Degree of Hypomyelination and Magnetic Resonance Spectroscopy Findings in Patients with Pelizaeus Merzbacher Phenotype

As only 10 - 30 % of patients with a Pelizaeus Merzbacher disease (PMD) phenotype carry mutations of the proteolipid protein (PLP) gene, we were interested if the degree and time-dependent progression of abnormal MRI and MRS findings would discriminate patients with mutations of the PLP gene (Pelizaeus Merzbacher disease, PMD) from patients without a defect of the PLP gene (Pelizaeus Merzbacher-like disease, PMLD). For a standardised intraindividual follow-up and for comparison of the degree of hypomyelination, we have applied a newly developed semiquantitative myelination score on a total of 18 MRI series of 4 PMD and 4 PMLD patients. We found severe hypomyelination (50 % of normal) in 2 PMD and in 2 PMLD patients, moderate hypomyelination (75 % of normal) in 2 PMD and mild hypomyelination (75 % of normal) in 2 PMLD patients. Our score revealed a clear correlation between the degree of hypomyelination and the severity of clinical handicap in PMD but not in PMLD patients. MRS showed heterogeneous cerebral metabolite patterns in both patient groups and seems to reflect a mixture of unspecific changes due to primary hypomyelination and secondary gliosis and demyelination. Neither by MRI nor by MRS were patterns found that would allow differentiation between PMD and PMLD patients.