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Loss of consciousness (LOC) at symptom onset is an important manifestation of early brain injury after subarachnoid hemorrhage (SAH) and a predictor of death or poor functional outcome at 12 months, a retrospective analysis has shown.

"LOC has important prognostic value, implying a more than 2.8-fold increase in the risk of death or severe disability at one year, even after controlling for age, admission clinical grade, aneurysm size, and admission physiological derangements," , of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues reported in .

Death or severe disability at 12 months was independently associated with LOC after adjusting for established risk factors for poor outcome, including poor admission clinical grade (adjusted odds ratio 1.94; 95% CI 1.38-2.72; P<0.001), said the investigators.

"Our findings indicate that LOC at onset of SAH is a simple and robust indicator of a severe bleeding event. Patients with LOC had significantly larger SAHs, intraventricular hemorrhages, and parenchymal intracerebral hemorrhages on admission CT scan findings. Loss of consciousness was also associated with global cerebral edema, which is thought to be an important marker of early brain injury after SAH."

There was no association between LOC at onset and delayed cerebral ischemia or aneurysm re-bleeding, said Mayer and colleagues.

In an accompanying editorial, , of St. Michael's Hospital and the University of Toronto, said this study "solidifies the finding that LOC at the time of SAH is an independent predictor of poor outcome."

The study included almost four times as many patients as previous investigations, and resulted in more robust findings, Macdonald pointed out. The study also serves to highlight "the importance of acute reductions in cerebral perfusion and probably of subarachnoid blood since these patients tend to have a larger SAH," said Macdonald.

The analysis was conducted with data from 1,460 patients with SAH who were part of a prospective observational cohort study at Columbia University known as the SAH Outcomes Project (SHOP), enrolled from August 1996 to July 2012.

A structured interview of the patient and first responders was used to identify LOC at onset. To assess functional recovery, 80.5% of patients were observed for up to one year.

Modified Rankin scale scores were assigned based on telephone or in-person interviews of the patient, family members, or caregiver. The study team adjudicated predefined complications while in hospital, said Mayer and colleagues.

In all, 590 patients (40.4%) reported LOC at onset of SAH. Loss of consciousness was associated with poor clinical grade, more subarachnoid and intraventricular blood seen on admission CT scan, and a higher frequency of global cerebral edema (P<0.001). LOC was also associated with more prehospital tonic-clonic activity (22.7% versus 4.2%; P<0.001) and cardiopulmonary arrest (9.7% versus 0.5%, P<0.001) versus patients who did not experience LOC.

In the 40% of patients with LOC who failed to regain consciousness within one hour after SAH, a primary reduction of cerebral perfusion pressure caused by severe intracranial hypertension could be to blame, said the investigators. Other factors that may contribute to cerebral blood flow reduction in early brain injury include:

• Autoregulatory failure

"Acute physiological derangements, such as extremes of blood pressure, hyperglycemia, hypoxemia and metabolic acidosis have been shown to predict both poor admission grade and long-term outcome and may exacerbate these processes and serve as targets for intervention," said the investigators. Approximately 70% of patients with SAH presenting with poor clinical grade on admission have evidence of acute ischemic injury on , they noted.

The timing of recovery of consciousness and assessment of LOC at multiple early time points should be more precisely tracked in future studies, said Mayer and colleagues, noting that in this study, the presence of significant cardiac arrhythmia on admission was not recorded. Similarly, early electroencephalograms were not used to determine the frequency of epileptiform activity; neither was admission MRI used to explore LOC as a potential risk factor for early ischemic injury.

"We assigned mRS scores without using a scripted interview, and had to impute one-year scores at 20% of our study population based on the best information available at three months," added the investigators.

Although Mayer and colleagues didn't find that LOC was associated with delayed cerebral ischemia (DCI), this might be explained by statistics, Macdonald noted in his editorial. It is possible, for instance, that LOC covaries or interacts with other predictors of DCI -- such as subarachnoid clot volume, neurologic grade, and smoking -- in such a way that only one or two of these variables reach statistical significance, he said.

From the American Heart Association:

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