Original Article
Intraventricular Hemorrhage Is Associated with Early Hydrocephalus, Symptomatic Vasospasm, and Poor Outcome in Aneurysmal Subarachnoid Hemorrhage Thomas J. Wilson,1 Neeraj Chaudhary2
William R. Stetler Jr.,1 Matthew C. Davis1 David A. Giles1 Adam Khan2 Joseph J. Gemmete1 Guohua Xi1 B. Gregory Thompson1 Aditya S. Pandey1
1 Department of Neurosurgery, University of Michigan, Ann Arbor,
Michigan, United States 2 Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States
Address for correspondence Thomas J. Wilson, MD, Department of Neurosurgery, University of Michigan, 1500 E. Medical Center Drive, Room 3552, TC, Ann Arbor, Michigan 48109-5338, United States (e-mail: [email protected]).
J Neurol Surg A 2015;76:126–132.
Abstract
Keywords
► ► ► ► ►
aneurysm hydrocephalus endovascular coiling subarachnoid hemorrhage
received October 16, 2013 accepted after revision May 23, 2014 published online December 29, 2014
Objective We hypothesized that the subset of patients with early hydrocephalus following aneurysmal subarachnoid hemorrhage may represent a subset of patients with a more vehement inflammatory reaction to blood products in the subarachnoid space. We thus examined risk factors for early hydrocephalus and examined the relationship between early hydrocephalus and symptomatic vasospasm as well as clinical outcome. Methods We retrospectively analyzed all patients presenting to our institution with subarachnoid hemorrhage over a 7-year period. We examined for risk factors, including early hydrocephalus, for poor clinical outcome and symptomatic vasospasm. Results We found intraventricular hemorrhage to be strongly associated with the development of early hydrocephalus. In univariate analysis, early hydrocephalus was strongly associated with both poor functional outcome and symptomatic vasospasm. In multivariate analysis, intraventricular hemorrhage and tobacco use were associated with symptomatic vasospasm; intraventricular hemorrhage, intraparenchymal hemorrhage, and symptomatic vasospasm were associated with poor functional outcome. Conclusions We found that intraventricular hemorrhage was strongly associated with early hydrocephalus. Further exploration of the mechanistic explanation is needed, but we suggest this may be from a combination of obstruction of cerebrospinal fluid pathways by blood products and inflammation in the choroid plexus resulting in increased cerebrospinal fluid production. Further, we suggest that both early hydrocephalus and cerebral vasospasm may be parts of the overall inflammatory cascade that occurs with intraventricular hemorrhage and ultimately results in a poorer clinical outcome.
© 2015 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1394189. ISSN 2193-6315.
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Intraventricular Hemorrhage Associated with Early Hydrocephalus
Acute hydrocephalus following aneurysmal subarachnoid hemorrhage (aSAH) was not reported in a large series until the 1970s.1–3 Following these reports, some dismissed the clinical significance of hydrocephalus.4 Particularly since the advent of computed tomography (CT), acute hydrocephalus has been increasingly recognized and treated. Prompt treatment of hydrocephalus related to aSAH has become one of the mainstays of treatment because it has been shown to improve outcomes.5 A wide variety of risk factors for the development of hydrocephalus have been suggested including increasing age, hypertension, posterior circulation aneurysm location, and increasing volume of cisternal blood.6 This begs the question: What is the pathophysiologic origin of acute hydrocephalus following aSAH? Hydrocephalus related to subarachnoid hemorrhage (SAH) is thought to occur via two mechanisms: (1) obstruction of normal communication of the cerebrospinal fluid (CSF) pathways by blood products, or (2) decreased reabsorption of CSF due to blood products affecting the arachnoid granulations.7 Most believe that acute hydrocephalus is predominantly due to the former and the latter makes a more significant contribution to chronic hydrocephalus because the adhesions that disrupt the arachnoid granulations take time to form.7–9 However, more recently, people have begun to explore the idea that increased CSF production may contribute to or be the primary mechanism of acute hydrocephalus.10 It may be that the inflammatory reaction to blood products in the ventricles and subarachnoid space varies from patient to patient and that the degree of inflammatory reaction to blood products in the ventricles and subarachnoid space determines the degree to which CSF obstruction versus CSF overproduction contribute to acute hydrocephalus. We hypothesized that the subset of patients with early hydrocephalus, hydrocephalus present at the time of initial presentation, may represent a subset of patients with a more vehement inflammatory reaction. We thus examined risk factors for early hydrocephalus and examined the relationship between early hydrocephalus and symptomatic vasospasm as well as clinical outcome.
Methods Study Design This cohort study was approved by the University of Michigan institutional review board, and data were obtained by retrospective chart review. Information technology personnel designed and implemented a search paradigm to query information systems to identify all patients admitted who underwent microsurgical clip ligation or endovascular coil embolization of a cerebral circulation aneurysm after presenting with SAH between January 1, 2005, and February 1, 2012. This patient list was cross-referenced with the operative reports in the medical record to confirm that aneurysm treatment was performed and that initial presentation had been with a ruptured aneurysm.
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Outcomes of Interest The two primary outcomes of interest were functional outcome as assessed by Glasgow Outcome Scale (GOS) score at 6 months following presentation and the occurrence of symptomatic vasospasm. Poor outcome was defined as a GOS of 1 to 3. Symptomatic vasospasm was defined as a clinical neurologic change thought to be secondary to vasospasm where vasospasm was confirmed by angiography (either CT angiography or conventional digital subtraction angiography) and in the absence of other causes such as rebleeding, hydrocephalus, electrolyte abnormalities, hypoxia, or seizures. Patients regardless of clinical status were monitored for symptomatic vasospasm in an intensive care setting for at least 14 days following hemorrhage by following the clinical examination for signs of deterioration and by following transcranial Doppler ultrasonography (TCD) performed every other day. When vasospasm was suspected by either change in clinical examination or by TCD, it was further evaluated using either a CT angiogram or conventional digital subtraction angiogram. Symptomatic vasospasm when present was treated first medically using fluid boluses and vasopressors to increase the mean arterial pressure. When this was ineffective, endovascular therapy was performed using either mechanical angioplasty or chemical angioplasty with intra-arterial nicardipine.
Variables Variables abstracted from the medical record and through review of radiographic studies included age, sex, obesity (body mass index >30 kg/m2), hypertension, coronary artery disease, tobacco use, aneurysm location, intraventricular hemorrhage on the initial CT scan at the time of presentation, intraparenchymal hemorrhage on the initial CT scan at the time of presentation, early hydrocephalus, chronic hydrocephalus, ventriculostomy placement, and CSF shunt placement. No radiologic parameters are consistently agreed on to diagnose hydrocephalus.11,12 In this study, early hydrocephalus was defined as hydrocephalus present on the initial CT scan at the time of presentation. Each CT scan was independently reviewed by one of the authors and assessed for hydrocephalus. This was then compared with the radiology report. When there was disagreement between the assessment of the radiologist and the author, an additional author reviewed the CT scan. If cortical atrophy versus hydrocephalus was considered, hydrocephalus was defined by enlargement of the temporal horns commensurate with the body of the lateral ventricles.11 Early hydrocephalus was tested for its association with poor functional outcome and symptomatic vasospasm. Each of the other variables was tested for its association with early hydrocephalus. Chronic hydrocephalus was defined as hydrocephalus present at 6 months following ictus that either continues to require medical management or that required placement of a CSF shunt. Ventriculostomy placement occurred based on the clinical status of the patient. When mental status was depressed and hydrocephalus was present, a ventriculostomy was placed. We do not use a clinical grade cut-off to determine ventriculostomy placement at our institution but rather evaluate each Journal of Neurological Surgery—Part A
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Introduction
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Intraventricular Hemorrhage Associated with Early Hydrocephalus case individually utilizing both the clinical examination and radiographic findings. Ventriculostomy placement occurred at the time that the examination was depressed and hydrocephalus was present, whether that was immediately upon admission or in a delayed fashion. Hydrocephalus requiring CSF diversion was always managed with ventriculostomy placement. Lumbar drains are not used to manage hydrocephalus in the setting of aSAH at our institution.
Statistical Analysis Statistical analysis was performed using commercially available software (SPSS v.18, IBM Corp., Somers, New York, United States). Univariate comparison of continuous variables with a normal distribution was assessed using two-sample t tests, and continuous variables not meeting the normality assumption were assessed using the Mann-Whitney U test. All categorical data were assessed by chi-square test or Fisher exact test, as appropriate. Logistic regression was used to test univariate and multivariate associations between our variables of interest and the dichotomous variable of early hydrocephalus. We planned a priori to include all variables with p < 0.20 in univariate analysis in our multivariate analyses. For all statistics, a p value < 0.05 was considered statistically significant.
Results During the study period, 321 patients presented to our institution with aSAH. Of these, 150 patients underwent coil embolization for treatment of their intracranial aneurysm; 171 patients had microsurgical clip ligation performed. Patients were predominantly female (69%) and predominantly had anterior circulation/posterior communicating artery aneurysms (83%). The average age of all patients was 54 years of age. Overall, 74% of patients had a good outcome, defined as GOS 4 to 5 at 6 months following presentation. Early hydrocephalus was present in 179 patients (56%). An additional 32
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patients (10%) developed subacute hydrocephalus requiring external ventricular drainage. Symptomatic vasospasm occurred in 84 patients (26%). Hunt and Hess grades for patients presenting with aSAH were 9 patients (3%) grade 1, 146 patients (45%) grade 2, 84 patients (26%) grade 3, 53 patients (17%) grade 4, and 29 patients (9%) grade 5. We first examined risk factors for early hydrocephalus (►Table 1). Factors in univariate analysis that were found to be associated with early hydrocephalus included posterior circulation aneurysm location, older age, and intraventricular hemorrhage. In multivariate analysis, both posterior circulation aneurysm location and intraventricular hemorrhage remained independently associated with early hydrocephalus. Intraventricular hemorrhage seemed to be the strongest associated variable with early hydrocephalus, with an odds ratio of 8.62 (95% confidence interval [CI], 5.10–14.49) for having early hydrocephalus when intraventricular hemorrhage is present versus 2.52 when a posterior circulation aneurysm was present (95% CI, 1.19–5.35). Next, we examined the data to see if an association exists between early hydrocephalus and symptomatic vasospasm (►Table 2). Both early hydrocephalus and intraventricular hemorrhage were found to be significantly associated with symptomatic vasospasm in univariate analysis. Given that intraventricular hemorrhage was strongly predictive of and associated with early hydrocephalus, only intraventricular hemorrhage remained independently associated with symptomatic vasospasm in multivariate analysis. In addition to intraventricular hemorrhage, tobacco use was significant in the multivariate model. The odds ratio of having symptomatic vasospasm if intraventricular hemorrhage was present was 2.84 (95% CI, 1.53–5.26). We then explored the relationship between early hydrocephalus and overall functional outcome (►Table 3). Factors found to be significantly associated with poor outcome in univariate analysis included older age, symptomatic vasospasm, presence of coronary artery disease, early
Table 1 Univariate and multivariate tests of association with early hydrocephalus Hydrocephalus (n ¼ 179)
No hydrocephalus (n ¼ 142)
Univariate p value
Obesity (n,%)
44 (25)
36 (25)
0.873
Hypertension (n,%)
92 (51)
67 (47)
0.453
CAD (n,%)
19 (11)
7 (5)
0.063
0.068
0.002
0.016
Aneurysm location (n,%) Anterior circulation
137 (77)
128 (90)
Posterior circulation
42 (23)
14 (10)
Sex (n,%)
Multivariate p value
0.248
Male
51 (28)
Female
49 (35)
128 (72)
93 (65)
Age (SD)
55.7 (13.4)
52.0 (14.4)
0.028
0.543
IVH (n,%)
135 (75)
35 (25)
< 0.001
< 0.001
IPH (n,%)
32 (18)
16 (11)
0.102
0.215
Abbreviations: CAD, coronary artery disease; IPH, intraparenchymal hemorrhage; IVH, intraventricular hemorrhage; SD, standard deviation. Journal of Neurological Surgery—Part A
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Table 2 Univariate and multivariate tests of association with symptomatic vasospasm Vasospasm (n ¼ 84)
No vasospasm (n ¼ 237)
Multivariate p value
0.228
Coil
44 (52)
106 (45)
Clip
40 (48)
131 (55)
Obesity (n,%)
22 (26)
58 (24)
0.755
Hypertension (n,%)
46 (55)
113 (48)
0.265
CAD (n,%)
5 (6)
21 (9)
0.404
Tobacco use (n,%)
56 (67)
130 (55)
0.061
0.042
Early hydrocephalus (n,%)
55 (65)
124 (52)
0.038
0.879
Anterior circulation
71 (85)
194 (82)
Posterior circulation
13 (15)
43 (18)
Male
20 (24)
80 (34)
Female
64 (76)
157 (66)
55.0 (15.0)
53.0 (12.2)
0.353
IVH (n,%)
60 (71)
110 (46)
< 0.001
IPH (n,%)
14 (17)
34 (14)
0.609
Aneurysm location (n,%)
0.580
Sex (n,%)
Age (SD)
0.093
0.184
0.002
Abbreviations: CAD, coronary artery disease; IPH, intraparenchymal hemorrhage; IVH, intraventricular hemorrhage; SD, standard deviation.
hydrocephalus, presence of intraventricular hemorrhage, and presence of intraparenchymal hemorrhage. Only symptomatic vasospasm, the presence of intraventricular hemorrhage, and the presence of intraparenchymal hemorrhage remained significant in multivariate analysis. All three variables were fairly similarly associated with the risk of a poor outcome. The odds ratios were symptomatic vasospasm 2.07 (95% CI, 1.13–3.77), intraparenchymal hemorrhage 2.36 (95% CI, 1.18–4.73), and intraventricular hemorrhage 2.17 (95% CI, 1.13–4.17). Finally, we examined the relationship between acute and chronic hydrocephalus as well as chronic hydrocephalus with symptomatic vasospasm. Overall, 66 of the 321 patients (21%) developed chronic hydrocephalus requiring either CSF shunting or continued medical management at 6 months following ictus. Of the 66 patients developing chronic hydrocephalus, 50 (76%) of them had acute hydrocephalus. Acute hydrocephalus was strongly associated with the development of subsequent chronic hydrocephalus (p < 0.001). All 66 patients with chronic hydrocephalus were managed with placement of a CSF shunt. A total of 84 patients developed symptomatic vasospasm. Of these patients, 30 (36%) of them had chronic hydrocephalus.
Discussion Acute hydrocephalus following aSAH is a major source of morbidity and mortality. Our reported rate of hydrocephalus was similar to previous reports that have shown that as many
as 87% of patients with SAH can present with hydrocephalus.13–20 Prompt CSF drainage has been recognized for many years to improve outcomes for patients and has become one of the hallmarks of management of aSAH.5,13 Most agree that acute hydrocephalus is caused at least in part by direct obstruction of CSF pathways by blood products; chronic hydrocephalus may be caused by decreased CSF reabsorption secondary to adhesions in the arachnoid granulations.7–9 Increased CSF production may also contribute to acute hydrocephalus in the aSAH patient population. We hypothesized that aSAH patients presenting with hyperacute hydrocephalus, hydrocephalus at the time of presentation, may represent a clinically distinct subset with increased risk for cerebral vasospasm and poor clinical outcome. We examined our aSAH patient population to evaluate risk factors in the development of early hydrocephalus as well as the relationship between early hydrocephalus and the development of cerebral vasospasm and poor clinical outcome. To our knowledge, this is the first report to examine patients with early (hyperacute) hydrocephalus as a distinct subset. We found that intraventricular hemorrhage was associated with early hydrocephalus and remained significant in multivariate analysis. Although we have no pathophysiologic examination in this study, one would hypothesize that the presence of hydrocephalus would be secondary to a combination of processes: presence of blood within the ventricular space leading to increased CSF production, presence of blood within the ventricular outflow leading to obstruction of flow, and long-term inflammation-based injury to the arachnoid Journal of Neurological Surgery—Part A
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Treatment (n,%)
Univariate p value
Intraventricular Hemorrhage Associated with Early Hydrocephalus
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Table 3 Univariate and multivariate tests of association with poor outcome Good outcome (n ¼ 239)
Poor outcome (n ¼ 82)
Treatment (n,%)
Univariate p value
Multivariate p value
0.395
Coil
124 (52)
47 (57)
Clip
115 (48)
35 (43)
Obesity (n,%)
54 (23)
26 (32)
0.101
0.170
Hypertension (n,%)
112 (47)
47 (57)
0.103
0.223
CAD (n,%)
14 (6)
12 (15)
0.015
0.069
Tobacco use (n,%)
144 (60)
42 (51)
0.154
0.251
Early hydrocephalus (n,%)
121 (51)
58 (71)
0.002
0.239
0.150
0.179
Anterior circulation
193 (81)
72 (88)
Posterior circulation
46 (19)
10 (12)
Male
70 (29)
30 (37)
Female
169 (71)
52 (63)
53.0 (12.7)
57.0 (17.0)
0.016
0.390
Aneurysm location (n,%)
Sex (n,%)
0.219
Age (y,SD) IVH (n,%)
111 (46)
59 (72)
< 0.001
0.021
IPH (n,%)
27 (11)
21 (26)
0.002
0.016
Symptomatic vasospasm (n,%)
52 (22%)
32 (39)
0.002
0.018
Abbreviations: CAD, coronary artery disease; IPH, intraparenchymal hemorrhage; IVH, intraventricular hemorrhage; SD, standard deviation.
villi leading to a lack of reabsorption CSF fluid. This correlates with a previously published rat model of hydrocephalus, where nearly half of rats with induced SAH developed hydrocephalus. In this model, the development of hydrocephalus was significantly associated with the presence of intraventricular hemorrhage and the extent of ventricular wall damage.21 In addition, in a rabbit model it has been shown that SAH induces increased water vesicles and CSF production in the choroid plexus.10 This was an early rather than a late phenomenon because the choroid plexus degraded over time. Thus in this model CSF production was increased acutely but actually was decreased over time.10 In addition, in an infectious model, infectious ventriculitis resulted in decreased CSF production acutely and ultimately necrosis of the choroid plexus.22 Thus conflicting evidence exists regarding CSF production in the acute stages following inflammation. A wide variety of cytokines including tumor growth factor (TGF)-β1 and TGF-β2 have been postulated to be involved in the posthemorrhagic inflammatory process, but to date none have been clearly shown to play a role or to be predictive of hydrocephalus.23 The posthemorrhagic inflammatory process remains poorly understood, and it is unclear at this point whether increased CSF production contributes to hyperacute hydrocephalus but remains one possible source. Posterior circulation aneurysm location was also a risk factor for early hydrocephalus, likely due to obstruction of the foramina of Luschka and foramen of Magendie by local blood products. Journal of Neurological Surgery—Part A
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We found that in addition to those patients having hyperacute hydrocephalus, an additional 10% of patients developed subacute hydrocephalus during their hospitalization requiring external ventricular drainage. We hypothesize that the mechanisms of hyperacute, subacute, and chronic hydrocephalus may be different, but additional pathophysiologic investigation is needed to test this hypothesis. Overall, 21% of patients had chronic hydrocephalus that had required placement of a CSF shunt. Hyperacute hydrocephalus was a significant risk factor for the eventual development of chronic hydrocephalus; 76% of the patients with chronic hydrocephalus had hyperacute hydrocephalus. Whereas hyperacute hydrocephalus was strongly associated with symptomatic vasospasm, chronic hydrocephalus was not. Only 36% of patients with symptomatic vasospasm had chronic hydrocephalus. This suggests that the factors responsible for the development of hyperacute hydrocephalus may also be responsible for symptomatic vasospasm and that the pathophysiologic mechanisms may be different than those responsible for chronic hydrocephalus. Cerebral vasospasm and resultant delayed ischemic neurologic deficits continue to cause significant morbidity and mortality in the SAH patient population.13 Radiographic cerebral vasospasm may be seen in 75% of the patient population, and clinically significant cerebral vasospasm is reported to occur in 20 to 40% of patients.24 In our series, 26% of patients developed symptomatic cerebral vasospasm. Although the exact mechanism of cerebral vasospasm has been
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Intraventricular Hemorrhage Associated with Early Hydrocephalus
resulting in increased CSF production. We also found that early hydrocephalus was associated with both symptomatic vasospasm and poor clinical outcome in univariate analysis. However, due to its strong correlation with intraventricular hemorrhage, intraventricular hemorrhage remained significantly associated with both symptomatic vasospasm and poor clinical outcome in multivariate analysis while early hydrocephalus lost significance. We suggest that both early hydrocephalus and cerebral vasospasm may be parts of the overall inflammatory cascade that occurs with intraventricular hemorrhage and ultimately results in poorer clinical outcome.
References 1 Kusske JA, Turner PT, Ojemann GA, Harris AB. Ventriculostomy for
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Conclusions We found that intraventricular hemorrhage was strongly associated with early hydrocephalus. Further exploration of the mechanistic explanation is needed, but we suggest this may be from a combination of obstruction of CSF pathways by blood products and inflammation in the choroid plexus
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the treatment of acute hydrocephalus following subarachnoid hemorrhage. J Neurosurg 1973;38(5):591–595 Pertuiset B, Houtteville JP, George B, Margent P. Early ventricular dilatation and hydrocephalus following rupture of supratentorial arterial aneurysms [in French]. Neurochirurgia (Stuttg) 1972; 15(4):113–126 Raimondi AJ, Torres H. Acute hydrocephalus as a complication of subarachnoid hemorrhage. Surg Neurol 1973;1(1):23–26 Vassilouthis J, Richardson AE. Ventricular dilatation and communicating hydrocephalus following spontaneous subarachnoid hemorrhage. J Neurosurg 1979;51(3):341–351 Hasan D, Vermeulen M, Wijdicks EF, Hijdra A, van Gijn J. Management problems in acute hydrocephalus after subarachnoid hemorrhage. Stroke 1989;20(6):747–753 Graff-Radford NR, Torner J, Adams HP Jr, Kassell NF. Factors associated with hydrocephalus after subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. Arch Neurol 1989; 46(7):744–752 Shah AH, Komotar RJ. Pathophysiology of acute hydrocephalus after subarachnoid hemorrhage. World Neurosurg 2013;80(3–4): 304–306 Dóczi T, Szerdahelyi P, Gulya K, Kiss J. Brain water accumulation after the central administration of vasopressin. Neurosurgery 1982;11(3):402–407 Hasan D, Tanghe HL. Distribution of cisternal blood in patients with acute hydrocephalus after subarachnoid hemorrhage. Ann Neurol 1992;31(4):374–378 Kanat A, Turkmenoglu O, Aydin MD, et al. Toward changing of the pathophysiologic basis of acute hydrocephalus after subarachnoid hemorrhage: a preliminary experimental study. World Neurosurg 2013;80(3–4):390–395 Barkovich AJ, Edwards MS. Applications of neuroimaging in hydrocephalus. Pediatr Neurosurg 1992;18(2):65–83 Diringer MN, Edwards DF, Zazulia AR. Hydrocephalus: a previously unrecognized predictor of poor outcome from supratentorial intracerebral hemorrhage. Stroke 1998;29(7):1352–1357 Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke 2012;43(6):1711–1737 Komotar RJ, Hahn DK, Kim GH, et al. The impact of microsurgical fenestration of the lamina terminalis on shunt-dependent hydrocephalus and vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 2008;62(1):123–132; discussion 132–134 Little AS, Zabramski JM, Peterson M, et al. Ventriculoperitoneal shunting after aneurysmal subarachnoid hemorrhage: analysis of Journal of Neurological Surgery—Part A
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elusive, most studies point to a complex inflammatory cascade secondary to the presence of toxins produced during the degradation of blood products within the subarachnoid space.24,25 Oxyhemoglobin, a hemoglobin degradation product, has several downstream inflammatory effects including increased reactive oxygen species formation, decreased nitric oxide, increased prostaglandin synthesis, and increased lipid peroxidation.26–30 Such metabolic products have the potential of causing both hydrocephalus and cerebral vasospasm. In univariate analysis, we did find that early hydrocephalus was associated with increased risk of cerebral vasospasm (65% of patients with vasospasm had early hydrocephalus). However, in multivariate analysis, this statistical significance was lost (p ¼ 0.879). The strong association of intraventricular hemorrhage and early hydrocephalus allowed early hydrocephalus to lose significance while intraventricular hemorrhage remained significant (p ¼ 0.002). The presence of early hydrocephalus in the aSAH patient population should lead to a decline in neurologic status secondary to ventricular enlargement and a rise in intracranial pressure. In univariate analysis, the presence of early hydrocephalus was associated with a poor outcome (71% of patients with a poor outcome had early hydrocephalus). As to be expected, symptomatic cerebral vasospasm was associated with poor outcome because delayed cerebral infarcts are related to symptomatic vasospasm and patients with delayed infarcts have previously been shown to have poorer neurologic outcome at the time of hospital discharge.31 As previously reported, intraparenchymal hemorrhage was associated with poor clinical outcome.32 Of note, intraventricular hemorrhage was associated with poor outcome independent of cerebral vasospasm. This suggests that intraventricular hemorrhage triggers a downstream cascade aside from the cascade leading to cerebral vasospasm that ultimately worsens neurologic injury. Early hydrocephalus was not a significant predictor of clinical outcome when utilized in a multivariate analysis most likely due to its strong association with intraventricular hemorrhage. Several limitations to this study exist. One of the main limitations was its retrospective nature. It is possible that we have an unrecognized biased sample. However, our rates of hydrocephalus and cerebral vasospasm are in line with previous reports suggesting a reasonably representative cohort. Additionally, we have no mechanistic data in this study. While we found an association between intraventricular hemorrhage and early hydrocephalus, cerebral vasospasm, and poor outcome, we did not explore any mechanisms experimentally. Further data and experiments are needed to fully explain these associations.
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Intraventricular Hemorrhage Is Associated with Early Hydrocephalus, Symptomatic Vasospasm, and Poor Outcome in Aneurysmal Subarachnoid Hemorrhage Thomas J. Wilson,1 Neeraj Chaudhary2
William R. Stetler Jr.,1 Matthew C. Davis1 David A. Giles1 Adam Khan2 Joseph J. Gemmete1 Guohua Xi1 B. Gregory Thompson1 Aditya S. Pandey1
1 Department of Neurosurgery, University of Michigan, Ann Arbor,
Michigan, United States 2 Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States
Address for correspondence Thomas J. Wilson, MD, Department of Neurosurgery, University of Michigan, 1500 E. Medical Center Drive, Room 3552, TC, Ann Arbor, Michigan 48109-5338, United States (e-mail: [email protected]).
J Neurol Surg A 2015;76:126–132.
Abstract
Keywords
► ► ► ► ►
aneurysm hydrocephalus endovascular coiling subarachnoid hemorrhage
received October 16, 2013 accepted after revision May 23, 2014 published online December 29, 2014
Objective We hypothesized that the subset of patients with early hydrocephalus following aneurysmal subarachnoid hemorrhage may represent a subset of patients with a more vehement inflammatory reaction to blood products in the subarachnoid space. We thus examined risk factors for early hydrocephalus and examined the relationship between early hydrocephalus and symptomatic vasospasm as well as clinical outcome. Methods We retrospectively analyzed all patients presenting to our institution with subarachnoid hemorrhage over a 7-year period. We examined for risk factors, including early hydrocephalus, for poor clinical outcome and symptomatic vasospasm. Results We found intraventricular hemorrhage to be strongly associated with the development of early hydrocephalus. In univariate analysis, early hydrocephalus was strongly associated with both poor functional outcome and symptomatic vasospasm. In multivariate analysis, intraventricular hemorrhage and tobacco use were associated with symptomatic vasospasm; intraventricular hemorrhage, intraparenchymal hemorrhage, and symptomatic vasospasm were associated with poor functional outcome. Conclusions We found that intraventricular hemorrhage was strongly associated with early hydrocephalus. Further exploration of the mechanistic explanation is needed, but we suggest this may be from a combination of obstruction of cerebrospinal fluid pathways by blood products and inflammation in the choroid plexus resulting in increased cerebrospinal fluid production. Further, we suggest that both early hydrocephalus and cerebral vasospasm may be parts of the overall inflammatory cascade that occurs with intraventricular hemorrhage and ultimately results in a poorer clinical outcome.
© 2015 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1394189. ISSN 2193-6315.
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Intraventricular Hemorrhage Associated with Early Hydrocephalus
Acute hydrocephalus following aneurysmal subarachnoid hemorrhage (aSAH) was not reported in a large series until the 1970s.1–3 Following these reports, some dismissed the clinical significance of hydrocephalus.4 Particularly since the advent of computed tomography (CT), acute hydrocephalus has been increasingly recognized and treated. Prompt treatment of hydrocephalus related to aSAH has become one of the mainstays of treatment because it has been shown to improve outcomes.5 A wide variety of risk factors for the development of hydrocephalus have been suggested including increasing age, hypertension, posterior circulation aneurysm location, and increasing volume of cisternal blood.6 This begs the question: What is the pathophysiologic origin of acute hydrocephalus following aSAH? Hydrocephalus related to subarachnoid hemorrhage (SAH) is thought to occur via two mechanisms: (1) obstruction of normal communication of the cerebrospinal fluid (CSF) pathways by blood products, or (2) decreased reabsorption of CSF due to blood products affecting the arachnoid granulations.7 Most believe that acute hydrocephalus is predominantly due to the former and the latter makes a more significant contribution to chronic hydrocephalus because the adhesions that disrupt the arachnoid granulations take time to form.7–9 However, more recently, people have begun to explore the idea that increased CSF production may contribute to or be the primary mechanism of acute hydrocephalus.10 It may be that the inflammatory reaction to blood products in the ventricles and subarachnoid space varies from patient to patient and that the degree of inflammatory reaction to blood products in the ventricles and subarachnoid space determines the degree to which CSF obstruction versus CSF overproduction contribute to acute hydrocephalus. We hypothesized that the subset of patients with early hydrocephalus, hydrocephalus present at the time of initial presentation, may represent a subset of patients with a more vehement inflammatory reaction. We thus examined risk factors for early hydrocephalus and examined the relationship between early hydrocephalus and symptomatic vasospasm as well as clinical outcome.
Methods Study Design This cohort study was approved by the University of Michigan institutional review board, and data were obtained by retrospective chart review. Information technology personnel designed and implemented a search paradigm to query information systems to identify all patients admitted who underwent microsurgical clip ligation or endovascular coil embolization of a cerebral circulation aneurysm after presenting with SAH between January 1, 2005, and February 1, 2012. This patient list was cross-referenced with the operative reports in the medical record to confirm that aneurysm treatment was performed and that initial presentation had been with a ruptured aneurysm.
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Outcomes of Interest The two primary outcomes of interest were functional outcome as assessed by Glasgow Outcome Scale (GOS) score at 6 months following presentation and the occurrence of symptomatic vasospasm. Poor outcome was defined as a GOS of 1 to 3. Symptomatic vasospasm was defined as a clinical neurologic change thought to be secondary to vasospasm where vasospasm was confirmed by angiography (either CT angiography or conventional digital subtraction angiography) and in the absence of other causes such as rebleeding, hydrocephalus, electrolyte abnormalities, hypoxia, or seizures. Patients regardless of clinical status were monitored for symptomatic vasospasm in an intensive care setting for at least 14 days following hemorrhage by following the clinical examination for signs of deterioration and by following transcranial Doppler ultrasonography (TCD) performed every other day. When vasospasm was suspected by either change in clinical examination or by TCD, it was further evaluated using either a CT angiogram or conventional digital subtraction angiogram. Symptomatic vasospasm when present was treated first medically using fluid boluses and vasopressors to increase the mean arterial pressure. When this was ineffective, endovascular therapy was performed using either mechanical angioplasty or chemical angioplasty with intra-arterial nicardipine.
Variables Variables abstracted from the medical record and through review of radiographic studies included age, sex, obesity (body mass index >30 kg/m2), hypertension, coronary artery disease, tobacco use, aneurysm location, intraventricular hemorrhage on the initial CT scan at the time of presentation, intraparenchymal hemorrhage on the initial CT scan at the time of presentation, early hydrocephalus, chronic hydrocephalus, ventriculostomy placement, and CSF shunt placement. No radiologic parameters are consistently agreed on to diagnose hydrocephalus.11,12 In this study, early hydrocephalus was defined as hydrocephalus present on the initial CT scan at the time of presentation. Each CT scan was independently reviewed by one of the authors and assessed for hydrocephalus. This was then compared with the radiology report. When there was disagreement between the assessment of the radiologist and the author, an additional author reviewed the CT scan. If cortical atrophy versus hydrocephalus was considered, hydrocephalus was defined by enlargement of the temporal horns commensurate with the body of the lateral ventricles.11 Early hydrocephalus was tested for its association with poor functional outcome and symptomatic vasospasm. Each of the other variables was tested for its association with early hydrocephalus. Chronic hydrocephalus was defined as hydrocephalus present at 6 months following ictus that either continues to require medical management or that required placement of a CSF shunt. Ventriculostomy placement occurred based on the clinical status of the patient. When mental status was depressed and hydrocephalus was present, a ventriculostomy was placed. We do not use a clinical grade cut-off to determine ventriculostomy placement at our institution but rather evaluate each Journal of Neurological Surgery—Part A
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Introduction
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Intraventricular Hemorrhage Associated with Early Hydrocephalus case individually utilizing both the clinical examination and radiographic findings. Ventriculostomy placement occurred at the time that the examination was depressed and hydrocephalus was present, whether that was immediately upon admission or in a delayed fashion. Hydrocephalus requiring CSF diversion was always managed with ventriculostomy placement. Lumbar drains are not used to manage hydrocephalus in the setting of aSAH at our institution.
Statistical Analysis Statistical analysis was performed using commercially available software (SPSS v.18, IBM Corp., Somers, New York, United States). Univariate comparison of continuous variables with a normal distribution was assessed using two-sample t tests, and continuous variables not meeting the normality assumption were assessed using the Mann-Whitney U test. All categorical data were assessed by chi-square test or Fisher exact test, as appropriate. Logistic regression was used to test univariate and multivariate associations between our variables of interest and the dichotomous variable of early hydrocephalus. We planned a priori to include all variables with p < 0.20 in univariate analysis in our multivariate analyses. For all statistics, a p value < 0.05 was considered statistically significant.
Results During the study period, 321 patients presented to our institution with aSAH. Of these, 150 patients underwent coil embolization for treatment of their intracranial aneurysm; 171 patients had microsurgical clip ligation performed. Patients were predominantly female (69%) and predominantly had anterior circulation/posterior communicating artery aneurysms (83%). The average age of all patients was 54 years of age. Overall, 74% of patients had a good outcome, defined as GOS 4 to 5 at 6 months following presentation. Early hydrocephalus was present in 179 patients (56%). An additional 32
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patients (10%) developed subacute hydrocephalus requiring external ventricular drainage. Symptomatic vasospasm occurred in 84 patients (26%). Hunt and Hess grades for patients presenting with aSAH were 9 patients (3%) grade 1, 146 patients (45%) grade 2, 84 patients (26%) grade 3, 53 patients (17%) grade 4, and 29 patients (9%) grade 5. We first examined risk factors for early hydrocephalus (►Table 1). Factors in univariate analysis that were found to be associated with early hydrocephalus included posterior circulation aneurysm location, older age, and intraventricular hemorrhage. In multivariate analysis, both posterior circulation aneurysm location and intraventricular hemorrhage remained independently associated with early hydrocephalus. Intraventricular hemorrhage seemed to be the strongest associated variable with early hydrocephalus, with an odds ratio of 8.62 (95% confidence interval [CI], 5.10–14.49) for having early hydrocephalus when intraventricular hemorrhage is present versus 2.52 when a posterior circulation aneurysm was present (95% CI, 1.19–5.35). Next, we examined the data to see if an association exists between early hydrocephalus and symptomatic vasospasm (►Table 2). Both early hydrocephalus and intraventricular hemorrhage were found to be significantly associated with symptomatic vasospasm in univariate analysis. Given that intraventricular hemorrhage was strongly predictive of and associated with early hydrocephalus, only intraventricular hemorrhage remained independently associated with symptomatic vasospasm in multivariate analysis. In addition to intraventricular hemorrhage, tobacco use was significant in the multivariate model. The odds ratio of having symptomatic vasospasm if intraventricular hemorrhage was present was 2.84 (95% CI, 1.53–5.26). We then explored the relationship between early hydrocephalus and overall functional outcome (►Table 3). Factors found to be significantly associated with poor outcome in univariate analysis included older age, symptomatic vasospasm, presence of coronary artery disease, early
Table 1 Univariate and multivariate tests of association with early hydrocephalus Hydrocephalus (n ¼ 179)
No hydrocephalus (n ¼ 142)
Univariate p value
Obesity (n,%)
44 (25)
36 (25)
0.873
Hypertension (n,%)
92 (51)
67 (47)
0.453
CAD (n,%)
19 (11)
7 (5)
0.063
0.068
0.002
0.016
Aneurysm location (n,%) Anterior circulation
137 (77)
128 (90)
Posterior circulation
42 (23)
14 (10)
Sex (n,%)
Multivariate p value
0.248
Male
51 (28)
Female
49 (35)
128 (72)
93 (65)
Age (SD)
55.7 (13.4)
52.0 (14.4)
0.028
0.543
IVH (n,%)
135 (75)
35 (25)
< 0.001
< 0.001
IPH (n,%)
32 (18)
16 (11)
0.102
0.215
Abbreviations: CAD, coronary artery disease; IPH, intraparenchymal hemorrhage; IVH, intraventricular hemorrhage; SD, standard deviation. Journal of Neurological Surgery—Part A
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Table 2 Univariate and multivariate tests of association with symptomatic vasospasm Vasospasm (n ¼ 84)
No vasospasm (n ¼ 237)
Multivariate p value
0.228
Coil
44 (52)
106 (45)
Clip
40 (48)
131 (55)
Obesity (n,%)
22 (26)
58 (24)
0.755
Hypertension (n,%)
46 (55)
113 (48)
0.265
CAD (n,%)
5 (6)
21 (9)
0.404
Tobacco use (n,%)
56 (67)
130 (55)
0.061
0.042
Early hydrocephalus (n,%)
55 (65)
124 (52)
0.038
0.879
Anterior circulation
71 (85)
194 (82)
Posterior circulation
13 (15)
43 (18)
Male
20 (24)
80 (34)
Female
64 (76)
157 (66)
55.0 (15.0)
53.0 (12.2)
0.353
IVH (n,%)
60 (71)
110 (46)
< 0.001
IPH (n,%)
14 (17)
34 (14)
0.609
Aneurysm location (n,%)
0.580
Sex (n,%)
Age (SD)
0.093
0.184
0.002
Abbreviations: CAD, coronary artery disease; IPH, intraparenchymal hemorrhage; IVH, intraventricular hemorrhage; SD, standard deviation.
hydrocephalus, presence of intraventricular hemorrhage, and presence of intraparenchymal hemorrhage. Only symptomatic vasospasm, the presence of intraventricular hemorrhage, and the presence of intraparenchymal hemorrhage remained significant in multivariate analysis. All three variables were fairly similarly associated with the risk of a poor outcome. The odds ratios were symptomatic vasospasm 2.07 (95% CI, 1.13–3.77), intraparenchymal hemorrhage 2.36 (95% CI, 1.18–4.73), and intraventricular hemorrhage 2.17 (95% CI, 1.13–4.17). Finally, we examined the relationship between acute and chronic hydrocephalus as well as chronic hydrocephalus with symptomatic vasospasm. Overall, 66 of the 321 patients (21%) developed chronic hydrocephalus requiring either CSF shunting or continued medical management at 6 months following ictus. Of the 66 patients developing chronic hydrocephalus, 50 (76%) of them had acute hydrocephalus. Acute hydrocephalus was strongly associated with the development of subsequent chronic hydrocephalus (p < 0.001). All 66 patients with chronic hydrocephalus were managed with placement of a CSF shunt. A total of 84 patients developed symptomatic vasospasm. Of these patients, 30 (36%) of them had chronic hydrocephalus.
Discussion Acute hydrocephalus following aSAH is a major source of morbidity and mortality. Our reported rate of hydrocephalus was similar to previous reports that have shown that as many
as 87% of patients with SAH can present with hydrocephalus.13–20 Prompt CSF drainage has been recognized for many years to improve outcomes for patients and has become one of the hallmarks of management of aSAH.5,13 Most agree that acute hydrocephalus is caused at least in part by direct obstruction of CSF pathways by blood products; chronic hydrocephalus may be caused by decreased CSF reabsorption secondary to adhesions in the arachnoid granulations.7–9 Increased CSF production may also contribute to acute hydrocephalus in the aSAH patient population. We hypothesized that aSAH patients presenting with hyperacute hydrocephalus, hydrocephalus at the time of presentation, may represent a clinically distinct subset with increased risk for cerebral vasospasm and poor clinical outcome. We examined our aSAH patient population to evaluate risk factors in the development of early hydrocephalus as well as the relationship between early hydrocephalus and the development of cerebral vasospasm and poor clinical outcome. To our knowledge, this is the first report to examine patients with early (hyperacute) hydrocephalus as a distinct subset. We found that intraventricular hemorrhage was associated with early hydrocephalus and remained significant in multivariate analysis. Although we have no pathophysiologic examination in this study, one would hypothesize that the presence of hydrocephalus would be secondary to a combination of processes: presence of blood within the ventricular space leading to increased CSF production, presence of blood within the ventricular outflow leading to obstruction of flow, and long-term inflammation-based injury to the arachnoid Journal of Neurological Surgery—Part A
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Treatment (n,%)
Univariate p value
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Table 3 Univariate and multivariate tests of association with poor outcome Good outcome (n ¼ 239)
Poor outcome (n ¼ 82)
Treatment (n,%)
Univariate p value
Multivariate p value
0.395
Coil
124 (52)
47 (57)
Clip
115 (48)
35 (43)
Obesity (n,%)
54 (23)
26 (32)
0.101
0.170
Hypertension (n,%)
112 (47)
47 (57)
0.103
0.223
CAD (n,%)
14 (6)
12 (15)
0.015
0.069
Tobacco use (n,%)
144 (60)
42 (51)
0.154
0.251
Early hydrocephalus (n,%)
121 (51)
58 (71)
0.002
0.239
0.150
0.179
Anterior circulation
193 (81)
72 (88)
Posterior circulation
46 (19)
10 (12)
Male
70 (29)
30 (37)
Female
169 (71)
52 (63)
53.0 (12.7)
57.0 (17.0)
0.016
0.390
Aneurysm location (n,%)
Sex (n,%)
0.219
Age (y,SD) IVH (n,%)
111 (46)
59 (72)
< 0.001
0.021
IPH (n,%)
27 (11)
21 (26)
0.002
0.016
Symptomatic vasospasm (n,%)
52 (22%)
32 (39)
0.002
0.018
Abbreviations: CAD, coronary artery disease; IPH, intraparenchymal hemorrhage; IVH, intraventricular hemorrhage; SD, standard deviation.
villi leading to a lack of reabsorption CSF fluid. This correlates with a previously published rat model of hydrocephalus, where nearly half of rats with induced SAH developed hydrocephalus. In this model, the development of hydrocephalus was significantly associated with the presence of intraventricular hemorrhage and the extent of ventricular wall damage.21 In addition, in a rabbit model it has been shown that SAH induces increased water vesicles and CSF production in the choroid plexus.10 This was an early rather than a late phenomenon because the choroid plexus degraded over time. Thus in this model CSF production was increased acutely but actually was decreased over time.10 In addition, in an infectious model, infectious ventriculitis resulted in decreased CSF production acutely and ultimately necrosis of the choroid plexus.22 Thus conflicting evidence exists regarding CSF production in the acute stages following inflammation. A wide variety of cytokines including tumor growth factor (TGF)-β1 and TGF-β2 have been postulated to be involved in the posthemorrhagic inflammatory process, but to date none have been clearly shown to play a role or to be predictive of hydrocephalus.23 The posthemorrhagic inflammatory process remains poorly understood, and it is unclear at this point whether increased CSF production contributes to hyperacute hydrocephalus but remains one possible source. Posterior circulation aneurysm location was also a risk factor for early hydrocephalus, likely due to obstruction of the foramina of Luschka and foramen of Magendie by local blood products. Journal of Neurological Surgery—Part A
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We found that in addition to those patients having hyperacute hydrocephalus, an additional 10% of patients developed subacute hydrocephalus during their hospitalization requiring external ventricular drainage. We hypothesize that the mechanisms of hyperacute, subacute, and chronic hydrocephalus may be different, but additional pathophysiologic investigation is needed to test this hypothesis. Overall, 21% of patients had chronic hydrocephalus that had required placement of a CSF shunt. Hyperacute hydrocephalus was a significant risk factor for the eventual development of chronic hydrocephalus; 76% of the patients with chronic hydrocephalus had hyperacute hydrocephalus. Whereas hyperacute hydrocephalus was strongly associated with symptomatic vasospasm, chronic hydrocephalus was not. Only 36% of patients with symptomatic vasospasm had chronic hydrocephalus. This suggests that the factors responsible for the development of hyperacute hydrocephalus may also be responsible for symptomatic vasospasm and that the pathophysiologic mechanisms may be different than those responsible for chronic hydrocephalus. Cerebral vasospasm and resultant delayed ischemic neurologic deficits continue to cause significant morbidity and mortality in the SAH patient population.13 Radiographic cerebral vasospasm may be seen in 75% of the patient population, and clinically significant cerebral vasospasm is reported to occur in 20 to 40% of patients.24 In our series, 26% of patients developed symptomatic cerebral vasospasm. Although the exact mechanism of cerebral vasospasm has been
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Intraventricular Hemorrhage Associated with Early Hydrocephalus
resulting in increased CSF production. We also found that early hydrocephalus was associated with both symptomatic vasospasm and poor clinical outcome in univariate analysis. However, due to its strong correlation with intraventricular hemorrhage, intraventricular hemorrhage remained significantly associated with both symptomatic vasospasm and poor clinical outcome in multivariate analysis while early hydrocephalus lost significance. We suggest that both early hydrocephalus and cerebral vasospasm may be parts of the overall inflammatory cascade that occurs with intraventricular hemorrhage and ultimately results in poorer clinical outcome.
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Conclusions We found that intraventricular hemorrhage was strongly associated with early hydrocephalus. Further exploration of the mechanistic explanation is needed, but we suggest this may be from a combination of obstruction of CSF pathways by blood products and inflammation in the choroid plexus
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the treatment of acute hydrocephalus following subarachnoid hemorrhage. J Neurosurg 1973;38(5):591–595 Pertuiset B, Houtteville JP, George B, Margent P. Early ventricular dilatation and hydrocephalus following rupture of supratentorial arterial aneurysms [in French]. Neurochirurgia (Stuttg) 1972; 15(4):113–126 Raimondi AJ, Torres H. Acute hydrocephalus as a complication of subarachnoid hemorrhage. Surg Neurol 1973;1(1):23–26 Vassilouthis J, Richardson AE. Ventricular dilatation and communicating hydrocephalus following spontaneous subarachnoid hemorrhage. J Neurosurg 1979;51(3):341–351 Hasan D, Vermeulen M, Wijdicks EF, Hijdra A, van Gijn J. Management problems in acute hydrocephalus after subarachnoid hemorrhage. Stroke 1989;20(6):747–753 Graff-Radford NR, Torner J, Adams HP Jr, Kassell NF. Factors associated with hydrocephalus after subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. Arch Neurol 1989; 46(7):744–752 Shah AH, Komotar RJ. Pathophysiology of acute hydrocephalus after subarachnoid hemorrhage. World Neurosurg 2013;80(3–4): 304–306 Dóczi T, Szerdahelyi P, Gulya K, Kiss J. Brain water accumulation after the central administration of vasopressin. Neurosurgery 1982;11(3):402–407 Hasan D, Tanghe HL. Distribution of cisternal blood in patients with acute hydrocephalus after subarachnoid hemorrhage. Ann Neurol 1992;31(4):374–378 Kanat A, Turkmenoglu O, Aydin MD, et al. Toward changing of the pathophysiologic basis of acute hydrocephalus after subarachnoid hemorrhage: a preliminary experimental study. World Neurosurg 2013;80(3–4):390–395 Barkovich AJ, Edwards MS. Applications of neuroimaging in hydrocephalus. Pediatr Neurosurg 1992;18(2):65–83 Diringer MN, Edwards DF, Zazulia AR. Hydrocephalus: a previously unrecognized predictor of poor outcome from supratentorial intracerebral hemorrhage. Stroke 1998;29(7):1352–1357 Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke 2012;43(6):1711–1737 Komotar RJ, Hahn DK, Kim GH, et al. The impact of microsurgical fenestration of the lamina terminalis on shunt-dependent hydrocephalus and vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 2008;62(1):123–132; discussion 132–134 Little AS, Zabramski JM, Peterson M, et al. Ventriculoperitoneal shunting after aneurysmal subarachnoid hemorrhage: analysis of Journal of Neurological Surgery—Part A
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elusive, most studies point to a complex inflammatory cascade secondary to the presence of toxins produced during the degradation of blood products within the subarachnoid space.24,25 Oxyhemoglobin, a hemoglobin degradation product, has several downstream inflammatory effects including increased reactive oxygen species formation, decreased nitric oxide, increased prostaglandin synthesis, and increased lipid peroxidation.26–30 Such metabolic products have the potential of causing both hydrocephalus and cerebral vasospasm. In univariate analysis, we did find that early hydrocephalus was associated with increased risk of cerebral vasospasm (65% of patients with vasospasm had early hydrocephalus). However, in multivariate analysis, this statistical significance was lost (p ¼ 0.879). The strong association of intraventricular hemorrhage and early hydrocephalus allowed early hydrocephalus to lose significance while intraventricular hemorrhage remained significant (p ¼ 0.002). The presence of early hydrocephalus in the aSAH patient population should lead to a decline in neurologic status secondary to ventricular enlargement and a rise in intracranial pressure. In univariate analysis, the presence of early hydrocephalus was associated with a poor outcome (71% of patients with a poor outcome had early hydrocephalus). As to be expected, symptomatic cerebral vasospasm was associated with poor outcome because delayed cerebral infarcts are related to symptomatic vasospasm and patients with delayed infarcts have previously been shown to have poorer neurologic outcome at the time of hospital discharge.31 As previously reported, intraparenchymal hemorrhage was associated with poor clinical outcome.32 Of note, intraventricular hemorrhage was associated with poor outcome independent of cerebral vasospasm. This suggests that intraventricular hemorrhage triggers a downstream cascade aside from the cascade leading to cerebral vasospasm that ultimately worsens neurologic injury. Early hydrocephalus was not a significant predictor of clinical outcome when utilized in a multivariate analysis most likely due to its strong association with intraventricular hemorrhage. Several limitations to this study exist. One of the main limitations was its retrospective nature. It is possible that we have an unrecognized biased sample. However, our rates of hydrocephalus and cerebral vasospasm are in line with previous reports suggesting a reasonably representative cohort. Additionally, we have no mechanistic data in this study. While we found an association between intraventricular hemorrhage and early hydrocephalus, cerebral vasospasm, and poor outcome, we did not explore any mechanisms experimentally. Further data and experiments are needed to fully explain these associations.
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