Imaging Study of the White Matter Lesions in Children With Metachromatic Leucodystrophy
Condition: Late Infantile Metachromatic Leukodystrophy
MeSH terms: Leukodystrophy, Metachromatic
Study type: Interventional

Summary: 
      High-field MRI and diffusion tensor imaging with 3D reconstruction of the myelin tracks, in
      combination with multivoxel proton spectroscopy, will allow to precise more accurately the
      evolution of the white matter lesions in patients affected with Metachromatic Leukodystrophy
      (particularly in the initial phase of the disease). This will increase the knowledge of the
      disease and provide new indicators for the selection and evaluation of patients eligible for
      new therapeutic approaches.
    

Detailed description: 
      Metachromatic Leukodystrophy (MLD) is a rare autosomal recessive disorder caused by the
      deficiency of the Arylsulfatase A enzyme (ARSA), resulting in accumulation of galactosyl
      sulfatide (cerebroside sulfate), a major constituent of the myelin sheath. Accumulation of
      sulfatides leads to a progressive degeneration of the white matter in the central and
      peripheral nervous systems (CNS, PNS) and to a neuronal degeneration. The late-infantile form
      of MLD, which is usually diagnosed in the second year of life, is the most frequent and
      severe form of the disease. The prognosis is severe, leading to vegetative stage or death
      within few years after the diagnosis. There is no treatment for patients affected with this
      early-onset form of the disease.

      Conventional MRI (1.5 Tesla) shows extensive involvement of the cerebral white matter
      (hypo-T1, hyper- T2 and FLAIR signals) indicative of rapidly progressing leukodystrophy.
      Early cortical atrophy reflects associated neuronal involvement. Proton MR spectroscopy
      demonstrates abnormalities of choline and N-acetyl-aspartate (demyelination, neuronal loss),
      which are non-specific but can serve as indicators to monitor the effects of any therapeutic
      intervention.

      In early-onset forms of MLD, conventional MRI becomes abnormal at a relatively advanced stage
      of the disease and the neuroradiological diagnosis may be difficult before the age of 2 - 2
      1/2 years of age. Moreover, topography and extent of detectable lesions are poorly correlated
      with the disease severity.

      In order to improve information provided by neuroimaging, this study aims to investigate
      prospectively and longitudinally (over a period of 6 months) white and grey matter lesions in
      10 MLD children aged 1 to 6 years, using high-field MRI (3 Teslas) and diffusion tensor
      imaging (DTI) with 3D reconstruction of the myelin tracks. The time interval between
      diagnosis and inclusion will not exceed 18 months, thus patients will be included at an early
      stage of their disease. Each time-point (T0 and 6 months) will also include neurological
      evaluation to correlate the imaging, cognitive and motor functions. Children will be included
      over a period of 5 years. The total duration of the study will be 5.5 years. Controls will
      include 25 age-matched children with cryptogenic partial epilepsy who should have a
      high-field MRI to detect structural abnormalities. Controls will have a MRI and cognitive
      evaluation at T0 and 12 months if necessary. This study will increase our knowledge of the
      natural history of MLD and provide new indicators for the selection and evaluation of
      patients eligible for new therapeutic approaches.
    

Intervention name(s): High-field MRI (3 Teslas); High-field MRI (3 Teslas)
Intervention type(s): Other; Other
Intervention description(s): anatomical location
conventional anatomical sequence T1, T2, FLAIR
diffusion tensor sequence (21 directions)
high angular resolution diffusion (HARDI) sequence
field map
reflexology T1, T2
spectroscopic imaging sequence; anatomical location
conventional anatomical sequence T1, T2, FLAIR
diffusion tensor sequence (21 directions)
high angular resolution diffusion (HARDI) sequence
field map
reflexology T1, T2
spectroscopic imaging sequence
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Metachromatic Leukodystrophy; Demyelinating Diseases; Magnetic Resonance Imaging; Diffusion Tensor Imaging; Relaxometry; Spectroscopy; Longitudinal Studies