Frontal Intermittent Rhythmic Delta Activity Is a Useful Diagnostic Tool of Neurotoxicity After CAR T-Cell Infusion.

Autor:	Huby S; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France. sophie.huby27@gmail.com., Gelisse P; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Tudesq JJ; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Labauge P; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Duflos C; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Cartron G; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Gallerand MA; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Platon L; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Badiou S; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Lamure S; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Menjot de Champfleur N; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Ayrignac X; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France., Taieb G; From the Department of Neurology (S.H., P.G., P.L., M.-A.G., X.A., G.T.), CHU Montpellier; Clinical Research and Epidemiology Unit (C.D.), CHU Montpellier; Department of Hematology (J.-J.T., G.C., S.L.), CHU Montpellier; Department of Intensive Care (L.P.), CHU Montpellier; Department of Biochemistry and Hormonology (S.B.), CHU Montpellier; Department of Neuroradiology (N.M.C.), CHU Montpellier, University of Montpellier; University of Montpellier (X.A.), INSERM (INM), Department of Neurology, Montpellier University Hospital; and University of Montpellier (G.T.), CNRS (IGF), Department of Neurology, Montpellier University Hospital, France.
Jazyk:	angličtina
Zdroj:	Neurology(R) neuroimmunology & neuroinflammation [Neurol Neuroimmunol Neuroinflamm] 2023 Apr 14; Vol. 10 (4). Date of Electronic Publication: 2023 Apr 14 (Print Publication: 2023).
DOI:	10.1212/NXI.0000000000200111
Abstrakt:	Background and Objectives: Chimeric antigen receptor (CAR) T-cell therapies have dramatically improved the prognosis of patients with relapsed or refractory hematologic malignancies; however, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in ∼100 and 50% of patients, respectively. This study aimed to determine whether EEG patterns may be considered as diagnostic tools for ICANS. Methods: Patients who received CAR T-cell therapy at Montpellier University Hospital between September 2020 and July 2021 were prospectively enrolled. Neurologic signs/symptoms and laboratory parameters were monitored daily for 14 days after CAR T-cell infusion. EEG and brain MRI were performed between day 6 and 8 after CAR T-cell infusion. EEG was performed again on the day of ICANS occurrence, if outside this time window. All collected data were compared between patients with and without ICANS. Results: Thirty-eight consecutive patients were enrolled (14 women; median age: 65 years, interquartile range: [55-74]). ICANS was observed in 17 of 38 patients (44%) after a median time of 6 days after CAR T-cell infusion (4-8). The median ICANS grade was 2 (1-3). Higher C-reactive protein peak (146 mg/L [86-256], p = 0.004) at day 4 (3-6), lower natremia (131 mmol/L [129-132], p = 0.005) at day 5 (3-6), and frontal intermittent rhythmic delta activity (FIRDA, p < 0.001) on EEG between days 6 and 8 after infusion were correlated with ICANS occurrence. FIRDA was only observed in patients with ICANS (N = 15/17, sensitivity of 88%) and disappeared after ICANS resolution, usually after steroid therapy. Except for hyponatremia, no other toxic/metabolic marker was associated with FIRDA ( p = 0.002). The plasma concentration of copeptin, a surrogate marker of antidiuretic hormone secretion, assessed at day 7 after infusion, was significantly higher in patients with (N = 8) than without (N = 6) ICANS ( p = 0.043). Discussion: FIRDA is a reliable diagnostic tool for ICANS, with a sensitivity of 88% and a negative predictive value of 100%. Moreover, as this EEG pattern disappeared concomitantly with ICANS resolution, FIRDA could be used to monitor neurotoxicity. Finally, our study suggests a pathogenic pathway that starts with increased C-reactive protein, followed by hyponatremia and eventually ICANS and FIRDA. More studies are required to confirm our results. Classification of Evidence: This study provides Class III evidence that FIRDA on spot EEG accurately distinguishes patients with ICANS compared with those without after CAR T-cell therapy for hematologic malignancy. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
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