Impact of global cerebral atrophy on clinical outcome after subarachnoid hemorrhage

Abstract

Object Atrophy in specific brain areas correlates with poor neuropsychological outcome after subarachnoid hemorrhage (SAH). Few studies have compared global atrophy in SAH with outcome. The authors examined the relationship between global brain atrophy, clinical factors, and outcome after SAH. Methods This study was a post hoc exploratory analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial, a randomized, double-blind, placebo-controlled trial of 413 patients with aneurysmal SAH. Patients with infarctions or areas of encephalomalacia on CT, and those with large clip/coil artifacts, were excluded. The 97 remaining patients underwent CT at baseline and 6 weeks, which was analyzed using voxel-based volumetric measurements. The percentage difference in volume between time points was compared against clinical variables. The relationship with clinical outcome was modeled using univariate and multivariate analysis. Results Older age, male sex, and systemic inflammatory response syndrome (SIRS) during intensive care stay were significantly associated with brain atrophy. Greater brain atrophy was significantly associated with poor outcome on the modified Rankin scale (mRS), severity of deficits on the National Institutes of Health Stroke Scale (NIHSS), worse executive functioning, and lower EuroQol Group–5D (EQ-5D) score. Adjusted for confounders, brain atrophy was not significantly associated with Mini-Mental State Examination and Functional Status Examination scores. Brain atrophy was not associated with angiographic vasospasm or delayed ischemic neurological deficit. Conclusions Worse mRS score, NIHSS score, executive functioning, and EQ-5D scores were associated with greater brain atrophy and older age, male sex, and SIRS burden. These data suggest outcome is associated with factors that cause global brain injury independent of focal brain injury.

Molecular Alterations in the Hippocampus after Experimental Subarachnoid Hemorrhage

“…This is consistent with studies in humans with SAH that show that cognitive dysfunction may be associated with temporal lobe volume loss in the absence of infarctions. 3,20 Animal studies in models of traumatic brain injury also found memory impairment in the absence of hippocampal cell death. 25 Role of Key Proteins in Long-Term Potentiation Enhanced expression of phosphorylated GluR1 by CamK-II is a key molecular event for induction and maintenance of LTP.…”

“…1 Brain magnetic resonance imaging (MRI) of patients after SAH shows that there may be atrophy in the medial temporal lobes and that this may correlate with neurocognitive deficits in the absence of any focal structural lesions. 2,3 The hippocampal formation in the medial temporal lobe has been postulated to be involved in cognitive functions such as learning and memory. Long-term potentiation (LTP), a form of synaptic plasticity, is believed to be a cellular substrate of memory and learning.…”

The Role of Microclot Formation in an Acute Subarachnoid Hemorrhage Model in the Rabbit

“…Compared to the mouse perichiasmatic injection model used by Sabri et al [29, 36], they observed a significant increase of microthrombosis in both the hippocampus and cerebral cortices. Although brain injury due to aneurysmal SAH causes global parenchymal damage [37, 38], vulnerability to subcortical brain regions may differ [39]. This might explain the SAH-induced significant increase of microthrombosis in the rabbit brain parenchyma at the hippocampal levels but not the cortex.…”

Cerebral Vasospasm in Patients over 80 Years Treated by Coil Embolization for Ruptured Cerebral Aneurysms

“…The overall correlation of poor outcome with advancing age has been partially explained by some factors, such as mRS scores at onset [19], brain atrophy [20], poor neurological grade at admission [21], increased amount of blood on CT, and preexisting medical diseases [8]. The greater incidence of poor outcome in elderly patients is multifactorial, and symptomatic vasospasm is probably just one of the factors involved in poor outcome.…”