My god, the ABSOLUTE FUCKING STUPIDITY DISPLAYED HERE! Very early rehabilitation does nothing towards the mortality risk! You are totally missing not stopping the 5 causes of the neuronal cascade of death in the first week thus not saving millions to billions of neurons. Those extra dead neurons are likely the reason for the increased mortality. Do you not understand cause and effect?
Efficacy and safety of very early rehabilitation for acute ischemic stroke: a systematic review and meta-analysis
Ying Lou
Zhongshuo Liu1,2
Litao Li- 1Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, China
- 2Graduate School of Hebei Medical University, Shijiazhuang, Hebei, China
- 3Hebei Provincial Key Laboratory of Cerebral Networks and Cognitive Disorders, Shijiazhuang, Hebei, China
Background: Early rehabilitation after acute ischemic stroke (AIS) contributes to functional recovery. However, the optimal time for starting rehabilitation remains a topic of ongoing investigation. This article aims to shed light on the safety and efficacy of very early rehabilitation (VER) initiated within 48 h of stroke onset.
Methods: A systematic search in PubMed, Embase, Cochrane Library, and Web of Science databases was conducted from inception to January 20, 2024. Relevant literature on VER in patients with AIS was reviewed and the data related to favorable and adverse clinical outcomes were collected for meta-analysis. Subgroup analysis was conducted at different time points, namely at discharge and at three and 12 months. Statistical analyses were performed with the help of the Meta Package in STATA Version 15.0.
Results: A total of 14 randomized controlled trial (RCT) studies and 3,039 participants were included in the analysis. VER demonstrated a significant association with mortality [risk ratio (RR) = 1.27, 95% confidence interval (CI) (1.00, 1.61)], ability of daily living [weighted mean difference (WMD) = 6.90, 95% CI (0.22, 13.57)], and limb motor function [WMD = 5.02, 95% CI (1.63, 8.40)]. However, no significant difference was observed between the VER group and the control group in adverse events [RR = 0.89, 95% CI (0.79, 1.01)], severity of stroke [WMD = 0.52, 95% CI (−0.04, 1.08)], degree of disability [RR = 1.06, 95% CI (0.93, 1.20)], or recovery of walking [RR = 0.98, 95% CI (0.94, 1.03)] after stroke. Subgroup analysis revealed that VER reduced the risk of adverse events in the late stage (at three and 12 months) [RR = 0.86, 95% CI (0.74, 0.99)] and degree of disability at 12 months [RR = 1.28, 95% CI (1.03, 1.60)], and improved daily living ability at 3 months [WMD = 4.26, 95% CI (0.17, 8.35)], while increasing severity of stroke during hospitalization [WMD = 0.81, 95% CI (0.01, 1.61)].
Conclusion: VER improves activities of daily living (ADLs) and lowers the incidence of long-term complications in stroke survivors. However, premature or overly intense rehabilitation may increase mortality in patients with AIS during the acute phase. PROSPERO registration number: CRD42024508180.
Systematic review registration: This systematic review was registered with PROSPERO (https://www.crd.york.ac.uk/PROSPERO/). PROSPERO registration number: CRD42024508180.
1 Introduction
Acute ischemic stroke (AIS) refers to the abrupt onset of focal neurological dysfunction resulting from insufficient blood supply to the brain or determined according to objective evidence of vascular origin observed through imaging or pathological examination (1). It features high incidence, recurrence, disability, and mortality worldwide (2), and represents approximately 80% of all stroke cases (3). In the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification system, large-artery atherosclerosis and cardioembolism are the main etiologies of stroke, with contributing risk factors including cardiovascular, endocrine, and others. Stroke, as the second leading cause of death and disability worldwide according to the Global Burden of Disease Study in 2016 (4), imposes substantial health and economic burdens in both developed and developing nations. Moreover, there has been a gradual increase in stroke incidence among young populations (5, 6). The progression of ischemic stroke is commonly categorized into acute, subacute, and chronic phases; however, the temporal boundaries of these stages are inconsistently defined. In the present study, acute stroke was defined as a stroke that occurs within 7 days after the onset, subacute stroke was a stroke occurring more than 7 days and less than 3 months after the onset, and chronic stroke generally referred to a non-recurrent stroke that lasts 3 months. Despite advancements in stroke unit management and early revascularization which promote timely recovery of brain blood flow in recent years, 50% of patients became chronically disabled with low life quality (7), because neural restoration was constrained by a narrow therapeutic window and irreversible damage to neuron. Some stroke survivors experience lingering complications and sequelae, particularly motor impairment and cognitive decline (8). In a recent study, it was demonstrated that acute or subacute stroke patients with Clostridium difficile infection exhibited significant improvement in basic living ability at discharge after 3 h of daily neurorehabilitation, but no significant difference was found in comparison to non-infected patients (9). Therefore, in addition to standard care, systematic, regular and intensive rehabilitation is of great importance in the early period of stroke even in the presence of other complications such as infections, unless patients have malaise or worse symptoms.
Post-stroke rehabilitation, as a long and relatively safe intervention, is conducive to restoring limb motivation, improving walking and balancing abilities, and reducing the incidence of disability, falls and cardiorespiratory diseases (10). Initiating rehabilitation promptly after the stabilization of vital signs would help to accelerate the recovery of central nervous system and prevent potential complications (11). Sun et al. suggested that early rehabilitation could influence the expression of serum inflammatory factors, such as vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin-10, and stromal cell-derived factor-1α, and motivate endothelial progenitor cells (12), thereby promoting endothelial formation and vascular regeneration in AIS (13). However, the optimal timing for commencing early rehabilitation after stroke remains controversial, with uncertainty regarding the safety and efficacy of very early rehabilitation (VER) in patients with AIS. Firstly, for patients with post-stroke paralysis, very early out-of-bed activities may precipitate falls due to weak limb strength or poor balancing ability. Moreover, significant head position change after stroke would decrease cerebral blood flow (14), which could aggravate ischemia in the infarct area and lead to deterioration of the disease, while maintaining a supine position could increase cerebral perfusion pressure and boost collateral circulation to support the ischemic penumbra (15, 16). Despite the absence of definitive evidence and a lack of consensus regarding the optimal rehabilitation strategy, which involves starting time, frequency and intensity (17, 18), VER has been advocated within some published stroke guidelines (19, 20), and merits further exploration. Notably, a recent meta-analysis of randomized controlled trials (RCTs) conducted in 2021 revealed positive efficacy of early rehabilitation at 3 months. No statistical difference in adverse events and disability rate was noted between the VER group and control group, but the study did not assess outcomes in different endpoints (21).
This meta-analysis included RCTs to evaluate the effects of initiating VER within 48 h of stroke onset on short- and long-term recovery. Additionally, a subgroup analysis at different time points (at discharge, 3 months and 12 months) was performed to observe the dynamic changes of the efficacy and safety of VER, which could serve as a reference for clinical practice.
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