Effect of Right Insular Involvement on Death and Functional Outcome After Acute Ischemic Stroke in the IST-3 Trial (Third International Stroke Trial)

Abstract

Background and Purpose-In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging. Methods-We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation. Results-Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right insular involvement was associated with increased odds of death when compared with noninsular strokes on the left side (adjusted odds ratio, 1.83; 95% confidence interval, 1.33−2.52), whereas the adjusted odds ratio comparing mortality after insular versus noninsular strokes on the left side was not significant. Among mild/moderate strokes, outcomes for right insular involvement were worse than for left insular, but among more severe strokes, the difference in outcomes was less substantial. Conclusions-We found an association between right insular involvement and higher odds of death and worse functional outcome. The difference between right-and left-sided insular lesions on outcomes seemed to be most evident for mild/ moderate strokes. Clinical Trial Registration-URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518.

Insular damage, new‐onset atrial fibrillation and outcome after acute intracerebral hemorrhage

“…Some authors often hypothesize that the high mortality after insular damage may be explained by cardiac arrhythmias or sudden death [1,9,10,17]. However, in accordance with a previous study, we did not find a clear increase of deaths attributable to cardiovascular causes [9].…”

“…The poor functional outcome and high mortality rates in patients with insular damage in our study may be explained partially by the impairment of motor function by large ICH and the loss of important cortical functions such as spatial neglect, impaired bodily awareness, aphasia or a decreased verbal memory that occurs in patients with insular lesions . Some authors often hypothesize that the high mortality after insular damage may be explained by cardiac arrhythmias or sudden death . However, in accordance with a previous study, we did not find a clear increase of deaths attributable to cardiovascular causes .…”

“…Clinical studies have shown an association between insular lesions and electrocardiographic changes including AF [1,2]. In addition, insular strokes, particularly right-sided, are associated with greater disability and increased risk of death [1,2,9,10].…”

Right insular cortex involvement is consistently associated with death after ischaemic stroke

“…Similarly to this study, we recently found that right insular involvement was independently associated with increased death 6 months after ischaemic stroke in the cohort of the Third International Stroke Trial (IST‐3) after adjusting for lesion size and stroke severity amongst other variables . Furthermore, right insular infarcts were also independently associated with disability and combined death or dependence.…”

“…Together, the study by Hanne et al . and ours contribute to highlight that ischaemic damage to the right insula is independently related to increased risk of death after stroke, ensuring the need to elucidate the underlying pathophysiology. Unfortunately, in neither study was the cause of death ascertained.…”