{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:37:33Z","timestamp":1792517853694,"version":"4.5.0"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    We report a 63-year-old male patient with diffuse large B-cell lymphoma (DLBCL) who developed delayed-onset neurotoxicity on day +22 following CD19-directed CAR T-cell therapy with axicabtagene ciloleucel (axi-cel), after an initial episode of CRS and ICANS. The underlying disease had relapsed with secondary central nervous system (CNS) involvement, highlighting a high-risk setting for neurotoxicity. Unlike classical ICANS, the syndrome featured progressive gait ataxia and hypokinetic movement disturbances\u2014clinical hallmarks of so-called movement and neurocognitive treatment-emergent adverse events (MNTs), a syndrome often referred to as parkinsonism due to characteristic features such as bradykinesia, rigidity, tremor, and cognitive slowing. To date, such MNTs have only been reported in patients receiving BCMA-targeted CAR T-cell products, primarily for multiple myeloma. Our report is, to the best of our knowledge, the first documented case of an MNT-like syndrome following CD19-directed CAR T-cell therapy. The patient\u2019s symptoms evolved subacutely, in the absence of radiographic progression, infection, or lymphoma relapse. Immunophenotyping revealed activated effector-memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (HLA-DR\n                    <jats:sup>+<\/jats:sup>\n                    \/CD38\n                    <jats:sup>+<\/jats:sup>\n                    \/CD28\n                    <jats:sup>-<\/jats:sup>\n                    \/PD1\n                    <jats:sup>+<\/jats:sup>\n                    ) in peripheral blood, and predominantly CAR T cells in cerebrospinal fluid. Neurofilament light chain (NfL) levels rose significantly in serum and CSF, indicating neuroaxonal injury. Steroid therapy led to partial clinical improvement. Follow-up neuropsychological testing revealed persistent deficits in attention and processing speed. This case broadens the known neurotoxicity spectrum of CAR T-cell therapies and underscores the need for heightened clinical vigilance and refined diagnostic criteria beyond ICANS, even in CD19-targeted settings.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1749587","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T06:35:57Z","timestamp":1771223757000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Non-ICANS neurotoxicities CD19-directed CAR T-cell therapy and the emergence of movement and neurocognitive treatment-emergent adverse events: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Torsten","family":"Schroeder","sequence":"first","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guranda","family":"Chitadze","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina","family":"Dargvainiene","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjark","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Gebauer","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, University Hospital Schleswig-Holstein L\u00fcbeck, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Frimmel","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Valerius","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Schub","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia D.","family":"Baldus","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Pott","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Leypoldt","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]},{"name":"Department of Neurology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klarissa","family":"St\u00fcrner","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"St\u00f6lzel","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Department of Haematology and Oncology, University Hospital Schleswig-Holstein Kiel, Kiel University","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1002\/hon.2595","article-title":"Managing the toxicities of CAR T-cell therapy","author":"Neelapu","year":"2019","journal-title":"Hematol Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-018-0582-9","article-title":"Neurotoxicity associated with CD19-targeted CAR-T cell therapies","volume":"32","author":"Gust","year":"2018","journal-title":"CNS Drugs"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-94353-0_27","volume-title":"Management 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