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

Authors :
ZANIGNI, STEFANO
TERLIZZI, ROSSANA
TONON, CATERINA
TESTA, CLAUDIA
MANNERS, DAVID NEIL
CAPELLARI, SABINA
CALANDRA BUONAURA, GIOVANNA
CORTELLI, PIETRO
LODI, RAFFAELE
Gallassi, Roberto
Poda, Roberto
Gramegna, Laura Ludovica
Sambati, Luisa
SAMBATI, LUISA
Zanigni, Stefano
Terlizzi, Rossana
Tonon, Caterina
Testa, Claudia
Manners, David Neil
Capellari, Sabina
Gallassi, Roberto
Poda, Roberto
Gramegna, Laura Ludovica
Calandra-Buonaura, Giovanna
Sambati, Luisa
Cortelli, Pietro
Lodi, Raffaele
Publication Year :
2015

Abstract

Introduction adult-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. Methods we performed brain MR scans including single-voxel proton-MR Spectroscopy ( 1 H-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. Results all 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. Conclusion in 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.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....cd33c1b95d51f65ada27284a0c3e8849