Contribution of diffusion tensor MR imaging in detecting cerebral microstructural changes in adults with neurofibromatosis

Abstract

BACKGROUND AND PURPOSE: After an early progression of signal intensity changes in T2-weighted MR images, also known as "neurofibromatosis bright objects," in patients with neurofibromatosis type 1 (NF-1), there is a tendency toward regression or even disappearance in early adulthood. The purpose of this study was to investigate whether adult patients with NF-1 exhibit generalized microstructural alterations even in normal-appearing brain regions. MATERIALS AND METHODS: Conventional and diffusion tensor MR imaging of the brain was obtained in 10 adult patients with NF-1 and 10 age-matched healthy volunteers. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain stem, basal ganglia, thalamus, corpus callosum, and frontal and parietooccipital white matter regions. RESULTS: Significantly increased ADC and decreased FA values were found in all regions of interest and in all patients with NF-1, irrespective of their scholastic achievement and subsequent professional performance, compared with control subjects (P < .001). There were no significant correlations with the age (P > .1) or with the lateralization between brain hemispheres (P > .05). CONCLUSION: Diffusion tensor imaging reveals globally elevated FA and decreased ADC values in the mature brains of patients with NF-1, which is most likely a consequence of diffuse and basic alterations in cerebral microstructure that result from the underlying gene mutation. ORIGINAL RESEARCH Contribution of Diffusion Tensor MR Imaging in Detecting Cerebral Microstructural Changes in Adults with Neurofibromatosis Type 1 S.L. Zamboni T. Loenneker E. Boltshauser E. Martin K.A. Il’yasov BACKGROUND AND PURPOSE: After an early progression of signal intensity changes in T2-weighted MR images, also known as “neurofibromatosis bright objects,” in patients with neurofibromatosis type 1 (NF-1), there is a tendency toward regression or even disappearance in early adulthood. The purpose of this study was to investigate whether adult patients with NF-1 exhibit generalized microstructural alterations even in normal-appearing brain regions. MATERIALS AND METHODS: Conventional and diffusion tensor MR imaging of the brain was obtained in 10 adult patients with NF-1 and 10 age-matched healthy volunteers. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain stem, basal ganglia, thalamus, corpus callosum, and frontal and parietooccipital white matter regions. RESULTS: Significantly increased ADC and decreased FA values were found in all regions of interest and in all patients with NF-1, irrespective of their scholastic achievement and subsequent professional performance, compared with control subjects (P .001). There were no significant correlations with the age (P .1) or with the lateralization between brain hemispheres (P .05). CONCLUSION: Diffusion tensor imaging reveals globally elevated FA and decreased ADC values in the mature brains of patients with NF-1, which is most likely a consequence of diffuse and basic alterations in cerebral microstructure that result from the underlying gene mutation. Neurofibromatosis type 1 (NF-1) is the most prevalent phakomatosis and is characterized by multiple neurofibromas of various organs, changes in skin pigmentation, and deformation of the skeleton. NF-1 is an autosomal dominant disorder, occurring with a prevalence of 2–3 cases per 10,000 population; half of the cases represent new mutations. Brain lesions in NF-1 include optic pathway gliomas, cerebral astrocytomas, aqueductal stenosis, and, predominantly in children, focal hyperintense areas in T2-weighted MR imaging also known as “neurofibromatosis bright objects” (NBO) or “focal areas of signal intensity”. The latter is considered a characteristic feature in children with NF-1, but it cannot be used as a diagnostic criterion. “Typical” NBOs do not exert mass effect, do not enhance with contrast agents, and are not visible on CT. In particular, they are not surrounded by edema. In most cases, NBOs are found in basal ganglia, thalamus, cerebellum, brain stem, and subcortical white matter (WM), with an incidence of 43%–77%. The frequency of occurrence seems to be related to both the presence of optic pathway gliomas and the age; NBOs begin to appear at the age of 3 years and increase in number and size until the age of 10 years, whereupon they decrease and most often disappear completely until adulthood. The exact nature and the relevance of NBOs are still unclear. It has been suggested that abnormal myelin might be their source. The commonly accepted theory is that spongiotic and vacuolating alterations of myelin structure are responsible, which is based on the few histopathologic examinations reported by DiPaolo et al, who also found microcalcifications in the globus pallidus. Patients with NF-1 often present with learning disabilities and megalencephaly, pointing to the possibility of a more generalized alteration of the brain microstructure. To better understand the underlying anatomic disturbances, the purpose of this study was to investigate whether adult patients with NF-1 exhibit generalized microstructural alterations even in normal-appearing brain regions. Therefore, we determined the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA) of different brain regions using diffusion tensor imaging (DTI). Materials and Methods Subjects. In this context, we refer to subjects affected by NF-1 as “patients.” The patients participating in this study were known previously to our NF clinic and were recruited through personal contacts to the Swiss Neurofibromatosis Organization. They fulfilled the diagnostic criteria for NF-1 based on a National Institutes of Health 1988 Consensus and were not known to suffer from obvious pathologic brain conditions (eg, brain tumor, epilepsy). There were 10 unrelated patients (4 women and 6 men), ranging in age from 18 to 36 years (mean age SD: 25.8 5.4 years). We focused on this age group because no myelin remodeling (NBO) is to be expected at this age. Two patients (P2, P6) attended special schools because of their marked and severe learning difficulties; the schooling of the other patients was age-appropriate. The professional training is as follows: P1 and P4 obtained a university degree. Six patients are in full-time employment and self-sufficient, 3 of them (P5, P9, P10) were in 3-year vocational training, and 3 (P3, P7, P8) in 2-year vocational training. P2 works part-time (manual work), whereas P6 lives in an institution for handicapped people. Ten age-matched healthy volunReceived June 15, 2006; accepted after revision July 25. From the MR Center (S.L.Z., T.L., E.M., K.A.I.), University Children’s Hospital, Zurich, Switzerland; Center for Integrative Human Physiology (T.L.), University of Zurich, Zurich, Switzerland; Department of Neurology (E.B.), University Children’s Hospital, Zurich, Switzerland; Department of Diagnostic Imaging (K.A.I.), Medical Physics, University Hospital, Freiburg, Germany. S.L.Z. and T.L. contributed equally to this work. Address correspondence to Thomas Loenneker, MR-Center, University Children’s Hospital, Steinwiesstr 75, 8032 Zurich, Switzerland; e-mail: thomas.loenneker@kispi.unizh.ch B RA IN

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@inproceedings{Zamboni2009ContributionOD, title={Contribution of diffusion tensor MR imaging in detecting cerebral microstructural changes in adults with neurofibromatosis}, author={Stefania Zamboni and Thomas Loenneker and Eugen Boltshauser}, year={2009} }