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Review
August 2017

Brain Calcifications in Adult-Onset Genetic LeukoencephalopathiesA Review

Author Affiliations
  • 1Department of Neurology, Montpellier University Hospital, Montpellier, France
  • 2Institut des Neurosciences Montpellier, Institut National de la Santé et de la Recherche Medicale (INSERM) Unité Mixte de Recherché 1051, Hopital Saint-Eloi, Montpellier, France
  • 3Normandie University, UNIROUEN, INSERM U1245 and Rouen University Hospital, Department of Genetics and Centre National de Référence pour les Malades Alzheimer Jeunes, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France
  • 4Genome Research, Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
  • 5Normandie University, UNIROUEN, INSERM U1245 and Rouen University Hospital, Department of Neurology and Centre National de Référence pour les Malades Alzheimer Jeunes, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France
JAMA Neurol. 2017;74(8):1000-1008. doi:10.1001/jamaneurol.2017.1062
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 Relevance  The 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.

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