Poor expression of miR-195-5p can assist the diagnosis of cerebral vasospasm after subarachnoid hemorrhage and predict adverse outcomes.

OBJECTIVE: Patients with spontaneous subarachnoid hemorrhage (SAH) may develop refractory arterial cerebral vasospasm (CVS), which is the leading cause of death in SAH patients. This study explored the clinical diagnostic value of serum miR-195-5p levels in CVS after SAH (SAH + CVS) and its relationship with the prognosis of SAH + CVS. METHODS: A total of 110 patients with spontaneous SAH were divided into the SAH group (N = 62) and SAH + CVS group (N = 58), with 60 healthy subjects as controls. The clinical data of blood glucose, blood sodium fluctuation, and serum lactic acid were recorded. miR-195-5p serum level was detected by RT-qPCR and its diagnostic value on SAH + CVS was analyzed by receiver operating characteristic curve. Serum levels of PDGF/IL-6/ET-1 and their correlation with miR-195-5p were analyzed using RT-qPCR, enzyme-linked immunosorbent assay, and Pearson's method. The patient prognosis was evaluated by Glasgow Outcome Scale. The effect of miR-195-5p levels on adverse prognosis was analyzed by Kaplan-Meier method and Cox regression analysis. RESULTS: miR-195-5p was lowly expressed in the serum of SAH patients and lower in SAH + CVS patients. Serum miR-195-5p level assisted the diagnosis of SAH and SAH + CVS and was negatively correlated with PDGF/IL-6/ET-1 levels and was an independent risk factor together with ET-1 and blood glucose for SAH + CVS. miR-195-5p low expression predicted a higher cumulative incidence of adverse outcomes and was an independent predictor of adverse outcomes. CONCLUSION: Poor expression of miR-195-5p can assist the diagnosis of SAH + CVS and predict higher adverse outcomes.

Primary angiitis of the central nervous system and reversible cerebral vasoconstriction syndrome: analysis of the National Inpatient Sample.

INTRODUCTION: Primary angiitis of the central nervous system (PACNS) and reversible cerebral vasoconstriction syndrome (RCVS) are two rare syndromes that affect the cerebral vasculature. Both conditions have been shown to cause severe neurologic complications. Distinguishing these two conditions in clinical practice is often challenging. Here, we compare the clinical features and outcomes of RCVS and PACNS hospitalizations against the general adult inpatient population. MATERIALS AND METHODS: We conducted a retrospective review of hospitalizations with a diagnosis of PACNS or RCVS from 2016 to 2018 in the National Inpatient Sample (NIS) database. Multivariate analysis was performed to calculate adjusted odds ratios (ORadj) for hospital outcomes. RESULTS: In the NIS, 3305 hospitalizations had a diagnosis of RCVS and 6035 hospitalizations had a diagnosis of PACNS. RCVS hospitalizations had a significantly greater association with cerebral aneurysms (ORadj 23.80), hemiplegia/hemiparesis following subarachnoid hemorrhage (SAH) (ORadj 324.09), ischemic stroke (ORadj 7.59), and nontraumatic SAH (ORadj 253.61). PACNS hospitalizations had a significantly greater association with hemiplegia/hemiparesis following cerebrovascular accident (CVA) (ORadj 6.16), ischemic stroke (ORadj 11.55), nontraumatic SAH (ORadj 7.29), seizure (ORadj 2.49), and in-hospital mortality (ORadj 2.85). CONCLUSIONS: We performed an analysis of the NIS to better understand RCVS and PACNS hospitalizations. Severe neurologic events including CVA and SAH were elevated in both, but SAH and related hemiplegia/hemiparesis were extremely common among RCVS hospitalizations. In-hospital mortality was elevated in PACNS but not RCVS. This information can be used to help clinicians better understand, distinguish, and diagnose these conditions. Key Points • Despite clear description of RCVS and PACNS in the medical literature, there remains a scarcity of national population-based studies comparing these two entities against the general adult inpatient population. • This study aims to fill knowledge gaps in this area. • Here, we compare the clinical features and outcomes of RCVS and PACNS hospitalizations against the general adult inpatient population.

Methodological assessment of guidelines for the diagnosis and management of cerebral vasospasm using the AGREE-II tool.

OBJECTIVE: Rupture of an intracranial aneurysm is the most common cause of spontaneous subarachnoid hemorrhage. Despite the recent advances in its early detection, diagnosis, and proper treatment, the outcome of patients experiencing aneurysmal subarachnoid hemorrhage (aSAH) remains poor. It is well known that cerebral vasospasm is the most troublesome complication of aSAH, while delayed cerebral ischemia related to cerebral vasospasm constitutes the major cause of unfavorable outcomes in patients with aSAH. The need for evidence-based guidelines is of great importance for the prevention, early detection, and efficient management of aSAH-induced vasospasm. Moreover, guidelines provide young physicians with a valuable tool for practicing defensible medicine. However, the methodology, clinical applicability, reporting clarity, and biases of guidelines must be periodically assessed. In this study, the authors sought to assess the reporting clarity and methodological quality of published guidelines and recommendations. METHODS: A search was performed in the PubMed, Scopus, and Web of Science databases. The search terms used were "clinical practice guidelines," "recommendations," "stroke," "subarachnoid hemorrhage," and "vasospasm" in all possible combinations. The search period extended from 1964 to September 2021 and was limited to literature published in the English language. All published guidelines and recommendations reporting on the diagnosis and management of vasospasm were included. Studies other than those reporting guidelines and recommendations were excluded. The eligible studies were evaluated by three blinded raters, employing the Appraisal of Guidelines for Research & Evaluation II (AGREE-II) analysis tool. RESULTS: A total of 10 sets of guidelines were evaluated in this study. The American Heart Association/American Stroke Association issued guidelines found to have the highest methodological quality and reporting clarity, followed by the European Stroke Organization guidelines and the English edition of the Japanese guidelines issued by the Japanese Society on Surgery for Cerebral Stroke. The interrater agreement was moderate in the current analysis. CONCLUSIONS: These findings support the idea that improvement of currently existing guidelines is feasible in the following domains: the rigor of guidelines and recommendations development, clinical applicability, editorial independence, and stakeholder involvement. Furthermore, periodic updating of published guidelines requires improvement in the future.

Chemical Angioplasty with Nitroglycerin for Vasospasm after Subarachnoid Hemorrhage: Case Series and Review

Introduction Vasospasm is a common and potentially devastating complication in patients with subarachnoid hemorrhage, causing high morbidity and mortality. There is no effective and consistent way to prevent or treat cerebral vasospasm capable of altering the morbidity and mortality of this complication. Animal and human studies have attempted to show improvement in aneurysmal vasospasm. Some sought their prevention; others, the treatment of already installed vasospasm. Some achieved only angiographic improvement without clinical correlation, others achieved both, but with ephemeral duration or at the expense of very harmful associated effects. Endovascular techniques allow immediate and aggressive treatment of cerebral vasospasm and include methods such as mechanical and chemical angioplasty. These methods have risks and benefits. Objectives To analyze the results of chemical angioplasty using nitroglycerin (GTN). In addition, to performa comprehensive review and analysis of aneurysmal vasospasm. Methods We describe our series of 77 patients treated for 8 years with angioplasty for vasospasm, either mechanical (with balloon), chemical (with GTN) or both. Results Eleven patients received only balloon; 37 received only GTN; 29 received both. Forty-four patients (70.1%) evolved with delayed cerebral ischemia and 19 died (mortality of 24.7%). Two deaths were causally related to the rupture of the vessel by the balloon. The only predictors of poor outcome were the need for external ventricular drainage in the first hours of admission, and isolated mechanical angioplasty. Conclusions Balloon angioplasty has excellent results, but it is restricted to proximal vessels and is not without complications. Chemical angioplasty using nitroglycerin has reasonable but short-lived results and further research is needed about it. It is restricted to vasospasm angioplasties only in hospitals, like ours, where better and more potent vasodilator agents are not available.

Reversible cerebral vasoconstriction syndrome (RCVS): an interesting case report.

BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome is a condition of transient cerebral vascular spasms, which usually presents with recurrent thunderclap headaches and recovers within 3 months. Several probable triggers and underlying factors, such as sex hormones, vasoactive drugs, head trauma or surgery, and tumors, have been implicated. CASE PRESENTATION: In this paper, we present a 53-year-old woman with thunderclap headaches and normal lab tests who was radio-clinically diagnosed with reversible cerebral vasoconstriction syndrome and treated accordingly. Then, she experienced the recurrence of RCVS after about 2 years and headaches after 1 year in association with high blood pressure, high blood sugar, hypothyroidism, hyperlipidemia, and a urine metanephrine level of 5 times higher than the normal limit, suggesting a diagnosis of pheochromocytoma. After confirmation of the diagnosis with further imaging studies, surgical removal of the tumor resolved all the signs and symptoms. CONCLUSION: Often underdiagnosed, pheochromocytoma could be an important condition associated with RCVS. It is important for clinicians to bear this diagnosis in mind while dealing with similar cases of recurrent thunderclap headaches.

Mechanically Induced Vasospasm and Postoperative Cerebral Infarction after Coil Embolization of Unruptured Cerebral Aneurysms in Anterior Circulation.

We occasionally encounter situations which requires retraction of the guiding system or administration of vasodilatory agents for mechanically induced vasospasm (MVS). However, whether MVS is associated with postoperative cerebral infarction has not been reported.To explore factors associated with MVS and to verify how MVS influences procedure outcomes,we reviewed consecutive cases of unruptured aneurysms in the anterior circulation treated with coil embolization between January 2017 and February 2020. Collected data included patients' clinical characteristics, devices, vessel tortuosity, severity of MVS, diameter of the parent vessel, and procedure duration. Significant MVS was defined as a condition necessitating a pause in the procedure. We also counted postoperative diffusion-weighted imaging (DWI) hyperintense spots (DHS). Parameters associated with MVS and postoperative DHS were investigated by multivariate logistic regression.A total of 103 cases met the eligibility criteria, with significant MVS occurring in 21 cases (20.3%), and postoperative DHS (≥3) confirmed in 30 cases (29.1%). Significant MVS was associated only with larger caliber at the tip of the guiding system compared with the parent vessel (p = 0.001). Postoperative DHS was associated with significant MVS (p = 0.002, OR: 5.313; 95% CI: 1.851-15.254).Significant MVS is a predictor of postoperative cerebral ischemia and occurs in patients with smaller caliber of the parent vessel. In patients with high-risk features for MVS, we should avoid navigating the guiding system forcibly through the narrow parent vessel. In other words, it is crucial to place the large-caliber guiding sheath/catheter proximally and only guide distally the intermediate catheter with better trackability.

Longitudinal imaging and evaluation of SAH-associated cerebral large artery vasospasm in mice using micro-CT and angiography.

Longitudinal in vivo imaging studies characterizing subarachnoid hemorrhage (SAH)-induced large artery vasospasm (LAV) in mice are lacking. We developed a SAH-scoring system to assess SAH severity in mice using micro CT and longitudinally analysed LAV by intravenous digital subtraction angiography (i.v. DSA). Thirty female C57Bl/6J-mice (7 sham, 23 SAH) were implanted with central venous ports for repetitive contrast agent administration. SAH was induced by filament perforation. LAV was assessed up to 14 days after induction of SAH by i.v. DSA. SAH-score and neuroscore showed a highly significant positive correlation (rsp = 0.803, p < 0.001). SAH-score and survival showed a negative significant correlation (rsp = -0.71, p < 0.001). LAV peaked between days 3-5 and normalized on days 7-15. Most severe LAV was observed in the internal carotid (Δmax = 30.5%, p < 0.001), anterior cerebral (Δmax = 21.2%, p = 0.014), middle cerebral (Δmax = 28.16%, p < 0.001) and basilar artery (Δmax = 23.49%, p < 0.001). Cerebral perfusion on day 5 correlated negatively with survival time (rPe = -0.54, p = 0.04). Arterial diameter of the left MCA correlated negatively with cerebral perfusion on day 3 (rPe = -0.72, p = 0.005). In addition, pseudoaneurysms arising from the filament perforation site were visualized in three mice using i.v. DSA. Thus, micro-CT and DSA are valuable tools to assess SAH severity and to longitudinally monitor LAV in living mice.

Unusual Presentation of Vasospasm Masking Underlying Pseudoaneurysm After Endoscopic Transsphenoidal Surgery in Pituitary Macroadenoma.

BACKGROUND: Vascular complications during transsphenoidal surgery can be devastating. Direct vascular injury during surgery can lead to various complications including pseudoaneurysm formation. Postoperative hematoma and direct vascular handling due to arachnoid tear can induce vasospasm. The vasospasm might present with varying clinical symptomatology and at times masks the underlying pathology as well. CASE DESCRIPTION: We present here a case of pituitary macroadenoma in whom the vasospasm caused vision loss and also concealed a developing pseudoaneurysm. CONCLUSIONS: Angiograms at regular intervals should be performed in cases where intraoperative vascular injury is suspected to detect such aneurysms and prevent catastrophe.

Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by an acute onset of severe headache and multi-focal segmental vasoconstriction of cerebral arteries resolving within 12 weeks. Diagnostic criteria include normal or near-normal findings in cerebrospinal fluid (CSF) analysis, especially leucocyte levels < 10/mm³. Distinguishing RCVS from primary angiitis of the central nervous system (PACNS) is essential to avoid unnecessary and sometimes unfavourable immunosuppressive treatment. We reviewed retrospectively the clinical and diagnostic data of 10 RCVS patients who presented in our neurological department from 1 January 2013 to February 2017. The main purpose was to verify whether CSF leucocyte counts < 10/mm³ serve to discriminate RCVS from PACNS. Five of six patients who underwent lumbar puncture presented with CSF leucocyte levels ≥ 10/mm³. Two patients had a history of misinterpretation of CSF pleocytosis as cerebral vasculitis and of immunosuppressive treatment. A complete restitution of cerebral vasoconstriction was evident in all. No patient had further cerebral strokes or bleedings without immunosuppressive treatment over more than 12 weeks. Despite the established diagnostic criteria, RCVS can manifest with CSF leucocyte levels > 10/mm³. Careful anamnesis and the response of 'vasculitis-like angiography' to nimodipine given as a test during angiography and as oral medication are key to differentiate RCVS from cerebral vasculitis.

Cerebral vasospasm after transsphenoidal surgery for pituitary adenoma: Case report and review of the literature.

INTRODUCTION: Cerebral vasospasm (CVS) is a rare complication of transsphenoidal surgery for pituitary adenomas. CASE REPORT: The authors describe a symptomatic cerebral ischemia due to an internal carotid, left middle cerebral artery and anterior cerebral artery vasospasm in a patient undergoing transsphenoidal surgery for a pituitary macro adenoma. The patient was successfully treated by an endovascular balloon angioplasty. CONCLUSION: This issue should be taken into account, even when rare, in every patient who has surgery for a pituitary tumor, particularly when it concerns a large macro adenoma with suprasellar extension. Special precautions must be taken to avoid this rare complication.

Effect of heparin on secondary brain injury in patients with subarachnoid hemorrhage: an additional 'H' therapy in vasospasm treatment.

OBJECTIVE: Secondary brain injury leads to high morbidity and mortality rates in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, evidence-based treatment strategies are sparse. Since heparin has various effects on neuroinflammation, microthromboembolism and vasomotor function, our objective was to determine whether heparin can be used as a multitarget prophylactic agent to ameliorate morbidity in SAH. METHODS: Between June 1999 and December 2014, 718 patients received endovascular treatment after rupture of an intracranial aneurysm at our institution; 197 of them were treated with continuous unfractionated heparin in therapeutic dosages after the endovascular procedure. We performed a matched pair analysis to evaluate the effect of heparin on cerebral vasospasm (CVS), cerebral infarction (CI), and outcome. RESULTS: The rate of severe CVS was significantly reduced in the heparin group compared with the control group (14.2% vs 25.4%; p=0.005). CI and multiple ischemic lesions were less often present in patients with heparin treatment. These effects were enhanced if patients were treated with heparin for >48 hours, but the difference was not significant. Favorable outcome at 6-month follow-up was achieved in 69% in the heparin group and in 65% in the control group. CONCLUSIONS: Patients receiving unfractionated continuous heparin after endovascular aneurysm occlusion have a significant reduction in the rate of severe CVS, have CI less often, and tend to have a favorable outcome more often. Our findings support the potential beneficial effects of heparin as a multitarget therapy in patients with SAH, resulting in an additional 'H' therapy in vasospasm treatment.

A segmentation-based volumetric approach to localize and quantify cerebral vasospasm based on tomographic imaging data.

INTRODUCTION: Quantification of cerebral vasospasm after subarachnoid hemorrhage (SAH) is crucial in animal studies as well as clinical routine. We have developed a method for computer-based volumetric assessment of intracranial blood vessels from cross-sectional imaging data. Here we demonstrate the quantification of vasospasm from micro computed tomography (micro-CT) data in a rodent SAH model and the transferability of the volumetric approach to clinical data. METHODS: We obtained rodent data by performing an ex vivo micro-CT of murine brains after sham surgery or SAH by endovascular filament perforation on day 3 post hemorrhage. Clinical CT angiography (CTA) was performed for diagnostic reasons unrelated to this study. We digitally reconstructed and segmented intracranial vascular trees, followed by calculating volumes of defined vessel segments by standardized protocols using Amira® software. RESULTS: SAH animals demonstrated significantly smaller vessel diameters compared with sham (MCA: 134.4±26.9µm vs.165.0±18.7µm, p<0.05). We could highlight this difference by analyzing vessel volumes of a defined MCA-ICA segment (SAH: 0.044±0.017µl vs. sham: 0.07±0.006µl, p<0.001). Analysis of clinical CTA data allowed us to detect and volumetrically quantify vasospasm in a series of 5 SAH patients. Vessel diameters from digital reconstructions correlated well with those measured microscopically (rodent data, correlation coefficient 0.8, p<0.001), or angiographically (clinical data, 0.9, p<0.001). CONCLUSIONS: Our methodological approach provides accurate anatomical reconstructions of intracranial vessels from cross-sectional imaging data. It allows volumetric assessment of entire vessel segments, hereby highlighting vasospasm-induced changes objectively in a murine SAH model. This method could also be a helpful tool for analysis of clinical CTA.

Impact of Target Arterial Residual Stenosis on Outcome After Endovascular Revascularization.

BACKGROUND AND PURPOSE: Acute intracranial occlusion can be associated with in situ thrombo-occlusion in relation to preexisting intracranial atherosclerotic disease. We aimed to assess residual stenosis at the site of a target arterial lesion (TAL) to determine whether residual stenosis at the TAL is associated with underlying intracranial atherosclerotic disease. METHODS: One hundred and sixty-three patients who underwent endovascular therapy for M1 middle cerebral artery occlusion and achieved angiographic reperfusion were selected for analysis. The presence of residual stenosis at the TAL was classified using the Arterial Occlusive Lesion (AOL) scale at postprocedural angiography, and the severity of stenosis was grouped into none, mild (<50%), moderate (50%-69%), severe (70%-99%), and occlusion on postprocedural and follow-up angiography. We also recorded the incidence of instant reocclusion occurring during the procedure and delayed reocclusion detected on follow-up angiography. RESULTS: Seventy-four patients (45.5%) showed target arterial residual stenosis (AOL 2). As to the TAL pathogenesis, 40 patients were classified into in situ thrombo-occlusion (54.1% of AOL 2 and 24.5% of M1 occlusion). The occurrence of instant or delayed reocclusion was independently associated with a low chance of favorable 3-month outcome. Furthermore, the occurrence of delayed reocclusion was associated with excellent pretreatment collateral flow and early neurological worsening, but not the severity of residual stenosis at the TAL. CONCLUSIONS: In population with a high prevalence of intracranial atherosclerotic disease, residual stenosis may be attributed to in situ thrombo-occlusion with underlying intracranial atherosclerotic disease in ≈25% of cases, hindering functional recovery via the occurrence of instant or delayed reocclusion.

Severe Cerebral Vasospasm and Childhood Arterial Ischemic Stroke After Intrathecal Cytarabine.

We report on 2 patients who developed widespread cerebral vasospasm and arterial ischemic strokes (AIS) after application of intrathecal (IT) cytarabine. In a 3-year-old child with acute lymphoblastic leukemia (ALL), left leg weakness, hyperreflexia, and clonus were noted 4 days after her first dose of IT cytarabine during the induction phase of her chemotherapy. Cerebral MRI revealed multiple acute cerebral ischemic infarcts and widespread cerebral vasospasm. A 5-year-old girl complained of right arm and leg pain and began limping 11 days after IT cytarabine. Symptoms progressed to right dense hemiplegia, left gaze deviation, headache, and speech arrest. MRI revealed 2 large cortical areas of diffusion restriction in the right frontal and left parietal lobes. Cerebral magnetic resonance angiography (MRA) showed irregular narrowing affecting much of the intracranial arterial circulation. Although the first child fully recovered from her neurologic symptoms, the second patient had persistent hemiplegia on follow-up. Including this report, there are now 4 pediatric ALL cases of severe cerebral vasospasm and AIS in the context of IT cytarabine administration, strongly suggesting a true association. Differential diagnosis and management issues are discussed. Along with the more widespread use of MRI and MRA, the true frequency of this severe adverse effect will become clearer in future. For any child with neurologic symptoms within hours or days of receiving IT cytarabine, a low threshold for cerebral imaging with MRI and MRA is recommended.

Detection of Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage Using Motor Evoked Potentials.

BACKGROUND: Early detection of vasospasm (VS) following aneurysmal subarachnoid hemorrhage (aSAH) is vital to trigger therapy and to prevent infarction and subsequent permanent neurological deficit. Although motor evoked potentials (MEPs) are a well-established method for intraoperative detection of cerebral VS and cerebral ischemia during aneurysm surgery, there are no studies investigating the diagnostic value of MEPs for detecting delayed VS following aSAH in an intensive care unit. OBJECTIVE: A prospective study was conceived to assess the diagnostic accuracy of MEPs in comparison with digital subtraction angiography. METHODS: MEP threshold changes were determined in patients both with and without angiographic VS following high-grade aSAHs. Sensitivity, specificity, and the positive and negative predictive values of significant MEP threshold increases, which indicate angiographic VS, were calculated. RESULTS: In all patients experiencing VS of the arteries supplying cerebral motor areas, a minimal MEP threshold increase of 50 mA (mean 66.25 mA) was observed, whereas a maximum MEP threshold increase of 30 mA was observed in patients without VS. Therefore, an increase from a baseline of ≥50 mA was considered significant and resulted in a sensitivity of 0.83, a specificity of 0.92, a positive predictive value of 0.83, and a negative predictive value of 0.92. CONCLUSION: VS following aSAH can be detected accurately by using MEPs. MEPs are a feasible bedside tool for online VS detection in an intensive care unit and, therefore, may complement existing diagnostic tools.

Complications and follow up of subarachnoid hemorrhages.

Complications of subarachnoid hemorrhage are the major life threatening and functional components of the follow up of a ruptured aneurysm. Knowing how to identify these is a key challenge. They vary in type throughout the postoperative follow up period. The aim of this article is firstly to list the main complications of the acute phase (rebleeding, acute hydrocephalus, acute ischemic injury and non-neurological complications), the subacute phase (vasospasm) and the chronic phase of subarachnoid hemorrhages: (chronic hydrocephalus and cognitive disorders) and to describe their major clinical and radiological features. Secondly, we describe the long-term follow up strategy for patients who have suffered a subarachnoid hemorrhage and have been treated endovascularly or by surgery. This follow up involves a combination of clinical consultations, cerebral MRI and at least one review angiogram.