Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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November 10, 2022
Immune Effector Cell–Associated Neurotoxicity Syndrome (ICANS)
- Background:
- Chimeric antigen receptor T-cell (CAR-T) therapy is a type of immunotherapy increasingly utilized in the treatment of refractory hematologic malignancies.1
- Immune effector cell–associated neurotoxicity syndrome (ICANS), is an adverse outcome with unknown frequency that requires immediate intervention.2
- Astrocytic clasmatodendrosis has been documented in an autopsy study of CAR-T neurotoxicity. This finding is not specific, but has been demonstrated in several conditions that are associated with disruption of the blood-brain barrier, including brain trauma, ischemia, Alzheimer disease, multiple sclerosis, hyperglycemia, and cerebral edema.3
- ICANS can occur in isolation or with cytokine release syndrome in patients with CAR-T.4,5
- Clinical Presentation:
- Common symptoms include delirium, aphasia, tremor, dysgraphia, and lethargy.
- Symptoms can progress to seizures, cerebral edema, and coma.
- The clinical timeline is highly variable. Most cases of ICANS develop within 5–12 days of CAR-T infusion and are typically reversible, but can be fatal. This patient had rapid progression of disease and died approximately 1 month after his initial neurologic symptoms.
- Key Diagnostic Features:
- The imaging findings are nonspecific with MR findings that can mimic ischemia or inflammation, thus communication of the syndrome and patient’s history are critical.5
- Leptomeningeal enhancement and T2 hyperintensity in the cerebral sulci; this patient’s sulcal disease was only visible on DWI (Figure B). Symmetric thalamic disease has also been reported.
- T2/FLAIR changes indicative of vasogenic edema and/or multifocal microhemorrhages may also be present.
- T2 hyperintensities in the supratentorial white matter; diffusion restriction in patchy areas of the cortex and/or white matter
- Normal MRA and lack of thrombi on cardiac echocardiogram
- Differential Diagnosis:
- Embolic disease
- Demyelination
- Vasculitis
- Hemophagocytic lymphohistiocytosis that presents with fever and causes multisystem inflammatory tissue destruction.
- Treatment:
- The incidence of this syndrome and treatment protocols are still being studied in patients treated with CAR-T.6
- This patient received dexamethasone, tocilizumab (IL-6 inhibitor), and prophylactic broad-spectrum antibiotics. His transesophageal echocardiogram was negative.
- Patients with severe cerebral edema can be treated with high-dose corticosteroids, hyperosmolar therapy, hyperventilation, or a ventriculoperitoneal shunt.
- As cellular immunotherapies increase in use, increased recognition and understanding of the diagnosis and treatment of ICANS is needed.
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