Stuttering as the first sign of CAR-T-cell-related encephalopathy syndrome (CRES)

Excerpt

A 26-year-old right-handed woman with treatment-refractory mediastinal diffuse large B-cell lymphoma (DLBCL) was admitted for chimeric antigen receptor (CAR) T-cell therapy with axicabtagene ciloleucel. Within hours of the infusion, she became tachycardic and developed fevers up to 102.9°F. The patient had undergone lymphodepletion with cyclophosphamide and had leukopenia and neutropenia at the time of her infusion. She was already on prophylactic famciclovir, atovaquone, and fluconazole. Cefepime was started empirically after the onset of her fever. An infectious evaluation with a chest X-ray and blood cultures did not reveal an infectious cause for her fever. The next morning (day 1) she had hypotension (BP 85/51) responsive to IV fluids, consistent with grade 2 cytokine-release syndrome (Porter et al. 2015). Ferritin and C-reactive protein (CRP) were elevated (465 μg/L and 37.3 mg/L, respectively) and increasing (558 μg/L and 45.1 mg/L, respectively, the following day). Tocilizumab was administered for the treatment of cytokine-release syndrome and levetiracetam was initiated for neurotoxicity prophylaxis. However, fever, tachycardia, and hypotension persisted. Ferritin and CRP continued to rise (834 μg/L and 55.8 mg/L, respectively), on day 3. On day 4, the patient developed headache and difficulty speaking, characterized by stuttering and hypophonia. The patient did not have a history or neurologic disease. She remained febrile (102.2°F) and tachycardic (100–110 bpm), and was fatigued and in moderate distress. She was awake, alert, and oriented to self, place, and time, able to count from 100 to 0 by 10 s, and able to name three different objects and her country’s prime minister. Writing was intact. Her CARTOX-10 [a recently proposed screening instrument for CAR-T-cell-related encephalopathy (CRES), where one point is assigned for orientation to year, month, city, hospital, and country’s President/Prime Minister (total of 5 points); naming three objects (maximum of 3 points), writing a standard sentence and counting backwards from 100 in tens (1 point), where normal cognition is defined by an overall score of 10 (Neelapu et al. 2018)] was 10, not meeting diagnostic criteria for CRES. However, her speech was markedly dysfluent with profound stuttering. The remainder of her neurologic examination was normal. Ferritin and CRP levels were improving (723 μg/L and 18.6 mg/L, respectively). …