Neuroimaging findings in immune effector cell associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy

Lapidus, Adam H; Anderson, Mary Ann; Harrison, Simon J.; Dickinson, Michael; Kalinčík, Tomáš; Lasocki, Arian

doi:10.1080/10428194.2022.2074990

Cited by 6 publications

(7 citation statements)

References 41 publications

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“…Some of the abnormal findings noted in another study include features consistent with encephalitis, stroke, leptomeningeal disease, and posterior reversible encephalopathy syndrome [10]. Our team proposed that MRI-related neurotoxicity abnormalities be classified according to anatomical (white matter, grey matter, brainstem, and leptomeninges) and pathological (ischaemia, haemorrhage involvement) involvement [24]. Consistent with other studies, the neuroimaging features of neurotoxicity appear to improve following steroid therapy [26].…”

Section: Discussionsupporting

confidence: 76%

“…Only two of 10 MRIs were noted to be abnormal in our cohort, with findings of diffusion restriction in the cerebellum in one and T2/FLAIR hyperintensity in the brainstem in the other. Most studies confirm that there is no specific neuroradiologic signature for patients with ICANS [10, 23–25]. Some of the abnormal findings noted in another study include features consistent with encephalitis, stroke, leptomeningeal disease, and posterior reversible encephalopathy syndrome [10].…”

Section: Discussionmentioning

confidence: 99%

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Patterns of neurotoxicity among patients receiving chimeric antigen receptor T‐cell therapy: A single‐centre cohort study

Sales,

Anderson,

Kuznetsova

et al. 2023

Euro J of Neurology

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Background and purposeImmune effector cell‐associated neurotoxicity syndrome (ICANS) is an important complication of chimeric antigen receptor T‐cell (CAR‐T) therapy. This study aims to identify the patterns of neurotoxicity among patients with ICANS at a tertiary referral centre in Australia.MethodologyThis single‐centre, prospective cohort study included all consecutively recruited patients who underwent CAR‐T therapy for eligible haematological malignancies. All patients underwent a comprehensive neurological assessment and cognitive screening before CAR‐T infusion, during the development of ICANS, and 1 month after treatment. Baseline demographic characteristics, incidence, and neurological patterns of neurotoxicity management were evaluated.ResultsOver a 19‐month period, 23% (12) of the 53 eligible patients developed neurotoxicity (10/12 [83%] being grade 1). All patients showed changes in handwriting and tremor as their initial presentation. Changes in cognition were manifested in most of the patients, with a more substantial drop noted in their Montreal Cognitive Assessment compared to immune effector cell‐associated encephalopathy scores. All manifestations of neurotoxicity were short‐lived and resolved within a 1‐month period, with a mean duration of 8.2 days (range = 1–33).ConclusionsThe patterns of CAR‐T‐related neurotoxicity often include change in handwriting, tremor, and mild confusional state, especially early in their evolution. These may remain undetected by routine neurological surveillance. These features represent accessible clinical markers of incipient ICANS.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Patterns of neurotoxicity among patients receiving chimeric antigen receptor T‐cell therapy: A single‐centre cohort study

Sales,

Anderson,

Kuznetsova

et al. 2023

Euro J of Neurology

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“…In the few patients in whom new imaging abnormalities developed, there were common patterns of abnormalities. Most of these findings were in patients with high‐grade (>grade 2) ICANS 5,7–12,24–26 . In the following sections of this review, we have categorized these imaging findings based on the possible underlying mechanisms of cytokine‐induced injury to increase the understanding of the complex pathophysiology of this entity.…”

Section: Neuroimaging Patterns Indicative Of Icansmentioning

confidence: 99%

“…Most of these findings were in patients with highgrade (>grade 2) ICANS. 5,[7][8][9][10][11][12][24][25][26] In the following sections of this review, we have categorized these imaging findings based on the possible underlying mechanisms of cytokine-induced injury to increase the understanding of the complex pathophysiology of this entity. One recognized pattern was subtle T2/FLAIR hyperintensities in bilateral thalami and the external capsules, without brainstem involvement.…”

Section: Neuroimaging Patterns Indicative Of Icansmentioning

confidence: 99%

Neuroimaging of complications arising after CD19 chimeric antigen receptor T‐cell therapy: A review

Pinto

Liu

Nelson

et al. 2023

Journal of Neuroimaging

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Chimeric antigen receptor (CAR) T cells targeting the CD19 (cluster of differentiation 19) cell surface glycoprotein have emerged as a highly effective immunologic therapy in patients with relapsed or refractory B‐cell malignancies. The engagement of CAR T cells with CD19 on the surface of neoplastic B cells causes a systemic cytokine release, which can compromise the blood‐brain barrier and cause an immune effector cell‐associated neurotoxicity syndrome (ICANS). In a small proportion of ICANS patients who demonstrate neuroimaging abnormalities, certain distinct patterns have been recognized, including signal changes in the thalami, external capsule, and brainstem, the subcortical and/or periventricular white matter, the splenium of the corpus callosum, and the cerebellum. On careful review of the underlying pathophysiology of ICANS, we noticed that these changes closely mirror the underlying blood‐brain barrier disruption and neuroinflammatory and excitotoxic effects of the offending cytokines released during ICANS. Furthermore, other uncommon complications of CD19 CAR T‐cell therapy such as posterior reversible encephalopathy syndrome, ocular complications, and opportunistic fungal infections can be catastrophic if not diagnosed in a timely manner, with neuroimaging playing a significant role in management. In this narrative review, we will summarize the current literature on the spectrum of neuroimaging findings in ICANS, list appropriate differential diagnoses, and explore the imaging features of other uncommon central nervous system complications of CD19 CAR T‐cell therapy using illustrative cases from two tertiary care institutions.

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“…Descriptions of novel distinctive features are pivotal to untangling this condition's clinical and instrumental signature in order to inform diagnosis and pathophysiology. Most patients present with unremarkable brain MRI, yet a few recurrent neuroradiological features have been recognized ( 4 , 9 , 10 ). Herein, we present a case of CAR T-cell therapy-related neurotoxicity associated with reversible corpus callosum abnormalities, which expand the spectrum of inflammatory neuroradiological abnormalities associated with ICANS.…”

Section: Introductionmentioning

confidence: 99%

Case report: Reversible punctate inflammatory foci in the corpus callosum: A novel radiological finding of CAR T-cell therapy-related neurotoxicity

et al. 2023

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IntroductionChimeric antigen receptor T-cell therapy-related neurotoxicity is a novel cytokine-mediated neurological syndrome that may present with a broad spectrum of manifestations. Descriptions of novel distinctive features are pivotal to untangling this condition's clinical and instrumental signature in order to inform diagnosis and pathophysiology.CaseA 27-year-old female patient received anti-CD19 CAR T cells for a refractory primary mediastinal B-cell lymphoma. At 6 days after the infusion, she developed mild ideo-motor slowing, dysgraphia, and drowsiness. Despite specific treatment with dexamethasone, her neurological status progressively worsened to a comatose state within 24 h. EEG and CSF analyses were non-specific, showing background slowing and inflammatory findings. Brain MRI revealed multiple focal punctate areas of T2-weighted hyperintensity localized in the body and isthmus of the corpus callosum. Following the administration of high-dose intravenous methylprednisolone, her neurological status resolved within 48 h. Notably, the follow-up brain MRI did not reveal any abnormalities in the corpus callosum, except for a reduction of fractional anisotropy.ConclusionReversible punctate inflammatory foci of the body and isthmus of the corpus callosum may represent a novel radiological finding of CAR T-cell therapy-related neurotoxicity.

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Neuroimaging findings in immune effector cell associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy

Cited by 6 publications

References 41 publications

Patterns of neurotoxicity among patients receiving chimeric antigen receptor T‐cell therapy: A single‐centre cohort study

Patterns of neurotoxicity among patients receiving chimeric antigen receptor T‐cell therapy: A single‐centre cohort study

Neuroimaging of complications arising after CD19 chimeric antigen receptor T‐cell therapy: A review

Case report: Reversible punctate inflammatory foci in the corpus callosum: A novel radiological finding of CAR T-cell therapy-related neurotoxicity

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