Institution of sustained endovascular treatment prior to clinical deterioration in patients with severe angiographic vasospasm: A retrospective observational study of clinico-radiological outcomes.

UNLABELLED: Severe angiographic vasospasm (aVSP) is a risk factor for infarction following subarachnoid haemorrhage and infarction is strongly associated with poor outcome. We present the clinico-radiological results of cohort with severe aVSP who underwent a program of angiographic surveillance and sustained endovascular treatment using multiple verapamil infusions and/or transluminal balloon angioplasty (TBA). METHODS: This was a dual-centre retrospective observational study. Angiographic screening for vasospasm was undertaken at days 5-7 post-ictus. Treatment was instituted principally on the basis of radiographic findings. The rate of infarction was evaluated on follow-up CT. Clinical outcome was assessed using the modified Rankin Scale (mRS). RESULTS: Fifty-seven WFNS grades 1-5 patients were studied. The mean number of procedures/patient was 6, range 2-13. Mean verapamil dose administered to the ICA was 14 mg and VA was 12 mg. Thirty-one patients underwent TBA (52.6%). The rate of proximal vessel infarction was 3/45 (6.7%) for patients presenting <72 hours. Rates of favourable outcome (mRS 0-2) were 16/19 (84.2%) for WFNS grades 1-2, 12/19 (63.2%) for grades 3-4 and 5/19 (26.3%) for grade 5 patients. Delayed presentation >72 hours was the only factor on multivariate analysis to significantly predict aVSP-infarction [OR19.3 (3.2-116.6) P=0.0012]. Large aVSP-infarction [OR19.0 (1.7-216.4) 0.0179] and poor WFNS grade [OR 6.6 (1.3-33.9) P = 0.0233] were significant predictors of poor outcome on multivariate analysis. CONCLUSION: This approach may result in low rates of aVSP-infarction and encouraging rates of favourable outcome when compared to literature benchmarks. Delayed presentation, however, predicts infarction and large infarct and poor initial grade significantly influence functional outcome.

Medical treatment of polymeric cerebral granulomatous reactions following endovascular procedures.

BACKGROUND: Endovascular procedures are standard of care for an increasing range of cerebrovascular diseases. Many endovascular devices contain plastic and are coated with a hydrophilic polymer which has been rarely described to embolize, resulting in distal granulomatous inflammatory lesions within the vascular territory. METHODS: We reviewed three cases of cerebral granulomatous reactions that occurred after endovascular intervention for internal carotid aneurysms. The patient procedure details, presentation, relevant investigations, and treatment course are described. We also provide a literature review on endovascular granulomatous reactions. RESULTS: These three cases represent the largest biopsy proven series of cerebral granulomatosis following endovascular intervention. We highlight the variable clinical presentation, with two of the three cases having an unusually delayed onset of up to 4 years following the intervention. We show the characteristic histological findings of granulomatous lesions with foreign body material consistent with a type IV reaction, radiological abnormalities of enhancing lesions within the vascular territory of the intervention, and the requirement of prolonged immunosuppression for maintenance of clinical remission, with two of the three patients requiring a corticosteroid sparing agent. In comparison with the available literature, in addition to hydrophilic gel polymer, we discuss that plastic from the lining of the envoy catheter may be a source of embolic material. We also discuss the recommendations of the Food and Drug Administration and the implementation of novel biomaterials for the prevention of these reactions in the future. CONCLUSIONS: There is a need for increased awareness of this severe complication of cerebral endovascular procedures and further longitudinal studies of its prevalence, optimal management and preventative measures.

Endovascular treatment of jugular bulb diverticula causing debilitating pulsatile tinnitus.

We describe the case of a patient who presented with debilitating pulsatile tinnitus in association with two jugular bulb diverticula. The diverticula were treated with stenting of the jugular bulb and coil embolization of the diverticula over two procedures. This resulted in successful resolution of symptoms and at 10 months follow-up the patient is asymptomatic. The technique is discussed with regard to similar published cases and surrogate measures of safety taken from the literature pertaining to idiopathic intracranial hypertension.

Delayed infarction following aneurysmal subarachnoid hemorrhage: Can the role of severe angiographic vasospasm really be dismissed?

BACKGROUND: The recent literature pertaining to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage has downplayed the role of angiographic vasospasm. However, it is our hypothesis that angiographic vasospasm has a significant pathophysiological role in this disease. We undertook an observational radiographic study of patients who presented in a delayed manner (>72 h from ictus) with evidence of severe angiographic vasospasm on initial angiography in order to describe an apparent association between vasospasm and infarct location. METHODS: This was a retrospective study of consecutive patients treated at our unit. Initial, subsequent, and follow-up cross-sectional imaging with CT or MRI was analyzed in conjunction with initial angiography. Sites of angiographic narrowing, angiographic hypoperfusion, and subsequent sites of infarction were assessed. RESULTS: Thirteen patients (6 women, 7 men) of mean age 49 years were assessed. Mean time to presentation was 6 days. All had severe angiographic vasospasm. Nine of the 13 patients suffered infarction; the infarcts in seven of the nine patients were large. There was correlation between sites of angiographic narrowing and infarction in all cases and eight of the nine cases showed angiographic hypoperfusion in a location corresponding to eventual infarct location. CONCLUSIONS: Severe angiographic vasospasm may be linked to infarction in patients who present late. These infarcts are mostly large despite maximal treatment. We question the notion that proximal vasospasm has a minor role in delayed ischemia.

Short term outcomes following clipping and coiling of ruptured intracranial aneurysms: does some of the benefit of coiling stem from less procedural impact on deranged physiology at presentation?

BACKGROUND: Endovascular coiling (EVC) has been shown to yield superior clinical outcomes to surgical clipping (SC) in the treatment of ruptured cerebral aneurysms. The reasons for these differences remain obscure. We aimed to assess outcomes of EVC and SC relative to baseline physiological derangement. METHODS: This was an exploratory analysis of prospectively collected trial data. Physiological derangement was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system. Other contributory variables such as age, World Federation of Neurosurgical Societies (WFNS) grade, and development of complications, including hydrocephalus and vasospasm, were included in the analysis. Clinical outcome was independently assessed at 90 days using the modified Rankin Scale (mRS). Hospital stay, ventilated days, and total norepinephrine dose were also used as secondary outcomes. Multivariate analysis was performed using binary logistic regression. RESULTS: EVC was performed in 69 patients and SC in 66 patients. More profound physiological derangement (APACHE II score >15) was the strongest predictor of poor outcome in the overall cohort (OR 17.80, 95% CI 4.78 to 66.21, p<0.0001). For those with more deranged physiology (APACHE II score>15; 59 patients), WFNS grade ≥4 (OR 6.74, 1.43 to 31.75) and SC (OR 6.33, 1.27 to 31.38) were significant predictors of poor outcome (p<0.05). Favorable outcome (mRS 0-2) was seen in 11% of SC patients compared with 38% of EVC patients in this subgroup. SC patients had significantly increased total norepinephrine dose, ventilated days, and hospital stay (p<0.05). CONCLUSIONS: More profound physiological derangement at baseline is a strong predictor of eventual poor outcome, and outcomes for patients with more profound baseline physiological derangement may be improved if undergoing a coiling procedure.

Rates of local procedural-related structural injury following clipping or coiling of anterior communicating artery aneurysms.

BACKGROUND: Surgical clipping and endovascular coiling yield similar functional outcomes for the treatment of saccular aneurysms of the anterior communicating (ACOM) artery. However, surgical treatment may be associated with greater rates of cognitive impairment due to injury of adjacent structures. We aimed to quantify the rates of injury (infarction/hemorrhage) for both clipping and coiling of ACOM aneurysms. METHODS: This was a retrospective dual-center radiological investigation of a consecutive series of patients with ruptured and unruptured ACOM aneurysms treated between January 2011 and October 2014. Post-treatment CT or MRI was assessed for new ischemic or hemorrhagic injury. Injury relating to the primary hemorrhage or vasospasm was differentiated. Univariate analysis using χ(2) tests and multivariate analysis using binary logistic regression was used. RESULTS: 66 patients treated with clipping were compared with 93 patients treated with coiling. 32/66 (48.5%) patients in the clipping group suffered treatment-related injury (31 ischemic, 1 hemorrhagic) compared with 4/93 (4.4%) patients in the coiling group (3 ischemic, 1 hemorrhagic) (p<0.0001). For patients with subarachnoid hemorrhage, the multivariate OR for infarction for clipping over coiling was 24.42 (95% CI 5.84 to 102.14), p<0.0001. The most common site of infarction was the basal forebrain (28/66 patients, 42.4%), with bilateral infarction in 4. There was injury of the septal/subcallosal region in 12/66 patients (18%). CONCLUSIONS: Clipping of ACOM aneurysms is associated with significantly higher rates of structural injury than coiling, and this may be a reason for superior cognitive outcomes in patients treated with coiling in previously published studies.

Endovascular treatment of jugular bulb diverticula causing debilitating pulsatile tinnitus.

We describe the case of a patient who presented with debilitating pulsatile tinnitus in association with two jugular bulb diverticula. The diverticula were treated with stenting of the jugular bulb and coil embolization of the diverticula over two procedures. This resulted in successful resolution of symptoms and at 10 months follow-up the patient is asymptomatic. The technique is discussed with regard to similar published cases and surrogate measures of safety taken from the literature pertaining to idiopathic intracranial hypertension.

The detrimental clinical impact of severe angiographic vasospasm may be diminished by maximal medical therapy and intensive endovascular treatment.

OBJECTIVE: Severe angiographic vasospasm (aVSP) is a risk factor for poor functional outcome following subarachnoid hemorrhage. We investigated the impact of angiographic surveillance and intensive endovascular treatment using transluminal balloon angioplasty (TBA) and/or verapamil infusion for severe aVSP through comparison of clinical outcomes in patients of similar presenting grade but with no/mild vasospasm. METHODS: This was an analysis of prospectively acquired clinical trial data. World Federation of Neurosurgical Societies (WFNS) grade 1-2 patients presenting within 72 h were included. Angiographic screening for vasospasm was undertaken at days 5-7 or in response to clinical deterioration. Severe aVSP was defined as >50% luminal narrowing on digital subtraction angiography. Treatment was instituted on the basis of radiographic findings and/or clinical deterioration. Discharge destination and favorable clinical outcomes (discharge Glasgow Outcome Score (GOS) 4-5, 90 day modified Rankin Scale (mRS) score 0-2, and GOS 4-5) for patients with severe aVSP were compared with those without significant vasospasm. Statistical analysis was undertaken using Fisher's exact test. RESULTS: 63 WFNS grade 1-2 patients with minimal vasospasm were compared with 17 WFNS grade 1-2 patients with severe aVSP treated with induced hypertension and endovascular therapy. Results were available in 62 and 16 patients, respectively. Rates of favorable outcome did not differ significantly between the two groups. For patients with treated severe vasospasm, 90 day mRS 0-2 was seen in 15/17 (88.2%) and GOS 4-5 was achieved in 16/17 (94.1%). CONCLUSIONS: An intensive endovascular approach of TBA and/or intra-arterial verapamil in combination with induced hypertension for severe aVSP may result in comparable clinical outcomes to those without vasospasm.

Bifurcation geometry and the presence of cerebral artery aneurysms.

OBJECT: The angles of arterial bifurcations are governed by principles of work minimization (optimality principle). This determines the relationship between the angle of a bifurcation and the radii of the vessels. Nevertheless, the model is predicated on an absence of significant communication between these branches. The circle of Willis changes this relationship because the vessels proximal to the ring of vessels have additional factors that determine work minimization compared with more distal branches. This must have an impact on understanding of the relationship between shear stress and aneurysm formation. The authors hypothesized that normal bifurcations of cerebral arteries beyond the circle of Willis would follow optimality principles of minimum work and that the presence of aneurysms would be associated with deviations from optimum bifurcation geometry. Nevertheless, the vessels participating in (or immediately proximal to) the circle of Willis may not follow the geometric model as it is generally applied and this must also be investigated. METHODS: One hundred seven bifurcations of the middle cerebral artery (MCA), distal internal carotid artery (ICA), and basilar artery (BA) were studied in 55 patients. The authors analyzed three-dimensional reconstructions of digital subtraction angiography images with respect to vessel radii and bifurcation angles. The junction exponent (that is, a calculated measure of the division of flow at the bifurcation) and the difference between the predicted optimal and observed branch angles were used as measures of deviation from the geometry thought best to minimize work. The mean junction exponent for MCA bifurcations was 2.9 +/- 1.2 (mean +/- standard deviation [SD]), which is close to the theoretical optimum of 3, but it was significantly smaller (p < 0.001; 1.7 +/- 0.8, mean +/- SD) for distal ICA bifurcations. In a multilevel multivariate logistic regression analysis, only the observed branch angles were significant independent predictors for the presence of an aneurysm. The odds ratio (OR) (95% confidence interval) for the presence of an aneurysm was 3.46 (1.02-11.74) between the lowest and highest tertile of the observed angle between the parent vessel and the largest branch. The corresponding OR for the smallest branch was 48.06 (9.7-238.2). CONCLUSIONS: The bifurcation beyond the circle of Willis (that is, the MCA) closely approximated optimality principles, whereas the bifurcations within the circle of Willis (that is, the distal ICA and BA) did not. This indicates that the confluence of hemodynamic forces plays an important role in the distribution of work at bifurcations within the circle of Willis. In addition, the observed branch angles were predictors for the presence of aneurysms.

A randomised controlled trial of induced hypermagnesaemia following aneurysmal subarachnoid haemorrhage.

BACKGROUND: The effect of serum magnesium concentration on the incidence of cerebral arterial vasospasm following aneurysmal subarachnoid haemorrhage (SAH) is unclear. OBJECTIVE: To test whether induced hypermagnesaemia reduces the incidence of cerebral arterial vasospasm following aneurysmal SAH. METHODS: The study was conducted at two tertiary hospitals in Australia and patients were recruited between 1 April 2005 and 31 December 2009. Within 72 hours of aneurysmal SAH, patients were randomly assigned to a high or normal target for serum magnesium concentration (1.60-2.50 mmol/L or 0.65-1.05 mmol/L, respectively). The primary end point was cerebral arterial vasospasm diagnosed by blinded assessment of digital subtraction angiography. Secondary outcomes included severity of vasospasm and functional recovery at 90 days. Analysis was by intention to treat. RESULTS: Of 162 patients, 81 were assigned to the normal range group and 81 were assigned to the high-range group; the primary outcome was available for 78 and 79 patients, respectively. The groups had similar baseline characteristics. Vasospasm occurred in 40 patients (50.6%) and 50 patients (64.1%) assigned to high-range and normal-range groups, respectively (adjusted OR, 0.51; 95% CI, 0.26-1.02; P = 0.06). At 90 days, neurological recovery between the groups was not significantly different (adjusted OR for worse outcome, 0.71; 95% CI, 0.39-1.32; P = 0.28). Patients in the high-range group were treated with more noradrenaline to support arterial blood pressure (79 [16- 218] mg) v 59 [14-129] mg; P = 0.03) and had lower mean (SD) serum calcium concentration (1.9 [0.2] mmol/L v 2.1 [0.2] mmol/L, P < 0.001). CONCLUSION: Patients assigned a higher serum magnesium concentration had a reduced incidence of vasospasm as seen by angiography, but the difference was not statistically significant. Clinically significant outcomes were not different between groups. A firm recommendation for induced hypermagnesaemia cannot be made from this study. TRIAL REGISTRATION NUMBER: ACTRN12605000058673.