Involvement of the optic nerve in mutated CSF1R-induced hereditary diffuse leukoencephalopathy with axonal spheroids

Abstract

Background: Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration and caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. Involvement of the optic nerves in hereditary diffuse leukoencephalopathy is rare.

Case presentation: We report the case of a 30-year-old Chinese woman with HDLS, who carried a heterozygous c.2345 G > A (p.782Arg > His) mutation in exon 18 of CSF1R. She developed a gradual decline in motor ability, as well as cognitive and visual function, over the course of 4 months. Brain T2 fluid-attenuated inversion recovery-weighted magnetic resonance imaging revealed high signal lesions in the bilateral frontoparietal and periventricular deep white matter. Optical coherence tomography showed that the right peripapillary retinal nerve fiber layer was atrophic in the temporal quadrant while the left peripapillary retinal nerve fiber layer was thin in the temporal superior quadrant.

Conclusions: A diagnosis of HDLS should be considered in patients with white matter lesions and optic nerves injury upon magnetic resonance imaging that mimics progressive multiple sclerosis.

Keywords: Colony-stimulating factor 1 receptor; Hereditary diffuse leukoencephalopathy with axonal spheroids; Leukoencephalopathy; Peripapillary retinal nerve fiber layer.

Fig. 1

Family pedigree. The arrow indicates the proband (present patient). Her mother developed a motor disorder at 40 years of age and died at 60 years of age. Her grandparents, father, brothers, sisters, and daughters were not affected

Fig. 2

Brain MRI, DWI, DTI, and MRS images. T2/Flair showed multifocal periventricular white matter lesions (a b and c), without enhancement (d). DWI shows high-signal intensities in periventricular white matters and corpus callosum (e f). DTI shows decreased numbers of corpus callosum fibers, while subcortical arcuate fibers are spared (g). MRS shows increased Cho levels, while NAA levels are decreased in the white matter lesions (h i)

Fig. 3

Optic nerves on MRI, showing that bilateral optic nerves are injured (red arrows)

Fig. 4

OCT shows that the right peripapillary retinal nerve fiber layer (pRNFL) is atrophic in the temporal quadrant, and the left pRNFL is thinning in the temporal superior quadrants. Green represents pRNFL thickness, which is within normal limits; yellow represents pRNFL thickness, which is below borderline; red represents pRNFL thickness, which is below normal limits

Fig. 5

VEP shows reduced bilateral P100 amplitudes, although P100 latencies are normal in both eyes

Fig. 6

Visual fields in the right eye are partially missing in the upper right, lower right, and lower left quadrants, especially in the lower right quadrant. Visual fields in the left eye are partially missing in the four quadrants, especially in the upper left and lower right quadrants

Fig. 7

Gene analysis of CSF1R. The sequencing result from exon 18 of CSF1R (NM_005211.3) indicates a heterozygous c.2345 G > A (p.782Arg > His) substitution in the patient