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

https://doi.org/10.1016/j.neurad.2014.12.002Get rights and content

Summary

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.

Introduction

Cerebral infarction is strongly associated with poor outcome following SAH [1], [2]. Aetiologies include the acute injury [3], aneurysm treatment, or delayed ischaemia [4]. Proposed mechanisms for delayed ischaemia, either alone or in combination [4], [5], include microthrombosis, spreading depolarisation with cortical ischaemia and angiographic vasospasm (aVSP). The contribution of the latter is controversial [5], [6], [7], largely stemming from the finding that endothelin-receptor antagonists reduce the rate of moderate-severe aVSP but not the rate of poor outcome [8], [9]. However, there is a strong correlation between the severity of aVSP and infarct incidence [10]. The majority of delayed infarcts occur in association with aVSP [10], [11], [12], mostly with severe aVSP [10], [13], [14], which results in the most significant perfusion deficits [14], [15], [16], [17]. Severe aVSP is associated with poor cognition, worse patient-relevant outcomes, and greater inpatient healthcare resource use [18].

Two endovascular approaches have been employed to treat vasospasm; prophylactic TBA before vasospasm onset [19] or, use of TBA and/or IA vasodilators as a rescue procedure in patients who deteriorate despite medical therapy. The former approach may result in unnecessary treatments. The latter relies on early detection of clinical deterioration. However, these patients are often poor grade, comatose or sedated and difficult to assess. They may suffer silent infarction that itself has a negative impact on outcome [20], [21], [22]. An alternative approach is to screen for vasospasm with the intention of treating it while it is minimally symptomatic. We routinely undertake a program of angiographic surveillance at days 5–7 post-ictus, at or just before the time that most patients become symptomatic [23], [24] with subsequent endovascular treatment (multiple procedures where necessary) based on symptomology and radiographic features. We hypothesised that using this approach and comparing to benchmarks in the literature, rates of infarction and clinical outcomes were favourable.

Section snippets

Methods

This was a dual-centre retrospective observational study of patients with severe aVSP following aneurysmal SAH treated between November 2009 and December 2013. The study was approved by the regional ethics committee. Patients included were defined as having severe aVSP on the basis of > 66% arterial narrowing [10] on initial screening or subsequent DSAs. Statistical analysis was performed using Openstat software, 2013. Univariate analysis of non-parametric variables and their relationship to

Results

Fifty-seven patients were included: 18 males (31.6%) and 39 females (68.4%) of mean age 50.4 ± 3.0 years. Clinico-radiological features at presentation are shown in Table 1. Twenty-two patients (38.6%) were clipped and 35 patients (61.4%) were coiled. The aneurysm responsible for the haemorrhage was anterior circulation in 47 (82.5%) [ACA 24, ICA 14 and MCA 9] and posterior circulation in 10 (17.5%). Seven aneurysms (12.3%) were large (≥ 10 mm) and one was giant. Eleven patients (19.3%) presented > 

Discussion

Two established philosophies exist for endovascular vasospasm management: prophylactic TBA or rescue therapy. We use an intermediate paradigm, identifying aVSP and commencing treatment prior to neurological deterioration or whilst the patient is minimally symptomatic. Rates of cerebral infarction and clinical outcome were assessed.

Rates of infarction associated with severe aVSP range from 46–81% (see Table 6) [10], [13], [14]. In contrast, when patients presented within 72 hours and were treated

Conclusion

This study suggests that an intensive endovascular approach of TBA and multiple IA verapamil infusions can result in low rates of vasospasm-associated infarction and encouraging rates of favourable outcome when compared to literature benchmarks if treatment is instituted early when the patient is minimally symptomatic. Delayed presentation, however, predicts infarction and large infarct and poor initial grade significantly influence functional outcome. Further investigation is needed to fully

Contributions

All authors contributed to the manuscript and study.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Ethics approval: Northern Sydney and Central Coast Ethics Committee.

Acknowledgements

Professor R.L. Macdonald (university of Toronto) and Actelion (San Francisco, California, USA) for providing clinical outcome data for patients with severe angiographic vasospasm in the CONSCIOUS-1 trial.

References (53)

  • R.L. MacDonald

    Does prevention of vasospasm in subarachnoid hemorrhage improve clinical outcome? Yes

    Stroke

    (2013)
  • J. Hou et al.

    Does prevention of vasospasm in subarachnoid hemorrhage improve clinical outcome? No

    Stroke

    (2013)
  • R.L. Macdonald et al.

    Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) Randomized, Double-Blind, Placebo-Controlled Phase 2 Dose-Finding Trial

    Stroke

    (2008)
  • R.W. Crowley et al.

    Angiographic Vasospasm Is Strongly Correlated With Cerebral Infarction After Subarachnoid Hemorrhage

    Stroke

    (2011)
  • M. Wagner et al.

    Beyond Delayed Cerebral Vasospasm: Infarct Patterns in Patients with Subarachnoid Hemorrhage

    Clin Neuroradiol

    (2013)
  • R.J. Brown et al.

    The Relationship Between Delayed Infarcts and Angiographic Vasospasm After Aneurysmal subarachnoid Hemorrhage

    Neurosurgery

    (2013)
  • T. Inagawa et al.

    Risk Factors Associated with Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage

    Neurol Med Chir (Tokyo)

    (2014)
  • S. Weidauer et al.

    Impairment of Cerebral Perfusion and Infarct Patterns Attributable to Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Prospective MRI and DSA Study

    Stroke

    (2007)
  • H. Vatter et al.

    Perfusion-diffusion mismatch in MRI to indicate endovascular treatment of cerebral vasospasm after subarachnoid haemorrhage

    J Neurol Neurosurg Psychiatry

    (2011)
  • J.W. Dankbaar et al.

    Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

    Neuroradiology

    (2009)
  • R. Dhar et al.

    Relationship between Angiographic Vasospasm and Regional Hypoperfusion In Aneurysmal Subarachnoid Hemorrhage

    Stroke

    (2012)
  • R.L. Macdonald et al.

    Quality of Life and Healthcare Resource Use Associated With Angiographic Vasospasm After Aneurysmal Subarachnoid Hemorrhage

    Stroke

    (2012)
  • M. Zwienenberg-Lee et al.

    Effect of prophylactic transluminal balloon angioplasty on cerebral vasospasm and outcome in patients with Fisher Grade III subarachnoid hemorrhage: results of a Phase II multicenter, randomized, clinical trial

    Stroke

    (2009)
  • R.L. Macdonald et al.

    Factors associated with the development of vasospasm after planned surgical treatment of aneurysmal subarachnoid hemorrhage

    J Neurosurg

    (2003)
  • M. Shimoda et al.

    Asymptomatic versus symptomatic infarcts from vasospasm in patients with subarachnoid hemorrhage: serial magnetic resonance imaging

    Neurosurgery

    (2001)
  • J.M. Schmidt et al.

    Frequency and clinical impact of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage

    J Neurosurg

    (2008)
  • View full text