Alterations in brain morphology by MRI in adults with neurofibromatosis 1

Abstract

Objective Neurofibromatosis 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. Methods Planar (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. Results Four 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. Conclusion Our findings are consistent with the hypothesis that dysregulation of brain myelin production is an important manifestation of NF1 in adults.

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

“…Several studies have examined changes in brain morphology in people with NF1, but most of these studies have small sample sizes and focus on affected children [ 5 – 21 ]. The most consistent findings in individuals with NF1 have been increased total brain volume, total white matter volume and corpus callosum (CC) area [ 6 – 21 ]. Some studies also found increased grey matter volume in children or young adults with NF1 [ 6 , 7 , 16 ].…”

“…Some studies also found increased grey matter volume in children or young adults with NF1 [ 6 , 7 , 16 ]. Other studies have examined grey matter and white matter composition of regional cranial structures, with the most consistent observation being increased corpus callosum area and size [ 8 , 10 , 14 , 15 , 17 , 19 – 21 ].…”

“…We previously examined brain morphology using planar MRI in a large group of adults with NF1 (n = 389) [ 21 ]. We found an increase in CC area as well as an increase in brainstem size in comparison to unaffected controls.…”

“…Several studies have attempted to correlate changes in brain morphology and volume with cognitive or behavioural abnormalities in individuals with NF1. All of these studies, except one (small sample size using 2D brain morphology measurements) [ 21 ], were conducted in affected children. As well, the correlations found were inconsistent across studies, perhaps due to limited sample sizes and numerous variables examined [ 6 – 9 , 13 , 14 , 16 , 18 – 20 ].…”

“…As well, the correlations found were inconsistent across studies, perhaps due to limited sample sizes and numerous variables examined [ 6 – 9 , 13 , 14 , 16 , 18 – 20 ]. Our previous study attempted to correlate CC and brainstem size to the severity of NF1, neurological features, and ADHD, as well as IQ and attentional deficits, but found no associations [ 21 ].…”