Cerebrospinal fluid volume as an early radiological factor for clinical course prediction after aneurysmal subarachnoid hemorrhage. A pilot study.

BACKGROUND: The pathological mechanisms following aneurysmal subarachnoid hemorrhage (SAH) are poorly understood. Limited clinical evidence exists on the association between cerebrospinal fluid (CSF) volume and the risk of delayed cerebral ischemia (DCI) or cerebral vasospasm (CV). In this study, we raised the hypothesis that the amount of CSF or its ratio to hemorrhage blood volume, as determined from non-contrast Computed Tomography (NCCT) images taken on admission, could be a significant predictor for CV and DCI. METHODS: The pilot study included a retrospective analysis of NCCT scans of 49 SAH patients taken shortly after an aneurysm rupture (33 males, 16 females, mean age 56.4 ± 15 years). The SynthStrip and Slicer3D software tools were used to extract radiological factors - CSF, brain, and hemorrhage volumes from the NCCT images. The "pure" CSF volume (VCSF) was estimated in the range of [-15, 15] Hounsfield units (HU). RESULTS: VCSF was negatively associated with the risk of CV occurrence (p = 0.0049) and DCI (p = 0.0069), but was not associated with patients' outcomes. The hemorrhage volume (VSAH) was positively associated with an unfavorable outcome (p = 0.0032) but was not associated with CV/DCI. The ratio VSAH/VCSF was positively associated with, both, DCI (p = 0.031) and unfavorable outcome (p = 0.002). The CSF volume normalized by the brain volume showed the highest characteristics for DCI prediction (AUC = 0.791, sensitivity = 0.80, specificity = 0.812) and CV prediction (AUC = 0.769, sensitivity = 0.812, specificity = 0.70). CONCLUSION: It was demonstrated that "pure" CSF volume retrieved from the initial NCCT images of SAH patients (including CV, Non-CV, DCI, Non-DCI groups) is a more significant predictor of DCI and CV compared to other routinely used radiological biomarkers. VCSF could be used to predict clinical course as well as to personalize the management of SAH patients. Larger multicenter clinical trials should be performed to test the added value of the proposed methodology.

Prospective Trial of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage via Lumbar Catheter (PILLAR).

Background and Purpose- The PILLAR (Extracorporeal Filtration of Subarachnoid Hemorrhage via Spinal Catheter) study is a first-in-human trial of cerebrospinal fluid (CSF) filtration in aneurysmal subarachnoid hemorrhage. The study evaluates the safety and feasibility of a novel filtration system to rapidly remove blood and blood breakdown products from CSF after securement of a ruptured aneurysm. Methods- Patients with aneurysmal subarachnoid hemorrhage had a dual-lumen lumbar, intrathecal catheter placed after aneurysm securement and received up to 24 hours of CSF filtration (neurapheresis therapy). The catheter aspirated blood-contaminated CSF from the lumbar cistern and returned filtered CSF to the thoracic subarachnoid space. Neuro checks were performed q2 hours, and CSF samples were collected for cell counts, total protein, and gram stain. Computed tomography scans were acquired at baseline and post-filtration. Clinical follow-up occurred at 2 weeks and 30 days. Results- Thirteen patients had a catheter placed (mean time 24:13 hours after ictus). The system processed 632.0 mL (180.6-1447.6 mL) CSF in 15:07 hours (5:32-24:00 hours) of filtration. The mean initial CSF red blood cell count, 2.78×105 cells/µL, reduced to 1.17×105 cells/µL after filtration (52.9% reduction), and total protein reduced 71%. Independent analysis of baseline and postfiltration computed tomographies found notable cisternal blood decrease, with 46.5% mean Hijdra Score reduction. Three mild, anticipated adverse events were reported. Conclusions- The initial safety and feasibility of Neurapheresis therapy in aneurysmal subarachnoid hemorrhage demonstrated the potential to safely filter CSF and remove blood and blood byproducts. Future studies are warranted. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT0287263.

Cell-Free Oxyhemoglobin in Cerebrospinal Fluid After Aneurysmal Subarachnoid Hemorrhage: Biomarker and Potential Therapeutic Target.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by the occurrence of delayed ischemic neurologic deficits (DIND), which impairs the clinical outcome of patients. The release of oxyhemoglobin (oxyHb) from lysing erythrocytes into cerebrospinal fluid (CSF) may critically contribute to the development of DIND. METHODS: Ventricular CSF of 18 high-grade (Fisher 3 and 4) aSAH patients was sampled daily from external ventricular drains between days 0 and 14 after bleeding. CSF was spectrophotometrically analyzed with precise quantification of cell-free oxyHb levels. RESULTS: OxyHb levels in CSF showed a delayed peak reaching the highest levels in the high-risk period for developing of DIND between days 3 and 14 after aneurysm rupture. Patients with DIND had a significantly higher cumulative oxyHb exposure within the first week after bleeding. CONCLUSIONS: OxyHb levels in CSF may be useful as a biomarker to predict DIND in aSAH patients. The contribution of oxyHb in CSF to the pathogenesis of DIND should be further investigated as a potential therapeutic target.

[Diagnostic challenges of aneurysmal subarachnoid hemorrhage]. / Aneurysmaattinen lukinkalvonalainen verenvuoto--diagnoosi kiven alla ja kivi hukassa?

Diagostic approach to aneurysmal subarachnoid hemorrhage (aSAH) is based on computer tomography (CT) imaging, although a lumbar puncture and subsequent cerebrospinal fluid analysis is sometimes necessary. Identification of the ruptured aneurysm is done using angiography. Despite of modern imaging techniques, diagnostic definition of aSAH is still occasionally challenging. We describe three cases in which the diagnosis of aSAH has been delayed, in spite of positive imaging or lumbar puncture findings.

Association of Hemodynamic Factors With Intracranial Aneurysm Formation and Rupture: Systematic Review and Meta-analysis.

BACKGROUND: Recent evidence suggests a link between the magnitude and distribution of hemodynamic factors and the formation and rupture of intracranial aneurysms. However, there are many conflicting results. OBJECTIVE: To quantify the effect of hemodynamic factors on aneurysm formation and their association with ruptured aneurysms. METHODS: We performed a systematic review and meta-analysis through October 2014. Analysis of the effects of hemodynamic factors on aneurysm formation was performed by pooling the results of studies that compared geometrical models of intracranial aneurysms and "preaneurysm" models where the aneurysm was artificially removed. Furthermore, we calculated pooled standardized mean differences between ruptured and unruptured aneurysms to quantify the association of hemodynamic factors with ruptured aneurysms. Standard PRISMA guidelines were followed. RESULTS: The hemodynamic factors that showed high positive correlations with location of aneurysm formation were high wall shear stress (WSS) and high gradient oscillatory number, with pooled proportions of 78.8% and 85.7%, respectively. Positive correlations were largely seen in bifurcation aneurysms, whereas negative correlations were seen in sidewall aneurysms. Mean and normalized WSS were significantly lower and low shear area significantly higher in ruptured aneurysms. CONCLUSION: Pooled analyses of computational fluid dynamics models suggest that an increase in WSS and gradient oscillatory number may contribute to aneurysm formation, whereas low WSS is associated with ruptured aneurysms. The location of the aneurysm at the bifurcation or sidewall may influence the correlation of these hemodynamic factors.

Search for Biomarkers of Intracranial Aneurysms: A Systematic Review.

INTRODUCTION: Intracranial aneurysms (IAs) remain a devastating clinical challenge, and the pathogenesis of IA formation and progression continues to be unclear. Biomarker analysis can help us understand IA development. The authors performed a systematic review of current literature on genetic and serum biomarkers for IAs in an attempt to identify diagnostic/prognostic factors for ruptured and unruptured aneurysms. METHODS: All relevant studies on PubMed that reported blood/cerebrospinal fluid (CSF) biomarkers and genes that regulate biomarker levels for IAs were assessed for whether the biomarkers/genes studied correlated with IA formation and rupture. RESULTS: Thirty-three studies were reviewed. IAs are associated with an increase in levels of immunologic markers, particularly complement C3 and C9, immunoglobulins IgG and IgM, M1/M2 macrophages, monocytes, and B and T lymphocytes; increase in blood and CSF levels of adhesion molecules; selectins found on vascular endothelium, platelets, and leukocytes; doubled ratios of elastase-to-alpha-1-antitrypsin as controls; elevated levels of neurofilament heavy chain SM135 and S-100 post rupture; and locus 19q13 with many candidate genes. CONCLUSION: Though the pathophysiology of the disease remains unclear, the current literature supports the role of inflammatory and cell adhesion molecules, enzymes and hormones that effect cerebral vasculature, and other cerebral proteins related to brain and vascular damage in both the formation and progression to rupture of IAs. Future investigations are needed to validate results from previous studies and identify new diagnostic/prognostic biomarkers of IAs.

Lipocalin-type prostaglandin D synthase scavenges biliverdin in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage.

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is the second major protein in human cerebrospinal fluid (CSF) and belongs to the lipocalin superfamily composed of various secretory lipophilic ligand transporter proteins. However, the endogenous ligand of L-PGDS has not yet been elucidated. In this study, we purified L-PGDS from the CSF of aneurysmal subarachnoid hemorrhage (SAH) patients. Lipocalin-type PG D synthase showed absorbance spectra with major peaks at 280 and 392 nm and a minor peak at around 660 nm. The absorbance at 392 nm of L-PGDS increased from 1 to 9 days and almost disappeared at 2 months after SAH, whereas the L-PGDS activity decreased from 1 to 7 days and recovered to normal at 2 months after SAH. These results indicate that some chromophore had accumulated in the CSF after SAH and bound to L-PGDS, thus inactivating it. Matrix assisted laser desorption ionization time-of-flight mass spectrometry of L-PGDS after digestion of it with endoproteinase Lys-C revealed that L-PGDS had covalently bound biliverdin, a by-product of heme breakdown. These results suggest that L-PGDS acted as a scavenger of biliverdin, which is a molecule not found in normal CSF. This is the first report of identification of a pathophysiologically important endogenous ligand for this lipocalin superfamily protein in humans.

Lack of functional patency of the lamina terminalis after fenestration following clipping of anterior circulation aneurysms.

OBJECT: Fenestration of the lamina terminalis (FLT) during aneurysm surgery for subarachnoid hemorrhage can, in theory, improve CSF circulation from the lateral and third ventricles to the cortical subarachnoid space, which may, in turn, decrease the incidence of hydrocephalus and vasospasm. However, the actual effects of FLT on CSF circulation have been difficult to determine, due to confounding factors. In addition, it is unclear whether the lamina terminalis remains functionally patent when the brain resumes its normal position. The goal of this study was to assess the functional patency of the fenestrated lamina terminalis in patients who underwent surgery for ruptured aneurysms. METHODS: This prospective study included 15 patients who underwent surgical clipping of ruptured anterior circulation aneurysms, with FLT performed during surgery. On postoperative Day 1, the external ventricular drain of each patient was closed, and 1 ml of Omnipaque 300, an iodine based contrast agent, was injected intraventricularly, accompanied by cranial maneuvering designed to position the contrast agent adjacent to the lamina terminalis. Three to 5 minutes after cranial maneuvering, the flow of contrast agent into the basal cisterns was assessed with CT imaging. Flow was verified by an increase in Hounsfield units in a prespecified "region of interest" within the basal cisterns on the CT scan. This procedure was performed using a standardized protocol designed in consultation with the Department of Radiology and approved by the institutional review board. One patient who underwent endoscopic third ventriculostomy was recruited as a positive control to validate the technique, and 1 patient who underwent aneurysm clipping but not FLT was recruited as a negative control. RESULTS: Seventeen patients consented to study participation. In the 15 patients who underwent aneurysm clipping and FLT, and the negative control patient who underwent aneurysm clipping but not FLT, the contrast agent followed the normal ventricular pathway from the lateral ventricles into the fourth ventricle, and did not appear in the basal cisterns. In the positive control patient, the contrast agent robustly and immediately filled the basal cisterns. CONCLUSIONS: Fenestration of the lamina terminalis did not result in functional patency of the lamina terminalis when performed as part of surgical clipping for ruptured aneurysms.

Hypophysitis secondary to ruptured Rathke's cyst mimicking neurosarcoidosis.

Hypophysitis secondary to a ruptured Rathke's cyst is rare. We describe a 53-year-old female who presented with headache and subsequently developed aseptic meningitis and panhypopituitarism. MRI findings and concomitant cardiac arrhythmia and peripheral vasculitis led to a provisional diagnosis of neurosarcoidosis. There were no respiratory manifestations of sarcoidosis. Improvement was noted with empirical treatment with steroids. Pituitary biopsy was undertaken to confirm the diagnosis prior to treatment with long-term immunosuppression for putative neurosarcoidosis. The biopsy revealed lymphocytic hypophysitis secondary to a ruptured Rathke's cyst. This report highlights a rare pathology and the importance of a tissue diagnosis before undertaking non-surgical management of a pituitary mass.

Detection of phosphorylated NF-H in the cerebrospinal fluid and blood of aneurysmal subarachnoid hemorrhage patients.

Blood and cerebrospinal fluid (CSF) of 30 Fisher grade 3 aneurysmal subarachnoid hemorrhage (ASAH) patients were analyzed for the presence of the phosphorylated axonal form of the major neurofilament subunit NF-H (pNF-H), a promising biomarker of axonal injury. Patient demographic data including development of vasospasm and outcome scores at 6 months after aneurysmal rupture (AR) were evaluated. Higher pNF-H blood levels in the first few days after AR were strongly predictive of a negative outcome. Blood pNF-H levels in most recovering patients showed a steady increase into the second week after AR, presumably reflecting axonal degeneration secondary to the original insult. Almost half of the patients studied showed sudden dramatic peaks of pNF-H protein release into CSF in the 3- to 14-day time period after AR, which must reflect profound, coordinated, and secondary loss of axons. Patients in whom vasospasm was detected had significantly more pNF-H in both blood and CSF compared with those in whom vasospasm was not detected. We conclude that the analysis of pNF-H levels in blood and CSF differentiates between patients with poor and favorable outcomes and also reveals several novel features of ASAH progression and recovery.

ICAM-1 and VCAM-1 expression following aneurysmal subarachnoid hemorrhage and their possible role in the pathophysiology of subsequent ischemic deficits.

BACKGROUND: The pathophysiology of ischemic cerebral lesions following aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. There is growing evidence that inflammatory reactions could be involved in the pathogenesis of such delayed occurring ischemic lesions. The aim of this study was to evaluate adhesion molecules with regard to these lesions following SAH. METHODS: Serum and cerebrospinal fluid (CSF) samples were taken daily from 15 patients up to day 9 after SAH and evaluated for intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). RESULTS: CSF and serum samples correlated well during nearly the whole time course (p < 0.0001). A secondary increase in ICAM-1 and VCAM-1 in the serum and CSF correlated with an increase in flow velocity in the transcranial Doppler (p > 0.0001 and p < 0.007) but not to a delayed lesion in the CT scan. CONCLUSION: We believe that inflammatory processes are involved in the pathogenesis of cerebral vasospasm but they might only be a part of a multifactorial pathogenesis.

Blood brain-barrier disruption of nonionic iodinated contrast medium following coil embolization of a ruptured intracerebral aneurysm.

Few reports of temporary disruption of the blood-brain barrier (BBB) following neurointerventional procedures, presumably caused by nonionic radiographic contrast medium (CM), exist in the literature. We described such a case in a 72-year-old man presenting with acute subarachnoid hemorrhage, who underwent coil embolization of a ruptured anterior communicating artery complex aneurysm. At the time of his follow-up CT examination, a large amount of iodine was found in the cerebrospinal fluid (CSF). Because of this experience, the iodine concentration in the CSF of five other patients who also underwent an intracranial endovascular procedure was measured. It was concluded that this increased iodine might have been caused by temporary leakage or breakdown of the BBB. Even if the total amount of CM may not be excessive, the disproportionately high concentration injected into a single vascular territory may pose a unique set of variables increasing the risk of BBB disruption.

Remodelling of cerebrospinal fluid lipoproteins after subarachnoid hemorrhage.

Lipoprotein particles (Lps) in normal human cerebrospinal fluid (CSF) are distinct from those found in plasma and include unique apolipoprotein E (apoE indicates protein; APOE, gene) containing lipoproteins rarely seen in human plasma. Less favourable neurological recovery after subarachnoid hemorrhage (SAH) has been observed in patients who possess the APOE epsilon4 allele raising the possibility that apoE influences neuronal survival after brain injury. We analysed Lps from control and SAH CSF testing the hypotheses that following brain injury CSF Lps undergo remodelling and apoE containing Lps are selectively depleted from brain injury CSF. Lipoproteins were fractionated using CSF from six control pools and six patients with SAH on a sepharose 6HR 10/30 size exclusion column. Fractions were assayed for total cholesterol (TC), free cholesterol (FC), phospholipid, triglyceride (TG), apoE, apolipoprotein B (apoB), and apolipoprotein AI (apoAI). Compared to control CSF there were significant (P<0.05) increases in TC, FC, TG, and apoAI in SAH CSF. Plasma sized apoB-containing lipoproteins and a very small apoAI-containing Lps were identified in the SAH CSF, which were not present in controls. However, despite the release of plasma lipoproteins into the subarachnoid space, there was no significant increase in CSF apoE. These data provide novel indirect evidence suggesting that after SAH CSF Lps undergo remodelling and apoE containing Lps are selectively reduced in brain injury CSF. The remodelling of CSF Lps and selective reduction of apoE containing lipoproteins may reflect an important response of the human brain to injury.

C-type natriuretic peptide concentrations in the plasma and cerebrospinal fluid of patients with subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm is a poor resulting outcome of a ruptured cerebral aneurysm; to clarify the mechanism of vasospasm it is important to improve this outcome. C-type natriuretic peptide (CNP) is present in the brain as a cerebral vasodilator; it is also an endothelium-derived relaxing factor produced via cGMP. We speculated that CNP might be an inhibitor of cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: To clarify the role of CNP in cerebral vasospasm after SAH, we conducted 1 week monitoring of CNP concentrations in the plasma and cerebrospinal fluid (CSF) of 26 patients who had undergone clipping within 24 hours of the occurrence of SAH, and divided them into group A (positive for angiographic spasm) and group B (negative for angiographic spasm). We also examined CNP concentrations in the CSF of patients who were receiving spinal anesthesia for small orthopedic operations, as reference patients. RESULTS: The CNP concentration in the CSF on day 1 was higher than in the reference patients and decreased in both test groups, but we did not observe any significant difference between the groups. CNP concentrations in the plasma did not change in either group. CONCLUSIONS: CNP concentrations in the CSF were high in the acute phase after SAH, whereas plasma CNP concentrations remained constant. However, our findings did not support our hypothesis because we did not find any relationship between vasospasm and changes in CNP concentrations in the CSF.

Bloody cerebrospinal fluid from patients with subarachnoid hemorrhage alters intracellular calcium regulation in cultured human vascular endothelial cells.

Endothelial cell dysfunction may contribute to cerebral vasospasm and aggravation of ischemic brain damage following subarachnoid hemorrhage (SAH). It has been suggested that oxyhemoglobin derived from subarachnoid blood clots might be a prime candidate for cerebral vasospasm. In this study, cisternal bloody cerebrospinal fluid (bCSF) was collected from SAH patients four and seven days after aneurysmal rupture, and the effects of bCSF on the cell growth and intracellular calcium ion ([Ca2+]i) dynamics were investigated in cultured human umbilical vein endothelial cells. CSF collected from patients undergoing other intracranial surgeries was used as a control. Pre-treatment with bCSF4 significantly facilitated cell proliferation and DNA synthesis in the cultured endothelial cells, and significantly enhanced histamine-induced [Ca2+]i increase, while acute treatment of the bCSF elicited no [Ca2+]i change. Pre-treatment with interleukin-1 beta showed a similar significant enhancement of the histamine-induced [Ca2+]i response, while pre-treatment with high concentrations of serum or interleukin-6 did not change the [Ca2+]i response. It is concluded that bCSF collected from SAH patients contains some substances which enhance endothelial cell proliferation and sensitivity to inflammatory mediator.

The relation between aneurysm size and outcome in patients with subarachnoid hemorrhage.

The balance of risks of treatment for unruptured aneurysms might change if the prognosis after rupture depends on the size of the aneurysm. In a prospective series of patients with subarachnoid hemorrhage in whom aneurysmal size was measured by CT angiography performed on admission, poor outcome occurred more often in patients with large (> or =10 mm) aneurysms (63%) than in patients with small (<10 mm) aneurysms (41%; RR = 1.5; 95% CI 1.0 to 2.2). The relative risk remained essentially the same after adjustment for age, gender, location of the aneurysm, and amount of cisternal blood.

Evaluation of big endothelin-1 concentrations in serum and ventricular cerebrospinal fluid after early surgical compared with nonsurgical management of ruptured intracranial aneurysms.

OBJECT: Whereas the removal of subarachnoid blood is possible during early-stage aneurysm surgery, this cannot be achieved in aneurysms treated by endovascular means. The levels of potential spasmogens in the cerebrospinal fluid (CSF) in patients receiving endovascular treatment might therefore be higher, with the potential for more severe post-subarachnoid hemorrhage (SAH) vasospasm. METHODS: Serum and CSF concentrations of big endothelin (ET)-1 were serially measured in patients with SAH receiving one of the following treatments: 1) early (within 72 hours of SAH) aneurysm surgical treatment (15 patients), 2) early endovascular treatment (17 patients), or 3) no intervention in the acute phase (12 patients). In patients suffering delayed infarctions higher levels of big ET-1 CSF were demonstrated than in those without infarctions (p = 0.01). In patients in whom surgery was performed in the acute phase lower big ET-1 CSF concentrations were demonstrated than in those who received embolization treatment or no treatment (p = 0.02). Subgroup analysis demonstrated that in patients receiving early endovascular treatment, higher big ET-1 CSF concentrations were revealed than in those undergoing early aneurysm surgery; this was true for patients with (microsurgerytreated, 1.84 +/- 0.83 pg/ml; and embolization-treated 2.19 +/- 0.54 pg/ml) and without (microsurgery-treated 1.76 +/- 0.61 pg/ml; and embolization-treated 2.01 +/- 0.48 pg/ml) delayed infarctions. CONCLUSIONS: Among patients with SAH who received treatment during the acute phase, those undergoing early aneurysm surgery were shown to have lower big ET-1 CSF levels than those receiving embolization and no treatment (that is, the nonsurgical treatment groups). The clinical significance of this finding remains to be established in future clinical trials, because in the present study the trend toward lower levels of big ET-1 CSF in the microsurgically treated group was not paralleled by a lower delayed stroke rate or an improvement in neurological outcome.

Acute and transient increase of lipocalin-type prostaglandin D synthase (beta-trace) level in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage.

We measured the concentration of lipocalin-type prostaglandin D synthase (PGDS) in cerebrospinal fluid (CSF) and serum in patients 1, 3, 5, 7, 9, 11, 14 and 17 days after subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms. The PGDS level in lumbar CSF increased about two-fold at day 3 (20.85 +/- 2.71 microg/ml, mean +/- SE) and at day 5 (25.24 +/- 3.76), as compared with the level at day 1 (11.25 +/- 1.07). The CSF level gradually decreased and returned to the day 1 level at day 17. The serum PGDS level was much lower than the CSF level (0.39 +/- 0.06 at day 1) and almost unchanged until day 17. The neuron-specific enolase level in CSF, as an index of brain damage, was maximum at day 1 (29.83 +/- 7.32 ng/ml) and decreased at day 3 and at day 5 (18.28 +/- 2.65 and 11.95 +/- 1.82, respectively). These results suggest that the transient and delayed increase in the PGDS level in CSF is due to its induction of PGDS in the arachnoid membrane after SAH.

[Cerebral hemodynamics and metabolism in the acute stage of cerebral aneurysm rupture]. / Tserebral'naia gemodinamika i metabolizm v ostroi stadii razryva anevrizm golovnogo mozga.

The relationship between lipid peroxidation products and the severity of arterial spasm was studied in 86 patients. For this, the level of radical production, the content of the end lipid peroxidation product malonic dialdehyde and the overall antioxidative activity of lumbar cerebrospinal fluid were determined during 24-hour Doppler monitoring of blood flow in the middle cerebral and internal carotid arteries. Following subarachnoidal hemorrhage, the activation of lipid peroxidation processes was shown to correlate with the severity of arterial spasm and it is likely to contribute to the development of late ischemias. Nimotop used to treat patients with significant arterial spasm caused a reduction in the rate of free radical lipid peroxidation to that characteristic for patients with moderate spasm. The findings suggest that it is expedient of including antioxidants into the combined therapy of patients with acute subarachnoidal hemorrhage.

Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage.

OBJECT: The goal of this study was to explore whether the levels of soluble adhesion molecules were elevated in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). This association was suggested by the known inflammatory response in vasospasm and the role of vascular adhesion molecules in regulating leukocytic adhesion to, and migration across, vascular endothelium. METHODS: A prospective analysis was performed on CSF samples obtained in 17 patients who had suffered a recent aneurysmal SAH and in 16 control patients by using quantitative enzyme-linked immunosorbent assays for E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and L-selectin. Levels of soluble forms of E-selectin (p=0.0013), ICAM-1 (p=0.0001), and VCAM-1 (p=0.048) were found to be elevated in the CSF of patients after SAH compared with levels in the CSF of norminal controls, patients with unruptured aneurysms, and patients tested months after SAH occurred. In addition, individual patients tested at the time of their initial ictus demonstrated a fall in adhesion molecule levels over time. Levels of E-selectin (p=0.044) were highest in patients who later developed moderate or severe vasospasm. CONCLUSIONS: Adhesion molecules are known to be involved in white cell adherence to the endothelium and subsequent diapedesis and migration in which a role in initiation of tissue damage is postulated. The authors have demonstrated the elevation of three adhesion molecules, with severely elevated levels of E-selectin seen in patients who later develop vasospasm. A correlation with a role of vascular adhesion molecules in the pathogenesis of cerebral vasospasm is suggested.