Use of the Cascade expandable net to treat cerebral vasospasm – initial clinical experience from a single centre with in vitro benchside tests

Background The use of self-expanding stents to treat post-hemorrhagic cerebral vasospasm was recently described. We sought to determine the clinical efficacy of the Cascade device to treat delayed cerebral vasospasm (DCV). We performed benchside tests to determine the chronic outward force exerted by the Cascade in comparison to the Solitaire. Methods The chronic outward force (COF) of the Cascade M agile and Cascade L Agile was tested with equivalent tests of the Solitaire 4x20mm. Further tests to determine the forces generated in pre-formed tubes of 1.5–6 mm were performed using both fully and partially unsheathed Cascades. A retrospective review to identify all patients with aSAH and DCV treated with a Cascade device between January 2020 and July 2021. We recorded the treatment arterial vessel diameters and hemorrhagic or ischemic complications. Results In vitro the Cascade generated greater radial force than the Solitaire. The force generated by the Cascade M Agile at 1.5 mm was approximately 64% higher than the Solitaire 6x40mm and approximately 350% higher than the Solitaire 4x20mm. 4 patients with DCV were identified all of whom were treated with a cascade device. In all cases there was a significant improvement in the diameter of the vasospastic vessels treated with an average diameter increase of approximately 300%. There were no complications from the Cascade. Delayed CT angiography showed persistent dilatation of the segments treated with the Cascade at 24 h. Conclusion The Cascade is a safe and effective device when used to treat DCV secondary to aSAH. Larger studies are required to validate our initial results.

Spontaneous Intracerebral Hemorrhage and Delayed Cerebral Vasospasm in a Patient with COVID-19 Infection

Introduction: The SARS-CoV-2 may cause vasculitis and thromboembolic events. We report on an unusual case of spontaneous intracerebral hemorrhage and delayed cerebral vasospasms in a patient with COVID-19. Case Presentation: A 65-year-old male was transferred to the emergency department due to a short period of unconsciousness. Twenty-two hours prior to presentation, the patient had a 39.5°C fever with breathing difficulties. Initial COVID-19 PCR was positive. While conscious and without any neurological impairment, a large right frontal intracerebral hemorrhage (ICH) was detected. A preoperative angiogram showed no pathological blood vessels or vasospasm. The patients had a generalized tonic-clonic seizure due to ICH progression, which led to an immediate microsurgical ICH removal. Thirteen days thereafter, the patient became unconscious again. Angiography revealed severe cerebral vasospasm (CV) that required repetitive percutaneous transluminal angioplasty (PTA) and intra-arterial nimodipine treatment. Conclusions: We present the first case of ICH and delayed vasospasm associated with COVID-19. In these patients, combined maximum surgical and endovascular therapy is needed.

Valproic Acid Reduces Vasospasm through Modulation of Akt Phosphorylation and Attenuates Neuronal Apoptosis in Subarachnoid Hemorrhage Rats

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating emergent event associated with high mortality and morbidity. Survivors usually experience functional neurological sequelae caused by vasospasm-related delayed ischemia. In this study, male Sprague-Dawley rats were randomly assigned to five groups: sham (non-SAH) group, SAH group, and three groups with SAH treated with different doses of valproic acid (VPA) (10, 20, 40 mg/kg, once-daily, for 7 days). The severity of vasospasm was determined by the ratio of cross-sectional areas to intima-media thickness of the basilar arteries (BA) on the seventh day after SAH. The BA showed decreased expression of phospho-Akt proteins. The dentate gyrus showed increased expression of cleaved caspase-3 and Bax proteins and decreased expression of Bcl-2, phospho-ERK 1/2, phospho-Akt and acetyl-histone H3 proteins. The incidence of SAH-induced vasospasm was significantly lower in the SAH group treated with VPA 40 mg/kg (p < 0.001). Moreover, all groups treated with VPA showed reversal of the above-mentioned protein expression in BA and the dentate gyrus. Treatment with VPA upregulated histone H3 acetylation and conferred anti-vasospastic and neuro-protective effects by enhancing Akt and/or ERK phosphorylation. This study demonstrated that VPA could alleviate delayed cerebral vasospasm induced neuro-apoptosis after SAH.

Levosimendan as a therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid hemorrhage?

BackgroundPoor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration. CI is mainly triggered by enhanced synthesis of serotonin (5-HT), prostaglandin F2alpha (PGF2a), and cytokines such as interleukins. Levosimendan (LV), a calcium-channel sensitizer, has already displayed anti-inflammatory effects in patients with severe heart failure. Therefore, we wanted to elucidate its potential anti-inflammatory role on the cerebral vasculature after SAH.MethodsExperimental SAH was induced by using an experimental double-hemorrhage model. Sprague Dawley rats were harvested on day 3 and day 5 after the ictus. The basilar artery was used for isometric investigations of the muscular media tone. Vessel segments were either preincubated with LV or without, with precontraction performed with 5-HT or PGF2a followed by application of acetylcholine (ACh) or LV.ResultsAfter preincubation with LV 10−4 M and 5-HT precontraction, ACh triggered a strong vasorelaxation in sham segments (LV 10−4 M, Emax 65%; LV 10−5 M, Emax 48%; no LV, Emax 53%). Interestingly, SAH D3 (LV 10−4, Emax 76%) and D5 (LV 10−4, Emax 79%) segments showed greater vasorelaxation compared with sham. An LV series after PGF2a precontraction showed significantly enhanced relaxation in the sham (P=0.004) and SAH groups (P=0.0008) compared with solvent control vessels.ConclusionsLV application after SAH seems to beneficially influence DCVS by antagonizing 5-HT- and PGF2a-triggered vasoconstriction. Considering this spasmolytic effect, LV might have a role in the treatment of SAH, additionally in selected patients suffering takotsubo cardiomyopathy.

A Highly Predictive MicroRNA Panel for Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage

Approximately one-third of aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral vasospasm (DCV) 3–10 days after aneurysm rupture resulting in additional, permanent neurologic disability. Currently, no validated biomarker is available to determine the risk of DCV in aSAH patients. MicroRNAs (miRNAs) have been implicated in virtually all human diseases, including aSAH, and are found in extracellular biofluids including plasma and cerebrospinal fluid (CSF). We used a custom designed TaqMan Low Density Array miRNA panel to examine the levels of 47 selected brain and vasculature injury related miRNAs in CSF and plasma specimens collected from 31 patients with or without DCV at 3 and 7 days after aSAH, as well as from eight healthy controls. The analysis of the first 18-patient cohort revealed a striking differential expression pattern of the selected miRNAs in CSF and plasma of aSAH patients with DCV from those without DCV. Importantly, this differential expression was observed at the early time point (3 days after aSAH), before DCV event occurs. Seven miRNAs were identified as reliable DCV risk predictors along with a prediction model constructed based on an array of additional 19 miRNAs on the panel. These chosen miRNAs were then used to predict the risk of DCV in a separate, testing cohort of 15 patients. The accuracy of DCV risk prediction in the testing cohort reached 87%. The study demonstrates that our novel designed miRNA panel is an effective predictor of DCV risk and has strong applications in clinical management of aSAH patients.