Cargando…

Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1

Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate w...

Descripción completa

Detalles Bibliográficos
Autores principales: Lau, Meghann W., Lee, Ryan W., Miyamoto, Robin, Jung, Eun Sol, Yanjanin Farhat, Nicole, Yoshida, Shoko, Mori, Susumu, Gropman, Andrea, Baker, Eva H., Porter, Forbes D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456286/
https://www.ncbi.nlm.nih.gov/pubmed/28933409
http://dx.doi.org/10.3390/diseases4030029
_version_ 1783241218637955072
author Lau, Meghann W.
Lee, Ryan W.
Miyamoto, Robin
Jung, Eun Sol
Yanjanin Farhat, Nicole
Yoshida, Shoko
Mori, Susumu
Gropman, Andrea
Baker, Eva H.
Porter, Forbes D.
author_facet Lau, Meghann W.
Lee, Ryan W.
Miyamoto, Robin
Jung, Eun Sol
Yanjanin Farhat, Nicole
Yoshida, Shoko
Mori, Susumu
Gropman, Andrea
Baker, Eva H.
Porter, Forbes D.
author_sort Lau, Meghann W.
collection PubMed
description Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and diffusion tensor imaging (DTI) of the corpus callosum and brainstem, which has shown that microstructural disorganization is associated with NPC1 severity. This study investigates the utility of cerebellar DTI in clinical severity assessment. We hypothesize that cerebellar volume, fractional anisotropy (FA) and mean diffusivity (MD) negatively correlate with NIH NPC neurological severity score (NNSS) and motor severity subscores. Magnetic resonance imaging (MRI) was obtained for thirty-nine NPC1 subjects, ages 1–21.9 years (mean = 11.1, SD = 6.1). Using an atlas-based automated approach, the cerebellum of each patient was measured for FA, MD and volume. Additionally, each patient was given an NNSS. Decreased cerebellar FA and volume, and elevated MD correlate with higher NNSS. The cognition subscore and motor subscores for eye movement, ambulation, speech, swallowing, and fine motor skills were also statistically significant. Microstructural disorganization negatively correlated with motor severity in subjects. Additionally, Miglustat therapy correlated with lower severity scores across ranges of FA, MD and volume in all regions except the inferior peduncle, where a paradoxical effect was observed at high FA values. These findings suggest that DTI is a promising prognostication tool.
format Online
Article
Text
id pubmed-5456286
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-54562862017-09-12 Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1 Lau, Meghann W. Lee, Ryan W. Miyamoto, Robin Jung, Eun Sol Yanjanin Farhat, Nicole Yoshida, Shoko Mori, Susumu Gropman, Andrea Baker, Eva H. Porter, Forbes D. Diseases Article Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and diffusion tensor imaging (DTI) of the corpus callosum and brainstem, which has shown that microstructural disorganization is associated with NPC1 severity. This study investigates the utility of cerebellar DTI in clinical severity assessment. We hypothesize that cerebellar volume, fractional anisotropy (FA) and mean diffusivity (MD) negatively correlate with NIH NPC neurological severity score (NNSS) and motor severity subscores. Magnetic resonance imaging (MRI) was obtained for thirty-nine NPC1 subjects, ages 1–21.9 years (mean = 11.1, SD = 6.1). Using an atlas-based automated approach, the cerebellum of each patient was measured for FA, MD and volume. Additionally, each patient was given an NNSS. Decreased cerebellar FA and volume, and elevated MD correlate with higher NNSS. The cognition subscore and motor subscores for eye movement, ambulation, speech, swallowing, and fine motor skills were also statistically significant. Microstructural disorganization negatively correlated with motor severity in subjects. Additionally, Miglustat therapy correlated with lower severity scores across ranges of FA, MD and volume in all regions except the inferior peduncle, where a paradoxical effect was observed at high FA values. These findings suggest that DTI is a promising prognostication tool. MDPI 2016-09-08 /pmc/articles/PMC5456286/ /pubmed/28933409 http://dx.doi.org/10.3390/diseases4030029 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lau, Meghann W.
Lee, Ryan W.
Miyamoto, Robin
Jung, Eun Sol
Yanjanin Farhat, Nicole
Yoshida, Shoko
Mori, Susumu
Gropman, Andrea
Baker, Eva H.
Porter, Forbes D.
Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1
title Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1
title_full Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1
title_fullStr Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1
title_full_unstemmed Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1
title_short Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1
title_sort role of diffusion tensor imaging in prognostication and treatment monitoring in niemann-pick disease type c1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456286/
https://www.ncbi.nlm.nih.gov/pubmed/28933409
http://dx.doi.org/10.3390/diseases4030029
work_keys_str_mv AT laumeghannw roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT leeryanw roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT miyamotorobin roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT jungeunsol roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT yanjaninfarhatnicole roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT yoshidashoko roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT morisusumu roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT gropmanandrea roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT bakerevah roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1
AT porterforbesd roleofdiffusiontensorimaginginprognosticationandtreatmentmonitoringinniemannpickdiseasetypec1