Central Nervous System Disorders Associated To Immune Checkpoint Inhibitors

2021 ◽  
Vol 17 ◽  
Author(s):  
Felipe Fanine de Souza ◽  
Julia Petry Trevisani ◽  
Letícia Caroline Breis ◽  
Luís Gustavo Marcelino Sizenando ◽  
Marco Antônio Machado Schlindwein ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Neurological Diseases ◽  
Cns Disorders ◽  
Central Nervous System Disorders ◽  
Wide Range ◽  
The Central Nervous System

: New therapies and alternatives for the containment of tumor progression are being proposed for the treatment of cancer. In this context, monoclonal therapies using immune checkpoint inhibitors (ICI) come as a therapeutic proposal. They are responsible for immunological control by blocking PD-1, PD-L1 and CTLA-4 molecules. However, among the effects caused by therapy, the use of medications is associated with neurological diseases reported as an adverse effect, affecting the central nervous system (CNS) and causing a wide range of symptoms. In this regard, the present bibliographic review presents the main CNS disorders associated with this therapy, in addition to the incidence, symptoms and treatment of these diseases.

scholarly journals Immune-Driven Pathogenesis of Neurotoxicity after Exposure of Cancer Patients to Immune Checkpoint Inhibitors

2020 ◽  
Vol 21 (16) ◽  
pp. 5774 ◽  
Author(s):  
Noelia Vilariño ◽  
Jordi Bruna ◽  
Foteini Kalofonou ◽  
Garifallia G. Anastopoulou ◽  
Andreas A. Argyriou
Keyword(s):  
Nervous System ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Importance ◽  
Complex Process ◽  
Wide Range ◽  
The Central Nervous System ◽  
Cancer Types

Over the last decade, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several cancer types. ICIs work through the blockage of immune inhibitory signals, while increasing the T-cell specific immune antitumoral response. However, due to the fact that ICIs’ mechanism of action is not tissue antigen-specific and not limited to the tumor microenvironment, the use of cancer immunotherapy can produce a broad range of immune-related adverse events (irAEs). Neurological immune-related adverse events (NirAEs) are rare (the overall incidence varies between 1% to 6%), and these adverse events mainly concern the peripheral nervous system, rather than the central nervous system. Due to their potential severity, which could cause interruptions to cancer treatment, NirAEs are of particular clinical importance. Currently, the pathogenesis of these complications is not completely understood, although T-cells seem to play a principal role. Nevertheless, the development of NirAEs is likely to be a multifactorial and complex process. This conclusion can be extracted from the wide range of neurological auto-inflammatory and autoimmune disorders triggered or exacerbated by ICIs, and the extensive variability of the limited histological findings reported. The aim of this review is to summarize the potential immune-driven pathological mechanisms of NirAEs.

Demyelinating disease of the central nervous system associated with Pembrolizumab treatment for metastatic melanoma

2018 ◽  
Vol 25 (7) ◽  
pp. 1005-1008 ◽  
Author(s):  
João Durães ◽  
Inês Coutinho ◽  
Angelina Mariano ◽  
Argemiro Geraldo ◽  
Maria Carmo Macário
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Demyelinating Disease ◽  
Checkpoint Inhibitors ◽  
Causative Role ◽  
First Case ◽  
The Central Nervous System

Immune checkpoint inhibitors are used in metastatic melanoma with good efficacy and safety profile. We report the first case of an inflammatory demyelinating disease of the central nervous system during treatment with Pembrolizumab and discuss the evidence in the literature supporting its causative role. The patient had a good clinical recovery after intravenous steroids, plasma exchange and discontinuation of Pembrolizumab. Due to the expected increase in the importance of immune checkpoint inhibitors in cancer treatment, it is important to be aware of neurological adverse events, as early treatment usually leads to good clinical responses.

scholarly journals Sigma receptors and neurological disorders

2021 ◽  
Author(s):  
Agnieszka Piechal ◽  
Alicja Jakimiuk ◽  
Dagmara Mirowska-Guzel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Present Review ◽  
Sigma Receptor ◽  
Sigma Receptors ◽  
Receptor Function ◽  
Central Nervous System Disorders ◽  
The Central Nervous System

AbstarctSigma receptors were identified relatively recently, and their presence has been confirmed in the central nervous system and peripheral organs. Changes in sigma receptor function or expression may be involved in neurological diseases, and thus sigma receptors represent a potential target for treating central nervous system disorders. Many substances that are ligands for sigma receptors are widely used in therapies for neurological disorders. In the present review, we discuss the roles of sigma receptors, especially in the central nervous system disorders, and related therapies. Graphic abstract

scholarly journals Central Nervous System Demyelination Associated With Immune Checkpoint Inhibitors: Review of the Literature

2020 ◽  
Vol 11 ◽  
Author(s):  
Marcos C. B. Oliveira ◽  
Marcelo H. de Brito ◽  
Mateus M. Simabukuro
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Cell Mediated Immune Response ◽  
Central Nervous System Demyelination

Immune checkpoint inhibitors (ICI) are a novel class of antineoplastic treatment that enhances immunity against tumors. They are associated with immune adverse events, and several neurological syndromes have been described, including multiple sclerosis and atypical demyelination. We performed a systematic literature review of case reports with neurological immune adverse events that presented with central nervous system demyelination, up to December 2019. We found 23 cases: seven with myelitis, four isolated optic neuritis, one neuromyelitis optica spectrum disorder, five multiple sclerosis, and six with atypical demyelination. Ipilimumab was the most frequently used ICI (11/23). The median time to develop symptoms from the onset of ICI was 6.5 weeks [range 1.0–43.0], and from last ICI dose was 14 days [range 0–161]. Anatomopathological examination was performed in four cases, with the finding of a T-cell mediated immune response. Outcomes were generally favorable after immunosuppression: 18 patients had improvement or a full recovery, three patients did not respond to treatment, three patients died, and in one, treatment was not reported. We describe the patients' clinical presentation, treatment administered, and outcomes. We further speculate on possible pathophysiological mechanisms and discuss potential treatments that may be worth investigating.

Central nervous system complications associated with immune checkpoint inhibitors

2020 ◽  
Vol 91 (7) ◽  
pp. 772-778 ◽  
Author(s):  
Alberto Vogrig ◽  
Sergio Muñiz-Castrillo ◽  
Bastien Joubert ◽  
Geraldine Picard ◽  
Veronique Rogemond ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

ObjectiveTo describe the spectrum and outcome of central nervous system complications associated with immune checkpoint inhibitors (CNS-ICI).MethodsPatients with CNS-ICI were identified and their characteristics compared with ICI-related peripheral neuropathy (PN-ICI).ResultsWe identified 19 patients with CNS-ICI. The patients were receiving nivolumab (n=8), pembrolizumab (n=6), a combination of ipilimumab-nivolumab (n=3), ipilimumab-durvalumab (n=1), or atezolizumab (n=1). Underlying malignancies included non-small-cell lung cancer (n=8), melanoma (n=3), and other less common tumours (n=8). Neurological phenotypes were limbic encephalitis (n=8), meningoencephalitis (n=4) and cerebellitis (n=4). Two patients developed isolated confusion and one parkinsonism. Associated autoantibodies included onconeural (Ma2, n=7; Hu, n=1), astrocytic (glial fibrillar acidic protein, n=2) and neuronal surface (contactin-associated protein-like 2, n=1) specificities. ICIs were withheld and corticosteroid treatment was given in all cases. Five patients received intravenous immunoglobulin, two rituximab, one plasmapheresis and one infliximab. Overall, six patients died. Readministration of ICI was attempted in three patients, without further relapses. Non-small-cell lung cancer was significantly more frequent in patients with CNS-ICI (p<0.01), while melanoma and ipilimumab treatment were more common in PN-ICI (p<0.01 and p=0.01). Conversely, CNS-ICI cases were more frequently antibody-positive than PN-ICI (p<0.01) and showed a strong trend towards poorer outcome (p=0.053).ConclusionThree main clinical phenotypes characterise CNS complications of ICIs, each with distinct immunological background, disease course and response to treatment. Other clinical manifestations (including parkinsonism and steroid-responsive confusion) are also possible. Underlying cancers, antibody prevalence and outcome appear different from those of patients with PN-ICI.

Paraneoplastic and Idiopathic Autoimmune Neurological Disorders Affecting the Central Nervous System and Autoimmune Dysautonomia

2019 ◽  
pp. 245-265
Author(s):  
Nicholas L. Zalewski ◽  
Sean J. Pittock
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Diagnostic Evaluation ◽  
Rapid Rate ◽  
Disease Category ◽  
Cns Disorders ◽  
Immune Mediated ◽  
The Central Nervous System

This chapter is an examination of immune-mediated central nervous system (CNS) disorders, which have increasingly been recognized as a critical disease category in the field of neurology. The chapter looks at clinical presentation, diagnostic evaluation, and treatment. The chapter also looks to the future. The field of immune-mediated neurological diseases is rapidly growing. New autoantibodies are being discovered at a rapid rate, helping unveil the mystery behind the challenging neurological presentations in many patients.

scholarly journals Neurosarcoidosis following Immune Checkpoint Inhibition

2018 ◽  
Vol 11 (2) ◽  
pp. 521-526 ◽  
Author(s):  
Anastasie M. Dunn-Pirio ◽  
Suma Shah ◽  
Christopher Eckstein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Relevant Literature ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Cns Involvement ◽  
Cns Metastases

Recently, immune checkpoint inhibitors have revolutionized cancer care by enhancing anti-tumor immunity. However, by virtue of stimulating the immune system, they can lead to immune-related adverse events (irAEs). Neurologic irAEs are uncommon but are becoming increasingly recognized and can be quite serious or even fatal. Furthermore, central nervous system (CNS) manifestations may be difficult to distinguish from CNS metastases, posing management challenges. Here, we describe a patient who developed exacerbation of sarcoidosis leading to CNS involvement following dual checkpoint blockade with nivolumab and ipilimumab for metastatic melanoma and review the relevant literature.

scholarly journals Neurotoxicities associated with immune checkpoint inhibitor therapy

2020 ◽  
Vol 19 ◽  
Author(s):  
Zhiyi Zhao ◽  
Chunlin Zhang ◽  
Lian Zhou ◽  
Pan Dong ◽  
Lei Shi
Keyword(s):  
Nervous System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Peripheral Neuropathies ◽  
The Central Nervous System ◽  
Checkpoint Inhibitor Therapy ◽  
Promising Treatment

: Immune checkpoint inhibitors (ICIs) have recently been used as a promising treatment for cancer while their toxicity and immune-related side effects can involve in any organ, including the nervous system. In contrast to other immune-related adverse events (irAEs), neurological irAEs (nAEs) are rare, with varying incidence and symptoms complexity. Although nAEs are uncommon, they can sometimes be severe and even lead to death. However, little attention has been paid to nAEs and the literatures are mostly clinical reports with only a few cases. We therefore conducted the present review with the aim of providing a comprehensive introduction of nAEs. In this review, we summarized various nAEs, including meningitis, encephalitis and hypophysitis in the central nervous system, and myositis, myasthenia gravis and peripheral neuropathies in the peripheral system. We also reviewed the current diagnosis and treatment methods for nAEs commonly used in clinical practice. In addition, we discussed about potential mechanisms regarding nAEs and proposed the possible approaches to preventing the risk of nAEs in patients treated with ICIs. There's still a lot to learn, such as whether and why patients with nAEs respond better to ICI-therapy. The mechanisms and significance of nAEs need to be fully clarified to address these issues and to optimize the treatment strategy.

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