CAR-T-cell-related encephalopathy syndrome (CRES) - ...

CAR-T-cell-related encephalopathy syndrome (CRES) - CAR T-Cell Therapy

 • Etiology is unclear; passive cytokine diffusion into brain (IL-6, IL-15 a/w neurotoxicity) vs CAR-T trafficking into CNS

 • Timing/Duration: typically lasts for 2-4 days, but can vary in duration from hours to weeks.

    - Can have biphasic presentation: 1st phase w/ fever and CRS (first 5 days); 2nd phase after fever/CRS subside with delayed neurotoxicity/seizures in 10% (3-4 weeks after infusion)

    - CRES a/w CRS generally of shorter duration, lower grade (grade 1-2) than post-CRS CRES (>grade 3, protracted)

 • Signs/Sx: toxic encephalopathy; earliest signs: diminished attention, language disturbance, impaired handwriting; other: AMS/agitation, somnolence, aphasia, tremors; severe CRES (grade >2): seizures, motor weakness, incontinence, increased ICP → papilledema, cerebral edema

 • Diagnosis: Neuro consult; CARTOX‐10 score; spot EEG (epileptiform, diffuse generalized slowing); funduscopic exam; MRI brain w/without contrast (usually negative) > CT; consider LP w/ opening pressure

 • Therapy: General: seizure prophylaxis with levetiracetam for 30d; consider ICU transfer (>grade 2), airway protection (grade 4)

    - 1st phase (a/w CRS): anti-IL-6 (tocilizumab/ siltuximab) can reverse CRES; glucocorticoids refractory or grade 2

    - 2nd phase (post-CRS): anti-IL-6 ineffective (presumed 2/2 ↓permeability of blood-brain barrier); glucocorticoids preferred

    - If cerebral edema: acetazolamide, glucocorticoids; HOB>30°; hyperventilate to PaCO2 30; mannitol; consult NSGY

 • Prognosis: CRES is generally reversible, rare fatal cases

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