Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating disease affecting around 9 / 100.000 people each year [8]. After SAH, the main predictors of outcome are the initial clinical grade either defined by the Hunt and Hess (H&H) or WFNS scale and the amount of subarachnoid blood load stratified according to the modified Fisher scale (mFisher) [34, 7]. Despite general advancements in critical care management for SAH patients, outcome in those with higher clinical grade or blood load remains poor [25, 9]. The initial aneurysm rupture results in a steep increase of intracranial pressure and resulting sudden drop in cerebral perfusion pressure [26]. It is currently assumed that this initial increase in intracranial pressure and consecutive drop in cerebral perfusion pressure has irreversibly initiated a deleterious cascade coined with the umbrella term early brain injury.
During the first two weeks post-hemorrhage, patients remain susceptible to ischemic strokes in which cerebral vasospasm plays an undisputed role alongside many other contributing factors [35]. This delayed cerebral ischemia (DCI) can eventually result in cerebral infarctions, further compromising long-term clinical outcome [36].
Obesity is an established risk factor for cardio- and cerebrovascular disease, surgical complications and nosocomial infections [2]. Contrary to this association, there is an “obesity paradox” where an increased body mass index (BMI) was associated with an overall lower mortality and complication rate, after ischemic stroke [31, 19] and intracerebral hemorrhage [5, 18]. SAH patients suffering from obesity do not fare worse or may even profit from obesity by unknown mechanisms in regard to DCI-development, clinical outcome, and overall rate of complications [24, 33, 6]. A single trial in SAH patients described a lower risk of DCI and DCI-related infarction associated with elevated BMI [29]. Nonetheless, the results of a systemic review addressing this obesity paradox in SAH remained inconclusive as most trials suffered restrictions in design, resulting in limited external validity [27].
Leptin, initially discovered as a regulator of food intake and energy expenditure, is emerging as a pleiotropic molecule involved in various physiological and pathological conditions [15, 13]. Under normal physiological circumstances, this peptide has an inhibitory effect on appetite via its modulation of the hypothalamic satiety center. Leptin is, however, also part of a broader neuronal circuit regulating weight and governing energy homeostasis. Crossing the blood-brain barrier, leptin acts on receptors within the central nervous system and exerts an anti-apoptotic effect, increases neuronal survival, and can induce neurogenesis as well as angiogenesis [21]. As part of the cytokine superfamily, leptin has structural and functional similarities with pro-inflammatory cytokines such as Interleukin-1, -6, and − 12, hence the name adipokine. Furthermore, the leptin receptor (OB-R) is related to class I cytokine receptors, including a common signal-transducing component from the IL-6-related family of cytokines [3]. In obesity, leptin resistance develops, leading to an inability to detect satiety despite sufficient available energy stores. Serum leptin concentrations correlate positively with the percentage of body fat, illustrating the insensitivity of most people suffering from obesity, to endogenous leptin production [4]. This makes leptin an interesting target to assess body fat content’s effects on DCI-occurrence and long-term outcome after SAH.
In this study we set out to assess the obesity paradox in a prospective SAH data collection, based on BMI but also on levels of leptin in cerebrospinal fluid (CSF) and serum, the latter as surrogate markers of body fat mass.