of CH. Symptoms and signs of neck involvement, such as a mechanical precipitation of attacks, a restriction in range of motion of the cervical spine, and the existence of ipsilateral neck, shoulder, or arm pain, seem to be reasonably valid for the diagnosis of CH, but its reliability and validity should be confirmed in larger studies. Positive diagnostic blockades of cervical structures or its nerve supply are not specific for CH. Neurophysiological investigations give some insight into the pathophysiological mechanisms of CH but are not diagnostic. In CH, calcitonin gene-related peptide levels do not differ between the symptomatic and the asymptomatic side, between the jugular and the cubital blood, and between days with and without headache. There is no evidence for an activation of the trigeminovascular system in CH. It can be concluded that CH is not just a migraine variant triggered by neck dysfunction but a functional entity.

Migraine and left-handedness are not associated. A new case-control study and meta-analysis.

To investigate the possible association between migraine and left-handedness, we enrolled 100 patients with a diagnosis of migraine according to the International Headache Society diagnostic criteria and 100 age- and sex-matched control subjects into a case-control study. Handedness was determined by the Edinburgh Handedness Inventory. There was no significant difference in the frequency or grade of left-handedness between the two groups. Additionally, we pooled our data with those from five similar studies, which did not alter the result. Thus, neither our study nor the meta-analysis support Geschwind and Behan's hypothesis of an association between migraine and left-handedness.

Headache associated with sexual activity: prognosis and treatment options.

The aim of this study was to provide data on the prognosis and treatment options of headache associated with sexual activity (HSA). Sixty patients diagnosed with HSA between 1996 and 2004 were followed up between 2003 and 2006 at least 12 months after the first interview. The further course of the disease and their contentedness with therapy were requested. On average, the second interview was performed 35.9 months after the first examination. Of the 45 patients who had suffered from single attacks or bouts prior to baseline examination, 37 had no further attacks. Seven patients suffered from at least one further bout with an average duration of 2.1 months. One patient developed a chronic course of the disease after an episodic start. Of the 15 patients with chronic disease at the first examination, seven were in remission and five had ongoing attacks at follow-up. Ten patients received indomethacin for preemptive therapy, with good results in nine patients. Eighteen patients received beta-blockers for prophylaxis, with good results in 15 patients. Episodic HSA occurs in approximately three-quarters and chronic HSA in approximately one-quarter of patients. Even in chronic HAS, the prognosis is favourable, with remission rates of 69% during an observation period of 3 years. For patients with longer-lasting bouts or with chronic HSA, prophylactic treatment with beta-blockers or preemptive therapy with indomethacin are often successful.

Comorbidity of migraine and headache associated with sexual activity.

In order to investigate the comorbidity of migraine and headache associated with sexual activity (HSA), we performed a case-control study based on migraine patients. By means of a questionnaire and a personal interview, 100 migraine patients and 100 control subjects were examined regarding a diagnosis of HSA. In five subjects from the migraine group vs. none from the control group, a diagnosis of HSA could be established (P = 0.021). Previous studies that have demonstrated comorbidity of migraine and HSA were all based on HSA patients. Thus, it can now be concluded that the association between the two headache disorders is bilateral. In addition, the prevalence of HSA in the general population can be estimated to average around at least 0.9%, which concurs with previously published data.

Long-term antibiotic treatment with roxithromycin in patients with multiple sclerosis.

BACKGROUND: There are conflicting results concerning an association between Chlamydia pneumoniae and MS (multiple sclerosis). In the present study, we investigated a possible therapeutic option with antibiotics. PATIENTS AND METHODS: In our randomized, placebo-controlled double-blind study, 28 patients with the confirmed diagnosis of MS [61% relapsing-remitting MS (RR-MS), 32% secondary chronic-progressive MS (SP-MS) and 7% primary chronic progressive MS (PP-MS)] were treated over a time period of 12 months with three cycles of a 6-week oral antibiotic therapy with roxithromycin (300 mg per day) or placebo. RESULTS: No significant differences were observed in patients with RR-MS regarding the expanded disability status scale (EDSS) and the relapse rate when comparing treatment with roxithromycin and placebo. CONCLUSION: Our study shows that the patients with MS do not profit from a long-term antibiotic treatment with roxithromycin compared to placebo treatment. A causative connection between bacterial infections with C. pneumonia and MS therefore does seem very unlikely.

Triptans in orgasmic headache.

Orgasmic headache (headache associated with sexual activity type 2 according to the International Headache Society classification) is a sudden severe headache which occurs at orgasm. Experiences with triptan therapy are described. Two out of four patients with severe headache continuing for >2 h had a positive response to acute triptan therapy. Two out of three patients using triptans as short-term prophylaxis reported a reliable response on several occasions. Triptans might be a treatment option to shorten orgasmic headache attacks after the diagnosis is clear and, particularly, subarachnoid haemorrhage has been excluded. In patients who chose to predict their sexual activity, short-term prophylaxis with oral triptans 30 min before sexual activity might be a therapeutic option in those not responsive to or not tolerating indomethacin.

The impact of different antimigraine compounds on platelet and erythrocyte aggregation.

Clinical and experimental data suggest that ergotamine compounds and triptans may contribute to vascular events such as myocardial infarction and stroke. The role of blood cell aggregation in this context is, however, not clarified. We aimed to evaluate the impact of different acute antimigraine compounds on platelet and erythrocyte aggregation in a human ex vivo experimental design. In 20 healthy subjects without migraine and in 20 healthy subjects with migraine without aura, platelet and erythrocyte aggregation were measured before and after intake of placebo, acetylsalicylic acid, ergotamine tartrate, zolmitriptan and sumatriptan. Platelet aggregation was measured by the so-called platelet reactivity index. Erythrocyte aggregation was measured by photometric assessment in an aggregometer. Ergotamine tartrate induced a significant increase of platelet aggregation, whereas acetylsalicylic acid induced a significant decrease in both subject groups. After placebo, after sumatriptan and after zolmitriptan, no significant changes of platelet aggregation were noted. Erythrocyte aggregation was affected by neither compound. We can conclude that platelet aggregation, but not erythrocyte aggregation, is increased after intake of ergotamine tartrate. This may in part contribute to vascular side-effects of this compound. Acetylsalicylic acid and the triptans appeared to be safe with respect to platelet and erythrocyte aggregation.

EFNS guideline on the drug treatment of migraine - report of an EFNS task force.

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life. To give evidence-based or expert recommendations for the different drug treatment procedures of the different migraine syndromes based on a literature search and an consensus in an expert panel. All available medical reference systems were screened for all kinds of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A,B, or C recommendations and good practice points. For the acute treatment of migraine attacks, oral non-steroidal anti-inflammatory drugs (NSAIDs) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAIDs and triptans, oral metoclopramide or domperidon is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. A status migrainosus can probably be treated by steroids. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis are amitriptyline, naproxen, petasites, and bisoprolol.

Treatment of childhood migraine attacks with oral zolmitriptan and ibuprofen.

The authors conducted a double-blind, placebo-controlled, crossover study to investigate the efficacy of oral zolmitriptan in the treatment of migraine in children and adolescents. Patients (n = 32) received placebo, zolmitriptan 2.5 mg, and ibuprofen 200 to 400 mg to treat three consecutive migraine attacks. Pain relief rates after 2 hours were 28% for placebo, 62% for zolmitriptan, and 69% for ibuprofen (p < 0.05). Both drugs are well tolerated with only mild side effects.

Pharmacologic treatment of central post-stroke pain.

OBJECTIVES: Almost 100 years after the first report of the thalamic syndrome, the scientific basis for the treatment of central post-stroke pain (CPSP) is remarkably small. Therefore, the authors aimed to provide evidence-based recommendations for the treatment of CPSP. METHODS: The authors performed a systematic review of the literature on the pharmacologic treatment of CPSP. All studies and case series were included and evaluated according to their level of evidence. Only CPSP was considered, not other types of central pain. RESULTS: Amitriptyline and lamotrigine are the only oral drugs proven to be effective in the treatment of CPSP in a placebo-controlled study. IV drugs such as lidocaine, propofol, and ketamine have shown efficacy for short-term control of CPSP, but their application and potential side effects make them unsuitable for long-term treatment. The novel antiepileptic drug gabapentin has been reported to control CPSP in a few patients. CONCLUSIONS: Amitriptyline, lamotrigine, and gabapentin provide a more favorable efficacy and safety profile than the classic antiepileptic drugs carbamazepine and phenytoin, for which no placebo-controlled evidence of efficacy was found. Clinical trials are urgently needed to optimize pharmacologic treatment of CPSP.

Calcitonin gene-related peptide in cervicogenic headache.

Trigeminovascular activation is involved in the pathophysiology of migraine and cluster headache. The marker evaluated best for trigeminovascular activation is calcitonin gene-related peptide (CGRP) in the cranial circulation. It is unknown whether trigeminovascular activation plays any role in cervicogenic headache (CEH). The objective of this study was to investigate CGRP plasma levels in CEH patients in relation to headache state. To compare plasma CGRP levels between the peripheral and the cranial circulation. Blood from both external jugular veins and from the antecubital vein was drawn from 11 patients with CEH. Plasma CGRP levels were measured by radioimmunoassay. No difference was found between CGRP levels assessed on days with and without headache. There was no difference between CGRP levels from the symptomatic and the asymptomatic external jugular vein and the antecubital vein. There is no evidence for an activation of the trigeminovascular system in CEH. In certain cases, clinical differentiation between CEH and migraine without aura is difficult. Plasma CGRP levels might serve as a biological marker to distinguish the two headache entities.

HIV associated arthritis: case report and review of the literature.

HIV infection can be associated with different types of arthropathies which are often underdiagnosed. We present the case of a 52 year old HIV positive man on highly active antiretroviral therapy including indinavir who developed an acute painful oligoarthritis. We present this case on HIV associated arthritis and include a review on other HIV specific types of arthritis (acute symmetric arthritis and painful articular syndrome) which are assumed as entities exclusively apparent in HIV patients. The pathophysiology of arthritis in HIV infected patients is not yet completely understood but a direct role of the HIV on the initiation of synovitis is suspected in some of them. Additionally, there is evidence that antiretroviral drugs, in particular the protease inhibitor indinavir, can lead to arthritic complications as well.

Botulinum toxin A in the prophylactic treatment of migraine--a randomized, double-blind, placebo-controlled study.

Botulinum toxin A has been suggested to be effective in the prophylactic treatment of migraine. However, only very few randomized, double-blind, placebo-controlled studies are available. We designed such a study with a specific focus on different injection sites. Sixty patients with a migraine according to the criteria of the International Headache Society were randomly assigned to receive either placebo in the frontal and neck muscles, or to receive 16 U botulinum toxin A in the frontal muscles and placebo in the neck muscles, or to receive in total 100 U botulinum toxin A in the frontal and neck muscles. The observation period was 3 months. In both treatment groups, 30% of patients showed a reduction of migraine frequency in month 3 by at least 50% compared with baseline, in the placebo group 25% of the patients showed such a reduction (P = 0.921). There were no significant differences between the three study groups with respect to reduction of migraine frequency, number of days with migraine, and the number of total single doses to treat a migraine attack. In the post hoc analysis, the reduction of all accompanying symptoms was significantly higher in the 16 U treatment group compared with the placebo group. In the 100 U treatment group significantly more adverse events occurred compared with the placebo group. All adverse events were mild and transient. Our study did not show any efficacy of botulinum toxin A in the prophylactic treatment of migraine. Only accompanying symptoms were significantly reduced in the 16 U but not in the 100 U treatment group. Future studies should focus on the efficacy of botulinum toxin A in specific subgroups of patients, on the efficacy of repetitive injections, and on other injection sites.

[The trigemino-cervical complex. Integration of peripheral and central pain mechanisms in primary headache syndromes]. / Der trigeminozervikale Komplex. Integration peripherer und zentraler Mechanismen in primären Kopfschmerzsyndromen.

The activation of the trigeminal nociceptive system is the neural substrate of pain in primary headache syndromes such as migraine and cluster headache. The nociceptive inflow from the meninges to the spinal cord is relayed in brainstem neurones of the trigemino-cervical complex (TCC). Two important mechanisms of pain transmission are reviewed: convergence of nociceptive trigeminal and cervical afferents and sensitization of trigemino-cervical neurones. These mechanisms have clinical correlates such as hyperalgesia, allodynia, spread and referral of pain to trigeminal or cervical dermatomes. Neurones in the TCC are subject to a modulation of pain-modulatory circuits in the brainstem such as the periaqueductal grey (PAG). Recent experimental and clinical findings of a modulation of these pain processes are discussed. The review focuses on TCC neurones as integrative relay neurones between peripheral and central pain mechanisms. The understanding of these mechanisms has implications for the understanding of the clinical phenomenology in primary headache syndromes and the development of therapeutical options.

Headache associated with sexual activity: demography, clinical features, and comorbidity.

OBJECTIVE: S: To provide data on the demography, clinical features, and comorbidity of headache associated with sexual activity (HSA). METHODS: Between 1996 and 2001, 51 patients with the diagnosis of HSA were questioned using a structured interview. RESULTS: The mean age at onset was 39.2 (+/-11.1) years. There was a clear male preponderance (2.9:1). The age at onset had two peaks, with a first peak between the 20th and 24th (n = 13) years of life and a second peak between the 35th and 44th (n = 20) years of life. Eleven patients had HSA type 1 (dull subtype), which gradually increased with increasing sexual excitement. The remaining (n = 40) had HSA type 2 (explosive subtype). The pain was predominantly bilateral (67%), and diffuse or occipital (76%). The quality was nearly equally distributed among dull, throbbing, and stabbing. HSA was not dependent on specific sexual habits and most often occurred during sexual activity with the usual partner (94%) and during masturbation (35%). There was a high comorbidity with migraine (25%), benign exertional headache (29%), and tension-type headache (45%). HSA types 1 and 2 did not significantly differ in demography, clinical features, or comorbidity, except for a higher probability of stopping the attack by breaking off sexual activity in HSA type 1. There were no cases with HSA type 3 (postural subtype). CONCLUSION: Mean age at onset, a male preponderance, a predominantly bilateral and occipital pain, and a high comorbidity with other primary headaches are in concordance with case reports in the literature. The authors found two peaks for the age at onset, however. There was no clinical evidence proving subtypes 1 and 2 to be distinct disorders. HSA types 1 and 2 may be different manifestations of the same disease rather than distinct entities.

Cognitive processing in headache associated with sexual activity.

Cognitive processing in headache associated with sexual Cognitive processing as measured by event-related potentials (ERP) in patients suffering from the explosive subtype of headache associated with sexual activity (HSA type 2) was investigated. Visual ERP were measured in 24 patients with HSA type 2 outside the headache period. The differences of the first and the second part of measurement were evaluated separately to determine the amount of cognitive habituation. Twenty-four sex- and age-matched healthy subjects and 24 patients with migraine without aura served as controls. A missing increase of P3 latency during the second part of the measurement was found in 79% of patients with HSA type 2 and in 75% with migraine, but only in 17% of the healthy controls (P < 0.001). The P3 amplitude was increased during the second part in 71% of patients with HSA type 2 and in 79% with migraine, but only in 33% of the healthy controls (P = 0.02). Mean P3 latency was decreased and mean P3 amplitude was increased during the second part of the measurement in HSA type 2 and in migraine but not in the healthy control group. Patients with HSA type 2 have a loss of cognitive habituation as measured by ERP. This specific information processing is very similar to that in migraine observed in previous studies.