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.

Importance of Thalamostriatal Pathway Associated With Neurocognitive Dysfunctions in Children With Neurofibromatosis Type 1: Diffusion Tensor Imaging Findings.

OBJECTIVE: To determine whether there is a difference between healthy control group and children with neurofibromatosis type 1 (NF1) in terms of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in different regions of the brain associated with neurocognitive functions and to investigate the correlation between diffusion tensor imaging parameters and neurocognitive dysfunctions. METHODS: The study included 28 children with NF1 and 21 controls. Nine distinct areas related to cognitive functions were selected for the analysis. The ADC and FA values were compared. RESULTS: There was a significant difference between NF1 and healthy control in terms of ADC values obtained from all areas. The ADC values at obtained from thalamus and striatum were positively correlated with the full-scale intelligence quotient (IQ), verbal IQ, and performance IQ. CONCLUSIONS: We are speculated that the development of microstructural damage in the thalamostriatal pathway may lead to neurocognitive dysfunction.

Neurosurgical contribution within a complex NF1 supraregional service.

OBJECTIVES: The goal of this study was to review and present neurosurgical related activity within a multidisciplinary nationally commissioned specialty neurofibromatosis type I (NF1) center. PATIENTS & METHODS: We reviewed all NF1 Neurosurgical MDTs, NF1 Neurosurgical clinics and all neurosurgical procedures carried out in NF1 patients over an 8-year period. RESULTS: Since the inception of the service in 2009, 1505 cases were discussed at our NF-1 multidisciplinary meeting, 171 clinic appointments in complex NF1 patients with neurosurgical pathologies and 43(cranial and spinal) operations were performed. CONCLUSIONS: The formation of a supraregional multidisciplinary team allows for a better understanding of the disease, a comprehensive evaluation of neuroimaging findings and a steep learning curve in the management of NF1 surgical conditions. We provide holistic treatment for these patients via direct care, specialist advice and liaison with local units.

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.

PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice.

Attention system abnormalities represent a significant barrier to scholastic achievement in children with neurofibromatosis-1 (NF1). Using a novel mouse model of NF1-associated attention deficit (ADD), we demonstrate a presynaptic defect in striatal dopaminergic homeostasis and leverage this finding to apply [(11)C]-raclopride positron-emission tomography (PET) in the intact animal. While methylphenidate and l-Deprenyl correct both striatal dopamine levels on PET imaging and defective attention system function in Nf1 mutant mice, pharmacologic agents that target de-regulated cyclic AMP and RAS signaling in these mice do not. These studies establish a robust preclinical model to evaluate promising agents for NF1-associated ADD.

Reduced thalamic 18F-flurodeoxyglucose retention in adults with neurofibromatosis type 1.

OBJECTIVE: Neurofibromatosis type1 (NF1) is associated with cognitive and motor deficits whose pathogenesis is not well understood. 18F-Flurodeoxyglucose positron emission tomography (FDG PET) might be used to investigate putative functional correlates in the brain. METHODS: Whole-body FDG PET including the brain had been performed in 29 NF1 patients suspected for malignant peripheral nerve sheath tumours (20 females, nine males, age 31.2+/-11.8 years). Twenty-nine age-matched and sex-matched subjects without evidence of neurological/psychiatric disease in whom FDG PET had been performed for NF1-unrelated oncological indication served as controls. Individual brain FDG retention images were stereotactically normalized and scaled to a common median retention value within the brain. Scaled FDG retention was compared between the NF1 group and the control group on a voxel-by-voxel base using ANCOVA in SPM2 with the FDG uptake period as covariate. The corrected significance level alpha=0.05 was used. Voxel-based analysis was complemented by volume of interest (VOI)-based analysis using predefined standard VOIs. RESULTS: The voxel-based group comparison revealed a significant reduction of scaled FDG retention in the thalamus of the NF1 subjects within a cluster of 11.6 ml. There were no further significant effects, neither hypo-retention nor hyper-retention. Reduction of relative FDG retention in the thalamus in the NF1 subjects was confirmed by VOI analysis. The magnitude of the reduction was about 8%. CONCLUSIONS: The thalamus appears to be affected in adults with NF1. The observed magnitude of the reduction of scaled thalamic FDG retention in adults is smaller than previously reported in children. This may be consistent with a stabilization of the disease process with age.

A systematic multiple stage surgical approach for attainment of satisfactory and favourable surgical results in an extremely severe von Recklinghausen's disease, elephantiasis neurofibromatosa.

This disease was first described by von Recklinghausen and Festscher and has been known as the von Recklinghausen's disease or neurofibromatosis (NF). Numerous articles have been published on this subject where majority of the authors have stressed their difficulty in achieving favourable surgical results. This disease is pathologically accepted to be of neuroectodermal origin with a positive family history in approximately 50% of the cases, autosomal dominant trait and is known to involve the periorbital regions, orbit (preoperative CT scan: upper left and right photographs), temporal region to a variable extent, mid-facial region to the mandibular region. The indicated treatment for this disease is surgery including cranio-maxillofacial surgery even though re-evaluation of the conventional methods of surgery should be considered. This particular case is an extremely difficult and challenging case for any reconstructive plastic surgeon and required extensive preoperative planning. The systematic multiple stage surgical approach for an extremely severe von Recklinghausen's disease, elephantiasis neurofibromatosa is presented and discussed in detail.

Positron emission tomography in children with neurofibromatosis-1.

Neurofibromatosis-1 is an autosomal dominant genetic disorder commonly associated with neuropsychological complications. Focal areas of high signal intensity on magnetic resonance imaging (MRI) scans occur commonly but have shown inconsistent correlation with neuropsychological problems. Positron emission tomography (PET) scans utilizing [18F]fluoro-2-deoxy-D-glucose and MRI studies were performed on 10 children with neurofibromatosis-1 and multiple focal areas of high signal intensity to evaluate the regional cerebral metabolic rate for glucose of these lesions and other central nervous system structures. Co-registered PET and MRI studies confirmed reduced glucose metabolism of large focal areas of high signal intensity. Visual inspection and semiquantitative analysis of PET images demonstrated thalamic hypometabolism and varying degrees of cortical inhomogeneity in all cases of neurofibromatosis-1 compared to normal controls. Although a primary defect of the thalamus or cerebral cortex has not been defined, the metabolic abnormalities of this study suggest a potential relationship between these structures and the neuropsychological dysfunctions noted in neurofibromatosis-1.

Moderate grade astrocytoma presenting in a 4-month-old child with a family history of von Recklinghausen's neurofibromatosis spanning four generations: a case report.

Intracranial gliomas are found in association with von Recklinghausen's neurofibromatosis. However, few truly neonatal lesions have been identified and studied. This case report concerns a 4-month-old child who was found to have a massive thalamic glioma of moderate grade. Four paternal generations had suffered from different manifestations of this transmissible autosomal-dominant (Ad) phakomatosis.

Computed tomography in the evaluation of the gluteal region.

The role of computed tomography (CT) in the evaluation of the gluteal region was assessed. Six cases of gluteal masses were studied preoperatively by CT; several were also studied with conventional radiographic methods, including barium enema, cystogram, and intravenous urogram. Our case material included an epithelioid sarcoma, Ewing's sarcoma, endodermal sinus tumor, cystic hygroma, neurofibromatosis, and a normal variant. The conventional radiologic studies were normal or demonstrated nonspecific soft tissue density mass effect. By comparison, CT, with its cross-sectional imaging capability, provided unique diagnostic information. CT depicted the presence and origin of a mass, provided tissue characterization, and showed the extent of the lesion, often demonstrating the gluteal mass as an extension of an intrapelvic lesion. CT was valuable in monitoring tumor response to therapy, detecting recurrences, and excluding normal variants as the cause for a gluteal mass. The information provided by CT was important in treatment planning.