Anterior Insular Resting-State Functional Connectivity is Related to Cognitive Reserve in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Cognitive dysfunction is common in multiple sclerosis (MS). The dorsal anterior insula (dAI) is a key hub of the salience network (SN) orchestrating access to critical cognitive brain regions. The aim of this study was to assess whole-brain dAI intrinsic functional connectivity (iFC) using resting-state functional MRI (rs-fMRI) in people with MS and healthy controls (HC) and test the relationship between cognitive reserve (CR) and dAI iFC in people with MS. METHODS: We studied 28 people with relapsing-remitting MS and 28 HC. CR index was quantified by combining premorbid IQ, leisure activities, and education level. For whole-brain iFC analyses, the bilateral dAI were used as seeds. Individual subject correlation maps were entered into general linear models for group comparison and to analyze the effect of CR index on dAI iFC, controlling for multiple comparisons. The correlation between CR index and iFC was assessed using a linear regression model. RESULTS: rs-fMRI analyses revealed a negative relationship between CR index and iFC within the left dAI and a left occipital cluster in people with MS including regions of the cuneus, superior occipital gyrus, and parieto-occipital sulcus. The regression analysis showed that people with MS and a higher CR index had a statistically significantly reduced iFC within the left dAI and the cluster. CONCLUSIONS: CR is relevant to functional connectivity within one of the main nodes of the SN, the dAI, and occipital regions in MS. These results have implications for how CR may modulate the susceptibility to cognitive dysfunction in MS.

Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography.

IMPORTANCE: Limited data exist regarding the natural history of proximal intracranial arterial occlusions. OBJECTIVE To investigate the outcomes of patients who had an acute ischemic stroke attributed to an anterior circulation proximal intracranial arterial occlusion. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study at 2 university-based hospitals from 2003 to 2005 in which nonenhanced computed tomography scans and computed tomography angiograms were obtained at admission of all adult patients suspected of having an ischemic stroke in the first 24 hours of symptom onset. EXPOSURE: Anterior circulation proximal intracranial arterial occlusion. MAIN OUTCOMES AND MEASURES: Frequency of good outcome (defined as a modified Rankin Scale score of ≤ 2) and mortality at 6 months. RESULTS: A total of 126 patients with a unilateral complete occlusion of the intracranial internal carotid artery (ICA; 26 patients: median National Institutes of Health Stroke Scale [NIHSS] score, 11 [interquartile range, 5-17]), of the M1 segment of the middle cerebral artery (MCA; 52 patients: median NIHSS score, 13 [interquartile range, 6-16]), or of the M2 segment of the MCA (48 patients: median NIHSS score, 7 [interquartile range, 4-15]) were included. Of these 3 groups of patients, 10 (38.5%), 20 (38.5%), and 26 (54.2%) with ICA, MCA-M1, and MCA-M2 occlusions, respectively, achieved a modified Rankin Scale score of 2 or less, and 6 (23.1%), 12 (23.1%), and 10 (20.8%) were dead at 6 months. Worse outcomes were seen in patients with a baseline NIHSS score of 10 or higher, with a modified Rankin Scale score of 2 or less achieved in only 7.1% (1 of 14), 23.5% (8 of 34), and 22.7% (5 of 22) of patients and mortality rates of 35.7% (5 of 14), 32.4% (11 of 34), and 40.9% (9 of 22) among patients with ICA, MCA-M1, and MCA-M2 occlusions, respectively. Age (odds ratio, 0.94 [95% CI, 0.91-0.98]), NIHSS score (odds ratio, 0.73 [95% CI, 0.64-0.83]), and strength of leptomeningeal collaterals (odds ratio, 2.37 [95% CI, 1.08-5.20]) were independently associated with outcome, whereas the level of proximal intracranial arterial occlusion (ICA vs MCA-M1 vs MCA-M2) was not. CONCLUSIONS AND RELEVANCE: The natural history of proximal intracranial arterial occlusion is variable, with poor outcomes overall. Stroke severity and collateral flow appear to be more important than the level of proximal intracranial arterial occlusion in determining outcomes. Our results provide useful data for proper patient selection and sample size calculations in the design of new clinical trials aimed at recanalization therapies.