4H Leukodystrophy: A Brain Magnetic Resonance Imaging Scoring System

Suzanne Vrij-Van Den Bos, Janna A. Hol, Roberta La Piana, Inga Harting, Adeline Vanderver, Frederik Barkhof, Ferdy Cayami, Wessel N. Van Wieringen, Petra J.W. Pouwels, Marjo S. Van Der Knaap, Geneviève Bernard, Nicole I. Wolf

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

4H (hypomyelination, hypodontia and hypogonadotropic hypogonadism) leukodystrophy (4H) is an autosomal recessive hypomyelinating white matter (WM) disorder with neurologic, dental, and endocrine abnormalities. The aim of this study was to develop and validate a magnetic resonance imaging (MRI) scoring system for 4H. A scoring system (0-54) was developed to quantify hypomyelination and atrophy of different brain regions. Pons diameter and bicaudate ratio were included as measures of cerebral and brainstem atrophy, and reference values were determined using controls. Five independent raters completed the scoring system in 40 brain MRI scans collected from 36 patients with genetically proven 4H. Interrater reliability (IRR) and correlations between MRI scores, age, gross motor function, gender, and mutated gene were assessed. IRR for total MRI severity was found to be excellent (intraclass correlation coefficient: 0.87; 95% confidence interval: 0.80-0.92) but varied between different items with some (e.g., myelination of the cerebellar WM) showing poor IRR. Atrophy increased with age in contrast to hypomyelination scores. MRI scores (global, hypomyelination, and atrophy scores) significantly correlated with clinical handicap (p < 0.01 for all three items) and differed between the different genotypes. Our 4H MRI scoring system reliably quantifies hypomyelination and atrophy in patients with 4H, and MRI scores reflect clinical disease severity.

Original languageEnglish
Pages (from-to)152-160
Number of pages9
JournalNeuropediatrics
Volume48
Issue number3
DOIs
Publication statusPublished - 1 Jun 2017

Cite this

Vrij-Van Den Bos, S., Hol, J. A., La Piana, R., Harting, I., Vanderver, A., Barkhof, F., ... Wolf, N. I. (2017). 4H Leukodystrophy: A Brain Magnetic Resonance Imaging Scoring System. Neuropediatrics, 48(3), 152-160. https://doi.org/10.1055/s-0037-1599141
Vrij-Van Den Bos, Suzanne ; Hol, Janna A. ; La Piana, Roberta ; Harting, Inga ; Vanderver, Adeline ; Barkhof, Frederik ; Cayami, Ferdy ; Van Wieringen, Wessel N. ; Pouwels, Petra J.W. ; Van Der Knaap, Marjo S. ; Bernard, Geneviève ; Wolf, Nicole I. / 4H Leukodystrophy : A Brain Magnetic Resonance Imaging Scoring System. In: Neuropediatrics. 2017 ; Vol. 48, No. 3. pp. 152-160.
@article{22e9abf1f5514b0c88203bf7ebe6b032,
title = "4H Leukodystrophy: A Brain Magnetic Resonance Imaging Scoring System",
abstract = "4H (hypomyelination, hypodontia and hypogonadotropic hypogonadism) leukodystrophy (4H) is an autosomal recessive hypomyelinating white matter (WM) disorder with neurologic, dental, and endocrine abnormalities. The aim of this study was to develop and validate a magnetic resonance imaging (MRI) scoring system for 4H. A scoring system (0-54) was developed to quantify hypomyelination and atrophy of different brain regions. Pons diameter and bicaudate ratio were included as measures of cerebral and brainstem atrophy, and reference values were determined using controls. Five independent raters completed the scoring system in 40 brain MRI scans collected from 36 patients with genetically proven 4H. Interrater reliability (IRR) and correlations between MRI scores, age, gross motor function, gender, and mutated gene were assessed. IRR for total MRI severity was found to be excellent (intraclass correlation coefficient: 0.87; 95{\%} confidence interval: 0.80-0.92) but varied between different items with some (e.g., myelination of the cerebellar WM) showing poor IRR. Atrophy increased with age in contrast to hypomyelination scores. MRI scores (global, hypomyelination, and atrophy scores) significantly correlated with clinical handicap (p < 0.01 for all three items) and differed between the different genotypes. Our 4H MRI scoring system reliably quantifies hypomyelination and atrophy in patients with 4H, and MRI scores reflect clinical disease severity.",
keywords = "4H, hypomyelination, leukodystrophy, MRI",
author = "{Vrij-Van Den Bos}, Suzanne and Hol, {Janna A.} and {La Piana}, Roberta and Inga Harting and Adeline Vanderver and Frederik Barkhof and Ferdy Cayami and {Van Wieringen}, {Wessel N.} and Pouwels, {Petra J.W.} and {Van Der Knaap}, {Marjo S.} and Genevi{\`e}ve Bernard and Wolf, {Nicole I.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1055/s-0037-1599141",
language = "English",
volume = "48",
pages = "152--160",
journal = "Neuropediatrics",
issn = "0174-304X",
publisher = "Hippokrates Verlag GmbH",
number = "3",

}

4H Leukodystrophy : A Brain Magnetic Resonance Imaging Scoring System. / Vrij-Van Den Bos, Suzanne; Hol, Janna A.; La Piana, Roberta; Harting, Inga; Vanderver, Adeline; Barkhof, Frederik; Cayami, Ferdy; Van Wieringen, Wessel N.; Pouwels, Petra J.W.; Van Der Knaap, Marjo S.; Bernard, Geneviève; Wolf, Nicole I.

In: Neuropediatrics, Vol. 48, No. 3, 01.06.2017, p. 152-160.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - 4H Leukodystrophy

T2 - A Brain Magnetic Resonance Imaging Scoring System

AU - Vrij-Van Den Bos, Suzanne

AU - Hol, Janna A.

AU - La Piana, Roberta

AU - Harting, Inga

AU - Vanderver, Adeline

AU - Barkhof, Frederik

AU - Cayami, Ferdy

AU - Van Wieringen, Wessel N.

AU - Pouwels, Petra J.W.

AU - Van Der Knaap, Marjo S.

AU - Bernard, Geneviève

AU - Wolf, Nicole I.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 4H (hypomyelination, hypodontia and hypogonadotropic hypogonadism) leukodystrophy (4H) is an autosomal recessive hypomyelinating white matter (WM) disorder with neurologic, dental, and endocrine abnormalities. The aim of this study was to develop and validate a magnetic resonance imaging (MRI) scoring system for 4H. A scoring system (0-54) was developed to quantify hypomyelination and atrophy of different brain regions. Pons diameter and bicaudate ratio were included as measures of cerebral and brainstem atrophy, and reference values were determined using controls. Five independent raters completed the scoring system in 40 brain MRI scans collected from 36 patients with genetically proven 4H. Interrater reliability (IRR) and correlations between MRI scores, age, gross motor function, gender, and mutated gene were assessed. IRR for total MRI severity was found to be excellent (intraclass correlation coefficient: 0.87; 95% confidence interval: 0.80-0.92) but varied between different items with some (e.g., myelination of the cerebellar WM) showing poor IRR. Atrophy increased with age in contrast to hypomyelination scores. MRI scores (global, hypomyelination, and atrophy scores) significantly correlated with clinical handicap (p < 0.01 for all three items) and differed between the different genotypes. Our 4H MRI scoring system reliably quantifies hypomyelination and atrophy in patients with 4H, and MRI scores reflect clinical disease severity.

AB - 4H (hypomyelination, hypodontia and hypogonadotropic hypogonadism) leukodystrophy (4H) is an autosomal recessive hypomyelinating white matter (WM) disorder with neurologic, dental, and endocrine abnormalities. The aim of this study was to develop and validate a magnetic resonance imaging (MRI) scoring system for 4H. A scoring system (0-54) was developed to quantify hypomyelination and atrophy of different brain regions. Pons diameter and bicaudate ratio were included as measures of cerebral and brainstem atrophy, and reference values were determined using controls. Five independent raters completed the scoring system in 40 brain MRI scans collected from 36 patients with genetically proven 4H. Interrater reliability (IRR) and correlations between MRI scores, age, gross motor function, gender, and mutated gene were assessed. IRR for total MRI severity was found to be excellent (intraclass correlation coefficient: 0.87; 95% confidence interval: 0.80-0.92) but varied between different items with some (e.g., myelination of the cerebellar WM) showing poor IRR. Atrophy increased with age in contrast to hypomyelination scores. MRI scores (global, hypomyelination, and atrophy scores) significantly correlated with clinical handicap (p < 0.01 for all three items) and differed between the different genotypes. Our 4H MRI scoring system reliably quantifies hypomyelination and atrophy in patients with 4H, and MRI scores reflect clinical disease severity.

KW - 4H

KW - hypomyelination

KW - leukodystrophy

KW - MRI

UR - http://www.scopus.com/inward/record.url?scp=85014114028&partnerID=8YFLogxK

U2 - 10.1055/s-0037-1599141

DO - 10.1055/s-0037-1599141

M3 - Article

VL - 48

SP - 152

EP - 160

JO - Neuropediatrics

JF - Neuropediatrics

SN - 0174-304X

IS - 3

ER -

Vrij-Van Den Bos S, Hol JA, La Piana R, Harting I, Vanderver A, Barkhof F et al. 4H Leukodystrophy: A Brain Magnetic Resonance Imaging Scoring System. Neuropediatrics. 2017 Jun 1;48(3):152-160. https://doi.org/10.1055/s-0037-1599141