Chimeric Antigen Receptor T Cell-Related Neurotoxicity: Mechanisms, Clinical Presentation, and Approach to Treatment

AbstractPurpose of reviewChimeric 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.Recent findingsCurrent 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.SummaryThe 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 o...
Source: Current Treatment Options in Neurology - Category: Neurology Source Type: research

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This article is part of the Special Issue “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures"
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures". PMID: 31420291 [PubMed - as supplied by publisher]
Source: Epilepsy and Behaviour - Category: Neurology Authors: Tags: Epilepsy Behav Source Type: research
Publication date: Available online 13 June 2019Source: SeizureAuthor(s): Tommaso Ercoli, Giovanni Defazio, Antonella MuroniAbstractHashimoto’s encephalopathy is a non-infectious, probably autoimmune encephalitis, characterized by varied signs coupled with elevated levels of anti-thyroid antibodies and, often, good response to corticosteroid therapy. Seizures, namely focal and generalized tonic-clonic seizures, myoclonus, and status epilepticus, are frequent manifestations of Hashimoto’s encephalopathy. Typically, seizures in these patients respond poorly to anti-epileptic drugs. Although cases of Hashimoto&rsqu...
Source: Seizure - Category: Neurology Source Type: research
Authors: Palomino-Lescano H, Segura-Chávez D, Quispe-Orozco D, Castro-Suarez S, De la Cruz W, Zapata-Luyo W, Delgado-Ríos J, Cam J, Alvarado-Morales M, Paredes-Carcasi L, Cornejo-Herrera I, Meza-Vega M Abstract Autoimmune encephalitis with antibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) is a disorder mediated by antibodies against neural surface antigens, whose early diagnosis and timely treatment improve the prognosis of the disease. Four cases with the definitive diagnosis of autoimmune encephalitis by anti-NMDAR are presented, treated at the National Institute of Neurological Scie...
Source: Revista Peruana de Medicina de Experimental y Salud Publica - Category: International Medicine & Public Health Tags: Rev Peru Med Exp Salud Publica Source Type: research
Conclusion: Patients with isolated thalamic atrophy were at a higher risk for not reaching 2-year NEDA-3 and for EDSS increase than patients with no identified brain atrophy. The groups were clinically indistinguishable. A single measurement of thalamic and whole brain atrophy could help identify patients needing most effective therapies from early on. Introduction The quantification of brain atrophy by MRI has become an increasingly important part of evaluating neurodegeneration in MS (1, 2). Atrophy measures can reflect the damage on the central nervous system (CNS) caused by the pathological processes of the dis...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conclusions: Seizures and encephalopathy are not rare in MOG encephalomyelitis, and are commonly associated with cortical and subcortical brain lesions. MOG-encephalomyelitis often presents with clinical meningoencephalitis symptoms and abnormal CSF findings mimicking central nervous system infection in pediatric and young adult patients. Background Immunoglobulin-G against myelin oligodendrocyte glycoprotein (MOG-IgG) is considered a potential demyelinating disease-associated autoantibody. Previous experimental studies have established MOG-IgG as a pathogenic antigen rather than an epiphenomenal bystander or a secon...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Shanshan Zhang1, Dongli Yuan2 and Ge Tan1* 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 2The Institute of Medical Information, Chongqing Medical University, Chongqing, China Primary systemic vasculitis can affect every structure in both the central and peripheral nervous system, causing varied neurological manifestations of neurological dysfunction. Early recognition of the underlying causes of the neurological symptoms can facilitate timely treatment and improve the prognosis. This review highlights the clinical manifestations of primary systemic vasc...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conclusion The choice of CMA estimates and sliding window parameters has a major impact on the performance of a clustering algorithm to identify distinct longitudinal adherence trajectories. We recommend (a) assuming constant adherence between refills, (b) avoiding dichotomization based on a threshold, and (c) exploring optimal sliding windows parameters in simulation studies or selecting shorter non-overlapping windows for the accurate and robust identification of different adherence patterns from electronic healthcare data. Author Contributions SA and DD programmed the simulations. SA performed the analyses and wrote ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion: Some patients with psychiatric syndromes and increased ANA titers may suffer from psychiatric variants of SLE, even if the American College of Rheumatology criteria for SLE are not met. Whether the psychiatric symptoms in our patient represent a prodromal stage with the later manifestation of full-blown SLE or a subtype of SLE with isolated CNS involvement remains unclear. Regardless, early diagnosis and initiation of immunosuppressive treatment are essential steps in preventing further disease progression and organ damage. Intrathecal ANAs with extractable nuclear antigen differentiation may be a more sensitiv...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
We read with interest, the article published by Gonzalez-Giraldo E and colleagues1 in October, 2018 issue, entitled “Treating Infantile Spasms with High-Dose Oral Corticosteroids: A Retrospective Review of 87 Children.”Authors retrospectively studied the effect of high dose oral steroids in children with epileptic spasm. We want to add few points.
Source: Pediatric Neurology - Category: Neurology Authors: Tags: Correspondence Source Type: research
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