Achim Frese

EFNS guideline on the drug treatment of migraine – revised 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.

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 association between migraine and juvenile stroke : a case-control study

Background.—Several studies suggest an association between migraine and juvenile stroke. Because of some shortcomings, we designed another case‐control study of a homogenous group of patients with juvenile cerebral ischemia. This study is part of a larger German epidemiological research project on the association of migraine with cerebrovascular disease.

Autonomic activation in experimental trigeminal pain

Autonomic activation ipsilateral and simultaneously to unilateral trigeminal pain is a hallmark of a group of primary headache syndromes. The most common of these syndromes is cluster headache, which is characterized by strictly unilateral autonomic symptoms such as ptosis, miosis, lacrimation, conjunctival injection, rhinorrhoea, and nasal congestion during the extreme pain attack, indicating parasympathetic hyperactivity. In fact, the autonomic disturbances are so prominent that this group of headache syndromes has been coined trigeminoautonomic cephalgias (TAC) (1). However, it seems frequently overlooked that other primary headache and facial syndromes may exhibit autonomic symptoms as well (2). Most recently, autonomic activation during severe unilateral migraine attacks (3) and first division trigeminal neuralgia (4) have been described. These descriptions prompt us to report a clinical observation made during recent and ongoing studies in experimental head pain.

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 ≥ 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.

Age of onset in cluster headache: the clinical spectrum (three case reports).

Cluster headache has a life time prevalence between 0.07% and 0.14% in population based studies (1–4) and predominantly begins at an age between 20 and 40 years with a statistical average of 28 years (3, 5, 6). In large sample studies, the age of onset varied, for instance, between 12 and 67 (7) or between 15 and 68 (8). However, the first cluster attack might occur in childhood (9–12) and at higher ages (5, 13, 14). The youngest patient with cluster headache reported in detail in the literature, to our knowledge, was 3 years old (9) and the oldest was 72 (14). Manzoni (5) reported patients with the age of one and with the age of 66, Torelli et al. (15) reported an age of onset of 71 years. However, no further data are available for these latter patients (in particular not how the diagnosis was established in the age of one). The longest remission periods for episodic cluster headache reported in the literature, as far as we are aware, were 11 years (8) and even 25 years (16). We report three cases of cluster headache who were admitted to our supraregional headache clinic and which present the extreme variability in the possible age of onset in cluster headache.

Event-related potentials in different subtypes of multiple sclerosis—a cross-sectional study

Impairment of cognitive skills is found in up to 65% of patients suffering from multiple sclerosis (MS). Little is known concerning the natural history or characteristics of progression of these cognitive dysfunctions. Furthermore, it has not been investigated to date whether there are differences in the course of cognitive impairment with respect to different diagnostic subgroups of MS. Event-related potentials (ERP) are an objective tool to evaluate cognitive processing. We performed a cross-sectional study on 179 consecutive patients suffering from MS (107 relapsing-remitting MS; 17 primary progressive MS; 50 secondary progressive MS; 5 undetermined). ERP were measured by a visual oddball paradigm, latencies of P3 components were correlated with demographic and clinical data. We found pathologically increased P3 latencies in 56% of all patients. Patients with secondary progressive MS showed significantly increased P3 latencies as compared to the other subgroups. There was a significant correlation between expanded disability status scale (EDSS) score and P3 latency (r=0.48; p<0.001). We conclude that ERP are an appropriate method to follow up cognitive dysfunction in MS and that cognitive dysfunction as measured by ERP is progressively impaired in the course of MS, in particular in the secondary progressive subtype.

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 β-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 β-blockers or preemptive therapy with indomethacin are often successful.

The cerebral hemodynamics of headache associated with sexual activity.

&NA; Headache associated with sexual activity is an idiopathic headache disorder and regarded to be a vascular headache but no pathophysiological studies have been performed to date to elucidate the underlying mechanisms. We investigated 12 patients with the explosive type of sexual headache according to the criteria of the International Headache Society during a headache‐free state by means of acetazolamide test and of stress Doppler sonography. Twelve age‐matched migraine patients and 14 healthy subjects served as control groups. Changes of blood pressure, cerebral blood flow velocity (CBFV), and pulsatility index (PI) were evaluated. Patients with sexual headache showed a significantly higher increase of blood pressure during standardized physical exercise as compared to healthy subjects and migraine patients. Changes of CBFV by physical exercise were not different between the three examination groups. After 1 g acetazolamide, CBFV showed a significantly higher increase in patients with sexual headache (plus 66%±16%) than in healthy subjects (plus 46%±18%), and PI showed a significantly lower decrease as compared to healthy subjects and migraine patients. These data suggest that in patients with sexual headache the metabolic rather than the myogenic component of the cerebral vasoneuronal coupling is impaired.

Cluster headache after dental extraction: implications for the pathogenesis of cluster headache?

Cluster headache (CH) is a disorder of unilateral attacks of severe periorbital, supraorbital or temporal pain, lasting 15±180 min (1). In general, attacks are accompanied by autonomic symptoms, i.e. ipsilateral miosis, lacrimation, conjunctival injection, nasal congestion and rhinorrhea. The episodic form of CH, found in about 80% of all CH patients, is characterized by its distinct temporal pattern. One to 8 headache attacks per day occur during bouts lasting 2 weeks to 3 months, followed by remission for months or years. Along with migraine and other rare hemicranias, CH is regarded as a primary headache disorder. More than 250 years after the ®rst known description of CH by van Swieten (2), the pathophysiology of this disorder is still controversial. Recent brain imaging studies demonstrated the activation of the ipsilateral hypothalamus during a CH attack (3). Moreover, morphological enlargement of the hypothalamus found in CH sufferers suggests an inborn predisposition for the development of CH (4). In this report, we present two patients who developed ipsilateral CH shortly after the extraction of an ipsilateral molar tooth. We review the literature on CH associated with head trauma or structural brain lesions and discuss the implications of these cases for the pathogenesis of CH.