Brain magnetic resonance metabolic and microstructural changes in adult-onset autosomal dominant leukodystrophy

•ADLD is a rare inherited disorder due to a duplication of LMNB1 gene.•Four subjects with LMNB1-duplication underwent conventional and advanced brain MRI.•Moderate-severe leukodystrophy was present in all ADLD patients.•1H MRS demonstrated pathological Lactate content in LMNB1mutated subjects.•FA in genu corpus callosum was reduced in LMNB1 mutated subjects.

Introductionadult-onset autosomal dominant leukodystrophy (ADLD) is a rare inherited disorder due to a duplication of lamin-B1 (LMNB1) gene. The aim of this study was to investigate brain metabolic and microstructural alterations by using advanced MR techniques.Methodswe performed brain MR scans including single-voxel proton-MR Spectroscopy (1H-MRS) of the lateral ventricles and parietal white matter and diffusion tensor imaging (DTI) in 4 subjects with LMNB1 gene duplication, 6 non-mutated relatives and 7 unrelated healthy controls. Cervical and thoracic spinal cord MR was performed in three symptomatic subjects with LMNB1 mutation. All participants underwent clinical and neuropsychological evaluation.Resultsall subjects with LMNB1 gene duplication presented pathological accumulation of lactate in lateral ventricles CSF and no alterations of brain white matter absolute metabolites concentrations or metabolites/Cr ratios. We found increased white matter intra- and extracellular water transverse relaxation times. Tract-based spatial statistics analysis detected a significantly reduced fractional anisotropy in the genu of the corpus callosum in mutated cases compared to unrelated healthy controls and non-mutated relatives. Moreover, we detected different degrees of the typical white matter signal intensity alterations and brain and spinal atrophy at conventional MRI in symptomatic subjects with LMNB1 mutation. A mild impairment of executive functions was found in subjects with LMNB1 gene mutation.Conclusionin subjects with LMNB1 gene duplication, we found a pathological increase in CSF lactate, likely due to active demyelination along with glial activation, and microstructural changes in the genu of the corpus callosum possibly underpinning the mild neuropsychological deficits.