Post-subarachnoid Hemorrhage Vasospasm Research Articles

Role of endovascular super selective intra-arterial injection of CA channel blocker agent (nimodipine) in management of cerebral vasospasm following aneurysmal SAH: a single institution experience

BackgroundVasospasm is a grave complication of aneurysmal subarachnoid hemorrhage (SAH) with a significant rate of morbidity and mortality. Endovascular intra-arterial injection of Ca channel blocker agent (Nimodipine) may offer a promising solution in refractory vasospasm.ResultsDuring the period between April 2017 and May 2019, 120 patients who presented with SAH due to a ruptured intracranial aneurysm were admitted to the neurosurgery department at Alexandria University Hospitals. Among them, 30 patients developed refractory vasospasm and were subjected to endovascular super selective intraarterial injection of nimodipine. The angiographic improvement was excellent in three (10%), good in 14 (46%) and poor in the remaining 13 procedures (43%). Clinical improvement was achieved in 15 cases while 15 cases showed no improvement on Modified Rankin Scale. No cases deteriorated following the injection.ConclusionsEndovascular chemical angioplasty using a ca channel blocker agent (Nimodipine) is a safe and efficient method for the treatment of refractory post aneurysmal SAH vasospasm. The quest is still needed for developing a better efficient agent to overcome the vasospasm dilemma.

Balloon-Assisted Coil Embolization and Balloon Angioplasty for Post Subarachnoid Hemorrhage Vasospasm: Initial Experience with Scepter Mini Balloon.

The scope of this technical note is to report our experience with balloon remodeling for wideneck aneurysms and balloon angioplasty of post-subarachnoid hemorrhage vasospasm using the novel Scepter Mini balloon (SMB). Five cases were treated with balloon remodeling for aneurysmal subarachnoid hemorrhage, 2 of which were additionally treated with angioplasty due to post-bleeding vasospasm. All patients had their aneurysm located on parent vessels with a diameter smaller than 2 mm. Complete occlusion was noted in all aneurysms, and the patients had no short-term complications attributed to the catheterization. Additionally, we confirm the previously reported smooth navigation of the balloon through vessels with tortuous anatomy without catheter-induced vasospasm. Based on our experience, the SMB can be a safe and efficient device for applying the balloon remodeling technique for distally located wide-neck aneurysms and distal balloon angioplasty.

The Impact of Intra-Arterial Papaverine-Hydrochloride on Cerebral Metabolism and Oxygenation for Treatment of Delayed-Onset Post-Subarachnoid Hemorrhage Vasospasm

Delayed posthemorrhagic vasospasm remains among the major complications after aneurysmal subarachnoid hemorrhage (SAH) and can result in devastating ischemic strokes. As rescue therapy, neurointerventional procedures are used for selective vasodilatation. To investigate the effects of intra-arterial papaverine-hydrochloride on cerebral metabolism and oxygenation. A total of 10 consecutive patients, suffering from severe aneurysmal SAH were prospectively included. Patients were under continuous multimodality neuromonitoring and required intra-arterial papaverine-hydrochloride for vasospasm unresponsive to hypertensive therapy. Cerebral metabolism (microdialysis), brain tissue oxygen tension (ptiO2), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were analyzed for a period of 12 h following intervention. A median dose of 125 mg papaverine-hydrochloride was administered ipsilateral to the multimodality probe. Angiographic improvement of cerebral vasospasm was observed in 80% of patients. During intervention, a significant elevation of ICP (13.7±5.2 mmHg) and the lactate-pyruvate ratio (LPR) (54.2±15.5) was observed, whereas a decrease in cerebral glucose (0.9±0.5 mmol/L) occurred. Within an hour, an increase of cerebral lactate (5.0±2.0 mmol/L) and glycerol (104.4±89.8 μmol/L) as well as a decrease of glucose (0.9±0.4 mmol/L) were measured. In 2 to 5 h after treatment, the LPR significantly decreased (pretreatment: 39.3±15.3, to lowest 30.5±6.7). Cerebral pyruvate levels increased in 1 to 10 h (pretreatment: 100.1± 33.1 μmol/L, to highest 141.4±33.7 μmol/L) after intervention. No significant changes in ptiO2 or CPP occurred. The initial detrimental effects of the endovascular procedure itself were outweighed by an improved cerebral metabolism within 10 h thereafter. As the effect was very limited, repeated interventions or continuous application should be considered.

A novel swine model of subarachnoid hemorrhage-induced cerebral vasospasm.

One of the most serious complications following subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI) secondary to symptomatic vasospasm. An animal model mimicking post SAH vasospasm is essential for enabling the translation of newer technologies from the conceptual phase to animal studies, and eventually to clinical trials. Various animal models of DCI following SAH have been reported, with canine models being the most common. Due to the similarity of the swine cardiovascular system and its dimensions to the human's system, the main objective of this study was to establish a consistent and quantitatively representative model of SAH-induced vasospasm in swine. Twelve female swines (57 ± 3 kg) were injected twice (with a 2-day interval between injections) with autologous blood into the subarachnoid space at the level of C2-3 vertebrae. Different volumes were injected to identify clinical and radiological changes. The effect of volume variations on hematoma size and vasospasm intensity in the circle of Willis arteries were studied 7-14 days after the first injection using ascending pharyngeal angiographic measurements of vessel diameter. Neurological outcome using a modified scoring table based on clinical parameters (e.g., appetite, behavior, walking, posture, and eye movement) was recorded. Our results demonstrate that between volume combinations, intrathecal injection of 12 ml followed by 15 ml, with a 2-day interval in between, resulted in the most extensive angiographically-assessed vasospasm 12 ± 2 days following the first injection. The degree of vasospasm in the intracranial internal carotid artery was 22% and 16% for the left and right sides, respectively. Vasoconstriction of the anterior cerebral artery was 34% and 27% for the left and right sides, respectively. The vasoconstriction was not associated with either overt clinical signs or clinical outcome, which is indicative of an ischemic event. The relative scarcity of swine models for SAH-induced vasospasm motivated us to develop and quantify a straightforward protocol for producing consistent mild-to-moderate vasospasm following SAH. As swine is commonly used in translational cardiovascular research, we believe that this study constitutes an important phase in the study of SAH and in developing pharmacological agents and medical devices for interventions.

Post-subarachnoid Hemorrhage Vasospasm in Patients with Primary Headache Disorders

Altered cerebral vasomotor reactivity leading to vasospasm can be seen both in patients with primary headache disorders (PHD) and in patients with subarachnoid hemorrhage (SAH). The pathogenesis of vasospasm in post-SAH patients and in headache disorder sufferers may be related. To address this hypothesis, we analyzed a large cohort of SAH patients to determine whether a diagnosis of PHD predisposes to vasospasm, delayed cerebral ischemia, or worsened clinical outcome. Prospectively collected data from patients enrolled in the SAH Outcomes Project between 1996 and 2006 were analyzed. Patients were segregated based on whether they had a diagnosis of PHD or not and were subsequently compared for differences in clinical and radiographic outcome. A total of 921 SAH patients were analyzed, 265 of which had a diagnosis of PHD. In total, symptomatic vasospasm was seen in 17%, while angiographic vasospasm was seen in 28%. Vasospasm rates were similar among patients with a PHD and in those without a PHD (p > 0.05). However, on multivariate analysis new ischemic infarcts were more common in patients with a PHD as compared to patients without a PHD (p = 0.015). Functional outcomes at 3 months were similar among PHD and non-PHD patients (p > 0.05). A history of PHD is associated with an increased rate of ischemic infarcts during admission for SAH. Increased rates of vasospasm within small cerebral blood vessels may be implicated. Further studies are warranted to more closely link the mechanisms of vasospasm in PHD and SAH patients.

Innovative approach for prevention and treatment of post subarachnoid hemorrhage vasospasm: A preliminary report

More than one third of patients with subarachnoid hemorrhage (SAH) develop clinically significant vasospasm, as a leading morbidity and mortality factor for these patients. It is widely accepted that a) Degradation products of blood are the causative factors of vasospasm b) The amount of subarachnoid blood seen on admission CT is correlated to the risk of vasospasm c) Reducing the subarachnoid clot burden at the time of surgery reduces the risk of vasospasm. But there is no existing method to clear the blood from subarachnoid spaces satisfactorily. We have evaluated safety and feasibility of fluid exchange catheter system in SAH, to achieve this goal. We were successful in clearing cisternal blood in three patients with aneurysmal rupture with fluid exchange catheter system. Baseline CT scan of brain was performed immediately after the surgery and then at the end of irrigation. The amount of subarachnoid blood was evaluated. This innovative, fluid exchange catheter system infuses and aspirates micro volumes of drug solution in a cyclic mode, ensuring isobaric exchange of fluids. The result is good clearance of blood in subarachnoid spaces were seen in all the patients. Also, significant improvement in neurological deficits secondary to vasospasm was seen. We conclude that the fluid exchange catheter system is safe and adoptable in neurosurgical practice.

Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine

Brain hemodynamics in cerebral malaria (CM) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA, we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity. Leukocyte sequestration further decreased perfusion by narrowing luminal diameters in the affected vessels and blocking capillaries. Remarkably, vascular collapse at various degrees was observed in 44% of mice with CM, which also presented more severe vasoconstriction. Coadministration of artemether and nimodipine, a calcium channel blocker used to treat postsubarachnoid hemorrhage vasospasm, to mice presenting CM markedly increased survival compared with artemether plus vehicle only. Administration of nimodipine induced vasodilation and increased pial blood flow. We conclude that vasoconstriction and vascular collapse play a role in murine CM pathogenesis and nimodipine holds potential as adjunctive therapy for CM.

Intranasal administration of E-selectin to induce immunological tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis

Evidence that inflammatory and immune mechanisms may have a critical role in the development of vasospasm after subarachnoid hemorrhage is accumulating. We examined, therefore, whether induction of immunological tolerance to the adhesion molecule that is uniquely expressed on activated endothelium, E-selectin, could inhibit the vasospasm provoked by subarachnoid blood in a rat subarachnoid hemorrhage model. We found that intranasal instillation of E-selectin every other day for 10 days on a mucosal tolerization schedule suppressed delayed type hypersensitivity to E-selectin confirming tolerance to that molecule and markedly suppressed basilar artery spasm after subarachnoid hemorrhage. The results of this proof-of-concept study suggest that agents that can mimic the local effects of the mediators of mucosal tolerance could have therapeutic potential for the management of post-subarachnoid hemorrhage vasospasm.

Cerebral Perfusion Imaging

There are multiple imaging techniques available to assess cerebral perfusion, including positron emission tomography (PET), xenon computed tomography (XeCT), single photon emission computed tomography (SPECT), perfusion-weighted MRI (PWI), and perfusion computed tomography (PCT). Current interest has focused mainly on their use in the setting of acute brain ischemia. Perfusion imaging may be able to distinguish infarcted from salvageable ischemic tissue as a guide to treatment. Perfusion techniques may also be helpful in cases of chronic ischemia, post-subarachnoid hemorrhage vasospasm, trauma, and contemplated therapeutic carotid artery occlusion.

Endothelial Nitric Oxide Synthase Gene Polymorphisms Predict Susceptibility to Aneurysmal Subarachnoid Hemorrhage and Cerebral Vasospasm

Rupture of an intracranial aneurysm (subarachnoid hemorrhage) is a potentially devastating condition frequently complicated by delayed cerebral ischemia from sustained contraction of intracranial arteries (cerebral vasospasm). There is mounting evidence linking the formation of intracranial aneurysms and the pathogenesis of post-subarachnoid hemorrhage vasospasm to aberrant bioavailability and action of the vasodilator molecule nitric oxide generated by isoforms of nitric oxide synthase. In humans, the gene encoding the endothelial isoform of nitric oxide synthase (eNOS) is known to be polymorphic, with certain polymorphisms associated with increased cardiovascular disease susceptibility. In this prospective clinical study involving 141 participants, we used gene microarray technology to demonstrate that the eNOS gene intron-4 27-base pair variable number tandem repeat polymorphism (eNOS 27 VNTR) predicts susceptibility to intracranial aneurysm rupture, while the eNOS gene promoter T-786C single nucleotide polymorphism (eNOS T-786C SNP) predicts susceptibility to post-subarachnoid hemorrhage vasospasm. We believe that genetic information such as this, which can be obtained expeditiously at the time of diagnosis, may be used as a helpful adjunct to other clinical information aimed at predicting and favorably modifying the clinical course of persons with intracranial aneurysms.

Cerebral angioplasty practice at major medical centers in the United States.

Concern has been expressed recently regarding the proliferation of angioplasty and/or stenting of cerebral vessels. However, little is known about the volume of angioplasties being performed or the number of experienced interventionalists. A questionnaire was mailed to directors of accredited radiology residency programs in the United States, to define the level of expertise available at teaching hospitals in terms of angioplasty and/or stenting. Of 200 programs surveyed, 111 responded (56 %). Of 111 program directors 47 (42%) indicated that cerebral angioplasty was being performed at their center. The greatest experience is currently for angioplasty of post-subarachnoid hemorrhage vasospasm (mean 16 procedures performed) and the least experience for dilation of basilar artery atherosclerosis (mean five procedures performed). The reported stroke and/or death rate in centers performing angioplasty of the extracranial carotid system is 1.5 %. Comparisons with other medical specialties (e.g., cardiologists, neurologists, neurosurgeons) are necessary to determine the full scope of extracranial neurovascular procedures being performed and the corresponding complication rates.

Cerebrovascular responses to subarachnoid blood and serotonin in the monkey.

Preliminary in vitro experiments were performed to determine the serum concentration of serotonin in the monkey, and the ability of cyproheptadine to block serotonin and serum-induced contractions in monkey cerebral arteries. Thirty-four cynomolgus monkeys were subsequently used to study changes in regional cerebral blood flow (CBF) obtained by the intracartoid 133Xe technique, and in the angiographic cerebral arterial caliber resulting from subarachnoid injection of artificial cerebrospinal fluid (CSF), blood, and serotonin. Five animals in each injection group were given 1.0 mg/kg intravenous cyproheptadine (a serotonin-blocking agent) during the post-injection period. Subarachnoid injection of artificial CSF produced no change in CBF or arterial caliber. Post-injection administration of cyproheptadine also had no effect on these parameters. A subarachnoid injection of fresh autogenous blood produced a significant but transient (less than 1 hour) decrease in CBF and moderate vasospasm, which lasted at least 3 hours. This vasospasm was essentially unaffected by intravenous cyproheptadine. The CBF and arterial caliber were unchanged following a subarachnoid injection of serotonin at concentrations (5 x 10(-6)M) present in normal monkey serum. In contrast, 5 x 10(-6) M serotonin invariably produced near maximal contractions in the in vitro cerebral artery preparations. Higher (x10) serotonin concentrations caused a transient CBF response similar to that obtained with blood. However, the cerebral vasospasm induced was of shorter duration than that obtained with blood. These results do not support a major role for serotonin in the production of post-subarachnoid hemorrhage vasospasm. Moreover, our data indicate that in vitro experiments do not reflect the ability of serotonin to constrict cerebral arteries in the intact animal.