Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia: An MRI Study of 16 French Cases

Abstract

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is an autosomal dominant leukoencephalopathy related to CSF1R gene mutations. A growing number of clinicoradiologic phenotypes have been described. In this study, we analyzed brain imaging findings in 16 patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia to refine radiologic diagnostic clues. T2/FLAIR white matter hyperintensities were present in all patients with frontal or frontoparietal predilection, with asymmetric distribution in more than one-third. Brain atrophy and callosal involvement were almost constant, and corticospinal tract involvement was frequent. Moreover, deep white matter hyperintense dots on DWI and deep punctate calcifications on CT were often found. Conversely, deep gray matter nuclei, external capsules, and brain stem were rarely involved. Our series emphasized the great variability of MR imaging findings seen in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. A complete imaging screening including DWI, T2*, and CT is mandatory to accurately assess patients with suspected inherited adult-onset leukoencephalopathy.

Fig 1.

Characteristic MR imaging abnormalities in patients with ALSP on FLAIR (A–H, K, L), T2WI (I), and T1WI (J) images. MR imaging usually discloses subtle (A) or marked (B) white mater hyperintensities with frontal predilection (B). WMH can be confluent (B) or patchy (C) and are usually asymmetric (D). Corticospinal tract involvement (A and E) and corpus callosum involvement (F and G) are frequent. At the posterior fossa level, WMH can be of a vascular-like type (H). Some patients can present with enlarged perivascular spaces on T2WI (I). T1WI frequently reveals atrophy, usually marked, with frontal predominance (J). During a 32-month follow-up (case 8), a clear increase of WMH and atrophy is seen (K and L). A cavum septum pellucidum is frequently observed (A and B).

Fig 2.

Typical DWI in ALSP. Persistent deep white matter diffusion-restricted lesions (A–C) with corresponding low ADC values (D–F) are found.

Fig 3.

Small calcifications in ALSP. CT images reveal punctate calcifications located in the subcortical parietal WM and the periventricular frontal WM (A–C). Sagittal reconstruction shows the typical stepping stone distribution (D).