PMC9674504_01
Initial representative MRI data before treatment (24 November 2021): FLAIR (a-c), T1 (d), T2 (e, f), and corresponding T1 post-gadolinium images (g, h) that resulted in a consensus diagnosis of "probable CLIPPERS." Features of CLIPPERS pathophysiology: the T2/FLAIR high signal is much larger than enhancement, an irregular low T1 signal, associated with diffuse pontine enlargement without signs of a strong mass effect. T1 post-gadolinium data show symmetrical punctate and curvilinear enhancing lesions in the bilateral pons (arrows). No lesions or enhancing foci were noted in the cervical spine.
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MRI of the brain uncovered disseminated and mostly symmetrical regions of distributed infiltrative aberrations localized bilaterally to the pons and to adjacent hindbrain structures (cerebellar peduncles and the mesencephalon) with similar multifocal spots in periventricular cerebral white matter manifesting T2/FLAIR signal hyperintensity (Fig. 1A-C, E, F). In the pons region, a punctate/curvilinear bilateral gadolinium enhancement on T1 (without ring enhancement) was noted: the cardinal feature of the condition in question (Fig. 1G, H). There was no cortical or spinal-cord involvement (Fig. 1).
Additional representative MRI data before treatment. DWI (a), ADC-map (b), time-of-flight angiography (c) and SWI data (d) that resulted in a consensus diagnosis of "probable CLIPPERS." Features of CLIPPERS pathophysiology: there was no restricted diffusion such as an insult or tumor, no appreciable vascular stenosis or malformations (we noted unremarkable asymmetry of vertebral arteries); deep curve vessel fragments (prominent veins) were seen on DWI and SWI (arrows).
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Deep curve vessel fragments (prominent veins) were seen on susceptibility-weighted imaging (Fig. 2D). There was no radiological evidence of a vascular pathology such as vasculitis or vascular lymphoma on the intra-extracranial MR-angiogram (Fig. 2C). There was no "DWI-bright" high signal or "ADC-dark" signal corresponding to lesion-restricted diffusion (Fig. 2A, B).
Representative MRI data after treatment with steroids (27 December 2021): FLAIR (a-c), ADC-map (d), T2 (e, f), and the corresponding T1 post gadolinium image (g, h) revealing almost complete resolution of the FLAIR signal aberration, of pontine enlargement, and of contrast enhancement after the brief course of steroids.
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PMC9674504_02
Initial representative MRI data before treatment (24 November 2021): FLAIR (a-c), T1 (d), T2 (e, f), and corresponding T1 post-gadolinium images (g, h) that resulted in a consensus diagnosis of "probable CLIPPERS." Features of CLIPPERS pathophysiology: the T2/FLAIR high signal is much larger than enhancement, an irregular low T1 signal, associated with diffuse pontine enlargement without signs of a strong mass effect. T1 post-gadolinium data show symmetrical punctate and curvilinear enhancing lesions in the bilateral pons (arrows). No lesions or enhancing foci were noted in the cervical spine.
gr1.jpg
PMC9674504_02_gr1.jpg
fig0001
MRI of the brain uncovered disseminated and mostly symmetrical regions of distributed infiltrative aberrations localized bilaterally to the pons and to adjacent hindbrain structures (cerebellar peduncles and the mesencephalon) with similar multifocal spots in periventricular cerebral white matter manifesting T2/FLAIR signal hyperintensity (Fig. 1A-C, E, F). In the pons region, a punctate/curvilinear bilateral gadolinium enhancement on T1 (without ring enhancement) was noted: the cardinal feature of the condition in question (Fig. 1G, H). There was no cortical or spinal-cord involvement (Fig. 1).
Additional representative MRI data before treatment. DWI (a), ADC-map (b), time-of-flight angiography (c) and SWI data (d) that resulted in a consensus diagnosis of "probable CLIPPERS." Features of CLIPPERS pathophysiology: there was no restricted diffusion such as an insult or tumor, no appreciable vascular stenosis or malformations (we noted unremarkable asymmetry of vertebral arteries); deep curve vessel fragments (prominent veins) were seen on DWI and SWI (arrows).
gr2.jpg
PMC9674504_02_gr2.jpg
fig0002
Deep curve vessel fragments (prominent veins) were seen on susceptibility-weighted imaging (Fig. 2D). There was no radiological evidence of a vascular pathology such as vasculitis or vascular lymphoma on the intra-extracranial MR-angiogram (Fig. 2C). There was no "DWI-bright" high signal or "ADC-dark" signal corresponding to lesion-restricted diffusion (Fig. 2A, B).
Initial PWI-derived regional CBF maps (a, d) with correlated T2 (b, e) and FLAIR (c, f) images showing decreased regional CBF in the affected pons tissue and in a white matter lesion in the right parietal lobe (CBF by 31% and cerebral blood volume by 64%).
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PWI, we delineated a region of interest of round and irregular shape in the lesions, followed by automatic transfer of the geometrical template to all synchronized images. PWI-derived regional cerebral blood flow (CBF)-mapped images revealed a "blue" pattern within pons peduncles and a cerebral white matter lesion (Fig. 3A, D), contrasting with severe T2- and FLAIR "shining" (Fig. 3).
Initial DTI tractography (a). Visual representation of corticospinal tract fibers in the region of the affected hindbrain. We noticed slightly asymmetrical irregular fibers with preserved density. 3D tractography of imaged neuronal bundles as constructed through similar pons regions in the patient (b) and a healthy control subject (c).
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Processing and analysis of the DTI data was performed using the DSI (diffusion spectrum imaging) Studio software (Fig. 4). Visual representation of corticospinal tract fibers in the region of the affected hindbrain on initial DTI tractography showed slightly asymmetrical irregular fibers with preserved density (Fig. 4A). In the affected pons tissue, fewer neuronal bundles passing through the corona radiata and corticospinal tract were noted on the corresponding 3D tractography (Fig. 4 B, C).
Images of an example of axial sections reconstructed from fast whole-brain 3D MPF in the patient before treatment (a-c) as compared with that of healthy women of the same age. The maps were obtained and reconstructed with the same scanner, protocol, and algorithm (d-f). A standard region of interest set (one operator) with quantitative data was utilized.
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Because the brainstem structures were completely devoid of normal-looking tissue, we employed 3D-MPF maps of healthy women of the same age; these maps were built and reconstructed with the same scanner, protocol, and algorithm (Fig. 5).
Representative MRI data after treatment with steroids (27 December 2021): FLAIR (a-c), ADC-map (d), T2 (e, f), and the corresponding T1 post gadolinium image (g, h) revealing almost complete resolution of the FLAIR signal aberration, of pontine enlargement, and of contrast enhancement after the brief course of steroids.
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fig0006