Neurological adverse events of immune checkpoint inhibitors: An update of clinical presentations, diagnosis, and management

Farina, Antonio; Villagrán-García, Macarena; Honnorat, Jérôme

doi:10.1016/j.neurol.2023.03.003

Cited by 16 publications

(45 citation statements)

References 53 publications

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“…anti γ-aminobutyric acid type B receptor) or nonparaneoplastic limbic encephalitis (e.g. antiglutamic acid decarboxylase 65 or -contactin-associated protein-like have been reported in a minority of cases [31 ▪▪ ]. Brain MRI frequently shows signal changes in the hippocampi and amygdala, in some cases with gadolinium enhancement, likely resulting from blood-brain barrier leakage [14] (Fig.…”

Section: Encephalitismentioning

confidence: 99%

Central nervous system adverse events of immune checkpoint inhibitors

Farina,

Villagrán-García,

Vogrig

et al. 2024

Current Opinion in Neurology

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Purpose of review Immune checkpoint inhibitors (ICI) may trigger immune-related adverse events which rarely affect the central nervous system (CNS-irAEs). Over the past few years, cumulative data have led to the characterization of well defined syndromes with distinct cancer and antibody associations as well as different outcomes. Recent findings The most frequent CNS-irAE is encephalitis, which includes three main groups: meningoencephalitis, a nonfocal syndrome usually responsive to corticosteroids; limbic encephalitis, associated with high-risk paraneoplastic neurological syndromes (PNS) antibodies (e.g. anti-Hu, anti-Ma2) and neuroendocrine cancers, characterized by poor treatment response and outcomes; and cerebellar ataxia, with variable outcomes (worse when high-risk PNS antibodies are detected). Additionally, a diffuse encephalopathy without inflammatory findings, with poor response to corticosteroids and high mortality has been described. The spectrum of CNS-irAEs also includes meningitis, myelitis, and rarer presentations. A subset of CNS-irAEs (i.e. limbic encephalitis and/or rapidly progressive cerebellar ataxia) is undistinguishable from ICI-naïve PNS. Summary The clinical and outcomes diversity of CNS-irAEs suggests different pathogenic mechanisms, which need to be understood to establish more effective and specific treatment modalities. It is crucial to identify biomarkers able to predict which patients will experience severe CNS-irAEs, to anticipate their diagnosis, and to predict long-term outcomes.

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Section: Encephalitismentioning

confidence: 99%

Central nervous system adverse events of immune checkpoint inhibitors

Farina,

Villagrán-García,

Vogrig

et al. 2024

Current Opinion in Neurology

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“…33,34 Among these irAEs, myalgia and myositis occurred in 4% and <1%, respectively, more frequently with anti-PD-1/PD-L1 antibodies than with anti-cytotoxic T lymphocyte-associated protein-4 antibodies, and more frequently in older patients. 33,34 Myalgia appears on average 4 weeks after the start of treatment, followed by muscle weakness, mainly in the proximal muscles, and ptosis and ocular motility disorders similar to myasthenia gravis. 34 Myocarditis is present in 25-40% of irAEs with skeletal muscle symptoms; CK is elevated in $70%, but normal in onethird, and the degree of elevation varies (Table 1).…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

“…Muscle biopsy reveals myofiber necrosis with infiltration of T cells (CD4 + , CD8 + ), B cells 2). 33,34 Glucocorticoids Glucocorticoid-induced myopathy, characterized by muscle weakness and muscle atrophy, has been recognized since the 1950s, when glucocorticoids were first used as therapeutic agents. In fact, in addition to therapeutic glucocorticoids, blood glucocorticoids are elevated in pathological conditions such as sepsis, cachexia, and starvation, and are known to be involved in the muscle atrophy associated with these conditions.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

“…Typically, adverse reactions associated with the release of immunosuppression by immune checkpoint inhibitors occur when T cells infiltrate various organs throughout the body, triggering an excessive immune response. Such adverse reactions have symptoms similar to those of autoimmune diseases and are referred to as immune‐related adverse events (irAEs) 33,34 …”

Section: Drugs That Cause a Certain Frequency Of Sarcopenia Or Myopathymentioning

confidence: 99%

“…The mechanism is not yet clear, but it is suspected to involve aberrant cytotoxic T‐cell activation and the production of autoantibodies (Table 2). 33,34 …”

Section: Drugs That Cause a Certain Frequency Of Sarcopenia Or Myopathymentioning

confidence: 99%

See 2 more Smart Citations

Drug‐related sarcopenia as a secondary sarcopenia

Kuzuya

2023

Geriatrics Gerontology Int

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Sarcopenia has a significant impact on falls, physical function, activities of daily living, and quality of life in older adults, and its prevention and treatment are becoming increasingly important as the global population ages. In addition to primary age‐related sarcopenia, activity‐related sarcopenia, disease‐related sarcopenia, and nutrition‐related sarcopenia have been proposed as secondary sarcopenia. Polypharmacy and potentially inappropriate medication based on multiple diseases cause health problems in older patients. In some cases, drugs used for therapeutic or preventive purposes act on skeletal muscle as adverse drug reactions and induce sarcopenia. Although sarcopenia caused by these adverse drug reactions may be more common in older patients, in particular those taking many medications, drug‐related sarcopenia has not yet received much attention. This review summarizes drugs that may induce sarcopenia and emphasizes the importance of drug‐related sarcopenia as a secondary sarcopenia. Geriatr Gerontol Int 2023; ••: ••–••.

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Paraneoplastic Calmodulin Kinase‐Like Vesicle‐Associated Protein (CAMKV) Autoimmune Encephalitis

Gilligan,

Lesnick,

Guo

et al. 2024

Annals of Neurology

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ObjectivesTo report an autoimmune paraneoplastic encephalitis characterized by immunoglobulin G (IgG) antibody targeting synaptic protein calmodulin kinase‐like vesicle‐associated (CAMKV).MethodsSerum and cerebrospinal fluid (CSF) samples harboring unclassified antibodies on murine brain‐based indirect immunofluorescence assay (IFA) were screened by human protein microarray. In 5 patients with identical cerebral IFA staining, CAMKV was identified as top‐ranking candidate antigen. Western blots, confocal microscopy, immune‐absorption, and mass spectrometry were performed to substantiate CAMKV specificity. Recombinant CAMKV‐specific assays (cell‐based [fixed and live] and Western blot) provided additional confirmation.ResultsOf 5 CAMKV‐IgG positive patients, 3 were women (median symptom‐onset age was 59 years; range, 53–74). Encephalitis‐onset was subacute (4) or acute (1) and manifested with: altered mental status (all), seizures (4), hyperkinetic movements (4), psychiatric features (3), memory loss (2), and insomnia (2). Paraclinical testing revealed CSF lymphocytic pleocytosis (all 4 tested), electrographic seizures (3 of 4 tested), and striking MRI abnormalities in all (mesial temporal lobe T2 hyperintensities [all patients], caudate head T2 hyperintensities [3], and cortical diffusion weighted hyperintensities [2]). None had post‐gadolinium enhancement. Cancers were uterine adenocarcinoma (3 patients: poorly differentiated or neuroendocrine‐differentiated in 2, both demonstrated CAMKV immunoreactivity), bladder urothelial carcinoma (1), and non‐Hodgkin lymphoma (1). Two patients developed encephalitis following immune checkpoint inhibitor cancer therapy (atezolizumab [1], pembrolizumab [1]). All treated patients (4) demonstrated an initial response to immunotherapy (corticosteroids [4], IVIG [2]), though 3 died from cancer.InterpretationCAMKV‐IgG is a biomarker of immunotherapy‐responsive paraneoplastic encephalitis with temporal and extratemporal features and uterine cancer as a prominent oncologic association. ANN NEUROL 2024

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Neurological adverse events of immune checkpoint inhibitors: An update of clinical presentations, diagnosis, and management

Cited by 16 publications

References 53 publications

Central nervous system adverse events of immune checkpoint inhibitors

Central nervous system adverse events of immune checkpoint inhibitors

Drug‐related sarcopenia as a secondary sarcopenia

Paraneoplastic Calmodulin Kinase‐Like Vesicle‐Associated Protein (CAMKV) Autoimmune Encephalitis

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