S100b und NSE bei Migränepatienten - Eine Studie über die Durchlässigkeit der Blut-Hirn-Schranke im Migräneanfall

Migraines, in addition to tension headaches, are among the most frequent primary causes of headaches (Diener, 2006). Even so, the actual causes of this disease are as yet unknown (Soyka, 1999). Over the years, a number of theories have been developed on the origins of migraines. As a result, we now assume that the human migraine aura is induced by Cortical Spreading Depression (Leão, 1944; Goadsby et al., 2002; Diener, 2006), whereas the headaches are triggered by a second mechanism – presumably via neurovascular inflammation (Moskowitz, 1990; Goadsby et al., 2002; Diener, 2006). The results of recent studies reporting on plasmaextravasation and the formation of oedemas in rats following artificially induced Cortical Spreading Depression (CSD), suggest a causal link between the two processes (Gursoy-Ozdemir et al., 2004; Imamura et al., 2007; Leira et al., 2007). A breakdown in the blood-brain barrier was determined within the framework of the inflammation triggered by CSD in rats (Gursoy-Ozdemir et al., 2004). As early on as 1977, Harper and colleagues suspected this to also be the case in migraine attacks. They based their theory on parallels between mediators involved in migraine development and mediators that influence the blood-brain barrier (Harper et al., 1977). Recent studies appear to confirm this link (e.g., Grant et al., 1998; Goadsby, 1997; Imamura et al., 2007; Leira et al., 2007). There are also several case descriptions that report on CT and MRI changes during migraine attacks that could subsequently no longer be determined (Alvarez-Cermeno et al., 1984 and 1986; Jain and Ahuja, 1986; Müller et al., 1987; Smith et al., 2002; Teepker et al., 2002). The aims of this study are to find further proof for the opening of the blood-brain-barrier during migraine attacks and to thereby add a further building block to our understanding of the development of migraines. In order to accomplish this, two biochemical markers will be used: the neuron-specific enolase (NSE)and S100b. Serum samples were taken from 21 migraine patients during migraine attacks, as well as during intervals when they were free of complaints (a minimum of 48 h after the headache event) and NSE and S100b were determined. These samples were compared with those of healthy patients. The Wilcoxon Signed ranks test and the Mann-Whitney U test were used for analysis of the results. Significantly higher S100b levels were determined in migraine patients both during attacks as well as during intervals when they were free of complaints. Furthermore, the S100b levels were significantly higher during the complaintfree interval than during the migraine attack. The NSE levels were significantly lower than those of healthy patients used for comparison, but no significant differences were determined between levels during migraine attacks and the complaint-free intervals. These experimental results can be interpreted in different ways. Both measurements constitute a snapshot in time and may correspond to varying progression in concentrations. This is of particular importance in the case of S100b, as different progressions permit different interpretations. In contrast, the data collected on NSE permits conclusive exclusion of the possibility of neuronal cell damage within the framework of migraine disease. A total of three progressions in concentrations are possible for S100b: 1. generally increased levels in migraine patients, that are reduced during migraine attacks, e.g., through consumption or a reduction in production 2. generally increased levels in migraine patients, the serum values for which only increase after the attack; (and are thereby determined in measurements made during the complaint-free intervals). 3. no general increase in serum levels in migraine patients, but increases in levels during migraine attacks that are maintained over a longer period than that selected for the second measurement. Different hypotheses can be formulated, depending on the progression in concentrations: According to the publications by Kanner, Kapural and Marchi and colleagues, an increase in S100b serum levels associated with unchanged or reduced NSE levels is to be regarded as a marker for a defective blood-brain barrier (Kapural et al., 2002; Kanner et al., 2003; Marchi et al., 2003, 2004 and 2007). In turn,this may occur permanently or only temporarily – if all possible progressions in concentrations are considered. Consideration of all studies conducted to date on migraines indicates that a temporary opening of the BBB during migraine attacks, the duration of which outlasts the attack for an indeterminate period, is most likely. Exactly when this occurs, how long it lasts for and whether this constitutes a possible cause or a reaction, or even a pathological mechanism, remains unclear.