From the Research
Pelizaeus-Merzbacher disease (PMD) is characterized by a diffuse pattern of hypomyelination on magnetic resonance imaging (MRI), which is essential for diagnosis, although confirmation requires genetic testing for PLP1 mutations. The characteristic MRI findings in PMD include hyperintense signal on T2-weighted images and FLAIR sequences in the cerebral white matter, with relative sparing of subcortical U-fibers 1. The white matter appears hypomyelinated rather than demyelinated, reflecting the developmental nature of this disorder. Additional findings may include reduced brain volume, thinning of the corpus callosum, and cerebellar atrophy in some cases. The pattern is often described as "tigroid" or "leopard skin," showing small focal areas of normal signal intensity within the abnormal white matter, representing islands of preserved myelin.
Some key points to consider when interpreting MRI findings in PMD include:
- The signal intensity of the brainstem and corticospinal tract of the internal capsule can be correlated with clinical severity 1
- Myelination age on T1-weighted images (T1WI) can be used to assess the severity of the disease, with myelination age "before birth" on T1WI associated with clinically severe phenotypes 1
- A random and patchy pattern of myelination on T2WI can be noted in some patients with PLP1 point mutation 1
- Advanced myelination can be observed in some patients on follow-up MRI scans 1
The imaging features of PMD reflect the underlying pathology of the disease, which is caused by mutations in the PLP1 gene leading to defective myelin formation 2, 3, 4, 5. MRI is a crucial tool in the diagnosis of PMD, and the imaging pattern can help distinguish PMD from other leukodystrophies, although some overlap exists with other hypomyelinating disorders. Serial MRIs may be useful to monitor disease progression, although the white matter abnormalities typically remain stable over time. The most recent and highest quality study on this topic is from 2024, which highlights the importance of MRI in the diagnosis and monitoring of PMD, and discusses the potential for novel therapeutic interventions 5.