Subarachnoid Hemorrhage-related Vasospasm Research Articles

Endovascular Rescue Therapies for Refractory Vasospasm After Subarachnoid Hemorrhage: A Prospective Evaluation Study Using Multimodal, Continuous Event Neuromonitoring.

Critical hypoperfusion and metabolic derangement are frequently encountered with refractory vasospasm. Endovascular rescue therapies (ERT) have proven beneficial in selected cases. However, angioplasty (AP) and intraarterial lysis (IAL) are measures of last resort and prospective, quantitative results regarding the efficacy (cerebral oxygenation, metabolism) are largely lacking. To evaluate the efficacy of ERTs for medically refractory vasospasm using multimodal, continuous event neuromonitoring. To detect cerebral compromise in a timely fashion, sedated patients with aneurysmal subarachnoid hemorrhage received continuous neuromonitoring (p ti O 2 measurement, intraparenchymal microdialysis). ERT (AP and/or IAL) was considered in cases of clinically relevant vasospasm refractory to conservative treatment measures. Oxygen saturation and cerebral and systemic metabolism before and after events of ERT was recorded. We prospectively included 13 consecutive patients and recorded a total of 25 ERT events: AP (n = 10), IAL (n = 11), or both (AP + IAL, n = 4). Average cerebral p ti O 2 was 10 ± 11 torr before and 49 ± 22 torr after ERT ( P < .001), with a lactate-pyruvate ratio decreasing from 146.6 ± 119.0 to 27.9 ± 10.7 after ERT ( P < .001). Comparable improvement was observed for each type of intervention (AP, IAL, or both). No significant alterations in systemic metabolism could be detected after ERT. Multimodal event neuromonitoring is able to quantify treatment efficacy in subarachnoid hemorrhage-related vasospasm. In our small cohort of highly selected cases, ERT was associated with improvement in cerebral oxygenation and metabolism with reasonable outcome. Event neuromonitoring may facilitate individual and timely optimization of treatment modality according to the individual clinical course.

Intra-arterial vasodilator therapy for parainfectious cerebral vasospasm

Cerebrovascular complications of bacterial meningitis may include vasculitis, vasospasm or vasoconstriction, delayed cerebral infarction, venous and arterial thrombosis, intracranial aneurysm formation. The role of invasive endovascular therapies has not been well studied for infectious vasospasm, which can lead to dire neurologic consequences. We present 2 patients who were diagnosed with bacterial meningitis. Brain MRI showed areas of acute ischemia. Neurologic worsening was seen in both patients despite aggressive medical management. Follow-up imaging demonstrated significant narrowing of the intracranial vessels with associated new scattered infarcts. Both patients underwent targeted intra-arterial vasodilator infusion with angiographically improved vessel caliber and distal flow. The neurological exam subsequently stabilized in both cases. Follow-up radiographic images demonstrated no further ischemia in one of the 2 patients. Vasculopathy and vasospasm causing delayed ischemic neurologic deficit is a rare, but severe complication of acute meningitis. It can be a significant predictor of poor prognosis, and the disease may progress despite aggressive medical therapy. Although frequently used in subarachnoid hemorrhage-related vasospasm, to our knowledge, this is the first report of endovascular vasodilator treatment as adjunctive intervention in patients with meningitis associated vasculopathy.

Transcranial Doppler ultrasound in neurovascular diseases: diagnostic and therapeutic aspects

Albeit no direct anatomical information can be obtained, neurosonological methods provide real-time determination of velocity, and spectral waveform of blood flow in basal intracranial arteries adds significant benefit to the care of the patients with neurovascular diseases. Several features, such as relative simplicity in terms of interpretation and performance, significantly low cost, totally non-invasiveness, portability, and excellent temporal resolution, make neurosonology increasingly popular tool for evaluation, planning, and monitoring of treatment, and for determining prognosis in various neurovascular diseases. Usefulness of transcranial Doppler in diagnosing/monitoring subarachnoid hemorrhage related vasospasm and sickle cell vasculopathy is already well known. Utility in diagnosis of intracranial arterial stenosis, acute occlusion and recanalization, intracranial hemodynamic effect of the cervical arterial pathologies, intracranial pressure increase, and cerebral circulatory arrest are also well established. Neurosonological determination of vasomotor reactivity, cerebral autoregulation, neurovascular coupling, and micro-embolic signals detection are useful in the assessment of stroke risk, diagnosis of right-to-left shunting, and monitoring during surgery and interventional procedures. Transcranial Doppler is also an evolving ultrasound method with a therapeutic potential such as augmentation of clot lysis and cerebral delivery of thrombolytic or neuroprotective agent loaded nanobubbles in neurovascular diseases. The aim of this study is to give an overview of current usage of the different ultrasound modalities in different neurovascular diseases.

From bench-to-bedside in catastrophic cerebrovascular disease: development of drugs targeting the endothelin axis in subarachnoid hemorrhage-related vasospasm

Survivors of aneurysmal subarachnoid hemorrhage (SAH) may suffer functional dependence, cognitive impairment, and mood disorders. Cerebral vasospasm and delayed cerebral ischemia are associated with poor outcome in SAH and have been the subjects of intense investigation for decades. Recently a series of clinical trials was performed in SAH patients using an endothelin receptor antagonist. The results of these trials emphasize the disconnect between attenuation of cerebral vasospasm and improvement in functional outcome. The purpose of this review article is to evaluate the utilization of animal models for the development of drugs targeting the endothelin pathway in SAH and, given the recent endothelin receptor antagonist clinical trial results and lessons from the ischemic neuroprotection field, reflect on an alternative approach to in vivo preclinical drug testing in SAH.

THE IMPACT OF BALLOON ANGIOPLASTY ON THE EVOLUTION OF VASOSPASM-RELATED INFARCTION AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

Vasospasm of the cerebral vessels remains a major source for morbidity and mortality after aneurysmal subarachnoid hemorrhage. The purpose of this study was to evaluate the frequency of infarction after transluminal balloon angioplasty (TBA) in patients with severe subarachnoid hemorrhage-related vasospasm. We studied 38 patients (median Hunt and Hess Grade II and median Fisher Grade 4) with angiographically confirmed severe vasospasm (>70% vessel narrowing). A total of 118 vessels with severe vasospasm in the anterior circulation were analyzed. Only the middle cerebral artery, including the terminal internal carotid artery, was treated with TBA (n = 57 vessel segments), whereas the anterior cerebral artery was not treated (n = 61 vessel segments). For both the treated and the untreated vessel territories, infarction on unenhanced computed tomographic scan was assessed as a marker for adverse outcome. Infarction after TBA occurred in four middle cerebral artery territories (four out of 57 [7%]), whereas the infarction rate was 23 out of 61 (38%) in the anterior cerebral artery territories not subjected to TBA (P < 0.001, Fisher exact test). Three procedure-related complications occurred during TBA (dissection, n = 1; temporary vessel occlusions, n = 2). One of these remained asymptomatic, whereas this may have contributed to the development of infarction on follow-up computed tomographic scans in two cases. In a population of patients with a high risk of infarction resulting from vasospasm after subarachnoid hemorrhage, the frequency of infarction in the distribution of vessels undergoing TBA amounts to 7% and is significantly lower than in vessels not undergoing TBA despite some risk inherent to the procedure.

Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage

Vasospasm is one of the leading causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Radiographic vasospasm usually develops between 5 and 15 days after the initial hemorrhage, and is associated with clinically apparent delayed ischemic neurological deficits (DID) in one-third of patients. The pathophysiology of this reversible vasculopathy is not fully understood but appears to involve structural changes and biochemical alterations at the levels of the vascular endothelium and smooth muscle cells. Blood in the subarachnoid space is believed to trigger these changes. In addition, cerebral perfusion may be concurrently impaired by hypovolemia and impaired cerebral autoregulatory function. The combined effects of these processes can lead to reduction in cerebral blood flow so severe as to cause ischemia leading to infarction. Diagnosis is made by some combination of clinical, cerebral angiographic, and transcranial doppler ultrasonographic factors. Nimodipine, a calcium channel antagonist, is so far the only available therapy with proven benefit for reducing the impact of DID. Aggressive therapy combining hemodynamic augmentation, transluminal balloon angioplasty, and intra-arterial infusion of vasodilator drugs is, to varying degrees, usually implemented. A panoply of drugs, with different mechanisms of action, has been studied in SAH related vasospasm. Currently, the most promising are magnesium sulfate, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, nitric oxide donors and endothelin-1 antagonists. This paper reviews established and emerging therapies for vasospasm.

SSRI and statin use increases the risk for vasospasm after subarachnoid hemorrhage

Use of medications with vasoconstrictive or vasodilatory effects can potentially affect the risk for vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Using International Classification of Diseases-9 diagnostic codes followed by medical record review, the authors identified 514 patients with SAH admitted between 1995 and 2003 who were evaluated for vasospasm between days 4 and 14. The authors determined risks for vasospasm, symptomatic vasospasm, and poor clinical outcomes in patients with documented pre-hemorrhagic use of calcium channel blockers, beta-receptor blockers, ACE inhibitors, aspirin, selective serotonin reuptake inhibitors (SSRIs), non-SSRI vasoactive antidepressants, or statins. Vasospasm developed in 62%, and symptomatic vasospasm in 29% of the cohort. On univariate analysis, the risk for all vasospasm tended to increase in patients taking SSRIs (p = 0.09) and statins (p = 0.05); SSRI use increased the risk for symptomatic vasospasm (p = 0.028). The Cochran-Armitage trend test showed that the proportion of patients taking SSRIs and statins increased significantly across three worsening categories (none, asymptomatic, symptomatic) of vasospasm. Logistic regression analysis showed that SSRI use tended to predict all vasospasm (O.R. 2.01 [0.91 to 4.45]), and predicted symptomatic vasospasm (O.R. 1.42 [1.06 to 4.33]). Statin exposure increased the risk for vasospasm (O.R. 2.75 [1.16 to 6.50]), perhaps from abrupt statin withdrawal (O.R. 2.54 [0.78 to 8.28]). Age < 50 years, Hunt-Hess grade 4 or 5, and Fisher Group 3 independently predicted all vasospasm, symptomatic vasospasm, poor discharge clinical status, and death. Selective serotonin reuptake inhibitor and statin users have a higher risk for subarachnoid hemorrhage-related vasospasm. Whether the underlying disease indication, direct actions, or rebound effects from abrupt drug withdrawal account for the associated risk warrants further investigation.