LAUSR

The prophylactic treatment of migraine is still challenging, not only because of the effectiveness of drugs given but also because of their side effects which result in a low therapy adherence [4]. Therefore, there is still a need for new, welltolerated, and effective drugs. In animal studies, it was shown that the modified amino acid acetyl-dl-leucine (already approved for the treatment of vertigo in 1957) normalizes neuronal membrane potential [7]. Since spreading depression and fluctuations of membrane potential are discussed as one of the crucial mechanisms of migraine [3], we hypothesized that this acetyl-dlleucine may be effective for the prophylactic treatment of migraine. Therefore, we evaluated its effects on the frequency of attacks of migraine with and without aura. In a prospective observational case series, ten patients (six females, age range 18–70 years, Table 1) were treated on an individual basis with acetyl-dl-leucine during a period from 01/2017 to 09/2018. All fulfilled the diagnostic criteria for migraine with or without aura [1], two also for additional vestibular migraine [5]. They gave their written informed consent. Patients took 1 g tid for 5 days orally as tablets each containing 500 mg, then 2 g in the morning and 1.5 g at noon and night, i.e., a total of 5 g/day (similar to previous studies for other diseases [2, 6]). None of the patients were taking other prophylactic treatment during this period. In the longer term, one patient reduced the dosage to 4 g/day. Patients received a diary to note the number of attacks of migraine, aura and days with headache (including migraine) per month. These outcomes were paired for each patient, before vs. during treatment using the Wilcoxon signed rank test. Before treatment, the median number of attacks of migraine per month was 6.5 (range 2–30, n = 10). When patients were treated for at least 3 months, the median number of migraine attacks per month was 1 (range 0–5, n = 10; p = 0.002). Before treatment, the median number of days with headache per month was 10.5 (range 4–25, n = 10), while during treatment it was 1.7 (range 0–8, n = 10; p = 0.006; Table 1). Three out of ten patients (no. 1, 6, 9) with migraine with visual aura reported that not only the number of days of migraine but also the number of auras per month was lower; two patients (no. 5, 10) had migraine in combination with vestibular migraine, in both of them the number of vertigo attacks also decreased (Table 1). In terms of side effects, the drug was well-tolerated: except for one patient who reported transient problems with night sleep after the dosage was increased to 5 g/day, no further adverse events were reported by the patients. Currently, on 09/2018, eight out of ten patients (two patients stopped medication because they were free of symptoms for more than 3 months) are still on treatment (treatment duration 4–17 months), demonstrating a good compliance and adherence. Based on the mode of action [7], this simple molecule reduced the number of attacks of migraine and days of headache per month. It is important to note that acetyl-dl-leucine also had an impact on the aura. Finally, it has a very good safety profile. This case series has some methodological limitations: small number of individuals; not placebo-controlled * Michael Strupp [email protected]