Biomarkers of vasospasm development and outcome in aneurysmal subarachnoid hemorrhage

https://doi.org/10.1016/j.jns.2014.04.020Get rights and content

Highlights

  • Subarachnoid hemorrhage is the main cause of sudden death from stroke.

  • No biomarker has been demonstrated as a useful tool for predicting SAH outcome.

  • Researches should define pathophysiologic processes responsible for CVS development.

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) is a neurologic emergency caused by a brain aneurysm burst, resulting in a bleeding into the subarachnoid space. Its incidence is estimated between 4 and 28/10,000 inhabitants and it is the main cause of sudden death from stroke. The prognosis of patients with SAH is directly related to neurological status on admission, to the magnitude of the initial bleeding, as well as to the development of cerebral vasospasm (CVS). Numerous researchers have studied the role of different biomarkers in CVS development. These biomarkers form part of the metabolic cascade that is triggered as a result of the SAH. Hence, among these metabolites we found biomarkers of oxidative stress, inflammation biomarkers, indicators of brain damage, and markers of vascular pathology. However, to the author knowledge, none of these biomarkers has been demonstrated as a useful tool for predicting neither CVS development nor outcome after SAH. In order to reach success on future researches, firstly it should be stated which pathophysiological process is mainly responsible for CVS development. Once this process has been determined, the temporal course of this pathophysiologic cascade should be characterized, and then, perform further studies on biomarkers already analyzed, as well as on new biomarkers not yet studied in the SAH pathology, focusing attention on the temporal course of the diverse metabolites and the sampling time for its quantification.

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).

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