Alterations in brain morphology by MRI in adults with neurofibromatosis 1

Su Wang,Su Wang,Per Suppa,Per Suppa,Per Suppa,Ralph Buchert,Jan M Friedman,Jan M Friedman,Ralph Buchert,Victor-Felix Mautner,Victor-Felix Mautner,Stephane Flibotte,Manraj K S Heran

doi:10.1186/s13023-021-02097-5

Abstract

ObjectiveNeurofibromatosis 1 (NF1) is a rare autosomal dominant disease that causes the dysregulated growth of Schwann cells. Most reported studies of brain morphology in NF1 patients have included only children, and clinical implications of the observed changes later in life remain unclear. In this study, we used MRI to characterize brain morphology in adults with NF1.MethodsPlanar (2D) MRI measurements of 29 intracranial structures were compared in 389 adults with NF1 and 112 age- and sex-matched unaffected control subjects. The 2D measurements were correlated with volumetric (3D) brain measurements in 99 of the adults with NF1 to help interpret the 2D findings. A subset (n = 70) of these NF1 patients also received psychometric testing for attention deficits and IQ and was assessed for clinical severity of NF1 features and neurological problems. Correlation analysis was performed between the MRI measurements and clinical and psychometric features of these patients.ResultsFour of nine corpus callosum measurements were significantly greater in adults with NF1 than in sex- and age-matched controls. All seven brainstem measurements were significantly greater in adults with NF1 than in controls. Increased corpus callosum and brainstem 2D morphology were correlated with increased total white matter volume among the NF1 patients. No robust correlations were observed between the 2D size of these structures and clinical or neuropsychometric assessments.ConclusionOur findings are consistent with the hypothesis that dysregulation of brain myelin production is an important manifestation of NF1 in adults.

Highlights

Neurofibromatosis 1 (NF1), an autosomal dominant disease caused by mutations of the NF1 gene, affects approximately 1 in 3000 live births [1,2,3]
Head magnetic resonance imaging (MRI) was obtained on 434 adults with NF1; each patient was imaged on three separate occasions, on average
Of the five measurements made for each ocular globe, only the anterior to posterior (AP) lengths were significantly reduced in both eyes in adults with NF1 compared to unaffected controls

Summary

Introduction

Neurofibromatosis 1 (NF1), an autosomal dominant disease caused by mutations of the NF1 gene, affects approximately 1 in 3000 live births [1,2,3]. Many studies have used magnetic resonance imaging (MRI) to study brain morphology in children and adults with NF1. NF1 neuroimaging studies have been especially focused on unidentified bright objects, optic nerve/ chiasmatic expansions, and tumours of the peripheral nerves or central nervous system [17, 18]. Wang et al Orphanet J Rare Dis (2021) 16:462 other, more subtle alterations of brain morphology on MRI examination, including increases in total white matter volume, total brain volume, corpus callosum (CC) area, CC length, and optic nerve tortuosity (ONT) [6, 7, 9, 10, 19,20,21,22,23,24,25,26,27,28]. The clinical implications, if any, of these findings are unclear, given the small number and young age of individuals with NF1 in most reported studies [10]

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