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. 2020 Nov 2;268(4):1544–1554. doi: 10.1007/s00415-020-10237-3

Table 2.

Grading of immune effector cell-associated neurotoxicity syndrome (ICANS) by American Society for Transplantation and Cellular Therapy (ASTCT) (adapted from [5], with kind permission, © 2018 American Society for Blood and Marrow Transplantation)

Neurotoxicity domain Grade 1 Grade 2 Grade 3 Grade 4
ICE score* 7–9 3–6 0–2 0 (patient is unrousable and unable to perform ICE)
Level of consciousness Awake spontaneously Awakens to voice Awakens only to tactile stimuli Patient is unrousable or requires vigorous tactile stimuli to arouse. Stupor or coma
Seizure N/a N/a Any clinical seizure, focal or generalised, that resolves rapidly. Or non-convulsive seizures on EEG that resolve with intervention Life threatening prolonged seizures (> 5 min), or repetitive clinical or electrical seizures without return to baseline in between
Motor findings N/a N/a N/a Deep focal motor weakness such as hemiparesis or paraparesis
Elevated ICP/cerebral oedema N/a N/a Focal/local oedema on neuroimaging Diffuse cerebral oedema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve palsy; or papilloedema; or Cushing’s triad

ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, raised ICP/cerebral oedema) not attributable to any other cause; for example, a patient with an ICE score of 3 who has a generalised seizure is classified as grade 3 ICANS

ICANS if unarousable. Depressed level of consciousness should be attributable to no other cause (e.g. no sedating medication). Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE v5.0, but they do not influence ICANS grading. Intracranial haemorrhage with or without associated oedema is not considered a neurotoxicity feature and is excluded from ICANS grading. It may be graded according to CTCAE v5.0

N/A not applicable

*A patient with an ICE score of 0 may be classified as grade 3 ICANS if awake with global aphasia, but a patient with an ICE score of 0 may be classified as grade 4