It has been reported that advanced age, initial stroke severity (NIHSS or Glasgow coma scale score), involvement of the adjacent (anterior or posterior cerebral artery) territories, anisocoria, early neurological deterioration, coronary artery disease, and internal carotid artery occlusion were the predictors of mortality and poor functional outcome in patients with LHI. However, all of these studies mentioned above were conducted in DHC cohorts [17, 23,24,25,26,27,28,29]. A number of clinical and radiological predictors of malignant brain edema, such as younger age, female sex, no previous ischemic stroke, history of hypertension, dominant hemisphere, have been extensively investigated for the last two decades . A meta analysis included 23 studies and found that large infarct size especially involving more than 50% of the MCA territory and a perfusion deficit of more than 66% on CT scan to be the most reliable predictors of maligant edema formation . Nevertheless, not all patients with LHI would develop the mMCAi . Thus, we conducted a prospective, non-selective cohort of patients with LHI to elucidate the factors that directly correlate with favorable outcome at 90 days. In the present study, we found that more than one third of patients with LHI have relatively favorable clinical outcomes at 90 days. In the multivariable logistic regression analyses, adjusted for potential confounding factors, we found that (1) younger age, lower baseline NIHSS score and statins used in the acute phase were independently related to favorable outcomes; (2) It was maligant brain edema and increased risk of pneumonia concommitant with surgery, rather than decompressive surgery itself independently associated with unfavorable outcome.
Whereas age is the leading risk factor and the strongest predictor of clinical outcome after ischemic stroke [31, 32], the influence of age on outcome has not yet been well investigated in LHI. As a general rule, young and middle-aged patients have less compensation capacity for space-occupying intracranial lesions than older patients with cerebral atrophy, however, those patients tend to have fewer comorbid conditions that are likely to increase the risk of mortality and poor functional outcome . The result of our study is in line with previous studies conducted in LHI patients that received DHC [23,24,25], which reported that younger age was associated with favorable outcome in non-selective patients with LHI.
Statins in acute phase
Of note, in our cohort, among those patients with favorable outcome at 90 days, 46.9% (53/113) use statins in acute phase of stroke, but only 25.7% (36/140) of those without favorable outcome use statins. Results from multivariable analysis of our cohort showed that statins use in acute phase was an independent predictor for 3-month favorable outcome in patients with LHI, regardless of the models adjusting for potential confounders by including or excluding stroke-related complications. Statins have been widely used for primary and secondary prevention of stroke for many years. Recently, statins have been found to play an important role in the neuroprotection of acute ischemic stroke in animal models, due to its pleiotropic effects besides lipid-lowering such as vasodilatory, angiogenesis, neurogenesis, synaptogenesis, antithrombotic, anti-inflammatory, antioxidant and anticonvulsant effects [34,35,36]. Meanwhile, cerebral arterial occlusion has been associated with reduced infarct volume and improved neurological function with use of statins in experimental animal models [34,35,36]. A recent research showed that pretreatment with statins is associated with better outcomes regarding neurological improvement, disability, survival, and stroke recurrence in large artery atherosclerotic stroke . A meta-analysis including 113,148 stroke patients suggested an association between prestroke statins use and improved stroke outcome at 90 days . Based on available evidence, it is recommended to continue with prestroke statin treatment in the acute phase ; however, routinely prescribing statins as neuroprotective agents is still controversial. Moreover, there are limited available data evaluating the association between statins use in acute phase and favorable outcome in patients with LHI. The result of our study provides initial evidence that statins used in acute phase may be associated with favorable outcome in patients with LHI. Considering the limitations of observational study, randomized controlled trials are needed to validate the findings.
DHC and stroke-related complications
In the present study, we found that patients with favorable outcome less frequently had received DHC and mechanical ventilation than those without favorable outcomes. Multivariable analysis not including stroke-related complications showed that DHC was independently associated with unfavorable outcome (model 1). However, when stroke-related complication was taken into consideration, DHC was no longer an independent factor correlated with unfavorable outcome, while brain edema and pneumonia were independently associated with unfavorable outcome (model 2). Data from a previous pooled analysis of three randomized trials had demonstrated that DHC reduced mortality without increasing the risk of very severe disability among patients 60 years of age or younger with mMCAi . DESTINY II trial indicated that DHC increased survival among patients older than 60 years of age with mMCAi, but most survivors were left with disabilities and needed assistance for daily living , which was also confirmed in a small sample randomized trial with Chinese patients . The results of present study showed that DHC was no longer independent factor associated with unfavorable outcome in patients with LHI after adjusting for age, baseline NIHSS score and stroke-related complication. Therefore, we could reasonablely speculate that it was malignant brain edema and increased risk of pneumonia concomitant with surgery, rather than DHC itself were independently associated with unfavorable outcome. In-hospital medical complications due to DHC can impact on the clinical outcomes of the patient with LHI. A national inpatient sample database over a 6-year period in the United States found the rates of pneumonia to be 11.1% in 252 patients studied and was associated with an increased rate of mortality . In a cohort study with patients undergoing DHC for space-occupying LHI, 42.4% of the patients suffered from at least one postoperative complication, with pulmonary problems being the most common cause (39% of all complications) . Stroke-related pneumonia was the most common medical complication in our study (36.3% in patients with favorable outcomes and 67.1% in those with unfavorable outcomes) and patients complicated with pneumonia showed 42% (95% CI 0.19–0.93) chance of favorable outcome compared with those patients without, after adjusting for age, baseline NIHSS score and other confounders. Since most pneumonia are potentially preventable or treatable, doctors should pay rigorous attention to the prevention, early detection and treatment of stroke-related pneumonia because of the higher events risk and concomitant poor outcome.
The results of the present study should be interpreted with caution given its limitations. First, it was a single hospital-based study, with limited generalisability. Some patients with LHI might not be hospitalized, especially those who died before admitted to hospital, so we could not exclude inclusion bias in this study. Second, we only conduct a 3-month follow-up so that the predictive effect on long-term outcomes remains unclear. Therefore, we cannot advise whether the factors we identified associated with favorable outcome in patients with LHI also have a long-term effect. Third, since our hospital is one of national advanced stroke center in China, admission to a stroke unit, early mobilisation, bedside swallow evaluation and rehabilitation have become routine practice in even every stroke patients, our prognostic model of LHI did not incorporate these factors such as admission to a stroke unit, early mobilisation, swallow status or other life-threatening impairment. Finally, follow-up in our study was performed by telephone interview or postal questionnaire instead of a clinic visit which may result in a reporting bias.