Curr Treat Option Ne
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Curr Treat Option Ne · Dec 2020
Red Blood Cell Transfusion and Transfusion Alternatives in Traumatic Brain Injury.
OPINION STATEMENT: Anemia develops in about 50% of patients hospitalized with traumatic brain injury (TBI) and is recognized as a cause of secondary brain injury. This review examines the effects of anemia and transfusion on TBI patients through a literature search to identify original research on anemia and transfusion in TBI, the effects of transfusion on brain physiology, and the role of erythropoietin or hemoglobin-based blood substitutes (HBBSs). However, the amount of high-quality, prospective data available to help make decisions about when TBI patients should be transfused is very small. ⋯ Administration of exogenous erythropoietin may have a small impact in further reducing the need for transfusion, but it also may increase complications, most notably deep venous thrombosis. Erythropoietin is currently of great interest as a potential neuroprotective agent, but until it is adequately evaluated in randomized controlled trials, it should not be used routinely for this purpose. HBBSs are also of interest, but existing preparations have not been shown to be beneficial-or even safe-in the context of TBI.
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Curr Treat Option Ne · Jul 2019
ReviewChimeric Antigen Receptor T Cell-Related Neurotoxicity: Mechanisms, Clinical Presentation, and Approach to Treatment.
Chimeric antigen receptor T cell (CAR-T) adoptive cell therapy is an effective treatment for patients with refractory B cell malignancies. As its use has grown, there has been an increase in the incidence of a serious, potentially fatal neurotoxicity known as immune effector cell-associated neurotoxicity syndrome (ICANS). This review discusses the clinical manifestations of this neurotoxicity syndrome, current grading systems, management strategies, and proposed biologic mechanisms leading to neurotoxicity. ⋯ Current research suggests that patients with a higher disease burden and higher CAR-T cell doses are positively associated with the development of ICANS, as are elevated serum levels of proinflammatory cytokines and the presence of cytokine release syndrome (CRS). While patterns observed on neuroimaging and electroencephalogram (EEG) are non-specific for the diagnosis of ICANS, each modality may provide helpful clinical information such as the detection of cerebral edema, the most serious of associated symptoms. Anti-epileptic medications and corticosteroids may ameliorate the symptoms of ICANS. The mechanism for ICANS is currently unknown; however, systemic inflammation and cytokine production triggering a cascade of endothelial activation and BBB disruption likely contribute. With limited treatment options available, further clinical research into the precise mechanism and treatment is urgently needed as the use of CAR-T and other adoptive cell therapies continues to grow.
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The purpose of this review article is to discuss the pathogenesis of acute and chronic immune-mediated neuropathies along with the recent advances in their treatment. ⋯ Since the first description of Guillain-Barre syndrome (GBS) more than a century ago, there have been numerous forms of immune-mediated neuropathies described expanding the spectrum. Understanding the role of the immune system in the pathogenesis of immune-mediated neuropathies has been an advancement towards the diagnosis and treatment. It is postulated that immune-mediated neuropathies are a group of diseases resulting from autoimmunity towards multiple components of peripheral nervous system. These have a wide range of pathologic mechanisms, defined clinical presentations, electro-diagnostic and laboratory findings which help in diagnosis and management. Although immunosuppression is the common modality of treatment for these disorders, uncovering distinct pathogenic mechanisms can allow for targeted immunomodulation.
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To give an overview on the current evidence for stereotactic radiosurgery of brain metastases with a special focus on multiple brain metastases. ⋯ While the use of stereotactic radiosurgery in patients with limited brain metastases has been clearly defined, its role in patients with multiple lesions (> 4) is still a matter of controversy. Whole-brain radiation therapy (WBRT) has been the standard treatment approach for patients with multiple brain lesions and is still the most commonly used treatment approach worldwide. Although distant brain failure is improved by WBRT, the overall survival is not readily impacted. As WBRT is associated with significant neurocognitive decline compared to stereotactic radiosurgery (SRS), SRS has been explored and increasingly utilized for selected patients with multiple brain metastases. Recent clinical data indicated the feasibility of stereotactic radiosurgery to multiple brain metastases with a similar survival in patients with more than 4 brain metastases versus patients with a maximum of 4 brain metastases. Also, neurocognitive function and quality of life was maintained after stereotactic radiosurgery which is essential in a palliative setting. The application of stereotactic radiosurgery with Gamma Knife, Cyberknife, or LINAC-based equipment has emerged as an effective and widely available treatment option for patients with limited brain metastases. Although not formally proven in prospective studies, SRS may also be considered as a safe and effective treatment option in selected patients with multiple brain metastases. Especially in patients with a favorable prognosis, survival over several years is observed also in the setting of multiple BM. For these patients, avoidance of the neurocognitive damage of WBRT is desirable, and SRS is often a more appropriate treatment in the current multimodality treatment of BM in which systemic treatment is often the cornerstone of the treatment. For patients with an intermediate (3-12 months) and poor prognosis (< 3 months), the application of WBRT becomes more and more controversial, because of its acute side effects, such as hair loss and fatigue and, thereby, detrimental effect on quality of life. For these patients, best supportive care, primary systemic treatment, and even SRS may be preferred over WBRT on an individualized patient basis.
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Curr Treat Option Ne · Oct 2018
ReviewNeurotoxicity of Anesthesia in Children: Prevention and Treatment.
The purpose of this review is to summarize the current evidence regarding the impact of the exposure to anesthetic and sedative agents on neurodevelopment during the period of rapid brain growth in the first 3 years of life. Though much of the definitive data demonstrating anesthesia-induced neurotoxicity has come from studies in young animals, the focus of this review is on emerging human data. ⋯ In 2016, the first prospective trials investigating the neurodevelopmental impact of early anesthetic exposure (GAS and PANDA studies) were published, both showing no significant impact on IQ from a single brief anesthetic. More recent population cohort analyses have shown varying, but minimal, impacts from early anesthetic exposure on academic performance and IQ, much smaller than that of maternal education and other environmental factors. Animal and human data document that post-anesthetic neurotoxicity is a genuine phenomenon, but its long-term clinical significance is uncertain. Most experts would agree that a single, brief anesthetic likely has no significant impact on neurodevelopment, but it is yet to be determined whether longer exposures or multiple anesthetics are associated with subsequent learning issues. Future research is aimed at determining the mechanisms of neuronal injury from exposure to anesthetic and sedative agents, adjunctive medications that may prevent or ameliorate this injury, and therapeutic approaches such as early intervention that can enhance recovery. While these studies are underway, it is recommended that exposure to anesthetic and sedative agents be minimized in young children and consideration be given to alternative methods of immobilization for nonpainful procedures such as radiologic imaging.