Cerebral vasospasm (CVS) is the most common neurological complication after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome and mortality.
Although the development and prevalence of cerebral vasospasm (CV) has been extensively investigated in adults, little data exist on the development of CV in children.
Children have a relatively high incidence of angiographically detectable, moderate-to-severe CV. Children rarely develop symptomatic CV and have good long-term outcomes, perhaps due to robust cerebral collateral blood flow. Criteria developed for detecting CV with TCD ultrasonography in adults overestimate the prevalence of CV in children. Larger studies are needed to define TCD ultrasonography-based CV criteria for children 6).
Mild, 120-140 cm/s
Moderate, 141-200 cm/s
Multivariate analysis showed that SAH Fisher scale III-IV was the most important risk factor for vasospasm followed by left ventricular hypertrophy (LVH), on electrocardiogram, cigarette smoking, and hypertension. angiographic vasospasm (AV) grade III-IV, symptomatic vasospasm (SV), and cerebral infarction occurred in 57%, 54%, and 39% of the 46 smokers with LVH, and in 43%, 49%, and 35% of the 68 patients who had both LVH and hypertension, respectively. CT-evident SAH, LVH, cigarette smoking, and hypertension are associated with vasospasm. In smokers or hypertensive patients, premorbid LVH appears to predict much more severe vasospasm 7).
A number of pathological processes have been identified in the pathogenesis of vasospasm including endothelial injury, smooth muscle cell contraction from spasmogenic substances produced by the subarachnoid blood clots, changes in vascular responsiveness and inflammatory response of the vascular endothelium.
The pathophysiology on cerebral vasospasm and delayed cerebral ischemia (DCI) remains poorly understood. Much research has been dedicated to finding genetic loci associated with vasospasm and ischemia.
In a study, endothelial nitric oxide (eNOS VNTR) and haptoglobin (Hp) polymorphisms appear to have the strongest associations with delayed ischemic neurologic deficit (DIND) and radiographic vasospasm, respectively 8).
The pathogenesis of vasospasm involves endogenous spasmogens including oxyhemoglobin and endothelin. These are believed to inhibit nitric oxide (NO) synthetase and subsequently reduce the level of endogenous vasodilators, thereby producing vasospasm 9) 10).
Diagnosis is made by some combination of clinical, cerebral angiographic, and transcranial doppler ultrasonographic factors.
Hemodynamic strategies and endovascular procedures may be considered for the treatment of cerebral vasospasm.
To date, the current therapeutic interventions remain ineffective being limited to the manipulation of systemic blood pressure, variation of blood volume and viscosity, and control of arterial carbon dioxide tension.In this scenario, the hormone erythropoietin (EPO), has been found to exert neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is systemically administered. However, recent translation of experimental data into clinical trials has suggested an unclear role of recombinant human EPO in the setting of SAH 12).
Nimodipine, a calcium channel antagonist, is so far the only available therapy with proven benefit for reducing the impact of DID. Aggressive therapy combining hemodynamic augmentation, transluminal balloon angioplasty, and intra-arterial infusion of vasodilator drugs is, to varying degrees, usually implemented. A panoply of drugs, with different mechanisms of action, has been studied in SAH related vasospasm. Currently, the most promising are magnesium sulfate, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, nitric oxide donors and endothelin-1 antagonists 13).
There are different drugs to treat cerebral perfusion pressure which are administrated orally or intra-arterially. While orally administrated, these drugs often do not reach their therapeutic concentration or they need a longer time to act. By intracisternal administration of these drugs, less time is needed to reach the appropriate therapeutic concentration. Papaverine is an alkaloid, which causes vasodilatory induction of cerebral and cardiac vessels through direct effect on the cells of smooth muscles. Mechanism of papaverine effect is the inhibition of cyclic adenosine monophosphate and cyclic guanosine 3 and 5 monophosphate intra-arterially 14).
Prophylaxis with nimodipine, hypertension, hypervolemia, and hemodilution (triple H) have been improved the outcome of the patients, however, they could not completely remove the effects of vasospasm 15) 16) 17).
The use of intravascular papaverine as an alternative treatment for reversible vasospasm is associated with various side effects including hemodynamic instability like bradycardia and hypotension. Some recent studies have pointed that washing aneurysmal arteries and subarachnoid space with papaverine may not have many complications and hemodynamic disorders besides preventing aneurysmal vasospasm 18)
Washing with papaverine significantly reduces cerebral blood flow and relieves vasospasm 19).
A substantial body of evidence supports the idea that CSF diversion could prevent VS, even if this issue is still much debated. External ventricular drainage (EVD) is the recommended procedure for posthemorrhagic hydrocephalus.
VS occurred in 8.75% of cases (7 patients) in the first groups, while in 22.95% (14 patients) in the second group. In addition, patients not treated with EVD display a prevalence of VS in lower Fisher grades compared to the other group.
Vasospasm is an important cause for mortality following aneurysmal subarachnoid hemorrhage aSAH affecting as many as 70% of patients. It usually occurs between 4th and 21st days of aSAH and is responsible for delayed ischemic neurological deficit (DIND) and cerebral infarction
It is one of the factors that can most significantly worsen the prognosis despite different treatments.
Transcranial doppler (TCD) evidence of vasospasm is predictive of delayed cerebral ischemia (DCI) with high accuracy. Although high sensitivity and negative predictive value make TCD an ideal monitoring device, it is not a mandated standard of care in aneurysmal subarachnoid hemorrhage (aSAH) due to the paucity of evidence on clinically relevant outcomes, despite recommendation by national guidelines. High-quality randomized trials evaluating the impact of TCD monitoring on patient-centered and physician-relevant outcomes are needed 21).