Neuroimaging patterns in patients with mitochondrial leukoencephalopathies.

Background And Objectives: Leukoencephalopathies are characterized by white matter (WM) abnormalities and include various primary mitochondrial diseases (MD) that impact mitochondrial function across all neuroglial cells. Understanding these associations is vital for effective clinical management.

Methods: We performed a retrospective analysis of patients with genetically confirmed MD who exhibited white matter abnormalities at a pediatric academic medical center. Data were obtained through medical record reviews, collecting information on demographics, genetic etiology, features of WM involvement, and other areas such as the basal ganglia, cortex, cerebellum, and spine on MRI. Biomarkers like CSF protein and plasma lactate levels were also recorded. Statistical analysis was conducted using R version 4.4.1 to assess significance of specific MRI features in relation to nuclear vs. mitochondrial DNA.

Results: Among 192 MD patients, 142 had available neuroimaging. Of these, 43 (30 %) patients with a median age of 15.5 months exhibited WM involvement, with 53.4 % being female. The most common findings were periventricular (32 %), diffuse (42 %), and multifocal (17 %) WM lesions, with corpus callosum involvement in 51 % of cases. Distinct patterns observed included cystic changes (19 %), diffusion restriction (42 %), and white matter volume loss (40 %). Genetic analysis revealed a diverse range of mutations affecting mtDNA (30 %) and nDNA (70 %) genes.

Discussion: Our study highlights specific neuroimaging patterns associated with leukoencephalopathies in MD. For example, periventricular involvement in MTRFR mutations and diffuse abnormalities in FBXL4 mutations reflect the variability of WM manifestations. These findings can help clinicians identify the genetic etiology in this patient cohort.