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Neuropediatrics 2017; 48(03): 152-160
DOI: 10.1055/s-0037-1599141
Original Article
Georg Thieme Verlag KG Stuttgart · New York

4H Leukodystrophy: A Brain Magnetic Resonance Imaging Scoring System

Suzanne Vrij-van den Bos   *
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
,
Janna A. Hol   *
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
,
Roberta La Piana   *
2   Laboratory of Neurogenetics of Motion and Department of Neuroradiology, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada
3   Department of Neurology and Neurosurgery, and Pediatrics, McGill University, Montreal, Canada
,
Inga Harting
4   Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany
,
Adeline Vanderver
5   Department of Neurology, Children's National Medical Center, Washington DC and George Washington University School of Medicine, Washington, Dist. of Columbia, United States
,
Frederik Barkhof
6   Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands
7   Institute of Neurology and Health Care Engineering, University College London, London, United Kingdom
,
Ferdy Cayami
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
8   Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
,
Wessel N. van Wieringen
9   Department of Clinical Epidemiology and Biostatistics, VU University Medical Center and Department of Mathematics, VU University, Amsterdam, The Netherlands
,
Petra J. W. Pouwels
10   Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands
11   Amsterdam Neuroscience, Amsterdam, The Netherlands
,
Marjo S. van der Knaap
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
11   Amsterdam Neuroscience, Amsterdam, The Netherlands
12   Department of Functional Genomics, VU University, Amsterdam, The Netherlands
,
Geneviève Bernard   ‡
3   Department of Neurology and Neurosurgery, and Pediatrics, McGill University, Montreal, Canada
13   Department of Medical Genetics, McGill University Health Center, Montreal Children's Hospital, Montreal, Canada
14   Child Health and Human Development Program, Research Institute of the McGill University Health Center, Montreal, Canada
,
Nicole I. Wolf   ‡
1   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
11   Amsterdam Neuroscience, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

03 November 2016

03 January 2017

Publication Date:
01 March 2017 (online)

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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 - leukodystrophy - MRI - hypomyelination

* The authors contributed equally to this work.


‡ The authors contributed equally to this work.


 

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