Asymmetry of thalamic hypometabolism on FDG-PET/CT in neurofibromatosis type 1: Association with peripheral tumor burden.

BACKGROUND AND PURPOSE: Thalamic hypometabolism is a consistent finding in brain PET with F-18 fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). However, the pathophysiology of this metabolic alteration is unknown. We hypothesized that it might be secondary to disturbance of peripheral input to the thalamus by NF1-characteristic peripheral nerve sheath tumors (PNSTs). To test this hypothesis, we investigated the relationship between thalamic FDG uptake and the number, volume, and localization of PNSTs. METHODS: This retrospective study included 22 adult NF1 patients (41% women, 36.2 ± 13.0 years) referred to whole-body FDG-PET/contrast-enhanced CT for suspected malignant transformation of PNSTs and 22 sex- and age-matched controls. Brain FDG uptake was scaled voxelwise to the individual median uptake in cerebellar gray matter. Bilateral mean and left-right asymmetry of thalamic FDG uptake were determined using a left-right symmetric anatomical thalamus mask. PNSTs were manually segmented in contrast-enhanced CT. RESULTS: Thalamic FDG uptake was reduced in NF1 patients by 2.0 standard deviations (p < .0005) compared to controls. Left-right asymmetry was increased by 1.3 standard deviations (p = .013). Thalamic hypometabolism was higher in NF1 patients with ≥3 PNSTs than in patients with ≤2 PNSTs (2.6 vs. 1.6 standard deviations, p = .032). The impact of the occurrence of paraspinal/paravertebral PNSTs and of the mean PNST volume on thalamic FDG uptake did not reach statistical significance (p = .098 and p = .189). Left-right asymmetry of thalamic FDG uptake was not associated with left-right asymmetry of PNST burden (p = .658). CONCLUSIONS: This study provides first evidence of left-right asymmetry of thalamic hypometabolism in NF1 and that it might be mediated by NF1-associated peripheral tumors.

Cerebral glucose metabolism in adults with neurofibromatosis type 1.

Previous studies with positron emission tomography (PET) and the glucose analog F-18-fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1) suggest reduced cerebral glucose metabolism in NF1 specifically in the thalamus. The latter is distinguished by extensive neural circuitry connections which makes thalamic hypoactivity in NF1 an interesting finding. Yet it is not very well confirmed, since previous studies were limited by small sample size and/or poorly matched control groups. Primary aim of the present study therefore was to compare brain FDG PET between a large sample of NF1 patients and a well-matched control group. Secondary aim was to test for an NF1-associated FDG effect in the amygdala, as increased blood flow in the amygdala has recently been detected in a mouse model of NF1. Fifty adult NF1 patients and 50 gender- and age-matched control subjects were included retrospectively. Voxel-wise comparison of brain FDG uptake was performed using the statistical parametric mapping (SPM8). Additional region-of-interest (ROI) analysis was performed using standard ROI templates. Voxel-based testing revealed a single 11.2 ml cluster of reduced FDG uptake in the thalamus of NF1 patients. There was no further significant cluster throughout the whole brain including the amygdala, neither hypo nor hyper. ROI-analysis confirmed reduction of thalamic FDG uptake in the NF1 group (p<0.0005) with a magnitude of 7.6%. In conclusion, adults with NF1 show reduced brain activity specifically in thalamus. There is no indication of abnormal brain activity in the amygdala in humans with NF1.