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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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
Issue number3
Publication statusPublished - 1 Jun 2017

Cite this