PMC8317246_01
Numerous gadolinium-enhancing lesions following initiation of BRAF/MEK inhibitors in a patient with multiple sclerosis. Key: Images are axial T1-weighted magnetic resonance imaging acquisitions from a 3T Siemens Verio scanner, following the administration of intravenous gadolinium contrast. At least 25 lesions in total demonstrated enhancement with nodular (dotted arrow), open-ring (solid arrow), and close-ring (dashed arrow) characteristics.
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One month later, an MRI was repeated and showed at least 25 new gadolinium-enhancing lesions with patterns consistent with demyelination (oval/ovoid, homogeneous and open-ring enhancement, and the central vein sign) rather than metastasis (Figures 1 and 2).
Characterization of lesions using susceptibility weighted imaging. Key: Left to right: axial T1-weighted post-gadolinium, FLAIR, and susceptibility-weighted images (SWIs) of the acute demyelination event following initiation of BRAF/MEK inhibitors in a patient with multiple sclerosis. The SWI was a single echo 3-dimensional sequence with a voxel size of 0.89 x 0.89 x 2.6 mm and scan time of ~3 minutes. Several of the enhancing lesions demonstrate susceptibility (darkening) on the SWIs, as well as enlargement of single or multiple central veins both characteristic of demyelination pathology. Eighty-three percent of T2 hyperintense lesions with a size of at least 3 mm in diameter (10/12) showed a hypointense central vein sign. The top and middle rows represent 2 anatomic slice levels. The bottom row shows zoomed high-resolution SWIs, optimized for brightness/contrast, to illustrate typical examples (arrows) of the hypointense central vein sign with hyperintense lesions.
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One month later, an MRI was repeated and showed at least 25 new gadolinium-enhancing lesions with patterns consistent with demyelination (oval/ovoid, homogeneous and open-ring enhancement, and the central vein sign) rather than metastasis (Figures 1 and 2).
Evolution of lesions. Key: Comparison axial FLAIR images at different time points; baseline magnetic resonance imaging (left), 1 month following BRAF/MEK inhibitors (center), and following B-cell depletion therapy (right). Note the acceleration of lesion load following BRAF/MEK therapy followed by marked improvement.
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Figure 3 shows the evolution of FLAIR lesions from baseline, to 1 month following BRAF/MEK therapy, followed by lesion recovery after B-cell therapy.