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Recognizing early MRI signs (or their absence) is crucial in diagnosing metachromatic leukodystrophy
Daphne H Schoenmakers1,2,3, Shanice Beerepoot1,2,4,5, Ingeborg Krägeloh-Mann6
1Department of Child Neurology, Amsterdam Leukodystrophy Center, Amsterdam UMC location Vrije Universiteit Amsterdam, Emma's Children's Hospital, Boelelaan 1117, Amsterdam, The Netherlands.
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.
Insights
Early-onset Metachromatic Leukodystrophy (MLD) may present with subtle or absent brain MRI white matter changes, potentially delaying diagnosis. Recognizing these early MRI findings is crucial for timely MLD diagnosis and intervention.
Area of Science:
- Neurology
- Radiology
- Genetics
Background:
- Metachromatic leukodystrophy (MLD) is a rare genetic disorder affecting white matter (WM).
- Brain MRI typically shows characteristic WM changes, aiding diagnosis.
- Early or pre-symptomatic MLD may lack typical MRI findings, complicating early detection.
Purpose of the Study:
- To characterize MRI white matter (WM) abnormalities in MLD patients at diagnosis.
- To correlate MRI findings with clinical presentation across different MLD subtypes and symptom onset.
- To highlight potential diagnostic delays due to atypical MRI findings in early-stage MLD.
Main Methods:
- Retrospective review of brain MRIs from 104 MLD patients across two centers.
- Evaluation of MLD MRI score and tigroid pattern presence.
- Assessment of MLD subtype, symptom status, phenotype (CNS/PNS, motor/cognitive/mixed), and CNS symptoms.
Main Results:
- Corpus callosum involvement was an early MRI sign in symptomatic patients (71-100%).
- Most symptomatic early-juvenile, late-juvenile, and adult MLD patients showed suggestive WM abnormalities.
- Notably, 47% of early-symptomatic late-infantile MLD patients had mild or no WM abnormalities on MRI, despite clinical symptoms.
Conclusions:
- Late-infantile MLD can present with non-specific or absent MRI WM changes, mimicking delayed myelination.
- These subtle MRI findings can significantly delay MLD diagnosis.
- Awareness of early MRI signs, including their absence, is critical for prompt diagnosis of MLD.
