Open AccessRecognizing early MRI signs (or their absence) is crucial in diagnosing metachromatic leukodystrophy
Author(s) -
Schoenmakers Daphne H.,
Beerepoot Shanice,
KrägelohMann Ingeborg,
Elgün Saskia,
Bender Benjamin,
Knaap Marjo S.,
Wolf Nicole I.,
Groeschel Samuel
Publication year - 2022
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51692
Subject(s) - medicine , metachromatic leukodystrophy , corpus callosum , leukodystrophy , white matter , magnetic resonance imaging , neuroimaging , pathology , juvenile , pediatrics , disease , radiology , psychiatry , genetics , biology
Objectives Metachromatic leukodystrophy (MLD) has characteristic white matter (WM) changes on brain MRI, which often trigger biochemical and genetic confirmation of the diagnosis. In early or pre‐symptomatic disease stages, these typical MRI changes might be absent, hampering early diagnosis. This study aims to describe the characteristics of MRI WM abnormalities at diagnosis, related to clinical presentation. Methods We retrospectively reviewed brain MRIs of MLD patients followed in 2 centers at the time of diagnosis regarding MLD MRI score and presence of tigroid pattern. In addition, MLD subtype, symptom status, CNS/PNS phenotype, motor/cognitive/mixed phenotype, and the presence of CNS symptoms were evaluated. Results We included 104 brain MRIs from patients with late‐infantile ( n = 43), early‐juvenile ( n = 24), late‐juvenile ( n = 20) and adult ( n = 17) onset. Involvement of the corpus callosum was a characteristic early MRI sign and was present in 71% of the symptomatic late‐infantile patients, 94% of the symptomatic early‐juvenile patients and 100% of the symptomatic late‐juvenile and adult patients. Symptomatic early‐juvenile, late‐juvenile and adult patients generally had WM abnormalities on MRI suggestive of MLD. By contrast, 47% of the early‐symptomatic late‐infantile patients had no or only mild WM abnormalities on MRI, even in the presence of CNS symptoms including pyramidal signs. Interpretation Patients with late‐infantile MLD may have no or only mild, nonspecific abnormalities at brain MRI, partly suggestive of ‘delayed myelination’, even with clear clinical symptoms. This may lead to significant diagnostic delay. Knowledge of these early MRI signs (or their absence) is important for fast diagnosis.