White matter is increased in the brains of adults with neurofibromatosis 1

Su Wang; Jan M Friedman; Per Suppa; Ralph Buchert; Victor-Felix Mautner

doi:10.1186/s13023-022-02273-1

White matter is increased in the brains of adults with neurofibromatosis 1

Orphanet J Rare Dis. 2022 Mar 5;17(1):115. doi: 10.1186/s13023-022-02273-1.

Authors

Su Wang¹, Jan M Friedman², Per Suppa³, Ralph Buchert^#⁴, Victor-Felix Mautner^#⁵

Affiliations

¹ Department of Medical Genetics, University of British Columbia, Children's and Women's Hospital, 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada.
² Department of Medical Genetics, University of British Columbia, Children's and Women's Hospital, 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada. jan.friedman@ubc.ca.
³ Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁴ Department of Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
⁵ Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

^# Contributed equally.

Abstract

Background: Neurofibromatosis 1 (NF1) is a rare autosomal dominant disease characterized by increased Schwann cell proliferation in peripheral nerves. Several small studies of brain morphology in children with NF1 have found increased total brain volume, total white matter volume and/or corpus callosum area. Some studies (mostly in children with NF1) also attempted to correlate changes in brain morphology and volume with cognitive or behavioural abnormalities, although the findings were inconsistent. We aimed to characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with NF1 in major intracranial sub-regions. We also aimed to assess the effect of age on these volumes and correlated brain white matter and grey matter volumes with neuropsychometric findings in adults with NF1.

Methods: We obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients.

Results: Total brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1.

Conclusion: Our findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.

Keywords: Adult brain volumetry; Age progression; Neurofibromatosis 1; Neuropsychometric; White matter.

MeSH terms

Adult
Brain / pathology
Child
Corpus Callosum / pathology
Humans
Magnetic Resonance Imaging
Neurofibromatosis 1* / pathology
White Matter* / pathology