儿童戈谢病骨骼影像特征分析

目的 探讨儿童戈谢病骨骼病变的X线平片及MRI表现特点.方法 109例戈谢病患儿均行常规脊柱正、侧位及双股骨正位X线检查,同时行骨盆止位检查18例,左腕正位检查14例;14例患儿同时行股骨MR平扫.MR扫描序列为标准T1WI、T2WI、T2压脂像冠状面及矢状而扫描.综合分析其影像特点.结果 骨骼异常X线征象包括:长骨干骺端烧瓶样畸形89例(81.7%)、骨质稀疏91例(83.5%)、长骨十骺端密度不同程度的减低86例(78.9%)、骨皮质变薄69例(63.3%)、溶骨性破坏31例(28.4%)、骨硬化12例(11.0%)、骨囊性病变16例(14.7%),病理性骨折26例(23.9%),其中椎体压缩性骨折24处、股骨颈陈旧性骨折5处、脊柱弧形后凸3例、股骨头碎裂变形4例、髋关节脱位4例.,14例股骨MRI显示,T1WI及T2WI骨髓内均可见异常信号,分别表现为T1WI、T2WI信号减低4例;在T2WI及压脂像信号广泛减低的基础上出现限局性高信号或混杂信号10例.结论 儿童戈谢病骨骼病变的影像表现有一定特征性,对临床诊治及观察疗效具有较大的帮助.

Abstract：

Objective To discuss the imaging features of skeletal changes in children with Gaucher disease on X-ray and MRI images.Methods One hundred and nine children with Gaucher disease were enrolled in this study.They all received routine X-ray for spine with anterior-posterior(A-P)and lateral view and bilateral femurs with A-P view.Among them.18 patients received X-ray for pelvic with A-P view.14 patients received X-ray for left wrist with A-P view.and 14 patients received MRI scan for femur.The MRI scan included T1-weighted imaging,T2-weighted imaging and fat-suppressed T2-weighted imaging with short tau inversion recovery(STIR)sequence.The imaging features of the X-ray and MRI images were analyzed retrospectively.Results The most common feature is osteoporosis,which presented in 91 cases (83.5%).Besides this,decreased density of metaphysis occurred in 86 cases(78.9%).erlenmeyer flask deformity of metaphysis occurred in 89 patients(81.7%),thinner cortex occurred in 69 cases(63.3%),osteolytic destruction occurred in 31 cases(28.4%).pathological fractures occurred in 26 cases (23.9%),osteosclerosis occurred in 12 cases(11.0%).cystic degeneration of bone occurred in 16 cases (14.7%),and dislocation of the hip occurred in 4 cases.All 14 patients received MRI presented abnormal signals.Among them,4 patients presented low signal intensity both on T1-weighted and T2-weighted images in bone marrow;the other ten presented high signal intensity mixed in low signal intensity areas on T2-weighted and fat-suppressed T2-weighted images.Conclusions The imaging features of skeletal changes in children with Gaucher disease are of some characteristics,which could provide useful information for the clinical treatment.     

Thalamic and dentate nucleus abnormalities in the brain of children with Gaucher disease

Gaucher disease (GD) represents the most common lysosomal storage defect. It is classified into three phenotypes: type 1 non-neuronopathic, type 2 acute neuronopathic, and type 3 subacute/chronic neuronopathic. Although children affected by GD may present with a broad spectrum of neurological signs, brain magnetic resonance imaging (MRI) findings are usually normal or non-specific. We report three cases of GD with previously undescribed brain MRI changes mainly affecting the thalami and/or the dentate nuclei. We discuss the possible etiopathogenesis of these abnormalities. Correlation between brain MRI abnormalities, neurological symptoms, and treatment efficacy is still unclear.     

Bone marrow relaxation times in Gaucher disease before and after enzyme replacement therapy

The aim of this work was to monitor the effectiveness of enzyme replacement therapy on the basis of the changes in T1 relaxation times in Gaucher patients. A total of 26 patients underwent MR before enzyme replacement therapy; of them, 18 have been followed-up. A total of 22 age-matched controls underwent the same MR study. Scans were focused on the femoral neck, and T1 relaxation times were measured by means of a mixed spin-echo inversion recovery sequence. The T1 relaxation times in Gaucher patients were significantly longer than normal (p < 0.05). After enzyme replacement therapy, T1 relaxation times gradually became closer to those of control subjects, and there was also a significant decrease (p < 0.01) with respect to values before therapy, probably due to an increase in the fat/water ratio. Evaluation of T1 relaxation time may supply a useful indication of Gaucher disease regression after enzyme replacement therapy particularly in those cases in which a normal skeletal appearance corresponds to prolonged T1 relaxation times. Received 28 February 1996; Revision received 20 May 1996; Accepted 21 August 1996     

Skeletal complications of type I Gaucher disease: the magnetic resonance features

Abnormalities on magnetic resonance imaging (MRI) are reported in six individuals with various skeletal complications of type I Gaucher disease. The changes were a nonhomogeneous reduction in both T1 and T2 marrow signals with increased T2 signals during avascular episodes. MRI proved an excellent technique for the assessment of bone marrow changes in Type I Gaucher disease and for assessing avascular complications. It was not able to differentiate between pseudo-osteomyelitis and pyogenic osteomyelitis without clinical correlation. The problems studied included the extent of intramedullary Gaucher cell infiltration, avascular necrosis of femoral heads, assessment of bone pain from pseudo-osteomyelitis and the relationship of skeletal disease to splenectomy.     

Gaucher disease in children: radiology of non-central nervous system manifestations

The radiological findings in paediatric Gaucher disease (GD) are reviewed and future challenges for radiology are discussed. This overview is based on a literature review and our experience of children with GD in one of two national institutions for paediatric GD in the UK. GD is known to progress more rapidly in childhood. Current imaging is mainly suitable for ascertaining the complications of GD. The UK recommendations for routine radiological surveillance are discussed. With enzyme replacement therapy (ERT), which dramatically modifies the course of the disorder, the challenge for radiology in the future is likely to be assessing treatment efficacy rather than the detection of disease complications. Disease manifestations are likely to change in those on ERT and the most notable recent alteration in the disease profile in childhood is the virtual disappearance of the acute bone crisis in this population.     

Liver scintigraphy in a patient with Gaucher disease

Liver scintigraphy including SPECT was performed in a patient with Gaucher disease and compared with other methods. Multiple photon-deficient areas in the liver and spleen were recognized, and in evaluating the reticuloendothelial system of the liver, liver SPECT image was superior to US, CT and MR images.     

Gaucher disease: assessment with MR imaging

The skeletal system, spleen, and liver of five patients with proved Gaucher disease were studied with magnetic resonance (MR) imaging. Homogeneous, low intensity signals resulting from relaxation times different than normal (longer T1 and shorter T2 values) were found in the marrow of long bones, vertebrae, and hips in all patients. In three patients, normal signals were noted in the patella, epiphysis of the knee, and capital femoral epiphysis. In two patients with acute bone pain in the tibial region, a higher signal was received from the tibial marrow. This signal was related to increased accumulation of fluid following an avascular episode. Soft tissues in the same area were also involved. Liver and spleen enlargement was readily visible, especially on coronal images. T1 values of spleen were significantly shorter than normal. MR imaging provides an excellent assessment of the extent of involvement of the liver, spleen, and bone marrow in Gaucher disease.     

Imaging of Gaucher disease

Gaucher disease is the prototypical lysosomal storage disease. It results from the accumulation of undegraded glucosylceramide in the reticuloendothelial system of the bone marrow, spleen and liver due to deficiency of the enzyme glucocerebrosidase. This leads to hematologic, visceral and skeletal maifestions. Build up of glucosylceramide in the liver and spleen results in hepatosplenomegaly. The normal bone marrow is replaced by the accumulating substrate leading to many of the hematologic signs including anemia. The visceral and skeletal manifestations can be visualized with various imaging modalities including radiography, computed tomography, magnetic resonance imaging (MRI) and radionuclide scanning. Prior to the development of enzyme replacement therapy, treatment was only supportive. However, once intravenous enzyme replacement therapy became available in the 1990s it quickly became the standard of care. Enzyme replacement therapy leads to improvement in all manifestations. The visceral and hematologic manifestations respond more quickly usually within a few months or years. The skeletal manifestations take much longer, usually several years, to show improvement. In recent years newer treatment strategies, such as substrate reduction therapy, have been under investigation. Imaging plays a key role in both initial diagnosis and routine monitoring of patient on treatment particularly volumetric MRI of the liver and spleen and MRI of the femora for evaluating bone marrow disease burden.     

Magnetic resonance spectroscopy in patients with Fabry and Gaucher disease

Objective

Fabry and Gaucher diseases are rare progressive inherited disorders of glycosphingolipid metabolism that affect multiple organ systems. The aim of this study was to investigate evidence for metabolic changes in the central nervous system involvement using proton magnetic resonance spectroscopic imaging.

Methods

Seven Fabry and eight Gaucher patients were included into this study. A two-dimensional, spectroscopic imaging method with an ultra-short echo-time of 11 ms was used at a 3 T whole body magnet. Absolute metabolic values were retrieved using internal water scaling. Results were compared, with sex- and age-matched controls.

Results

In contrast to previous findings, absolute and relative metabolite values of N-acetyl-aspartate (NAA) or NAA/Creatine (Cr), Cr, Choline (Cho) or Cho/Cr and myo-Inositol (mI) or mI/Cr revealed no, differences between Fabry and Gaucher Type 1 (GD1) patients and controls. Average values were, 10.22, 6.32, 2.15 and 5.39 mMol/kg wet weight for NAA, Cr, Cho and mI, respectively. In this study, we found significantly decreasing NAA/Cho with increasing age in all three groups (Fabry, GD1, patients and healthy controls) (between 5 and 8% per decade).

Conclusions

There were no changes of the quantified metabolites detected by MRS in normal appearing white matter. This study shows the importance of sex- and age-matched controls.     

Radiological aspects of Gaucher disease

Advances in imaging and the development of commercially available enzyme therapy have significantly altered the traditional radiology of Gaucher disease. The cost of treatment and need for monitoring response to therapy have magnified the importance of imaging. There are no recent comprehensive reviews of the radiology of this relatively common lysosomal storage disease. This article describes the modern imaging, techniques and radiological manifestations of Gaucher disease.     

Bilateral symmetrical cortical osteolytic lesions in two patients with Gaucher disease

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder characterized by the reduced or absent activity of glucocerebrosidase. The disease is split into three types. Type 3, or chronic neuronopathic GD, manifests with heterogeneous clinical presentations. Skeletal manifestations of GD can include abnormal bone remodeling resulting in the characteristic Erlenmeyer flask deformities, painful bone crises, osteopenia, and an increased frequency of fractures. Osteolytic lesions can also occur but are rare and tend to be large, expanding intramedullary lesions with cortical thinning. We present two adolescent patients with type 3 GD who developed bilateral symmetrical cortical osteolytic lesions. The lesions in both cases demonstrate predominant cortical scalloping with fairly indolent growth. Neither patient manifests some of the more common bony manifestations of GD—bone crises or osteonecrosis. These atypical and unique skeletal findings in two unrelated probands with type 3 GD further expand the extent of phenotypic variation encountered in this single gene disorder.     

Quantitative imaging of Gaucher disease.

Twenty-three patients with type 1 Gaucher disease were evaluated with a battery of quantitative imaging techniques. Plain radiographs were used to measure cortical thickness and Erlenmeyer flask deformity. Xenon-133 uptake was measured in scans of the lower extremities. Dual-energy quantitative computed tomography was used for calculation of trabecular bone and bone marrow fat content in the spine and long bones. Magnetic resonance (MR) imaging was performed to evaluate disease extent and three-dimensional splenic volume. MR images were also used to provide quantitative measurements of each vertebral fat fraction. Each imaging modality was correlated with the others as well as with the clinical history of skeletal complications and the hematocrit and acid phosphatase activity. There was a strong relationship between splenic volume and disease severity as measured clinically and with laboratory testing. The spinal fat fraction also correlated with these measures of disease severity and with the femoral fat fraction and xenon uptake. No measurement allowed discrimination of patients with from those without skeletal complications.     

Spectrum of abdominal sonographic findings in 103 pediatric patients with Gaucher disease

The purpose of this study was to catalogue spleen and liver features by US in a cohort of 103 pediatric patients with Gaucher disease, and to document response to enzyme replacement therapy by serial US examination. There were 42 boys and 61 girls, 2 were splenectomized. Forty-eight patients received enzyme replacement therapy (ERT). At presentation all patients evinced organomegaly and 4.9% had focal (splenic or hepatic) lesions (hypo- and hyper-echoic or mixed). Fifteen patients began ERT before 11 years of age. There was a mean liver volume reduction from 230 to 137% after 2 years of ERT, with further reduction of 91% up to 6 years later. Mean spleen volume reduction was 38.4% at 2 years of ERT and a further reduction to 40.8% at last evaluation. Fourteen children began ERT between ages 11 and 16 years. Mean liver reduction was from 230 to 124% at 2 years and further reduction to mean of 104% recently. Mean splenic reduction was 37.7% after 2 years of ERT, with a mean of 43.8% recently (mean 4.5 years later). Organ volume changes in untreated and treated children were documented by US which is the modality of choice for repeat measures in this population. Our results highlight the initial dramatic and then continued response to ERT in pediatric patients with Gaucher disease.