Measuring cognitive outcome after subarachnoid hemorrhage

I think, therefore I am. —René Descartes The intellect has long been regarded as the quintessential attribute of the human species. The ability to contemplate, conjecture, plan, communicate both with and without language, calculate, appreciate, learn, reminisce, and love is precious to each individual. Neurological diseases that rob patients of these abilities either slowly (eg, Alzheimer’s disease) or suddenly (eg, traumatic brain injury, stroke) are regarded as anathema by society and, in some instances, are feared as much as death itself. Thus, in a disease such as subarachnoid hemorrhage (SAH) from a ruptured aneurysm, which can result not only in death, but innumerable other permanent neurological sequelae, it is important to include an assessment of the patient’s cognitive outcome together with other aspects of the patient’s disability, handicap, and social and behavioral impairments, to better plan for overall care needs, including return to driving and employment, and to maximize quality of life for survivors. Until recently, surprisingly little attention to cognitive outcome has been paid in reports of case series or clinical trials in SAH. Among the 906 patients enrolled in the Randomized Trial of Nicardipine in Subarachnoid Hemorrhage, conducted at 41 neurosurgical centers in North America between 1987 and 1989, 503 (55.5%) were reported to have returned to their premorbid state (Good Recovery on the Glasgow Outcome Scale) at 3 months after the ictus (unpublished data). Yet, of the 512 patients who were employed at the time of the hemorrhage, only 169 (33%) had returned to work, suggesting more extensive disability in these patients than could be appreciated by the Glasgow Outcome Scale, a crude but reproducible assessment of functional disability. Thus, it came as somewhat of a surprise to the clinical community when the International Study of Unruptured Intracranial Aneurysms Investigators reported that, among 1,917 patients undergoing surgery for previously unruptured intracranial aneurysms, 9% had major impairment in cognitive function as measured by the Mini-Mental State Examination 12 months after the surgery. Previous reports of morbid complication rates for unruptured aneurysm surgery had been in the 4% range. In this issue of Annals of Neurology, Anderson and colleagues report the neurocognitive outcomes in the 1,001 patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST), a prospective, multicenter, randomized controlled clinical trial comparing moderate intraoperative hypothermia (32.5–33.5°C) induced by external cooling with intraoperative normothermia (36–37°C) in patients with recently ruptured intracranial aneurysms. Although hypothermia has robust neuroprotective effects in experimental models of traumatic brain injury, as well as focal and global cerebral ischemia, and has been shown to reduce poor outcomes in patients successfully resuscitated from cardiac arrest, the investigators have previously reported that intraoperative hypothermia had no detectable treatment effect in IHAST as measured at 3 months with the Glasgow Outcome Scale, the Rankin Scale (another global measure of handicap), the Barthel Index (an assessment of ability to complete a list of tasks involved in activities of daily living), or the National Institutes of Health Stroke Scale (a crude but reproducible graded neurological examination). However, appreciating that major cognitive impairment was highly prevalent among survivors of SAH, and not well detected by their primary outcome measurement tools, the investigators prospectively sought to measure performance on a battery of neuropsychological tests to further characterize the cognitive outcomes of their patients. Neuropsychological testing has been used previously to measure outcome in patients with subarachnoid hemorrhage. However, this is the first large-scale, randomized clinical trial in SAH to use these measures. Clinical trials are always a balance between what is ideal and what is practical, and the investigators’ reported experience in this article is probative. Standard neuropsychological test batteries are generally too long and arduous to be easily administered in a standardized fashion to a large number of stroke victims. Moreover, because the trial was international in scope, the investigators had language barriers to hurdle. Thus, an abbreviated battery of five tests was selected based on correlation studies conducted on a test population of SAH patients at the University of Iowa. Definitions of “impairment” on each test were defined by two standard deviations below ageand education-adjusted norms, a more conservative strategy than that used in other clinical reports. A composite score for each patient was then computed using the mean of the individual test scores. Mini-Mental State Examinations were also performed. The investigators report that there was no statisti-