Biomarkers of vasospasm development and outcome in aneurysmal subarachnoid hemorrhage
Introduction
Aneurysmal subarachnoid hemorrhage (SAH) is a neurologic emergency caused by a brain aneurysm burst, resulting in a bleeding into the space surrounding the central nervous system (CNS), which is normally filled with cerebrospinal fluid (CSF). The aneurismal SAH accounts for about 80% of all nontraumatic extravasated bleeding into the subarachnoid space [1]. Its incidence is estimated between 4 and 28/10,000 inhabitants and it is the main cause of sudden death from stroke [2]. Despite researcher efforts focused on improving outcome for patients suffering a SAH, the rate of fatal outcome remains high. Approximately 15% of patients die after the aneurysm burst, while 25–50% die within a month of the bleeding. In reference to survivors, 40% of them present disabling sequelae [3], [4], [5]. Numerous studies have observed that the prognosis of patients with SAH is directly related to neurological status on admission, stratified according to the Hunt–Hess scale, the World Federation of Neurological Surgeon (WFNS) scale and the Johns Hopkins University Classification [6], as well as the occurrence of delayed ischemia deficit consequence of cerebral vasospasm (CVS) development, related to the magnitude of the initial bleeding on head CT-scan, stratified according to the Fisher scale and the Modified Fisher Scale [2], [7]. Nevertheless, the complications that can occur after the initial bleeding are largely responsible for the high morbidity and mortality of SAH [8]. The patocronia of them is well known: hydrocephalus and rebleeding, which occur on the first 24–48 h; and CVS, which takes place from day 4 until the second week. The CVS is characterized by diffuse and long-lasting (more than two weeks) narrowing of arteries. It is estimated that CVS is responsible for neurological deterioration and even for death of 15–20% of SAH patients [3]. Presumably, it is the unique kind of acute cerebral ischemia that might be preventable trough an early detection and implementation of invasive and non-invasive procedures [9]. Up to date, monitoring of this phenomenon is made by clinical examination, transcranial Doppler-sonography records and cerebral arteriography [10], [11], [12]. Although numerous researchers have studied the role of different biomarkers in CVS development and SAH outcome, there are currently no established biomarkers for early diagnosis of CVS development or monitoring its progression, tool that would help physicians during treatment decision making.
Section snippets
Pathophysiologic cascade
As a consequence of bleeding red blood cells (RBCs) suffer lysis shortly after the injury, resulting in a release of large quantities of free hemoglobin (Hgb) into the subarachnoid space, which is extremely toxic [13]. This free Hgb is neutralized, in part, by its high affinity interaction with haptoglobin (Hp), a protein synthesized in the hepatocytes [13]. As a result of bleeding in SAH, a primary immune response is immediately triggered, mediated by macrophages and neutrophils [14], [15],
Perspective
Despite the existence of multiple metabolites whose concentration or activity result altered in a SAH, none of them has been established in clinical practice for SAH patients' management. To the authors' knowledge, the various studies conducted have analyzed the role of biomarkers of oxidative stress, biomarkers of vascular injury, inflammatory biomarkers, or brain damage biomarkers, individually, in the SAH pathology. We hypothesize that, perhaps, the success of future studies is not the
Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Acknowledgments
This research was made possible by funding from the Junta de Andalucía Health Department 2012 Grant Fund (PI-0136-2012).
References (185)
Epidemiology and clinical presentation of aneurysmal subarachnoid hemorrhage
Neurosurg Clin N Am
(1998)- et al.
Epidemiology of aneurysmal subarachnoid hemorrhage
Neurosurg Clin N Am
(2010) - et al.
Proteomic biomarker discovery in cerebrospinal fluid for cerebral vasospasm following subarachnoid hemorrhage
J Stroke Cerebrovasc Dis
(2012) - et al.
Emergency transcranial Doppler ultrasound: predictive value for the development of symptomatic vasospasm in spontaneous subarachnoid hemorrhage in patients in good neurological condition
Med Intensiva
(2012) - et al.
Signaling mechanisms in cerebral vasospasm
Trends Cardiovasc Med
(2005) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm
Cell
(1994)- et al.
Cytokine signaling modules in inflammatory responses
Immunity
(2008) - et al.
Mitochondrial respiratory chain and free radical generation in stroke
Free Radic Biol Med
(2005) Oxidative damage in the central nervous system: protection by melatonin
Prog Neurobiol
(1998)- et al.
Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury?
Lancet Neurol
(2002)