Migraine patients show a specific cognitive processing with a loss of habituation in the interval and a normal habituation in the attack as measured by event-related potentials (ERPs). It is unknown whether the loss of habituation changes during the migraine interval or is a stable state. Serotonin (5HT) metabolism is involved in the pathophysiology of migraine and also in the generation of ERPs. We enrolled 14 patients with regular migraine attacks in order to measure visually evoked ERPs repetitively during the migraine interval and in the migraine attack. Cognitive habituation was evaluated by analysis of P3 latency. Platelet serotonin content and free serotonin plasma level were measured at the same time points. The loss of habituation increased continuously during the migraine interval and abruptly normalized in the migraine attack (p < 0.05, time series analysis). The platelet 5HT content decreased significantly in the migraine attack (p < 0.03) and was at its maximum in the middle of the interval. The P3 latency was significantly increased in the attack (p < 0.01) and was significantly inversely correlated with the platelet 5HT content (r = -0.44, p < 0.001). Free 5HT plasma levels did not show any significant change. Our findings suggest that loss of cognitive habituation continuously increases during the migraine interval until its normalization in the migraine attack. This phenomenon cannot be attributed to serotonergic transmission. In patients with regular changes of cognitive habituation before the migraine attack, it might be possible to predict the attack by analysing ERPs.

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.

We report the first four German cases of hypnic headache according to the criteria suggested in the literature. Furthermore, we present the results of polysomnography in two theses cases with hypnic headache occurring during REM sleep. In one case, hypnic headache was also associated with periodic limb movements. Although mean nocturnal oxygen saturation was decreased in another patient, nightly oxygen inhalation did not result in an improvement of the headache.

Drug-induced headache is a well-known complication of the treatment of primary headache disorders, and its successful management is only possible by withdrawal therapy. However, it is unknown whether ambulatory or stationary withdrawal is the therapy preferred. We conducted a prospective study on the outcome of stationary versus ambulatory withdrawal therapy in patients with drug-induced headache according to the International Headache Society criteria. Out of 257 patients with the diagnosis of drug-induced headache during the study period, 101 patients (41 after ambulatory and 60 after stationary withdrawal therapy) could be followed up for 5.9 +/- 4.0 years. The total relapse rate after successful withdrawal therapy was 20.8% (14.6% after ambulatory and 25.0% after stationary withdrawal therapy, p < 0.2). The main risk factors for a relapse were male sex (OR = 3.9, CI = 1.3-11.6), intake of combined analgesic drugs (OR = 3.8, CI = 1.4-10.3), administration of naturopathy (OR = 6.0, CI = 1.2-29.3), and a trend to tension-type headache as the primary headache disorder (OR = 1.9, CI = 0.6-53.0). Our data suggest that neither the method of withdrawal therapy nor the kind of analgesic and other antimigraine drugs has a major impact on the long-term result after successful withdrawal therapy. Patients with risk factors according to our findings should be informed and monitored regularly, and combined drugs should be avoided. Furthermore, our data suggest that there is a need for research on individual psychological and behavioral risk factors for relapse after successful withdrawal therapy in drug-induced headache.

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.