Peer-Review ReportHow Large Is the Typical Subarachnoid Hemorrhage? A Review of Current Neurosurgical Knowledge
Introduction
Subarachnoid hemorrhage (SAH) commonly occurs spontaneously, usually from a ruptured cerebral aneurysm, and subsequently precipitates widespread brain dysfunction. The estimated annual incidence of aneurysmal SAH in the Western world is 6–8 per 100,000 (19), accounting for 1%–7% of all strokes (65). Up to 50% of cases result in fatality and 10%–15% of patients die before reaching a hospital (275). For those that survive, preventing further morbidity revolves around minimizing the risk of rebleeding, as well as preventing delayed ischemic neurologic deficits secondary to cerebral vasospasm. Symptomatic cerebral ischemia peaks between 7 and 10 days post-SAH (123) and remains the most significant cause of death and disability following an SAH. Therefore, to devise sound treatment strategies for SAH, accurate and representative animal models are necessary.
The amount of hemorrhage is thought to be important for the mechanism by which bleeding stops and possibly restarts, as the initial flow rate of SAH has a positive linear correlation with the volume of hemorrhage volume, regardless of cerebral perfusion pressure (21, 168). The amount of hemorrhage in the subarachnoid space is also directly correlated with cerebral vasospasm (70). Animal models have corroborated this, demonstrating that oxyhemoglobin from extravasated erythrocytes, as well as other molecular mechanisms, can cause vasospasm (51).
The kinetics of SAH are complicated (Figure 1), with red blood cells not incorporated in the subarachnoid clot circulating throughout the cerebrospinal subarachnoid space, where they ultimately undergo lysis (94) and phagocytosis (111). Although intact erythrocytes have been shown to return from cerebrospinal fluid (CSF) to the circulation in animals (243), this is not the case in humans (268). Therefore, the total hemorrhage is composed of blood in the subarachnoid clot, plus erythrocytes dispersed in the CSF at any one time (Figure 2). Red blood cells in the CSF spread with CSF flow (114) and usually appear in the lumbar theca within hours of SAH. The red cell count peaks rapidly and fades more slowly, with the exact rates being quite variable (268).
There is a need for accurate representation of SAH in animal models, so that brain physiology, erythrocyte kinetics, and the development of vasospasm can be further studied. Unfortunately, quantifying the amount of SAH in humans is rarely addressed, with only a few comparisons in the animal literature, and virtually none in the human literature (21, 70). To delineate the current state of neurosurgical knowledge in terms of quantifying SAH, we performed a review of clinical and experimental literature and conducted a survey of AANS members.
Section snippets
Materials and Methods
Clinical and experimental studies on SAH volume and erythrocyte counts in human cerebrospinal fluid, published between 1956 and 2010, were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. We probed the current state of neurosurgical knowledge in terms of size of SAH by using a strategy that involved three independent lines of inquiry. First, we performed a structured literature search for information on subarachnoid clot volume
Results
The human literature search yielded 4817 English-language publications. After removing the abstracts that referred to diagnostic imaging (n = 3059), case reports (n = 786), and opinion articles (n = 650), we were left with 322 case series and reviews. The literature searches yielded almost no information on the total volume of an aneurysmal hemorrhage. Burnett et al. (21) mention that most hemorrhages total less than 150 mL, but cite no references. Most articles (7, 16, 38, 70, 75, 89, 106, 172
Discussion
Despite the morbidity and mortality associated with SAH from a ruptured aneurysm, very little is known about the exact volume of blood required to elicit neurologic symptoms or vasospasm. From the studies of Fisher et al. (70) and others, a larger quantity of SAH is strongly correlated with worsened clinical outcome. However, our ability to accurately measure the quantity of SAH through advanced imaging is limited by resolution. In addition, prediction of SAH volume from the RBC count in the
Conclusion
This is the first effort to combine multiple sources of data to estimate the average SAH volume of 35 mL. The amount of SAH is an important consideration for studying clinical outcome and evaluating the utility of animal models. It is possible that with advanced imaging techniques available today, a more accurate estimate of SAH may be obtained. However, SAH remains one of the deadliest diseases that neurosurgeons treat, and all efforts should be made to accurately study and treat this disorder.
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.