Immune Effector Cell-Associated Neurotoxicity Syndrome

Aka: Immune Effector Cell-Associated Neurotoxicity Syndrome, ICANS

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II. Definitions

  1. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
    1. Chemotherapy-induced neurologic toxicity that may be serious
    2. Most commonly associated with CAR T-Cell Therapy or Bispecific T Cell Therapy

III. Pathophysiology

  1. Unclear mechanism

IV. Causes

  1. CAR T-Cell Therapy
  2. Bispecific T Cell Therapy

V. Risk Factors

  1. Younger age
  2. Neurologic or medical comorbidities
  3. High tumor burden
  4. High intensity lymphodepleting therapy
  5. Cytopenias
  6. Early and severe Cytokine Release Syndrome (CRS)

VI. Findings

  1. Timing
    1. Onset of neurologic symptoms within 1 week of starting Chemotherapy
    2. Starts with inattention and language deficits and may progress rapidly over hours to days
    3. Typically resolves within 7-10 days, but severe cases may require prolonged ICU care
      1. Some deaths have occurred related to cerebral edema
  2. Neurologic findings
    1. Headache
    2. Inattention
    3. Word finding difficulty
    4. Focal neurologic deficits
    5. Encephalopathy
    6. Cerebral edema (may be life-threatening)
    7. Seizures
    8. Altered Level of Consciousness (to transient Coma)

VII. Grading

  1. Grade 1 (Mild)
    1. Inattention and mild Disorientation
    2. Mild expressive or Receptive Aphasia (but patient can still communicate)
  2. Grade 2 (Moderate)
    1. Altered Level of Consciousness (but responds to voice)
  3. Grade 3/4 (Severe)
    1. Significant language deficits
    2. Responsive only to touch or noxious stimulation
    3. Seizures

VIII. Labs

  1. Lactate Dehydrogenase (LDH) increased
  2. Thrombocytopenia
  3. Acute phase reactants increased
  4. Cytokine levels increased

IX. Diagnostics

  1. Electroencephalogram (EEG)
    1. Abnormal with frontal or diffuse theta-delta slowing

X. Imaging

  1. MRI Brain
    1. White matter and sulcus changes from cerebral edema in severe cases

XI. Management

  1. Urgent oncology Consultation
  2. Corticosteroids

XII. References

  1. Bierowski and Nyalakonda (2025) Crit Dec Emerg Med 39(6): 4-21
  2. Sterner (2022) Front Immunol 13:879608 +PMID: 36081506 [PubMed]

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