Cerebral Artery Vasospasm Research Articles

Vasospasm in cerebral inflammation.

All forms of cerebral inflammation as found in bacterial meningitis, cerebral malaria, brain injury, and subarachnoid haemorrhage have been associated with vasospasm of cerebral arteries and arterioles. Vasospasm has been associated with permanent neurological deficits and death in subarachnoid haemorrhage and bacterial meningitis. Increased levels of interleukin-1 may be involved in vasospasm through calcium dependent and independent activation of the myosin light chain kinase and release of the vasoconstrictor endothelin-1. Another key factor in the pathogenesis of cerebral arterial vasospasm may be the reduced bioavailability of the vasodilator nitric oxide. Therapeutic trials in vasospasm related to inflammation in subarachnoid haemorrhage in humans showed a reduction of vasospasm through calcium antagonists, endothelin receptor antagonists, statins, and plasminogen activators. Combination of therapeutic modalities addressing calcium dependent and independent vasospasm, the underlying inflammation, and depletion of nitric oxide simultaneously merit further study in all conditions with cerebral inflammation in double blind randomised placebo controlled trials. Auxiliary treatment with these agents may be able to reduce ischemic brain injury associated with neurological deficits and increased mortality.

The role of arterioles and the microcirculation in the development of vasospasm after aneurysmal SAH.

Cerebral vasospasm of the major cerebral arteries, which is characterized by angiographic narrowing of those vessels, had been recognized as a main contributor to delayed cerebral ischemia (DCI) in subarachnoid hemorrhage (SAH) patients. However, the CONSCIOUS-1 trial revealed that clazosentan could not improve mortality or clinical outcome in spite of successful reduction of relative risk in angiographic vasospasm. This result indicates that the pathophysiology underlying DCI is multifactorial and that other pathophysiological factors, which are independent of angiographic vasospasm, can contribute to the outcome. Recent studies have focused on microcirculatory disturbance, such as microthrombosis and arteriolar constriction, as a factor affecting cerebral ischemia after SAH. Reports detecting microthrombosis and arteriolar constriction will be reviewed, and the role of the microcirculation on cerebral ischemia during vasospasm after SAH will be discussed.

Endothelin systems in the brain: involvement in pathophysiological responses of damaged nerve tissues.

In addition to their potent vasoconstriction effects, endothelins (ETs) show multiple actions in various tissues including the brain. The brain contains high levels of ETs, and their production is stimulated in many brain disorders. Accumulating evidence indicates that activation of brain ET receptors is involved in several pathophysiological responses in damaged brains. In this article, the roles of brain ET systems in relation to brain disorders are reviewed. In the acute phase of stroke, prolonged vasospasm of cerebral arteries and brain edema occur, both of which aggravate brain damage. Studies using ET antagonists show that activation of ETA receptors in the brain vascular smooth muscle induces vasospasm after stroke. Brain edema is induced by increased activity of vascular permeability factors, such as vascular endothelial growth factor and matrix metalloproteinases. Activation of ETB receptors stimulates astrocytic production of these permeability factors. Increases in reactive astrocytes are observed in neurodegenerative diseases and in the chronic phase of stroke, where they facilitate the repair of damaged nerve tissues by releasing neurotrophic factors. ETs promote the induction of reactive astrocytes through ETB receptors. ETs also stimulate the production of astrocytic neurotrophic factors. Recent studies have shown high expression of ETB receptors in neural progenitors. Activation of ETB receptors in neural progenitors promotes their proliferation and migration, suggesting roles for ETB receptors in neurogenesis. Much effort has been invested in the pursuit of novel drugs to induce protection or repair of damaged nerve tissues. From these studies, the pharmacological significance of brain ET systems as a possible target of neuroprotective drugs is anticipated.

Remote post-conditioning reduces hypoxic damage early after experimental stroke

Objectives: Given that reliable markers for early ischemic brain damage are lacking, we set out to test whether pimonidazole can be used as a reliable tool in the quantification of hypoxic insults, at early time points following experimental stroke.Methods: We have used semi-quantitative Western blotting detection of pimonidazole adducts in a rat model of reversible middle cerebral artery occlusion (MCAO), treated with remote post-conditioning.Results: First, we demonstrated that a linear relationship exist between pimonidazole binding in the ischemic hemisphere and duration of ischemia, in animals subjected to 5, 15, 30, or 60 minutes of occlusion followed by 120 minutes of reflow. Then we showed a significant reduction in pimonidazole binding in the infarcted hemisphere, when rats with 60 minutes of MCAO, immediately after establishment of cerebral reflow, had 3×15 minutes intermittent hind limb ischemia followed by 24-hour survival. We analysed the middle cerebral arteries from animals with 60 minutes of MCAO and early remote post-conditioning, followed by 30 minutes, 24, or 48 hours of reflow. At 24 hours of reflow increases in phosphorylated protein kinase C-alpha with concomitantly increased levels of p38 phosphorylation were observed.Conclusions: Our investigation demonstrates that pimonidazole can be used for quantifying ischemic impact in stroke, even after very short survival times. It furthermore shows that early remote post-conditioning reduces ischemic damage, probably through hyperpolarization and reduced reflow vasospasm in the conduit middle cerebral arteries.

The use of heart rate variability for the early detection of treatable complications after aneurysmal subarachnoid hemorrhage

High-grade aneurysmal subarachnoid hemorrhage patients are monitored in the ICU for up to 21 days, as they are at risk for complications such as vasospasm of cerebral arteries, cardiac arrhythmias and neurogenic stress cardiomyopathy. The diagnosis of these treatable complications is often delayed by the limitations of monitoring capabilities. We applied computational analysis to a cohort of 24 aneurysmal subarachnoid hemorrhage patients, to identify heart rate variability and ECG frequency profiles that may be potential biomarkers of severe vasospasm, reversible cardiomyopathy and death.

Abstract 53: Cerebral Hemodynamic Changes in Patients with Wartime Traumatic Brain Unjury

Cerebral vasospasm (VSP) is a frequent complication after aneurysmal and traumatic subarachnoid hemorrhage (SAH) and carries significant morbidity and mortality. Traumatic brain injury (TBI) is associated with the severest casualties from Operation Iraqi Freedom and Operation Enduring Freedom. From Oct. 1, 2008 the US Army Medical Department initiated a transcranial Doppler (TCD) ultrasound service for TBI; included patients were retrospectively evaluated for TCD-determined incidence of posttraumatic cerebral vasospasm and intracranial hypertension after wartime TBI. Patients were identified using a computerized registry and a prospective TCD database maintained in the Sentient NeuroCare Services. TCD recordings of mean cerebral blood flow velocities (CBFV) and Pulsatility Indices of the anterior and posterior circulation vessels were recorded using a 2-MHz transducer (Doppler Box, DWL/Compumedics, USA, Germany/Australia). Comprehensive TCD protocol was applied in all cases: if mean CBFV equaled or exceeded 100 cm/sec., 140 cm.sec and 200 cm/sec the TCD signs of mild vasospasm, moderate vasospasm and severe vasospasm respectively were considered present. 122 patients were investigated with daily TCD studies and comprehensive TCD protocol and published diagnostic criteria for VSP and raised intracranial pressure (ICP) were applied. TCD signs of mild, moderate and severe VSP involving anterior circulation vessels were observed in 71%, 42% and 16% of patients, respectively. TCD signs of mild, moderate and severe VSP involving posterior circulation vessels were observed in 57%, 32% and 14% of patients, respectively. TCD signs of intracranial hypertension were recorded in 43%, eight patients (7%) underwent transluminal angioplasty for post-traumatic symptomatic vasospasm treatment. These findings demonstrate that cerebral arterial VSP and intracranial hypertension are frequent and significant complications of combat TBI, therefore daily TCD monitoring is recommended for their recognition and subsequent management. Acknowledgements. The opinions and views expressed herein belong solely to those of the authors. They are not nor should they be implied as being endorsed by the Uniformed Services University of the Health Sciences, Department of the Army, Department of the Navy, Department of Defense or any other branch of the Federal government of the United States. This paper supported in part, by the US Army Medical Research and Material Command’s Telemedicine and Advanced Technology Research Center (Fort Detrick, MD, USA).

Abstract 55: Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Using Variations of Dynamic Cerebral Autoregulation

The risk of delayed cerebral ischemia (DCI) after cerebral aneurysm rupture is increased in patients with large cerebral artery vasospasm (VS). The predictive value of VS is, however, far to be optimal. Assessment of cerebral microcirculation impairment using dynamic cerebral autoregulation (DCA) measurement might improve our ability to predict DCI in these patients. Methods. We included consecutive patients with low-grade aneurysmal subarachnoid hemorrhage (SAH) (WFNS 1 to 3) within 4 days of aneurysm rupture. DCA was evaluated using the moving correlation coefficient Mx calculated from spontaneous fluctuations of cerebral blood flow velocities and arterial blood pressure. Impairment of DCA was defined as Mx ≥ 0.3. Transcranial colour-coded sonography was performed every 48 hours to look for VS. Diagnosis of VS was based on a Lindegaard ratio >3 (MCA), or mean flow velocities > 130 cm/s (ACA). DCI was defined as neurologic deterioration caused by brain ischemia confirmed by brain imaging. Results. Thirty patients (19 women; mean age ± SD: 44.7 ± 12.1 years) were included. Twenty (66.7%) patients had VS. DCI occurred in six (20%) patients after a median delay of 10 days (range 8 to 13 days). Mx (mean ± SD) was heightened at baseline (0.43 ± 0.2) and at day 7 (0.46 ± 0.2), then decreased at day 14 (0.37 ± 0.18 (p = 0.034). Isolated measures of VS and Mx were not associated with DCI. However, the elevation of Mx between baseline and day 7 in patients with VS was predictive of subsequent DCI (positive likelihood ratio=5.01; negative likelihood ratio=0.19; P=0.005). Conclusion. Findings suggest that DCA assessment may help to predict better the risk of DCI after cerebral aneurysm rupture than the simple recordings of mean flow velocities.

Cerebral Vasospasm with Ischemia following a Spontaneous Spinal Subarachnoid Hemorrhage

Cerebral vasospasm is a well-known consequence of aneurysmal subarachnoid hemorrhage (SAH) triggered by blood breakdown products. Here, we present the first case of cerebral vasospasm with ischemia following a spontaneous spinal SAH. A 67-year-old woman, who was on Coumadin for atrial fibrillation, presented with chest pain radiating to the back accompanied by headache and leg paresthesias. The international normalized ratio (INR) was 4.5. Ten hours after presentation, she developed loss of movement in both legs and lack of sensation below the umbilicus. Spine MRI showed intradural hemorrhage. Her coagulopathy was reversed, and she underwent T2 to T12 laminectomies. A large subarachnoid hematoma was evacuated. Given her complaint of headache preoperatively and the intraoperative finding of spinal SAH, a head CT was done postoperatively that displayed SAH in peripheral sulci. On postoperative day 5, she became obtunded. Brain MRI demonstrated focal restricted diffusion in the left frontoparietal area. Formal angiography revealed vasospasm in anterior cerebral arteries bilaterally and right middle cerebral artery. Vasospasm was treated, and she returned to baseline within 48 hours. Spontaneous spinal SAH can result in the same sequelae typically associated with aneurysmal SAH, and the clinician must have a degree of suspicion in such patients. The pathophysiological mechanisms underlying cerebral vasospasm may explain this unique case.

Derivation of Transcranial Doppler Criteria for Angiographically Proven Middle Cerebral Artery Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Transcranial Doppler (TCD) has been subjected to criticism for detecting vasospasm (VSP). Our study's aim is to derive criteria for middle cerebral artery (MCA) vasospasm (MCA-VSP) based on cerebral angiography (CA). A prospective data of patients with aneurysmal subarachnoid hemorrhage (aSAH) from January 2004 to August 2009. TCD was performed daily from day 2 to 14 from symptom's onset. Follow-up CA was done at day 7-9. TCD mean flow velocities (MFV) of all vessels at baseline (b), middle (m) and before CA (preangio) were recorded. Several MCA MFV ratios were computed. Moderate to severe VSP on CA was defined as >1/3 luminal narrowing. Univariate and stepwise logistic regression analysis were performed. One hundred sixty-nine patients (338 MCA) with aSAH were included, mean age: 54.8 ± 13, women: 103 (62%). Twenty-nine patients (8.6%) had angiographic MCA-VSP. TCD scoring system of 3 points for MCA-VSP was computed based on (a) bMCA MFV ≥ 120 cm/s (sensitivity: 59.3%, specificity: 85%, PPV: 36.4%, NPV: 93.5%, P < .001) (1 point), Preangio MCA MFV ≥ 150 cm/s (79.3%, 89.9%, 39%, 97.3%, <.001) (1 point), and affected preangio MCA/bMCA MFV ratio ≥ 1.5 (84%, 63%, 25.6%, 96.3%, .001) (1 point). The score of 3 has 96% sensitivity and 96% specificity (OR: 300) whereas the score of 1 has 12% sensitivity and 58% specificity (OR: 4.3) for identifying MCA-VSP. TCD stringent criteria for moderate to severe MCA-VSP are feasible and applicable in aSAH population.

In Vitro Study of Cerebrospinal Fluid Dynamics in a Shaken Basal Cistern after Experimental Subarachnoid Hemorrhage

BackgroundCerebral arterial vasospasm leads to delayed cerebral ischemia and constitutes the major delayed complication following aneurysmal subarachnoid hemorrhage. Cerebral vasospasm can be reduced by increased blood clearance from the subarachnoid space. Clinical pilot studies allow the hypothesis that the clearance of subarachnoid blood is facilitated by means of head shaking. A major obstacle for meaningful clinical studies is the lack of data on appropriate parameters of head shaking. Our in vitro study aims to provide these essential parameters.Methodology/Principal FindingsA model of the basal cerebral cistern was derived from human magnetic resonance imaging data. Subarachnoid hemorrhage was simulated by addition of dyed experimental blood to transparent experimental cerebrospinal fluid (CSF) filling the model of the basal cerebral cistern. Effects of various head positions and head motion settings (shaking angle amplitudes and shaking frequencies) on blood clearance were investigated using the quantitative dye washout method. Blood washout can be divided into two phases: Blood/CSF mixing and clearance. The major effect of shaking consists in better mixing of blood and CSF thereby increasing clearance rate. Without shaking, blood/CSF mixing and blood clearance in the basal cerebral cistern are hampered by differences in density and viscosity of blood and CSF. Blood clearance increases with decreased shaking frequency and with increased shaking angle amplitude. Head shaking facilitates clearance by varying the direction of gravitational force.Conclusions/SignificanceFrom this in vitro study can be inferred that patient or head shaking with large shaking angles at low frequency is a promising therapeutic strategy to increase blood clearance from the subarachnoid space.

Myosin Regulatory Light Chain Diphosphorylation Slows Relaxation of Arterial Smooth Muscle

The principal signal to activate smooth muscle contraction is phosphorylation of the regulatory light chains of myosin (LC(20)) at Ser(19) by Ca(2+)/calmodulin-dependent myosin light chain kinase. Inhibition of myosin light chain phosphatase leads to Ca(2+)-independent phosphorylation at both Ser(19) and Thr(18) by integrin-linked kinase and/or zipper-interacting protein kinase. The functional effects of phosphorylation at Thr(18) on steady-state isometric force and relaxation rate were investigated in Triton-skinned rat caudal arterial smooth muscle strips. Sequential phosphorylation at Ser(19) and Thr(18) was achieved by treatment with adenosine 5'-O-(3-thiotriphosphate) in the presence of Ca(2+), which induced stoichiometric thiophosphorylation at Ser(19), followed by microcystin (phosphatase inhibitor) in the absence of Ca(2+), which induced phosphorylation at Thr(18). Phosphorylation at Thr(18) had no effect on steady-state force induced by Ser(19) thiophosphorylation. However, phosphorylation of Ser(19) or both Ser(19) and Thr(18) to comparable stoichiometries (0.5 mol of P(i)/mol of LC(20)) and similar levels of isometric force revealed differences in the rates of dephosphorylation and relaxation following removal of the stimulus: t(&frac12;) values for dephosphorylation were 83.3 and 560 s, and for relaxation were 560 and 1293 s, for monophosphorylated (Ser(19)) and diphosphorylated LC(20), respectively. We conclude that phosphorylation at Thr(18) decreases the rates of LC(20) dephosphorylation and smooth muscle relaxation compared with LC(20) phosphorylated exclusively at Ser(19). These effects of LC(20) diphosphorylation, combined with increased Ser(19) phosphorylation (Ca(2+)-independent), may underlie the hypercontractility that is observed in response to certain physiological contractile stimuli, and under pathological conditions such as cerebral and coronary arterial vasospasm, intimal hyperplasia, and hypertension.

Le syndrome de vasoconstriction cérébrale réversible

The reversible cerebral vasoconstriction syndrome (RCVS) is an under-estimated transient acute cerebrovascular disorder. It has long been mistaken as central nervous system vasculitis whereas it is now believed to result from an acute but prolonged vasospasm of cerebral arteries. This disorder can be precipitated by postpartum or vasoactive drug. However, it occurs spontaneously in a significant number of cases. The characteristic clinico-radiological presentation and disease course of the RCVS has been delineated only recently. Mean age at onset is 40–45years, with a female predominance. A provocative factor can be identified in 12–60% out of the patients. Clinical presentation is predominantly marked by recurrent thunderclap headaches, but can be complicated with focal neurological deficit or seizures. Brain imaging is normal in most cases, but can reveal hemorrhagic or ischemic complications. Cortical subarachnoid hemorrhage is a suggestive finding. A posterior reversible encephalopathy syndrome (PRES) can be seen occasionally. Cerebral angiography reveals multifocal arterial narrowing with string and bead appearance. Cerebrospinal fluid reveals no or mild abnormalities. The disease resumes spontaneously within several days to weeks, whereas vasoconstriction reverses within 1 to 3months. This clinico-radiological presentation should be promptly recognized in order to avoid unnecessary investigations and aggressive treatment, and lead to search for a triggering factor. Further studies are required in order to clarify the precipitating role of several drugs, and clinical trials are needed to reduce the occurrence of strokes.

The Effect of Vasospasm on Cerebral Perfusion: A Colour Duplex Study of the Extra- and Intracranial Cerebral Arteries

To assess whether middle cerebral artery (MCA) vasospasm reduces the flow volume in the corresponding extracranial internal carotid artery (ICA) or global cerebral blood flow volume (CBFV) in subarachnoid haemorrhage (SAH) patients, a colour duplex ultrasound study of the intra- and extracranial cerebral arteries was performed. MCA vasospasm was defined as a time-averaged maximum flow velocity (TAMX) exceeding 120 cm/s. ICA flow volumes and CBFV, were compared in each patient at maximum TAMX recorded in one MCA (“maximum-vasospasm”) and when TAMX in the same vessel was closest to mean reference values (“no-vasospasm”). Additionally, the CBFV course during the first 3 weeks after SAH was evaluated longitudinally. Data from age- and gender-matched healthy test persons served as control. In 28 patients with MCA vasospasm, 337 measurements were completed. Global CBFV was significantly reduced starting from day 3 after SAH. ICA flow volumes and CBFV were not different when comparing at “maximum-vasospasm” and “no-vasospasm”. Compared with the control group, both were lower at either condition. Thus, in SAH patients, vasospasm even severe, in general does not further diminish ICA flow volumes and global CBFV, which are reduced already before the onset of vasospasm.

Intraventricular Nicardipine for Aneurysmal Subarachnoid Hemorrhage Related Vasospasm: Assessment of 90 Days Outcome

Delayed cerebral arterial vasospasm is one of the leading causes of death and disability after aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the safety of intraventricular nicardipine (IVN) for vasospasm (VSP) in aSAH patients, and outcomes compared with a control population. A retrospective case-control study was conducted for aSAH patients treated with IVN at Mayo Clinic, Jacksonville, FL, from March 2009 to January 2011. Controls were matched by age, gender, and Fisher grade. Safety was evaluated by the incidence of intracranial bleeding and infection. Outcome was measured by Glasgow Outcome Scale at 30 and 90 days. IVN effects on VSP were evaluated by transcranial Doppler (TCD). Thirteen aSAH patients and one arteriovenous malformation (AVM)-related SAH patient received IVN for VSP and were matched with 14 aSAH patients without IVN therapy for a total of 28 cases. Median dose was 4 mg (range 3-7), and median number of doses was seven (range 1-17). Mean flow velocity decreased after IVN (120.2 and 101.6 cm/s-82.0 and 72.8 cm/s, right and left middle cerebral arteries, respectively). No significant difference was seen in clinical outcomes between controls and cases at 30 days (P = 0.443) and 90 days (P = 0.153). There were no incidences of bleeding or infection with 111 nicardipine injections. IVN appears relatively safe and effective in treating VSP by TCD, but there was no difference in clinical outcomes between nicardipine and control patients at 30 and 90 days. In the future, larger studies are needed to evaluate the clinical outcome with IVN.

An observational pilot study of CSF diversion in subarachnoid haemorrhage

A primary focus of hospital treatment following admission for subarachnoid haemorrhage (SAH) is a prevention of cerebral artery vasospasm, which may result in ischaemic stroke. Intraventricular catheter (IVC) insertion to facilitate cerebral spinal fluid (CSF) drainage and intracranial pressure (ICP) monitoring may reduce the incidence or severity of vasospasm, but insufficient evidence exists from which clinicians may determine the best practice of CSF management. The aim of this study was to provide the pilot data to explore the impact of different methods of CSF drainage on outcomes in patients with SAH. In this non-randomized observational study, patients diagnosed with SAH who had ICP monitoring in situ were prospectively enrolled. Group assignment was determined by the method of external ventricular drainage (EVD) management prescribed by the attending physician prior to enrollment. The 37 subjects were disproportionately divided: open-EVD group (N = 24) and monitor-ICP group (N = 13). There were no statistically significant differences by group assignment with respect to vasospasm, length of stay (LOS), highest average ICP, total CSF drained and disability upon discharge between groups. Although not significant, our results show that the monitor-ICP group trended towards improved clinical outcomes. These results provide sufficient equipoise to support further research in ICP management in patients with SAH using a randomized clinical trial. This study provides a solid foundation for the development of a randomized trial exploring two different methods of ICP monitoring and CSF diversion during the acute phase of care following aneurysm rupture.

Detection and Monitoring of Vasospasm and Delayed Cerebral Ischemia: A Review and Assessment of the Literature

Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can be evaluated using clinical assessment, non-invasive and invasive techniques. An electronic literature search was conducted on English-language articles investigating DCI in human subjects with subarachnoid hemorrhage. A total of 31 relevant papers were identified evaluating the role of clinical assessment, transcranial Doppler, computed tomographic angiography, and computed tomographic perfusion. Clinical assessment by bedside evaluations is limited, especially in patients initially in poorer clinical condition or who are receiving sedative medication for whom deterioration may be more difficult to identify. Transcranial Doppler is a useful screening tool for middle cerebral artery vasospasm, with less utility in evaluating other intracranial vessels. Computed tomographic angiography correlates well with digital subtraction angiography. Computed tomographic perfusion may help predict DCI when used early or identify DCI when used later.

A Computational Simulation of the Effect of Hemodilution on Oxygen Transport in Middle Cerebral Artery Vasospasm

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage is a potentially severe sequel. The induction of hypertension, hypervolemia, and hemodilution is advocated for vasospasm, but it is unclear whether hemodilution confers any benefit. A finite element model of oxygen transport in the proximal middle cerebral artery (MCA) was used to evaluate the complex relationship among hematocrit, viscosity, oxygen content, and blood flow in the setting of vasospasm. A single-phase non-Newtonian finite element model based on three-dimensional incompressible Navier-Stokes equations was constructed of the M1 segment. The model was solved at vessel stenoses ranging from 0% to 90% and hematocrit from 0.2 to 0.6. A small area of poststenotic recirculation was seen with mild (30%) stenosis. Poststenotic eddy formation was noted with more severe (60% to 90%) stenosis. Volumetric flow was inversely related to hematocrit at mild stenosis (0% to 30%). With near-complete stenosis (90%), a paradoxical increase in flow was seen with increasing hematocrit. Oxygen transport across the segment was related to hematocrit at all levels of stenosis with increasing oxygen transport despite a reduction in blood flow, suggesting that with clinically significant vasospasm in the MCA, hemodilution does not improve oxygen transport, but to the contrary, that ischemia may be worsened.

Dissociation of Vasospasm and Secondary Effects of Experimental Subarachnoid Hemorrhage by Clazosentan

Endothelin receptor antagonists such as clazosentan decrease large-artery vasospasm after experimental and clinical subarachnoid hemorrhage. We used clazosentan to gain insight into the pathophysiology of subarachnoid hemorrhage by determining if decreasing vasospasm is associated with alleviation of other secondary complications of subarachnoid hemorrhage such as oxidative stress, endothelial nitric oxide synthase dysfunction, microthromboembolism, and neuronal injury. Mice were subjected to subarachnoid hemorrhage by injection of blood into the chiasmatic cistern. They were treated with clazosentan or vehicle by continuous intraperitoneal infusion for 48 hours. Middle cerebral artery vasospasm, superoxide anion radical, peroxynitrite, microthromboemboli, endothelial nitric oxide synthase uncoupling, cerebral blood flow, neuronal injury, and mortality were assessed. Clazosentan preserved cerebral blood flow, alleviated vasospasm, and decreased mortality but did not affect superoxide anion radical, peroxynitrite, or microthromboemboli in the brain. Endothelial nitric oxide synthase uncoupling and neuronal injury also were not reduced by clazosentan. This study shows large-artery vasospasm is pathophysiologically independent of some other effects of subarachnoid hemorrhage. The findings have implications for development of treatments for this disease.

Use of Cervical Spinal Cord Stimulation in Treatment and Prevention of Arterial Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Based on past laboratory and anecdotal clinical experience, we hypothesized that prolonged cervical spinal cord stimulation (SCS) in the acute settings of aneurysmal subarachnoid hemorrhage (aSAH) would be both safe and feasible, and that 2-week stimulation will reduce incidence of cerebral arterial vasospasm. The goal of our clinical study was to establish feasibility and safety of cervical SCS in a small group of selected aSAH patients. Single-arm non-randomized prospective study of cSCS in aSAH patients involved percutaneous implantation of 8-contact electrode in 12 consecutive aSAH patients that satisfied strict inclusion criteria. The electrode insertion was performed immediately upon surgical or endovascular securing of the ruptured aneurysm while the patient was still under general anesthesia. Patients were stimulated for 14 consecutive days or until discharge. There were no complications related to the electrode insertion or to SCS during the study and no long-term side effects of SCS during 1-year follow-up. There was 1 unrelated death and two electrode pullouts. This article summarizes technical details of SCS electrode insertion and the stimulation parameters used in the research study. Our study of SCS for prevention of vasospasm after aSAH conclusively shows both safety and feasibility of this promising treatment approach. Despite high level of acuity in aSAH patients, impaired level of consciousness, frequent patient re-positioning, need in multiple tests and variety of monitors, SCS electrodes may be safely implanted and maintained for the two-week period. Long-term follow up shows no adverse effects of cervical SCS in this patient category.

Ostemyelitis of the clivus due to Fusobacterium necrophorum

Introduction: Septic jugular thrombosis with secondary osteomyelitis of the clivus due to Fusobacterium necrophorum is a rare complication of Lemierres syndrome. Other complications that can occur include cavernous sinus thrombosis and cerebral arterial vasospasm. Case Report: We present a case of a young girl illustrating the clinical findings of Lemierre's syndrome in addition to other complications that may occur. Retropharyngeal infection with internal jugular venous thrombosis was present in this case along with Fusobacterium necrophorum septicemia. Lemierre's syndrome consists of oropharyngeal infection with internal jugular vein thrombosis, anaerobic septicemia and septic embolization to multiple organ systems. Osteomyelitis of the clivus is a rare, but important complication associated with this syndrome. Fusobacterium necrophorum, the usual pathogen implicated in Lemierre's syndrome has rarely been known to be the sole pathogen implicated in childhood osteomyelitis secondary to septic jugular vein thrombosis. It is important to recognize some of the complications of septic jugular vein thrombosis to reduce morbidity and mortality. Conclusion: Awareness of the clinical and radiologic findings that may be seen in pediatric retropharyngeal infections along with awareness of the possible complications can help guide early treatment or surgical intervention.