title: Brain magnetic resonance metabolic and microstructural changes in adult-onset autosomal dominant leukodystrophy.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Functional MR Unit, Policlinico S. Orsola - Malpighi, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Zanigni
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Terlizzi
authors.affiliation: Functional MR Unit, Policlinico S. Orsola - Malpighi, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. Electronic address: caterina.tonon@unibo.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Tonon
authors.affiliation: Functional MR Unit, Policlinico S. Orsola - Malpighi, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Testa
authors.affiliation: Functional MR Unit, Policlinico S. Orsola - Malpighi, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: David Neil
authors.initials: DN
authors.lastname: Manners
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gallassi
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Poda
authors.affiliation: Functional MR Unit, Policlinico S. Orsola - Malpighi, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Laura Ludovica
authors.initials: LL
authors.lastname: Gramegna
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Calandra-Buonaura
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Sambati
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.affiliation: Functional MR Unit, Policlinico S. Orsola - Malpighi, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Lodi
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002574:Cervical Vertebrae; D003401:Creatine / Q000378:metabolism; D056324:Diffusion Tensor Imaging; D056344:Executive Function / Q000502:physiology; D005190:Family; D005260:Female; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D034921:Lamin Type B / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066244:Proton Magnetic Resonance Spectroscopy; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013904:Thoracic Vertebrae; D066127:White Matter / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D034921:Lamin Type B; D019344:Lactic Acid; D003401:Creatine
keywords: ADLD; DTI.; Lactate; Lamin B1; MR spectroscopy