Immune Effector Cell-Associated Neurotoxicity Syndrome: A Practical Overview for the General Neurologist

Neurol Clin Pract. 2026 Feb;16(1):e200575. doi: 10.1212/CPJ.0000000000200575. Epub 2025 Dec 22.

Abstract

Purpose of review: The purpose of this review was to consolidate the clinical, radiographic, and laboratory findings of patients with immune effector cell-associated neurotoxicity syndrome (ICANS) to give physicians a comprehensive overview of its diagnosis and management.

Recent findings: ICANS is a rare but potentially lethal complication of chimeric antigen receptor (CAR) T-cell therapy in patients with hematologic malignancies including leukemia, lymphoma, and multiple myeloma. They often have nonspecific neurologic symptoms, such as language difficulties, encephalopathy, and tremors. Workup may involve brain imaging, EEG, or lumbar puncture, but often, these are normal or nonspecific. Laboratory studies, particularly C-reactive protein and ferritin, can help physicians determine which patients are at risk of developing ICANS and how severe the symptoms may become. While most cases of ICANS resolve spontaneously with supportive measures, studies have shown that steroids play an integral role in treating patients who develop neurotoxicity secondary to CAR T-cell therapy.

Summary: By recognizing the signs and symptoms of ICANS, physicians can begin interventions early in the disease course and potentially mitigate any long-term effects. Although most patients recover without residual deficits, rapid progression to death has been reported in a minority of cases. Workup for other etiologies should be performed as clinically indicated, and abnormal findings should be treated according to standard-of-care practices.

Publication types

  • Review