Current Approaches to the Treatment of Cerebral Vasospasm Following Subarachnoid Haemorrhage

Current Approaches to the Treatment of Cerebral Vasospasm Following Subarachnoid Haemorrhage

Crowley R Webster, Dumont Aaron S , Kassell Neal F
Published: European Neurological Review - Volume 3 - Issue I
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Cerebral vasospasm following subarachnoid haemorrhage (SAH) is the leading potentially treatable cause of morbidity and mortality in patients who experience the rupture of an intracranial aneurysm.1,2 A significant predictor of outcome in patients with aneurysmal SAH, cerebral vasospasm is radiographically present in up to 70% of patients and is clinically evident in 20–30%.1,3 Annually, between seven and 20 people per 100,000 will experience a ruptured intracranial aneurysm.4–6 Fifty per cent of these patients will eventually die, while 15% will be rendered severely disabled. Only one-fifth to one-third of patients who experience a ruptured intracranial aneurysm will go on to have a moderate or good recovery.7,8 In large part, this poor prognosis is due to the significant death and disability associated with vasospasm. Approximately 50% of patients with symptomatic vasospasm will develop infarctions, and 15–20% will develop a disabling stroke or die of ischaemia.9,10

Cerebral vasospasm following subarachnoid haemorrhage (SAH) is the leading potentially treatable cause of morbidity and mortality in patients who experience the rupture of an intracranial aneurysm.1,2 A significant predictor of outcome in patients with aneurysmal SAH, cerebral vasospasm is radiographically present in up to 70% of patients and is clinically evident in 20–30%.1,3 Annually, between seven and 20 people per 100,000 will experience a ruptured intracranial aneurysm.4–6 Fifty per cent of these patients will eventually die, while 15% will be rendered severely disabled. Only one-fifth to one-third of patients who experience a ruptured intracranial aneurysm will go on to have a moderate or good recovery.7,8 In large part, this poor prognosis is due to the significant death and disability associated with vasospasm. Approximately 50% of patients with symptomatic vasospasm will develop infarctions, and 15–20% will develop a disabling stroke or die of ischaemia.9,10

Despite the clinical significance of cerebral vasospasm and the extensive research efforts dedicated towards elucidating its pathogenesis and therapy, vasospasm remains an incompletely understood clinical problem. Although progress has been made in the diagnosis and treatment of SAH, the overall prognosis of patients with ruptured intracranial aneurysms remains poor. This article will review current strategies for the management of cerebral vasospasm.

Treatment of Cerebral Vasospasm
Several promising theories have developed from the intense research efforts aimed at cerebral vasospasm following SAH. However, as yet no individual theory has been able to completely explain its pathogenesis, which is complex and likely multifactorial; therefore, therapies directed at the treatment of cerebral vasospasm vary widely in both the intended target and the effect. These therapies can be broadly categorised into four groups according to the mechanism by which they are designed to reduce vasospasm, although no treatment has been found to be universally efficacious. These groups include therapies that prevent arterial narrowing, reverse arterial narrowing, enhance cerebral perfusion and protect against and rescue from cerebral ischaemia (see Table 1). While these groups are not mutually exclusive, and treatment options can potentially affect vasospasm through a variety of ways, they underscore the various ways in which the treatment of cerebral vasospasm can be approached. In order to treat vasospasm aggressively one must first treat the ruptured aneurysm itself, ideally within the first two days after aneurysmal rupture.4 Once the aneurysm is secured, the treating physician has the complete armamentarium available for the treatment of vasospasm.

Removal of Blood Clot
Cerebral vasospasm has been shown to arise from the presence of clot, specifically red blood cells (RBCs),11 within the subarachnoid space. A volume-dependent relationship exists between clot burden and subsequent risk of vasospasm.12–15 While conflicting opinions remain regarding the exact components within the clot that incite cerebral vasospasm, it is clear that the presence of clot is related to an increased risk of vasospasm.

Knowing that the presence of blood clot can incite cerebral vasospasm, it follows that reducing this clot burden may be an effective treatment for its prevention. Reducing the blood clot associated with SAH, either with direct removal during surgery or with the delivery of catheter-infused tissue plasminogen activator (tPA) into subarachnoid cisterns, has been previously described in the literature.16–19 Indlay and colleagues19 conducted the only randomised trial looking at intra-operative recombinant (r-tPA) therapy, with its injection into the basal subarachnoid cisterns following surgical management of ruptured intracranial aneurysms. They found that several groups tended towards lesser degrees of vasospasm when r-tPA was administered; however, the only statistically significant improvement was seen when it was administered in the setting of thick subarachnoid clots. A later meta-analysis studied a total of 652 patients who were treated with intracisternal thrombolytics.16 This study concluded that, despite a lack of large, randomised, prospective trials, thrombolytic therapy provided a statistically significant beneficial effect. Their analysis found no difference between those who received intra-operative injections and those who received post-operative treatments. However, the dearth of well-designed prospective, randomised studies means that there are no consistent data supporting this routine practice.

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