Symptomatic Intracerebral Hemorrhage More Likely with Right Hemispheric Acute Ischemic Stroke

Craig S. Anderson, MD, PhD, the George Institute for Global Health

Craig S. Anderson, MD, PhD

Patients with right hemispheric acute ischemic stroke were revealed to be more likely to experience symptomatic intracerebral hemorrhage (sICH) after intravenous alteplase than those with left hemispheric acute ischemic stroke.¹

After utilizing for several variables, it was shown that right hemispheric acute ischemic stroke was found to be independently associated with sICH according to the National Institutes of Health’s Stroke Scale (NIHSS) and the European Co-operative Acute Stroke Study-II (ECASS2) definitions, with respective odds ratios (OR) of 1.69 (95% CI, 1.17 to 2.43) and 1.77 (95% CI, 1.12 to 2.79).

Whole observational data has shown right hemispheric stroke has led to worse outcomes, a team of investigators sought to determine the outcomes when patients were administered intravenous thrombolysis. The results were presented by Sohei Yoshimura, PhD, a fellow in Neurological and Mental Health at the George Institute for Global Health, at STROKE 2018, the joint congress of the Stroke Society of Australasia’s (SSA) 28^th annual meeting and the 14^th Smart Strokes Australasian Nursing and Allied Health Stroke Conference, in Sydney, Australia.

To make their assessment, investigators took data from patients included in the ENCHANTED trial—which was led by current co-author Craig S. Anderson, MD, PhD, and found significantly fewer symptomatic intracerebral hemorrhages associated with low-dose alteplase²—and compared patients with right hemispheric (n = 1203) and left hemispheric acute ischemic stroke (n = 1286).

"Using data from ENCHANTED, a large, international, clinical trial that has examined different doses of the intravenous clot-busting drug, alteplase or tPA, the characteristics and prognosis between participants with left- and right-sided hemispheric acute ischemic stroke in the brain were examined," Anderson told NeurologyLive. "The findings were of no difference in the severity of stroke, but of differences in the risk factors (ie hypertension and previous stroke) and patterns of the changes between the left and right hemisphere of patients. However, these differences did not translate into any differences in the patterns of recovery from using intravenous alteplase, although those with an acute ischemic stroke affecting the right hemisphere tended to be more likely to have the bleeding complication of symptomatic intracerebral hemorrhage."

The patients with right hemispheric stroke were additionally shown to be more likely to have hemiplegia, hemianopia, visuospatial disorder, a higher baseline Glasgow Coma Scale, early ischemic change, cerebral vessel occlusion, and cardioembolic stroke. However, patients with right hemispheric stroke were less likely to have hypertension, prior stroke, or dysphagia.

Within 24 hours and within 1 week, there were no differences between NIHSS score or neurological deterioration. Additionally, at 3 months, no observable differences were seen between causes of death, and death or disability. “Right hemispheric AIS patients were more likely to have sICH after thrombolysis. There was no significant difference in early death or neurological deterioration and functional outcome,” Yoshimura and colleagues wrote.

These findings add to the ongoing compilation of informative data from the ENCHANTED trial. Earlier this year, additional data were published by Guofang Chen, MD, and colleagues, which showed that the combined history of prior stroke and the presence of diabetes mellitus was not independent predictor of poor outcomes in patients with acute ischemic stroke treated with intravenous alteplase.³ At 90 days those factors were both unassociated with poor outcomes, whether defined by modified Rankin scale (mRS) scores 2-6 (OR 0.85; 95% CI, 0.55 to 1.32; P = .476) or mortality (OR, 1.25; 95% CI, 0.62 to 2.52; P = .533).

"A key finding of the ENCHANTED study was of lower risks with a lower dose of intravenous alteplase, in particular, that of symptomatic intracerebral hemorrhage, but this was offset by fewer patients making an excellent recovery with low-dose alteplase," Anderson said. "These new findings provide reassurance over the consistency of benefit of alteplase across different types of patients but they also highlight differences in the characteristics of patients affected by acute ischemic stroke between the left and right cerebral hemisphere."

The original 2016 ENCHANTED trial found that major sICH occurred in 1% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group (P = .01).

Additionally, the original data showed that death or disability at 90 days occurred in 53.2% (n = 855) of the 1607 patients receiving 35.5-mg, low-dose alteplase compared to 51.1% (n = 817) of the 1599 patients receiving 56-mg, standard-dose alteplase (OR, 1.09; 95% CI, 0.95 to 1.25; upper boundary exceeded noninferiority margin of 1.14; P = .51). The low-dose of alteplase was non-inferior in the ordinal analysis of modified Rankin scale scores (unadjusted common OR, 1.00; 95% CI, 0.89 to 1.13; P = .04).

"There has been some uncertainty among doctors over whether there are any differences in the prognosis for recovery according to the side of the brain that is affected by a stroke from a blocked blood vessel, so-called ‘acute ischemic stroke’," Anderson explained. "Moreover, there are well-recognized limitations to the scales that are available to measure the severity of the neurological deficit in such patients, and this may contribute to the assessment of the balance of potential benefits and risks of using clot-busting treatment to rapidly open up the blocked blood vessel."

REFERENCES

1.

Yoshimua

S, Carcel C, Wang X, et al. Comparison between right and left acute ischemic stroke patients treated with intravenous alteplase in the ENCHANTED trial. Presented at: STROKE 2018; August 8, 2018; Sydney, Australia. Accessed August 10, 2018.

2. Anderson CS, Robinson TG, Lindley RI, et. al. Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke. N Engl J Med. 2016; 374:2313-2323.

doi

: 10.1056/NEJMoa1515510.

3. Chen G, Wang X, Robinson TG, et al. Comparative effects of low-dose versus standard-dose alteplase in ischemic patients with prior stroke and/or diabetes mellitus: The ENCHANTED trial. J Neurol Sci. 2018;387:1-5.

doi

: 10.1016/j.jns.2018.01.014.