TY  - JOUR
UR  - http://doi.org/10.1212/NXG.0000000000000135
SN  - 2376-7839
N2  - OBJECTIVE: To provide an overview of the phenotype of 2 clinically, radiologically, and pathologically similar leukodystrophies, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and alanyl-transfer RNA synthetase 2 mutation-related leukodystrophy (AARS2-L), and highlight key differentiating features. METHODS: ALSP and AARS2-L cases were identified from the adult-onset leukodystrophy database at our institution. In addition, cases with imaging findings were identified from a literature review. The phenotypic features were determined by combining published cases with those from our database. RESULTS: A combined total of 74 cases of ALSP and 10 cases of AARS2-L with neuroimaging data were identified. The mean age at onset was 42 years in ALSP and 26 years in AARS2-L. Cognitive and motor symptoms were the most common symptoms overall in both. Ovarian failure was exclusive to AARS2-L, present in all known female cases. Both ALSP and AARS2-L showed a confluent, asymmetric, predominantly frontoparietal, periventricular pattern of white matter disease with subcortical U-fiber sparing; pyramidal tract and corpus callosum involvement; and diffusion changes in the white matter which we have termed "deep white matter diffusion dots." Central atrophy and corpus callosal thinning were prominent in ALSP and disproportionately mild in AARS2-L when present. ALSP also occasionally showed ventricular abnormalities and calcifications in the frontal periventricular white matter, features not seen in AARS2-L. AARS2-L demonstrates white matter rarefaction which suppresses on fluid-attenuated inversion recovery MRI sequences, a feature not seen in ALSP. CONCLUSIONS: ALSP and AARS2-L share similar clinical, imaging, and pathologic characteristics with key differentiating features that we have highlighted.
ID  - discovery1545364
A1  - Lakshmanan, R
A1  - Adams, ME
A1  - Lynch, DS
A1  - Kinsella, JA
A1  - Phadke, R
A1  - Schott, JM
A1  - Murphy, E
A1  - Rohrer, JD
A1  - Chataway, J
A1  - Houlden, H
A1  - Fox, NC
A1  - Davagnanam, I
JF  - Neurology Genetics
AV  - public
Y1  - 2017/04//
VL  - 3
TI  - Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy
IS  - 2
N1  - Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is properly cited.
ER  -