{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:54:42Z","timestamp":1760057682019,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background: Metachromatic leukodystrophy (MLD) is a rare autosomal recessive disorder that causes demyelination of both the central (CNS) and peripheral nervous systems (PNS). Objective: This study aims to report a unique MLD case presenting with cranial neuropathies and ataxia, initially without white matter changes on MRI, leading to diagnostic uncertainty. Results: A 20-month-old presented with bilateral abduction deficits, facial diplegia, and ataxia, raising the possibility of an acquired demyelinating condition. An MRI scan showed the enhancement of multiple cranial nerves, but normal white matter. A follow-up MRI showed new white matter changes that spared the U-fibers, suggesting a leukodystrophy. Biochemical assays were suggestive of metachromatic leukodystrophy, which was confirmed with genetic testing demonstrating a homozygous c.848+3A &gt; G variant in ARSA. Conclusions: Our patient suggests that the initial presentation of MLD may mimic an acquired demyelinating condition and manifest with multiple cranial nerve palsies before more typical white matter changes evolve.<\/jats:p>","DOI":"10.3390\/neurolint17020028","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T07:48:22Z","timestamp":1739778502000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metachromatic Leukodystrophy Presenting with Multiple Cranial Nerve and Lumbosacral Nerve Root Enhancement Without White Matter Changes"],"prefix":"10.3390","volume":"17","author":[{"given":"Ruben","family":"Jauregui","sequence":"first","affiliation":[{"name":"Department of Neurology, NYU Grossman School of Medicine, 222 E 41st St, 14th Floor, New York, NY 10017, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mekka R.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Neurology, NYU Grossman School of Medicine, 222 E 41st St, 14th Floor, New York, NY 10017, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Mehuron","sequence":"additional","affiliation":[{"name":"Department of Radiology, NYU Grossman School of Medicine, New York, NY 10017, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3781-7324","authenticated-orcid":false,"given":"Steven L.","family":"Galetta","sequence":"additional","affiliation":[{"name":"Department of Neurology, NYU Grossman School of Medicine, 222 E 41st St, 14th Floor, New York, NY 10017, USA"},{"name":"Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY 10017, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9740-1286","authenticated-orcid":false,"given":"Devorah","family":"Segal","sequence":"additional","affiliation":[{"name":"Department of Neurology, NYU Grossman School of Medicine, 222 E 41st St, 14th Floor, New York, NY 10017, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shaimardanova, A.A., Chulpanova, D.S., Solovyeva, V.V., Mullagulova, A.I., Kitaeva, K.V., Allegrucci, C., and Rizvanov, A.A. (2020). Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches. Front. Med., 7.","DOI":"10.3389\/fmed.2020.576221"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00401-017-1739-1","article-title":"Leukodystrophies: A proposed classification system based on pathological changes and pathogenetic mechanisms","volume":"134","author":"Bugiani","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Thibert, K.A., Raymond, G.V., Tolar, J., Miller, W.P., Orchard, P.J., and Lund, T.C. (2016). Cerebral Spinal Fluid levels of Cytokines are elevated in Patients with Metachromatic Leukodystrophy. Sci. Rep., 6.","DOI":"10.1038\/srep24579"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ejpn.2024.03.003","article-title":"Newborn screening in metachromatic leukodystrophy\u2014European consensus-based recommendations on clinical management","volume":"49","author":"Laugwitz","year":"2024","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S0140-6736(21)02017-1","article-title":"Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: Long-term results from a non-randomised, open-label, phase 1\/2 trial and expanded access","volume":"399","author":"Fumagalli","year":"2022","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s10545-011-9361-1","article-title":"Metachromatic leukodystrophy: Natural course of cerebral MRI changes in relation to clinical course","volume":"34","author":"Groeschel","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"999","DOI":"10.3174\/ajnr.A0526","article-title":"Multiple cranial nerve enhancement: A new MR imaging finding in metachromatic leukodystrophy","volume":"28","author":"Maia","year":"2007","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1742","DOI":"10.1212\/WNL.0000000000008400","article-title":"Teaching NeuroImages: A rare case of metachromatic leukodystrophy with multiple bilateral cranial nerve enhancement","volume":"93","author":"Sonowal","year":"2019","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.pediatrneurol.2008.11.015","article-title":"Isolated cranial nerve enhancement in metachromatic leukodystrophy","volume":"40","author":"Singh","year":"2009","journal-title":"Pediatr. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejpn.2022.01.020","article-title":"Acute-onset paralytic strabismus in toddlers is important to consider as a potential early sign of late-infantile Metachromatic Leukodystrophy","volume":"37","author":"Beerepoot","year":"2022","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/14737175.2020.1699060","article-title":"An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies","volume":"20","author":"Ashrafi","year":"2020","journal-title":"Expert. Rev. Neurother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00247-008-0849-2","article-title":"Optic nerve and chiasm enlargement in a case of infantile Krabbe disease: Quantitative comparison with 26 age-matched controls","volume":"38","author":"Patel","year":"2008","journal-title":"Pediatr. Radiol."},{"key":"ref_14","first-page":"1228","article-title":"Optic nerve enlargement in Krabbe\u2019s disease","volume":"20","author":"Jones","year":"1999","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e126","DOI":"10.1212\/WNL.0b013e3182563bad","article-title":"Intracranial optic nerve enlargement in infantile Krabbe disease","volume":"78","author":"Shah","year":"2012","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s13023-023-02814-2","article-title":"A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel","volume":"18","author":"Armstrong","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1001\/jamaneurol.2016.2067","article-title":"Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Juvenile Metachromatic Leukodystrophy Compared with Nontransplanted Control Patients","volume":"73","author":"Groeschel","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13023-015-0313-y","article-title":"Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: The largest single-institution cohort report","volume":"10","author":"Boucher","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1002\/acn3.51796","article-title":"Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy","volume":"10","author":"Beerepoot","year":"2023","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1056\/NEJM199001043220106","article-title":"Treatment of late infantile metachromatic leukodystrophy by bone marrow transplantation","volume":"322","author":"Krivit","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/sj.bmt.1705581","article-title":"Early marrow transplantation in a pre-symptomatic neonate with late infantile metachromatic leukodystrophy does not halt disease progression","volume":"39","author":"Bredius","year":"2007","journal-title":"Bone Marrow Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/bmt.2008.275","article-title":"Metachromatic leukodystrophy: An overview of current and prospective treatments","volume":"42","author":"Biffi","year":"2008","journal-title":"Bone Marrow Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.jcyt.2024.03.487","article-title":"Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States","volume":"26","author":"Adang","year":"2024","journal-title":"Cytotherapy"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bean, K., Jones, S.A., Chakrapani, A., Vijay, S., Wu, T., Church, H., Chanson, C., Olaye, A., Miller, B., and Jensen, I. (2024). Exploring the Cost-Effectiveness of Newborn Screening for Metachromatic Leukodystrophy (MLD) in the UK. Int. J. Neonatal Screen., 10.","DOI":"10.3390\/ijns10030045"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1056\/NEJMc2407165","article-title":"Newborn Screening and Presymptomatic Treatment of Metachromatic Leukodystrophy","volume":"391","author":"Laugwitz","year":"2024","journal-title":"N. Engl. J. Med."}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/2\/28\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:35:35Z","timestamp":1760027735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/2\/28"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,16]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["neurolint17020028"],"URL":"https:\/\/doi.org\/10.3390\/neurolint17020028","relation":{},"ISSN":["2035-8377"],"issn-type":[{"type":"electronic","value":"2035-8377"}],"subject":[],"published":{"date-parts":[[2025,2,16]]}}}