Figure 2.
Figure 2. Brain imaging and electroencephalography during neurotoxicity. (A) Normal CT of the brain at onset of neurotoxicity (top) and subdural hematoma 13 days later (A′). (B) Axial MRI of the brain with normal FLAIR (top) and diffusion-weighted imaging (DWI, bottom) sequences during acute neurotoxicity. (C) Axial FLAIR image (top) in a patient with severe neurotoxicity demonstrating a lesion (arrowheads) of the splenium of the corpus callosum partly characterized by restricted diffusion on DWI sequences (bottom). (D) Axial FLAIR hyperintensities of the brainstem (left) and the periventricular white matter (middle) were found in a patient with left-sided visual field deficit who presented 30 days after CAR T-cell infusion. Periventricular lesions were characterized by restricted diffusion on DWI sequences (right). Luxol fast blue (LFB) with hematoxylin and eosin (H&E) (E), neurofilament (F), and CD3 (G) stains of a tissue specimen taken from the periventricular lesion in panel D shows axonal injury of the optic radiation (original magnification, ×400). H&E-LFB demonstrates vacuolization and axonal spheroid formation (arrows). Immunohistochemical staining for neurofilament shows enlarged circular brown material consistent with axonal spheroids within white matter, a finding characteristic for Wallerian degeneration. Immunohistochemical staining for CD3 highlights T cells in scant numbers, primarily present in perivascular regions. (H) Electroencephalography of a patient who developed myoclonus and confusion 10 days after CAR T-cell infusion. Low-frequency blunted generalized periodic discharges admixed with rhythmicity on an alternating background between δ and θ slowing are displayed. The snapshot is seen in a longitudinal bipolar montage (left-right-left-right-midline): sensitivity, 7 μV/mm; time base, 30 mm/s; low-frequency filter, 1 Hz; high-frequency filter, 70 Hz; and notch, 60 Hz. (I, left) Axial FLAIR image in a patient with confusion after rituximab-lenalidomide infusion shows bilateral curvilinear hyperintensities in the juxtacortical frontoparietal white matter without restricted diffusion on DWI sequences (right). (J) Axial T1-weighted MRI postcontrast and FLAIR images demonstrate a radiosurgery lesion pre-CAR T-cell infusion (left) and evidence of radiation necrosis with contrast enhancement after CAR T-cell infusion (J′).

Brain imaging and electroencephalography during neurotoxicity. (A) Normal CT of the brain at onset of neurotoxicity (top) and subdural hematoma 13 days later (A′). (B) Axial MRI of the brain with normal FLAIR (top) and diffusion-weighted imaging (DWI, bottom) sequences during acute neurotoxicity. (C) Axial FLAIR image (top) in a patient with severe neurotoxicity demonstrating a lesion (arrowheads) of the splenium of the corpus callosum partly characterized by restricted diffusion on DWI sequences (bottom). (D) Axial FLAIR hyperintensities of the brainstem (left) and the periventricular white matter (middle) were found in a patient with left-sided visual field deficit who presented 30 days after CAR T-cell infusion. Periventricular lesions were characterized by restricted diffusion on DWI sequences (right). Luxol fast blue (LFB) with hematoxylin and eosin (H&E) (E), neurofilament (F), and CD3 (G) stains of a tissue specimen taken from the periventricular lesion in panel D shows axonal injury of the optic radiation (original magnification, ×400). H&E-LFB demonstrates vacuolization and axonal spheroid formation (arrows). Immunohistochemical staining for neurofilament shows enlarged circular brown material consistent with axonal spheroids within white matter, a finding characteristic for Wallerian degeneration. Immunohistochemical staining for CD3 highlights T cells in scant numbers, primarily present in perivascular regions. (H) Electroencephalography of a patient who developed myoclonus and confusion 10 days after CAR T-cell infusion. Low-frequency blunted generalized periodic discharges admixed with rhythmicity on an alternating background between δ and θ slowing are displayed. The snapshot is seen in a longitudinal bipolar montage (left-right-left-right-midline): sensitivity, 7 μV/mm; time base, 30 mm/s; low-frequency filter, 1 Hz; high-frequency filter, 70 Hz; and notch, 60 Hz. (I, left) Axial FLAIR image in a patient with confusion after rituximab-lenalidomide infusion shows bilateral curvilinear hyperintensities in the juxtacortical frontoparietal white matter without restricted diffusion on DWI sequences (right). (J) Axial T1-weighted MRI postcontrast and FLAIR images demonstrate a radiosurgery lesion pre-CAR T-cell infusion (left) and evidence of radiation necrosis with contrast enhancement after CAR T-cell infusion (J′).

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