Transient Ischemic Attacks Preceding Ischemic Stroke and the Possible Preconditioning of the Human Brain: A Systematic Review and Meta-Analysis

 Evidence seems to suggest having a TIA means your subsequent stroke might be lighter. I highly doubt you could construct clinical human research on this. Lets give you a TIA and then a see if your subsequent stroke is less damaging.

Transient Ischemic Attacks Preceding Ischemic Stroke and the Possible Preconditioning of the Human Brain: A Systematic Review and Meta-Analysis

Sherief Ghozy^1*†, Salah Eddine Oussama Kacimi^2†, Mohammed Elfil^3†, Mohamed Gomaa Sobeeh^4,5, Abdullah Reda⁶, Kevin M. Kallmes^7,8, Alejandro A. Rabinstein⁹, David R. Holmes Jr.¹⁰, Waleed Brinjikji^1,11, Ramanathan Kadirvel¹ and David F. Kallmes¹

• ¹Department of Radiology, Mayo Clinic, Rochester, MN, United States
• ²Faculty of Medicine, University of Tlemcen, Tlemcen, Algeria
• ³Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, United States
• ⁴Faculty of Physical Therapy, Cairo University, Cairo, Egypt
• ⁵Faculty of Physical Therapy, Sinai University, Cairo, Egypt
• ⁶Faculty of Medicine, Al-Azhar University, Cairo, Egypt
• ⁷Nested Knowledge, St. Paul, MN, United States
• ⁸Superior Medical Experts, St. Paul, MN, United States
• ⁹Department of Neurology and Neurocritical Care, Mayo Clinic, Rochester, MN, United States
• ¹⁰Department of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN, United States
• ¹¹Department of Neurosurgery, Mayo Clinic Rochester, Rochester, MN, United States

Stroke is a leading cause of mortality and disability worldwide. Transient ischemic attack (TIA) is defined as transient brain ischemia with temporary neurological deficits. In animal models, prior TIA seems to enhance brain ischemic tolerance to withstand further ischemic events, which might be explained by brain preconditioning. Thus, this review aims to formulate evidence of whether TIAs can induce positive preconditioning and enhance the functional outcomes in patients suffering from subsequent ischemic strokes. Five databases were searched (PubMed, Embase, SAGE, Web of Science, and Scopus), and twelve studies were included in the quantitative analysis. Studies were eligible when comparing patients with acute ischemic stroke (AIS) and previous TIA with those with AIS without TIA. Comparisons included the National Institute of Health Stroke Scale (NIHSS) score at admission and 7 days from the stroke event, modified Rankin score (mRS), and Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) classification. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were used to describe our results using the random effect model. Our results revealed that patients with stroke and prior TIAs had lower NIHSS scores at admission than those without prior TIAs. However, the NIHSS score was not significantly different between the two groups at 7 days. Furthermore, there was no statistically significant difference between both groups in terms of mortality. Despite the differences in the admission mRS score groups, patients with prior TIAs had lower mRS scores at discharge.

Introduction

Stroke is one of the most common causes responsible for mortality, morbidity, and loss of function worldwide (1). Furthermore, it has been reported that after the age of 55, the risk of having stroke doubles per each subsequent decade, with overburdened healthcare economics for these patients (2). Consequently, many management approaches have been extensively reported in the literature, which mainly target decreasing the incidence of severe events and mortality after a stroke event, in addition to enhancing recovery and rehabilitation among the survivors (3–6).

Although ischemia accounts for a significant part of brain tissue injury during stroke, reperfusion also contributes to brain tissue damage (7). Many explanations have been proposed to explain the underlying pathophysiology of the reperfusion injury, including the potential dysregulation of the intracellular calcium (8), impaired ion transport across the plasma membrane (8, 9), and increased synthesis and release of pro-inflammatory cytokines and reactive oxygen species (10, 11), all of which can cumulatively lead to the opening of the mitochondrial permeability transition pores resulting into tissue necrosis (12, 13). Thus, many approaches have been suggested to regulate the process of ischemia-reperfusion and enhance the clinical and prognostic outcomes. Ischemic preconditioning (IPC) has shown a potential as a modality in reducing the severity of the post-ischemic events. However, controversies still exist in literature about the potential neuroprotective effects that this approach might have (14).

Ischemic tolerance has been primarily described in experimental studies as a process during which the brain is subjected to a short period of ischemia which might enable the brain to be more tolerant when exposed to a more persistent ischemic event (15–19). Therefore, it has been proposed that pre-stroke exposure to Transient ischemic attacks (TIAs) might have a potential neuroprotective role when persistent ischemia affects the same exposed region. However, clinical studies reported contradicting findings regarding the ability of TIAs to alleviate the severity of cerebral ischemic injury (20–23). Accordingly, we aimed to conduct this systematic review and meta-analysis to formulate evidence whether TIAs can induce positive brain preconditioning and enhance the functional outcomes in patients suffering from subsequent AIS.

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