Immune effector cell-associated neurotoxicity syndrome (ICANS)

Case contributed by Frank Gaillard
Diagnosis almost certain


Neurological decline 4 days following CAR T-cell infusion for diffuse large B-cell lymphoma.

Patient Data

Age: 60 years
Gender: Male

No intracranial hemorrhage. No intra- or extra-axial mass or collection. No evidence of acute established infarct. Grey white matter differentiation is preserved. The posterior fossa is unremarkable. Ventricular and sulcal morphology is within normal limits. The basal cisterns are clear. Orbits, paranasal sinuses and mastoid air cells are clear.

Conclusion: no acute intracranial pathology.

Progressive neurological deterioration with reduced GCS and an apparent spinal level at T6. Patient intubated.

In comparison with prior CT performed 3 as previously there is development of gross sulcal effacement and progressive hypoattenuation throughout the white matter indicating generalized cerebral edema. No cerebral herniation appreciated. No subarachnoid hemorrhage identified. Brainstem is unremarkable. No bony abnormality, soft tissues are unremarkable.

Conclusion: gross generalized cerebral edema, which is new compared with CT performed 3 days previously.

Extensive white matter FLAIR hyperintensities involving the centrum semiovale, extreme capsule and periventricular white matter. Further FLAIR signal abnormality surrounding the cerebral aqueduct and fourth ventricle, as well as in the imaged upper cervical cord. Scattered foci of susceptibility artifact consistent with microhemorrhages, in the brainstem and corona radiata. Cortical increased diffusion restriction in the right precentral gyrus, bilateral occipital lobes and left parietal lobe. Further foci of punctate diffusion restriction in both cerebellar hemispheres. On post-contrast imaging, there is no abnormal focus of contrast enhancement. Normal ventricular size. Small bilateral mastoid effusions.


Extensive white matter changes in this clinical context are consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) - ASTCT grade 4.

Microhemorrhages and small cortical restricted diffusion are also present and have also described in ICANS.

Extensive myelopathy throughout the entire spinal cord, consistent with ICANS. No features of intraspinal infection or hematoma. Extensive symmetric signal abnormality in the paraspinal musculature, may be due to acute denervation change or, more likely, in this clinical context, myositis in the setting of cytokine release syndrome.

Case Discussion

This patient had concurrent cytokine release syndrome. Outcome unknown.

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