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

Stefano Zanigni, Rossana Terlizzi, Caterina Tonon, Claudia Testa, David Neil Manners, Sabina Capellari, Roberto Gallassi, Roberto Poda, Laura Ludovica Gramegna, Giovanna Calandra-Buonaura, Luisa Sambati, Pietro Cortelli, Raffaele Lodi

Research output: Contribution to journalArticle

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 (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. 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.

Original languageEnglish
Pages (from-to)24-31
Number of pages8
JournalBrain Research Bulletin
Volume117
DOIs
Publication statusPublished - Aug 1 2015

Fingerprint

Magnetic Resonance Spectroscopy
Brain
Gene Duplication
Corpus Callosum
Lateral Ventricles
Mutation
Lactic Acid
Spatial Analysis
Diffusion Tensor Imaging
Anisotropy
Executive Function
Demyelinating Diseases
lamin B1
Neuroglia
Genes
Atrophy
Protons
Thorax
White Matter
Water

Keywords

  • ADLD
  • DTI
  • Lactate
  • Lamin B1
  • MR spectroscopy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

In: Brain Research Bulletin, Vol. 117, 01.08.2015, p. 24-31.

Research output: Contribution to journalArticle

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. / Brain magnetic resonance metabolic and microstructural changes in adult-onset autosomal dominant leukodystrophy. In: Brain Research Bulletin. 2015 ; Vol. 117. pp. 24-31.
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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 (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. 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.",
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AU - Zanigni, Stefano

AU - Terlizzi, Rossana

AU - Tonon, Caterina

AU - Testa, Claudia

AU - Manners, David Neil

AU - Capellari, Sabina

AU - Gallassi, Roberto

AU - Poda, Roberto

AU - Gramegna, Laura Ludovica

AU - Calandra-Buonaura, Giovanna

AU - Sambati, Luisa

AU - Cortelli, Pietro

AU - Lodi, Raffaele

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N2 - 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 (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. 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.

AB - 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 (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. 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.

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KW - MR spectroscopy

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