Brain Calcifications in Adult-Onset Genetic Leukoencephalopathies

Abstract

IMPORTANCE Adult-onset genetic leukoencephalopathies and leukodystrophies are increasingly recognized as a heterogeneous group of disorders with new diagnostic approaches and potential treatments. In the new era of genomics, the challenging interpretation of individual genetic variations requires an accurate phenotypic description and classification. Clinical and magnetic resonance imaging (MRI)-based approaches have been proposed to improve the diagnostic process of adult-onset leukoencephalopathies. Cerebral calcifications, when associated with white matter hyperintensities, are of major importance in the decision-making process to focus the diagnosis among the diversity of rare causes.OBSERVATIONS This literature review demonstrated that the morphologic features and topography of the calcifications observed in a careful combined analysis of computed tomographic and MRI scans may help indicate the diagnosis of adult-onset genetic leukoencephalopathies. Vascular genetic leukoencephalopathies are an important cause of leukoencephalopathy with calcifications. Among them, COL4A1-related disorders are frequently associated with spotlike calcifications in the basal ganglia. Adult-onset leukoencephalopathy with axonal spheroids, a probably underestimated disorder, is associated with a specific pattern of calcifications: small, symmetric, sparing the basal ganglia, and a stepping stone appearance in the frontal pericallosal region. Moreover, disorders primarily associated with basal ganglia calcifications, such as primary familial brain calcifications, can be associated with marked leukoencephalopathy. CONCLUSIONS AND RELEVANCEThe number of identified causes of adult-onset genetic leukoencephalopathies has recently increased. A diagnostic algorithm should take into account the pattern of calcifications to better target the genetic analyses.

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

“…7,17 Other series have suggested that small calcifications with a stepping stone distribution were characteristic of the disease, but their frequency has not been reported to date. 6,18 Here, we found calcifications in 4/6 patients who had undergone CT, stressing that they are likely frequent in ALSP. Of note, none of our patients with calcifications on CT had identifiable T2* hypointensities.…”

Biallelic COLGALT1 variants are associated with cerebral small vessel disease

“…The radiographic features of the 2 patients were also comparable with those of COL4A1/COL4A2 ‐related disease. Typical MRI features observed in COL4A1/COL4A2 ‐related disease include vascular leukoencephalopathy, porencephalic cavity, deep hemorrhages, microbleeds, lacunae, deep calcifications, dilated perivascular spaces, and intracranial aneurysms . In Patient 1, subependymal hemorrhage, porencephaly, microbleeds, and calcifications were observed.…”

Adult Leukodystrophies: A Step-by-Step Diagnostic Approach

“…Cysts.-Leukoencephalopathy with calcifications and cysts is a genetic disorder related to a mutation in the small nucleolar RNA, C/D box 118 (SNORD118) gene, which was identified recently. This disease is considered a microangiopathy, and as can be observed of other vasculopathies, asymmetric involvement of white matter may be a characteristic on MR images (Fig 17) (64)(65)(66).…”

“…The calcifications tend to be large and can be observed anywhere in the brain but mostly in the basal ganglia. Gadolinium contrast enhancement sometimes can be observed (64)(65)(66).…”