Persistent Diffusion-weighted Imaging Abnormalities in Adult Leukodystrophies

HomeRadioGraphicsVol. 39, No. 4 PreviousNext Letters to the EditorFree AccessPersistent Diffusion-weighted Imaging Abnormalities in Adult LeukodystrophiesLaurens J.L. De Cocker Laurens J.L. De Cocker Author AffiliationsDepartment of Radiology, AZ Maria Middelares, 9000 Ghent, Belgiume-mail: [email protected]Laurens J.L. De Cocker Published Online:Jul 8 2019https://doi.org/10.1148/rg.2019190028MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Editor:With great interest, I read the article “Adult Leukodystrophies: A Step-by-Step Diagnostic Approach” (1) in the January-February 2019 issue of RadioGraphics. I would like to congratulate the authors on their instructive approach to suggesting a diagnosis on the basis of the MRI characteristics of adult leukodystrophies.As the authors acknowledged, the characterization of all possible types of leukodystrophies and eventual atypical presentations was beyond the scope of their review (1). Nevertheless, to enhance the proposed diagnostic approach, I would like to add a distinctive diffusion-weighted imaging feature, namely the presence of persistent abnormalities at diffusion-weighted imaging. These diffusion abnormalities are easy to discern and are key to the diagnosis of not only adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) (1,2) but also to the diagnosis of two leukodystrophies that have only recently been recognized, namely adult-onset leukoencephalopathy caused by mutations in the alanyl–tRNA synthetase 2 gene (AARS2-L) and adult-onset neuronal intranuclear inclusion disease (NIID) (3,4).ALSP and AARS2-L both typically show bilateral lesions in the deep white matter with restricted diffusion, most often punctate, which unlike ischemic lesions, persist over time (2–3). If such lesions are present, the two entities can be distinguished by the presence of accompanying punctate white matter calcifications seen exclusively in ALSP (1–3). In addition, only ALSP is associated with ventricular anomalies such as a cavum septi pellicidi (3). The definitive diagnosis can be made with genetic analysis and is of importance since stem cell transplant is a promising treatment of ALSP.NIID has clinical and imaging features very similar to the fragile X–associated tremor and/or ataxia syndrome discussed in the article (1), but only NIID typically shows highly characteristic symmetric high signal intensity along the junction between cortical gray matter and subcortical white matter at diffusion-weighted imaging (4). This imaging feature is considered the strongest and easiest indicator of NIID (4), while symmetric high signal intensity in the medial part of the cerebellar hemisphere right beside the vermis (the “paravermal area”) on fluid-attenuated inversion-recovery (FLAIR) images is an ancillary imaging finding in many patients (5). Because a causative gene has not yet been identified, diagnosis in as many cases and families as possible is required to unravel the remaining mysteries of this leukodystrophy (4).The addition of this diffusion-weighted imaging feature is complementary to the proposed step-by-step diagnostic approach by Resende et al (1), and I hope this letter will contribute to reaching a final diagnosis in even more patients with adult leukodystrophy.References1. Resende LL, de Paiva ARB, Kok F, da Costa Leite C, Lucato LT. Adult leukodystrophies: a step-by-step diagnostic approach. RadioGraphics 2019;39(1):153–168. Link, Google Scholar2. Codjia P, Ayrignac X, Mochel F, et al. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: an MRI study of 16 French cases. AJNR Am J Neuroradiol 2018;39(9):1657–1661. Crossref, Medline, Google Scholar3. Lakshmanan R, Adams ME, Lynch DS, et al. Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy. Neurol Genet 2017;3(2):e135. Crossref, Medline, Google Scholar4. Sone J, Mori K, Inagaki T, et al. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. Brain 2016;139(Pt 12):3170–3186. Crossref, Medline, Google Scholar5. Sugiyama A, Sato N, Kimura Y, et al. MR imaging features of the cerebellum in adult-onset neuronal intranuclear inclusion disease: 8 cases. AJNR Am J Neuroradiol 2017;38(11):2100–2104. Crossref, Medline, Google ScholarReferences1. Resende LL, de Paiva ARB, Kok F, da Costa Leite C, Lucato LT. Adult leukodystrophies: a step-by-step diagnostic approach. RadioGraphics 2019;39(1):153–168. Link, Google Scholar2. Lakshmanan R, Adams ME, Lynch DS, et al. Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy. Neurol Genet 2017;3(2):e135. Crossref, Medline, Google Scholar3. Dallabona C, Diodato D, Kevelam SH, et al. Novel (ovario) leukodystrophy related to AARS2 mutations. Neurology 2014;82(23):2063–2071. Crossref, Medline, Google ScholarReferences1. Resende LL, de Paiva ARB, Kok F, da Costa Leite C, Lucato LT. Adult leukodystrophies: a step-by-step diagnostic approach. RadioGraphics 2019;39(1):153–168. Link, Google Scholar2. Codjia P, Ayrignac X, Mochel F, et al. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: an MRI study of 16 French cases. AJNR Am J Neuroradiol 2018;39(9):1657–1661. Crossref, Medline, Google Scholar3. Lakshmanan R, Adams ME, Lynch DS, et al. Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy. Neurol Genet 2017;3(2):e135. Crossref, Medline, Google Scholar4. Sone J, Mori K, Inagaki T, et al. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. Brain 2016;139(Pt 12):3170–3186. Crossref, Medline, Google Scholar5. Sugiyama A, Sato N, Kimura Y, et al. MR imaging features of the cerebellum in adult-onset neuronal intranuclear inclusion disease: 8 cases. AJNR Am J Neuroradiol 2017;38(11):2100–2104. Crossref, Medline, Google ScholarLucas Lopes Resende , Anderson Rodrigues Brandão de Paiva, Fernando Kok, Claudia da Costa Leite, Leandro Tavares LucatoLucas Lopes Resende , Anderson Rodrigues Brandão de Paiva, Fernando Kok, Claudia da Costa Leite, Leandro Tavares LucatoAuthor AffiliationsNeuroradiology Section, Instituto de Radiologia (InRad), Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), R. Dr. Ovídio Pires de Campos 75, São Paulo, SP 05403-010, Brazil (L.L.R., C.d.C.L., L.T.L.)Neurogenetics Unit, Department of Neurology, Hospital das Clínicas da Universidade de São Paulo, São Paulo, Brazil (A.R.B.d.P., F.K.)e-mail: [email protected]Dr Resende and colleagues respond:We would like to thank Dr De Cocker for the comments on our article (1). The presence of persistent abnormalities at diffusion-weighted imaging might sometimes contribute to reaching a final diagnosis in patients with adult leukodystrophy, including those with primary mitochondrial disorders.Recently we were able to review a case of one of the entities cited by Dr De Cocker, namely adult-onset leukoencephalopathy due to mutations in the alanyl–tRNA synthetase 2 gene (AARS2-L) (2,3).AARS2-L is a leukoencephalopathy caused by mutations in the exons 4 and 9 of the alanyl–tRNA synthetase 2 gene (AARS2) that leads to errors in the mitochondrial aminoacyl tRNA synthetase gene responsible for encoding alanine into mitochondrial tRNA during mitochondrial translation. It has been found to be the cause of an ovarioleukodystrophy and infantile cardiomyopathy (2,3).AARS2-L tends to occur in the 3rd decade of life, and women tend to have ovarian failure and leukodystrophy. Symptoms include motor dysfunction, cognitive impairment, gait abnormalities, seizures, and incontinence. A small number of patients may present with sensory disturbance (2,3).T2-weighted MRI may show frontoparietal predominant, slightly asymmetric, confluent hyperintense white matter signal abnormalities, which have a predilection for the periventricular and deep white matter and tend to spare the subcortical U fibers. Involvement of the corpus callosum, pyramidal tract, and caudate heads and mild atrophy might also be seen. The diffusion-weighted imaging hallmark of AARS2-L is the presence of multifocal and punctate abnormalities in the deep white matter, which are roughly parallel to the ependymal surface of the lateral ventricles. This pattern might mimic the internal border zone infarction. However, in AARS2-L, these abnormalities persist and progress over months to years, which helps differentiate them from areas of acute infarction (1,2).Images from the case we reviewed might better illustrate this condition. The patient is a 34-year-old man with 2 years of progressive gait ataxia, dysarthria, and cognitive deterioration. Brain MRI demonstrated multiple and confluent periventricular T2-hyperintense white matter lesions with a posteroanterior gradient, involving corticospinal tracts (Fig E1; A, B) and the callosal splenium (Fig E1, C). Remarkably, there was some signal suppression on fluid-attenuated inversion-recovery (FLAIR) images that involved both peritrigonal regions (Fig E1, B). Lesions in the corona radiata with mild mass effect (Fig E1, D) and foci of restricted diffusion (Fig E1; E, F) were noted. MR spectroscopy showed metabolic abnormalities, especially an abnormal peak of lactate (Fig E1, G). References1. Resende LL, de Paiva ARB, Kok F, da Costa Leite C, Lucato LT. Adult leukodystrophies: a step-by-step diagnostic approach. RadioGraphics 2019;39(1):153–168. Link, Google Scholar2. Lakshmanan R, Adams ME, Lynch DS, et al. Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy. Neurol Genet 2017;3(2):e135. Crossref, Medline, Google Scholar3. Dallabona C, Diodato D, Kevelam SH, et al. Novel (ovario) leukodystrophy related to AARS2 mutations. Neurology 2014;82(23):2063–2071. Crossref, Medline, Google ScholarArticle HistoryPublished online: July 08 2019Published in print: July 2019 FiguresReferencesRelatedDetailsCited ByDistinctive diffusion-weighted imaging features in late-onset genetic leukoencephalopathiesLaurens J. L.De Cocker, MauricioCastillo2021 | Neuroradiology, Vol. 63, No. 1Radiopaedia.orgRohitSharma, YurangaWeerakkody2020Radiopaedia.orgRohitSharma, TheRadswiki2011Recommended Articles Imaging of Creutzfeldt-Jakob Disease: Imaging Patterns and Their Differential DiagnosisRadioGraphics2017Volume: 37Issue: 1pp. 234-257Imaging Patterns of Toxic and Metabolic Brain DisordersRadioGraphics2019Volume: 39Issue: 6pp. 1672-1695COVID-19–associated Diffuse Leukoencephalopathy and MicrohemorrhagesRadiology2020Volume: 297Issue: 1pp. E223-E227Neuroimaging of Emergent and Reemergent InfectionsRadioGraphics2019Volume: 39Issue: 6pp. 1649-1671Primary Mitochondrial Disorders of the Pediatric Central Nervous System: Neuroimaging FindingsRadioGraphics2020Volume: 40Issue: 7pp. 2042-2067See More RSNA Education Exhibits Neuroradiological Aspects of Congenital Infections and MimicsDigital Posters2022The Enigma of Encephalitis Based on MRI Patterns: When Can You Solve the Mystery?Digital Posters2020From The Fragile X Premutation To The Hot Cross Bun: An MRI Unique Guide For Assessment Of Posterior Fossa Adult DiseasesDigital Posters2021 RSNA Case Collection Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE)RSNA Case Collection2021Creutzfeldt-Jakob DiseaseRSNA Case Collection2021Progressive multifocal leukoencephalopathy RSNA Case Collection2021 Vol. 39, No. 4 Supplemental MaterialMetrics Altmetric Score PDF download