gms | German Medical Science

Objective: An acute increase in intracranial pressure and reduction of cerebral blood flow are thought to initiate Early Brain Injury (EBI) after SAH, a crucial contributor to overall outcome. In this period, oxidative stress, inflammatory factors, and neuronal apoptosis are triggered. After experimental SAH, the circadian molecule melatonin showed both antioxidant and anti-inflammatory impacts. We prospectively assessed the endogenous melatonin level in SAH patients in the context of disease severity and outcome.

Methods: We prospectively enrolled 30 consecutive adult patients (57.9±12yrs) with acuteaSAH from 02/2015 to 05/2017. Thirty adult patients undergoing elective aortic surgery (56.9±11.7yrs) served as a control group (cG). All relevant demographic data, modified Fisher score (mFS), clinical course and complications (including DCI, infarcts) as well as outcome (GOS) after three months were recorded. Samples of serum were collected from each patient (from 11:00 am to 05:00 pm) at different time points: after ictus (d0), early (EPd1-4), in the critical (CPd5-8, CPd9-12, CPd13-15) and in late phase (LPd16-21). For measuring of melatonin, ELISA kits from IBL International GmbH were used. The lower limit of quantification (LLOQ) was set by 3pg/ml.

Results: In 80 out of 183 samples (43.7%), melatonin remained below the LLOQ (46.7% in cG, 41.7% in d0, 55.2% in EPd1-4, 72% in CPd5-8, 38% in CPd9-12, 32% in CPd13-15, 14.8% in LPd16-21), indicating a predominant decrease of melatonin in the critical phase. Cases with LLOQ in CPd5-8showed significantly more infarcts (p<0.05). Higher levels of melatonin initially (EP) were associated with a lower incidence of DCI (p<0.05).Samples in patients with ruptured anterior communicating artery aneurysms (AComA) showed significantly increased melatonin levels in the early and the critical phase (p=0.05, p<0.05).

Conclusion: To our knowledge, this is first clinical data detailing a characteristic course of melatonin levels after aSAH. In the acute/critical phase melatonin levels are decreased, whereas higher levels initially are associated with a more benign clinical course, possibly due to its antioxidant and anti-inflammatory impact. The close proximity of the melatonin-controlling suprachiasmatic nucleus to the AcomA-complex may explain the significant elevation of melatonin in these cases.