Cerebral vasospasm following subarachnoid hemorrhage

Cerebral vasospasm following subarachnoid haemorrhage is a major complication of subarachnoid haemorrhage (SAH). It is overtaking rebleed as the major cause of mortality and morbidity in the subgroup of patients with SAH who reach hospital and receive medical care. 

It is seen in 40-70% of SAH patients on vascular imaging, and becomes clinically apparent in 20-30% of patients, typically from the 4^th to 10^th day post bleed.

Pathology

After decades of research the exact mechanism(s) responsible remain elusive although a number of candidate agents are demonstrated to play a role. These include:

• NO (nitrous oxide)
• endothelin ¹ 
• oxyhaemoglobin
• others:
  • thrombin
  • serotonin
  • thromboxane A2
  • noradrenalin
  • sphingosine 1-phosphate

Most likely the 'true' pathway involves multiple agents interacting with each other, both biochemically and via changes in gene expression, accounting for the delay of onset.

Oxyhaemoglobin, highest in concentration in arterial blood, appears to simultaneously up-regulate the expression of endothelin 1 (ET-1) and reduce the efficacy of NO.

This results in alteration of normal vascular tone, resulting in narrowing of the large vessels. Increasingly it is also becoming apparent that small caliber vessels which are in contact with CSF blood are narrowed also - down to 15 micrometers -  far too small to be visualised on angiography, let alone CTA/MRA.  

The result, if severe enough, is to reduce perfusion of brain parenchyma resulting in ischaemic symptoms, infarction, and its sequelae. 

The degree of vasospasm is difficult to predict but correlates with the original Fisher scale and more accurately with the modified Fisher scale.

Treatment and prognosis

Aggressive, early and prophylactic treatment can markedly reduce the incidence of vasospasm, but often requires early securing of the ruptured aneurysm. Three main modalities are employed:

Triple H therapy

Haemodilution, Hypertension, Hypervolaemia to maintain adequate cerebral perfusion pressure is achieved with hydration and inotropes if necessary. This often requires admission to a neuroICU with central venous catheter and intracranial pressure (ICP) monitoring.

Calcium channel blockers

Nimodipine is the best known and most widely used calcium channel blocker, which dilate vessels especially leptomeningeal collateral.

Endovascular intervention

In severe cases, intra-arterial therapy can be beneficial. Intra-arterial delivery of a calcium channel blocker such as Nimodipine or Verapamil has replaced previously used drugs such as Papaverine. They are administered by slow bolus injection into the relevant vascular territory via a standard diagnostic catheter, with careful monitoring of blood pressure. Treatment may need to be repeated daily for 3-5 days.

Balloon angioplasty is a more invasive neurointerventional technique requiring a guiding catheter and placement of an endovascular micro balloon over a guide wire across the affected segment. Expanding the balloon disrupts the smooth muscle fibres within the vessel wall. There is a risk of vessel dissection or rupture. Once treated the spasm does not usually reoccur.

Other experimental treatments include:

• intrathecal sodium nitroprusside
• mechanical (surgical) evacuation of subarachnoid blood
• intrathecal fibrinolytics

Differential diagnoses

• reversible cerebral vasoconstriction syndrome (RCVS)
• cerebral vasculitides