Assessment of disease severity in late infantile neuronal ceroid lipofuscinosis using multiparametric MR imaging. Academic Article uri icon

Overview

MeSH

  • Age Factors
  • Aminopeptidases
  • Artifacts
  • Biomarkers
  • Child
  • Child, Preschool
  • Databases, Factual
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Disease Progression
  • Female
  • Humans
  • Male
  • Serine Proteases

MeSH Major

  • Brain
  • Magnetic Resonance Imaging
  • Neuronal Ceroid-Lipofuscinoses
  • Severity of Illness Index

abstract

  • LINCL is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene that encodes for tripeptidyl peptidase 1, a lysosomal enzyme necessary for the degradation of products of cellular metabolism. With the goal of developing quantitative noninvasive imaging biomarkers sensitive to disease progression, we evaluated a 5-component MR imaging metric and tested its correlation with a clinically derived disease-severity score. MR imaging parameters were measured across the brain, including quantitative measures of the ADC, FA, nuclear spin-spin relaxation times (T2), volume percentage of CSF (%CSF), and NAA/Cr ratios. Thirty MR imaging datasets were prospectively acquired from 23 subjects with LINCL (2.5-8.4 years of age; 8 male/15 female). Whole-brain histograms were created, and the mode and mean values of the histograms were used to characterize disease severity. Correlation of single MR imaging parameters against the clinical disease-severity scale yielded linear regressions with R2 ranging from 0.25 to 0.70. Combinations of the 5 biomarkers were evaluated by using PCA. The best combination included ADC, %CSF, and NAA/Cr (R2=0.76, P<.001). The multiparametric disease-severity score obtained from the combination of ADC, %CSF, and NAA/Cr whole-brain MR imaging techniques provided a robust measure of disease severity, which may be useful in clinical therapeutic trials of LINCL in which an objective assessment of therapeutic response is desired.

publication date

  • April 2013

has subject area

  • Age Factors
  • Aminopeptidases
  • Artifacts
  • Biomarkers
  • Brain
  • Child
  • Child, Preschool
  • Databases, Factual
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuronal Ceroid-Lipofuscinoses
  • Serine Proteases
  • Severity of Illness Index

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3644851

Digital Object Identifier (DOI)

  • 10.3174/ajnr.A3297

PubMed ID

  • 23042927

Additional Document Info

start page

  • 884

end page

  • 889

volume

  • 34

number

  • 4