NEUROFIBROMATOSIS TYPE I: NEUROPSYCHOLOGY AND MRI CORRELATES

R Feldmann. M Oelerich, T Allkemper, U Wiegard, M Pietsch, J Weglage

Department of Pediatrics, and Department of Radiology, University of Münster, Germany

OBJECTIVE: Neurofibromatosis type 1 (NF1) is the most common phakomatosis and the most common single gene disorder affecting the central nervous system. It is inherited by a gene located in chromosome 17. Physical features include café au lait spots, neurofibromas, skeletal dysplasias, freckling in the axillary or inguinal regions, and Lisch nodules, NF1 is associated with various CNS lesions, including optic pathway and cerebral astrocytomas, neurofibromas, neurofibrosarcomas, and nonneoplastic areas of high signal intensity. These focal areas of high signal intensity (fasi) on proton-density and T₂-weighted images seen in patients with NF1 are generally found in the cerebellar peduncles, basal ganglia, brain stem, and optic radiations. It has been assumed that these MR imaging abnormalities represent areas of delayed or disordered myelination. Cognitive and behavioural problems are frequent clinical manifestations in children with NF1, although most seem to have average intelligence. In order to determine if there is an association between high-intensity lesions on MRI findings and cognitive and behavioural deficits, we examined the neuropsychological abilities, clinical manifestations, and cranial MRI scans of 100 children with NF1. We hypothesized that the cognitive and behavioural abilities of NF1 patients who had high-intensity signal lesions would be poorer than those of NF1 patients with normal MRI scans.

METHODS: 100 patients (age mean = 16.2, SD = 9,3; 56 male, 44 female), who met the NIH clinical criteria for NF1 were studied using MR imaging. MRI studies were performed on a 1.5 Tesia clinical imaging system (Magnetom SP 63, Siemens, Germany). Axial PD- and T2-weighted spin-echo (SE) images as well as coronal and sagittal Tl-weighted SE images were acquired after injection of a standard dose of 0.1 mmol GD-DTPA/kg bodyweight. A detailed neurological examination was carried out by one of the participating pediatric neurologists. The neuropsychological assessment for each patient included measures of psychometric intelligence (WISC-R), memory, attention, and motoric abilities. The psychologist was blind to the neuroradiological findings. The pediatric patients' emotional problems and competencies were investigated using Achenbach's Child Behaviour Checklist (CBCL) and Youth Self Report (YSR).

RESULTS: 62 of the 100 subjects had the characteristic fasi or UBO on T₂-weighted MRI scans. As a group, the 100 patients performed within normal limits of Verbal, Performance and Full-scale scores of WISC-R (90,89,88). However, the mean of Verbal, Performance and Full-scale scores for the NF1 patients with normal MRI scans were close to average (99,98,99) while those for the patients who had fasi/ubo were depressed to 85,84,83. Patients with fasi/ubo scored significantly lower than patients with normal MRI scans on measures of competence and problems (CBCL, YSR).

CONCLUSIONS: Due to moderate sample sizes, former studies denied or discussed a relationship between hyperintensities and cognitive functioning in patients with NF1. Our study is now revealing a strong relationship between cognitive and behavioural problems and focal areas of high signal intensity (fasi or ubo) in children with NF1. The long term effects of the hyperintensities remain to be documented.