RT Journal Article
SR Electronic
T1 Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP jnnp-2018-319481
DO 10.1136/jnnp-2018-319481
A1 David S Lynch
A1 Charles Wade
A1 Anderson Rodrigues Brandão de Paiva
A1 Nevin John
A1 Justin A Kinsella
A1 Áine Merwick
A1 Rebekah M Ahmed
A1 Jason D Warren
A1 Catherine J Mummery
A1 Jonathan M Schott
A1 Nick C Fox
A1 Henry Houlden
A1 Matthew E Adams
A1 Indran Davagnanam
A1 Elaine Murphy
A1 Jeremy Chataway
YR 2018
UL http://jnnp.bmj.com/content/early/2018/11/22/jnnp-2018-319481.abstract
AB Adult-onset leukodystrophies and genetic leukoencephalopathies comprise a diverse group of neurodegenerative disorders of white matter with a wide age of onset and phenotypic spectrum. Patients with white matter abnormalities detected on MRI often present a diagnostic challenge to both general and specialist neurologists. Patients typically present with a progressive syndrome including various combinations of cognitive impairment, movement disorders, ataxia and upper motor neuron signs. There are a number of important and treatable acquired causes for this imaging and clinical presentation. There are also a very large number of genetic causes which due to their relative rarity and sometimes variable and overlapping presentations can be difficult to diagnose. In this review, we provide a structured approach to the diagnosis of inherited disorders of white matter in adults. We describe clinical and radiological clues to aid diagnosis, and we present an overview of both common and rare genetic white matter disorders. We provide advice on testing for acquired causes, on excluding small vessel disease mimics, and detailed advice on metabolic and genetic testing available to the practising neurologist. Common genetic leukoencephalopathies discussed in detail include CSF1R, AARS2, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and mitochondrial and metabolic disorders.