case_images: PMC10548379_01
case_images: Clinical timeline. CUS: Cranial Ultrasonography, EF: Executive Functioning, FIQ: Full IQ, IQ: Intelligence Quotient, PIQ: Performance IQ, PRI: Perceptual Reasoning Index, PSI Processing Speed Index TOL: Tower of London, VCI: Verbal Comprehension Index, VIQ: Verbal Index, WM: White Matter, WMI Working Memory Index. Age is given in years. Modifications in neuroradiological features are shown as '+' in consideration of the involvement of WM, calcifications, and cysts: + mild ++ moderate +++ severe ++++ extremely severe. WM assessment refers to represent severity of leukodystrophy and not its topology. Similarly, cysts evaluation refers to qualitative assessment.
case_images: fneur-14-1245014-g001.jpg
case_images: PMC10548379_01_fneur-14-1245014-g001.jpg
case_images: fig1
case_images: Fondazione Stella Maris because of psychomotor delay (timeline of major clinical and neuroradiological assessments in Figure 1). Family history was not contributory. Brain imaging again revealed an increase in cysts size and a worsening of white matter lesions (Figure 2 pre B1). By the fourth month of treatment, a further improvement in the neuroradiological appearance was observed, with a reduction in white matter involvement in the juxtacortical regions, in the external capsular claustrum and in the posterior limb of the internal capsule and periventricular regions (Figure 2 B1). After 7 months of therapy, further neuroradiological and clinical improvements were documented, albeit to a lesser degree than during the first months of treatment (Figure 2 B1).
case_images: Neuroradiological data pre- and post-treatment with bevacizumab. Comparative brain MRI before and after the first and second cycle of treatment with bevacizumab. Before the initiation of treatment (pre B1) T2-weighted images (a,g,m) showed extensive and asymmetric hyperintensity of the periventricular and deep white matter, with involvement also of the juxtacortical U-fibers (a,m: white arrowheads) more extensive on the left, with lobar macrocysts (*) delimited by hypointensity in T2 Star Weighted ANgiography (SWAN) (s) due to calcium and hemosiderin deposition. Additional microcysts, microcalcifications and microdeposits of hemosiderin were present in the periventricular white matter, around the walls of the small cysts, and in the region of the putamen on the right and the caudate on the left (s: arrow). Four (b,h,n) and 7 months (c,i,o) after starting a first cycle of treatment there was a progressive reduction in the extent of the signal alteration, which first affected the white matter of the U fibers (b,c,n,o: white arrowheads), external capsular claustrum and posterior limb of the internal capsule and periventricular white matter (small white arrowheads). MRI images after discontinuation of treatment (pre B2) showed a reappearance of signal alterations in the same regions in which regression was observed (d,j,p vs a,g,m: white arrowheads). After initiation of the second treatment cycle, progressive improvement of signal alterations was observed in the same regions as after the first cycle (e,f,k,l). In addition, a reduction of signal hypointensities in SWAN sequences was observed in the frontal white matter on the left, around, and in proximity to, the cyst wall (v,w,x: arrowheads). Note the apparent decrease in abnormal white matter volume after treatment (c,o; f,r).
case_images: fneur-14-1245014-g002.jpg
case_images: PMC10548379_01_fneur-14-1245014-g002.jpg
case_images: fig2
case_images: Brain imaging again revealed an increase in cysts size and a worsening of white matter lesions (Figure 2 pre B1). By the fourth month of treatment, a further improvement in the neuroradiological appearance was observed, with a reduction in white matter involvement in the juxtacortical regions, in the external capsular claustrum and in the posterior limb of the internal capsule and periventricular regions (Figure 2 B1). After 7 months of therapy, further neuroradiological and clinical improvements were documented, albeit to a lesser degree than during the first months of treatment (Figure 2 B1). In our case, MRI follow up at one and 8 months after treatment cessation showed a worsening in neuroimaging (Figure 2 pre B2). After 4 months of treatment, MRI revealed an improvement in the appearance of the white matter, with the same topological distribution observed previously (Figure 2 B2). Further marked modifications were observed after 10 months of treatment, including a reduction of white matter abnormalities, a mild enlargement of the periencephalic subarachnoid space and variation in cysts' volume (Figures 2 B2, 3).
case_images: Volumetric variation of macrocysts. Graphical representation overtime of cysts' volume according to timepoints described in main text and in Figure 2.
case_images: fneur-14-1245014-g003.jpg
case_images: PMC10548379_01_fneur-14-1245014-g003.jpg
case_images: fig3
case_images: Modifications in cysts' volume and shape were also recorded (Figure 3). Further marked modifications were observed after 10 months of treatment, including a reduction of white matter abnormalities, a mild enlargement of the periencephalic subarachnoid space and variation in cysts' volume (Figures 2 B2, 3).