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 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.

Homozygous Mutations in CSF1R Cause a Pediatric-Onset Leukoencephalopathy and Can Result in Congenital Absence of Microglia

“…However, the phenotype of the individual from family CSF1R_01 (II-1) was significantly more severe than the individual from family CSF1R_02 (II-4), who remains alive at 24 years of age, and whose brain MRI findings overlap with ALSP. 50 We speculate that the p.His643Gln single amino acid substitution is hypomorphic and results in relatively more CSF1R protein function than the exon 13 splice acceptor mutation (c.1754À1G>C) seen in CSF1R_01. Consistent with this hypothesis is the fact that the siblings reported by Monies et al, 33 who likely had a null mutation (c.1620T>A [p.Tyr540*]), demonstrated a perinatal lethal phenotype.…”

Adult-onset diffuse leukoencephalopathy with axonal spheroids and pigmented glia presenting with acute stroke-like symptoms: A rare clinical scenario

“…These calcifications may occur in a symmetric “stepping stone” pattern in the pericallosal regions (adjacent to the frontal horns of the lateral ventricles) or scattered in the frontal and parietal white matter. ALSP does not show calcifications in the basal ganglia, thalamus or cerebellum which helps to differentiate it from other metabolic and genetic conditions [4 , 9 , 10 , 13 , 14 , 16] . MR spectroscopy studies have shown decreased N-acetylaspartate and increased choline and myoinositol in involved regions, however, these are nonspecific findings [4 , 7 , 17] .…”

“…We performed an extensive review of literature to highlight the characteristic imaging features of ALSP [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [12] , [13] , [14] , [15] , [16] , [17] . Bilateral T2/FLAIR hyperintensities in the periventricular and deep white matter of the frontal and parietal lobes are the hallmarks of ALSP on MRI.…”

“…Absence of anterior temporal and external capsule involvement ruled out cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [ 4 , 9 , 11 ]. The striking areas of restricted diffusion in the deep white matter, corpus callosum and right corticospinal tract raised suspicion for ALSP [3 , [6] , [7] , [8] , [9] , [10] , [12] , [13] , [14] , [15] , [16] , [17] . The subsequent noncontrast enhanced CT (NECT) study ( Fig.…”

Genetic forms of frontotemporal lobar degeneration: Current diagnostic approach and new directions in therapeutic strategies

“…Extensive white matter T2-hyperintensities and thinning of corpus callosum are distinctive MRI findings [64,67]. A rapid clinical deterioration, the appearance of (mostly generalized) seizures and diffuse white matter involvement with bifrontal atrophy at MRI are important clues for this genetic form.…”