Grade

Patients with poor WFNS (4–5), Hunt and Hess (4–5), grade do poorly. If no treatment is offered, the mortality rate approaches 100%. Ross and colleagues report on treating poor-grade aSAH patients with late surgery and early coiling. Their data suggest no added benefit by early coiling of poor-grade patients. With active treatment, good outcome has been reported in 50% of Grade 4 patients and 20% of Grade 5 patients. Patients older than 80 years do poorly. Poor-grade patients more often have associated hydrocephalus with an incidence estimated to be 50%. Management of these patients includes placement of an external ventricular drain (EVD) and following 24 hours of observation, 47% of this subgroup will have had made no improvement. In their series, these patients were treated conservatively with a mortality rate of 100% (mean of 2.6 days after presentation). Interestingly, men seem to do worse than woman, with the outcome discrepancy independent of age. Other clinical series show some improvement in 40% to 80% of cases following EVD placement.

Global Cerebral Edema

Global cerebral edema, as seen on CT scan, is associated with poorer outcome. Claassen and colleagues found that the admission CT scan showed edema in 6% to 8% and that edema developed later in 12%. Global cerebral edema is clinically suggested by an altered level of consciousness and or poor WFNS grade upon presentation. When reviewing mortality at 3 months, the global edema subgroup had a 48% to 50% mortality rate as compared with those without at 18%. Kreiter and colleagues also found poorer cognitive outcome in patients with global brain edema.

Rehemorrhage

The most treatable cause of poor outcome is rehemorrhage. Rehemorrhage poses the greatest threat to life during the initial stages of aSAH and is associated with a mortality rate of 50% to 70%. Rehemorrhage is the highest on day 1 post ictus (4%), then decreasing to 2% per day for the following 4 weeks. After 3 months, the rehemorrhage rate is at 3% per year. In patients managed conservatively, a mortality of 20% to 30% is reported at 30 days. Some studies report the incidence of ultra-early bleeding at 15%. Ultra-early rehemorrhage occurs within 24 hours of the initial ictus, with most hemorrhages occurring between 0 and 12 hours. Some reports indicate 87% of events occurring within the first 6 hours, specifically the first 2 hours. Risk factors for ultra-early bleeding is poorer grade at time of presentation, high initial blood pressure, and extended period between ictus and presentation to hospital.

Rehemorrhage rates for poor-grade patients are higher (20%) than good-grade patients (5%). The rehemorrhage rate in coiled patients was higher but the mortality rate in any rehemorrhaged patient is exceedingly high. Sluzewski and colleagues reported a 1.27% incidence of late rehemorrhage following coiling. Late rehemorrhage had less of an effect on patient outcome than early rehemorrhage. The rehemorrhage events occurred between 8 and 40 months in this review. Factors associated with early rehemorrhage included small aneurysm size and an associated intracerebral hematoma on the initial CT scan. Risk factors for late rehemorrhage include large aneurysm size and incomplete occlusion/obliteration of the aneurysm.

Age

Age affects associated clinical outcomes as well as the initial risk of aSAH. Data from the Framingham study showed an increased incidence in aSAH as the population grows older. The International Cooperative Study of the Timing of Aneurysm Surgery found a linear association between advancing age and worse outcome. Aging patients have a higher probability of dying or sustaining permanent neurologic damage or dying from vasospasm than younger patients. The complication rate increased from 28% in the sub-40-year group to 46% in the patients older than 70 years. Discharge glasgow outcome scores at 3 months are worse for older patients. In Lanzino and colleagues’ series, patients aged 40 years or younger made a good recovery 73% of the time, with the same degree of recovery found in only 25% of patients aged 70 years or older. Mortality rates are also worse for older patients (35% in the >70-year group) as compared with younger patients (12% in the <40-year group) with the same clinical presentation.

Lanzino and colleagues extensively analyzed the effect of age on aSAH. They found that older patients were more likely to present with a lower level of consciousness, have a poorer WFNS score, have a thicker subarachnoid blood load, and were more likely to have associated intraventricular blood. These patients were more likely to have hydrocephalus and showed an increased rehemorrhage rate (4.5% in the sub-40-year group to 16.4% in the above 70-year group). The thicker SAH blood load and increased intraventricular hemorrhage is in part explained by the increased subarachnoid spaces and ventricular size secondary to atrophy of the aging brain.

In older patients, increased systolic blood pressure is more common and is associated with a poorer WFNS grade. Advancing age was also associated with increased comorbidities, including hypertension, diabetes, pulmonary dysfunction, cardiac disease, and cerebrovascular disease. Older patients were also found not to have larger aneurysms. Despite having a larger subarachnoid blood load, older patients showed less angiographic vasospasm. This might be related to decreasing vascular compliance and a more rigid vascular vessel wall secondary to hypertension and increasing age.

The exact age at which poor outcome seems to be more common is hard to predict. In most studies, the relationship between advancing age and poor outcome is a linear one. Statistical series suggests that better outcomes are to be anticipated in patients younger than 60 years of age. The aging brain seems to be less able to cope with the secondary effects of an aSAH. The reasons are a combination of factors, ranging from structural changes, biochemical, and reduced plasticity.

Hyperglycemia

Hyperglycemia and its predictive role in outcome has been investigated. It is well known that following aSAH, plasma glucose levels are elevated. This may reflect a stress response. Studies have found plasma glucose levels, taken less than 72 hours following the ictus, to be elevated and to correlate with the severity of the bleed and clinical condition of the patient. Juvela and colleagues, testing admission plasma glucose levels, found that hyperglycemia predicted a poor outcome. Lanzino and colleagues suggested that hyperglycemia does not increase the risk for vasospasm (radiographic and/or symptomatic) or cerebral infarction. Finding hyperglycemia (day 3–7 post aSAH) in a patient with vasospasm was associated with a poorer outcome. The harmful effects of hyperglycemia during episodes of cerebral ischemia have also been reported.

Medical Complications

Solenski and colleagues reported on the medical complications associated with aSAH and the associated impact on outcome. Their work found that extracranial causes directly contributed to death in 23% of cases, increasing the significance of extracranial causes on par with vasospasm and rehemorrhage as a cause of poor outcome and death. Management of these patients needs a multidisciplinary approach.

Gruber and colleagues reviewed aSAH patient admissions to a neuro critical care unit over a 5-year period. Neurologic failure (Hunt and Hess grades 4 and 5) occurred in 36.8% of patients with an associated mortality rate of 40.4%. Of these patients, 51.7% had isolated neurologic failure and 48.3% showed at least one additional organ system failure. Isolated central nervous system (CNS) failure carried a17.4% mortality but the addition of an extracerebral organ failure increased mortality to 65.1%. Eighty-one percent of patients admitted developed some degree of organ dysfunction, 26% developing organ failure. Single-organ failure was the commonest (16%) followed by two organ system failure (4.9%) and 3 or more system failure in 4.1%. Mortality rates increased from 30.7% (single-system failure) to 91% for two and 100% for 3 or more organ failure.

Le Roux and colleagues found that medical conditions complicated and negatively affected the outcome of subarachnoid patients. Pneumonia and sepsis were common culprits. Close to half (41.8%) of patient deaths, excluding prehospital deaths, are associated some degree of extracranial organ dysfunction. The development of the systemic inflammatory response syndrome (SIRS) heralds a negative turning point in disease progression. SIRS may be the common initiating pathway to patient demise. The detailed pathophysiology of this process is beyond the scope of this article and the reader is referred to the references listed. Suffice to say that Gruber and colleagues found 29% of patients admitted to ICU to develop SIRS and 10.3% develop septic shock. The associated mortality rates were 40.3% for SIRS and 80.0% for septic shock against the backdrop of aSAH.

The association of poor outcome and fever has been reviewed. Oliveira-Filho and colleagues found that patients with vasospasm had an increased risk of developing fever. They concluded that the risk of a poor outcome increased with the duration of a fever, independent from vasospasm, disease severity, and infections per se.

Alcohol Consumption

Alcohol consumption has been implicated in the outcome of aSAH. Juvela and colleagues reported on this association and found that patients with a history of heavy alcohol intake were more likely to have a poor outcome. In their series, 12% to 13% of aSAH could be attributed to heavy alcohol intake. Heavy drinking more often preceded episodes of aSAH and most patients who presented following alcohol intake, did so in the “hung-over” phase. Patients with heavy alcohol intake were more likely to present in a poorer grade following an ictus and were more likely to die following rehemorrhage or a delayed ischemic event. They were also more prone to additional medical problems. In this regard, a history of heavy alcohol intake probably represents a marker of a specific lifestyle, associated with increased incidence of cigarette smoking, poor nutritional practices with increased body mass index, hypertension, dyslipidemias, and limited physical exercise.

Cocaine

Conway and Tamargo reviewed patients who presented with aSAH following cocaine use. Conflicting reports in the literature initially suggested a worse outcome in this subset of patients. Their analysis suggested that there is an increased incidence of vasospasm (63% vs 30% in control group) following aSAH but that outcome is not statistically any different. Consensus has not yet been reached with other authors reporting poorer results. If aSAH was related to cocaine usage, the patient population tended to be younger (average 36 years) and a disproportionate number of anterior circulation aneurysms (97% vs 84% in the control group) were present. Most patients in this subset practiced polypharmacy (81% of cocaine users) and had other comorbid factors associated, including HIV, bacterial infections, and viral hepatitis.

Statins

Statin users were reported to show a better outcome following aSAH. This was attributable to reduced vasospasm and improved cerebral hemodynamics. Parra and colleagues could not demonstrate this benefit. Tseng and colleagues in a follow-up to their initial article indicated benefit by reduced incidence of vasospasm or need to treat vasospasm and improved psychological outcome. The Statins for Aneurysmal Subarachnoid Hemorrhage (STASH) trial, assessing statin therapy on long-term outcome, is ongoing.

Aneurysm Size and Location

Some authors have suggested a larger SAH volume with the rupture of small aneurysms. As SAH blood load is associated with vasospasm, this may lead to poorer outcome. Although Taylor and colleagues found smaller aneurysms to produce larger bleeds, outcome was not affected by size. Salary and colleagues found no relationship between aneurysm size and SAH blood load or outcome.

The effect on outcome of location of the aneurysm has been investigated. Kassell and colleagues found that patients with aneurysms located on the internal carotid artery or middle cerebral artery had an overall better outcome as compared with patients with lesions of the anterior cerebral artery and/or vertebro-basilar system. Säveland and Brandt concurred with this. Anterior circulation aneurysms tend to fare better than posterior circulation lesions.

Gender

Gender differences do not seem to affect the outcome of aSAH. Females predominate in most series (ruptured and unruptured, clinical or autopsy-based ). Women tend to be older at presentation (51.4 years vs 47.3 years for males) and more often have multiple aneurysms (32.4% vs 17.6% for males). In children and adolescents, males predominate. The sex ratio remains 1:1 up to the third decade and then gradually changes to a female predominance. Female patients tended to have more aneurysms on the internal carotid artery (36.8% vs 18.0% in males), whereas men had more on the anterior cerebral artery system (46.1% vs 26.6% in females). Vasospasm was encountered equally in both sexes.

WFNS Grades 1 and 2

Predicting outcome in patients with a good WFNS grade (Grades 1 and 2) is more complicated. Historically, Grade 1 patients made a good outcome 72% of the time and Grade 2 in 52% (3-month outcome). When applying the National Institutes of Health Stroke Scale (NIHSS) to admission clinical findings, different outcome data are obtained. The NIHSS allows for a more detailed neurologic assessment. When evaluating the various aspects of the NIHSS, four clinical aspects are found to have statistical significance. These include (1) worst motor (arm) score, (2) dysphasia, (3) visual field deficits, and (4) level of consciousness. The presence of a positive sign (any one of the four clinical aspects) would imply a poorer outcome. Patients classified as WFNS Grade 1 with positive findings of the NIHSS showed a good outcome in 48% (vs 72%). The same was found for Grade 2 WFNS with positive NIHSS findings with good outcome found in 41% (vs 52%). The addition of these additional clinical factors thus improves the predictive value, but the practically of this has been doubted by some.

Biomarkers

Various biochemical markers have been tested to try to predict outcome following aSAH. No biomarker has yet been shown to provide a prediction method with enough sensitivity and specificity to accurately estimate clinical outcomes. Some of these tested methods have shown promise. These methods include serum S-100 plasma protein levels (associated and indicative of brain damage following SAH), plasma endothelin levels (associated with vasospasm and delayed cerebral ischemia), free fatty acid concentration in cerebrospinal fluid (may play a role in evolution of and hence prediction of vasospasm), and genetic markers such as apolipoprotein E genotype. Genetic testing may aid in the future outcome prediction of patients with aSAH.