Tal Laor

Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis

BACKGROUND Angiomyolipomas in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis are associated with mutations in tuberous sclerosis genes resulting in constitutive activation of the mammalian target of rapamycin (mTOR). The drug sirolimus suppresses mTOR signaling. METHODS We conducted a 24-month, nonrandomized, open-label trial to determine whether sirolimus reduces the angiomyolipoma volume in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Sirolimus was administered for the first 12 months only. Serial magnetic resonance imaging of angiomyolipomas and brain lesions, computed tomography of lung cysts, and pulmonary-function tests were performed. RESULTS Of the 25 patients enrolled, 20 completed the 12-month evaluation, and 18 completed the 24-month evaluation. The mean (+/-SD) angiomyolipoma volume at 12 months was 53.2+/-26.6% of the baseline value (P<0.001) and at 24 months was 85.9+/-28.5% of the baseline value (P=0.005). At 24 months, five patients had a persistent reduction in the angiomyolipoma volume of 30% or more. During the period of sirolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 second (FEV1) increased by 118+/-330 ml (P=0.06), the forced vital capacity (FVC) increased by 390+/-570 ml (P<0.001), and the residual volume decreased by 439+/-493 ml (P=0.02), as compared with baseline values. One year after sirolimus was discontinued, the FEV1 was 62+/-411 ml above the baseline value, the FVC was 346+/-712 ml above the baseline value, and the residual volume was 333+/-570 ml below the baseline value; cerebral lesions were unchanged. Five patients had six serious adverse events while receiving sirolimus, including diarrhea, pyelonephritis, stomatitis, and respiratory infections. CONCLUSIONS Angiomyolipomas regressed somewhat during sirolimus therapy but tended to increase in volume after the therapy was stopped. Some patients with lymphangioleiomyomatosis had improvement in spirometric measurements and gas trapping that persisted after treatment. Suppression of mTOR signaling might constitute an ameliorative treatment in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. (ClinicalTrials.gov number, NCT00457808.)

DIAGNOSTIC IMAGING IN THE EVALUATION OF VASCULAR BIRTHMARKS

This article reviews the role of modern diagnostic imaging in the evaluation of patients with vascular birthmarks. There are two main categories of vascular anomalies: hemangiomas and vascular malformations. The findings on plain radiography, sonography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, and the appropriate sequence of investigation for the different vascular anomalies are discussed.

MR imaging insights into skeletal maturation: what is normal?

Skeletal growth and maturation in children is a dynamic process that can be documented with magnetic resonance (MR) imaging. There are predictable normal developmental changes that must be differentiated from pathologic processes. This review discusses the histologic structure and MR imaging appearance of normal development-related changes of the musculoskeletal system in children, including those that may be mistaken for abnormalities.

Physeal widening in the knee due to stress injury in child athletes.

OBJECTIVE The objective of our study was to describe the MRI appearance of and possible mechanism responsible for physeal widening in the knees of high-level child athletes. CONCLUSION Widened physes in the knees of skeletally immature child athletes have MR signal characteristics similar to the normal physis but likely are a sign of stress injury. These children should cease the offending sport and rest the knee to allow rapid healing.

Severe scrotal pain in boys with Henoch-Schönlein purpura: incidence and sonography

Background. Henoch-Schönlein purpura (HSP) is a systemic vasculitis with multiorgan involvement. The scrotal involvement and its sonographic appearance are less well recognized than that of the kidneys and abdomen, and the reported incidence is varied.¶Objective. To review the incidence of significant scrotal involvement in boys with HSP and its sonographic characteristics.¶Materials and methods. Thirteen boys (ages 4–11 years) out of 87 boys diagnosed with HSP, over a 15-year period had significant scrotal complaints. Seven underwent sonographic evaluation to define the extent of scrotal involvement and because testicular torsion was being considered.¶Results. Scrotal involvement producing significant pain occurred in 15 % of boys with HSP. The majority of boys had the diagnosis of HSP established before developing scrotal complaints. Sonographic findings consistently included an enlarged, rounded epididymis, thickened scrotal skin, and a hydrocele. The testes themselves were usually sonographically normal.¶Conclusions. Scrotal involvement in boys with HSP is not uncommon. The sonographic findings in the scrotum are sufficiently characteristic to allow distinction from torsion in most cases.

Congenital absence of the portal vein: Case report and MR demonstration

Congenital absence of the portal vein (CAPV) is a rare anomaly that results from aberrant venous development in early embryonic life. The intestinal and splenic venous drainage bypasses the liver and drains directly into the inferior vena cava (IVC), the left renal vein, or the left hepatic vein. We describe a case where prenatal ultrasonography demonstrated an unusual C-shaped vessel between the umbilical vein and a dilated IVC, and failed to show a portal vein. Ultrasonography and magnetic resonance imaging and magnetic resonance angiography at 4 months of age again found no portal vein. The superior mesenteric vein drained into the left renal vein.

Accuracy of MR imaging for detecting epiphyseal extension of osteosarcoma

Background. Too few patients are receiving epiphyseal-sparing limb salvage procedures for osteosarcoma. Objective. To determine how magnetic resonance (MR) imaging can best predict the epiphyseal extension of osteosarcoma. Materials and methods. Forty children underwent complete pretreatment static and dynamic contrast-enhanced MR imaging (DEMRI). Static MR images [T1-weighted and short tau inversion recovery (STIR)] of the epiphyses were read in three ways: (1) for suspicion of any abnormality (tumor or edema), (2) for suspicion of tumor, excluding suspected edema, and (3) validating the second method by using a scale to rate the likelihood of tumor. Presentation imaging was compared to histopathologic findings after chemotherapy and resection. The receiver operating characteristic (ROC) method was used to analyze the scaled ratings of static MR and DEMRI values. Results. At delayed resection, 20 of 40 children with osteosarcoma had confirmed epiphyseal tumor; however, 32 epiphyses were abnormal on STIR and 28 abnormal on T1. Differentiating suspected tumor from edema increased the accuracy to an Az (area under the ROC curve) of 0.94 for both T1-weighted and STIR static sequences. T1-weighted MR had better specificity and STIR better sensitivity at any given rating. DEMRI was slightly less accurate (Az = 0.90). Conclusion. Static MR imaging most accurately detected epiphyseal extension of osteosarcoma when readers distinguished suspected tumor from edematous or normal tissue.

MR imaging of soft tissue tumors and tumor-like lesions

The evaluation of a soft tissue mass in a child should proceed with a differential diagnosis in mind, based on the clinical history, age of the child, and location of the abnormality. Small, superficial masses can be initially evaluated with sonography. More extensive or deep lesions usually require cross-sectional imaging. With the exception of myositis ossificans, magnetic resonance (MR) imaging has largely replaced the use of computed tomography. MR imaging is used to delineate the extent of a lesion, to evaluate response to therapy, and to monitor postoperative complications. There is great overlap in the MR imaging characteristics of benign and malignant lesions, making tissue sampling imperative for diagnosis.

MRI Appearance of Chronic Stress Injury of the Iliac Crest Apophysis in Adolescent Athletes

OBJECTIVE The objective of our study was to describe the MRI appearance of chronic repetitive stress injury of the iliac crest apophysis in adolescent athletes. CONCLUSION Increased signal intensity on water-sensitive sequences and mild widening of the physis, often with adjacent bone marrow and muscle edema, are characteristic of chronic stress injury of the iliac apophysis in adolescent athletes who may present with hip, pelvic, or back pain.

Quantitative assessment of the T2 relaxation time of the gluteus muscles in children with Duchenne muscular dystrophy: a comparative study before and after steroid treatment.

Objective To determine the feasibility of using T2 mapping as a quantitative method to longitudinally follow the disease activity in children with Duchenne muscular dystrophy (DMD) who are treated with steroids. Materials and Methods Eleven boys with DMD (age range: 5-14 years) underwent evaluation with the clinical functional score (CFS), and conventional pelvic MRI and T2 mapping before and during steroid therapy. The gluteus muscle inflammation and fatty infiltration were evaluated on conventional MRI. The histograms and mean T2 relaxation times were obtained from the T2 maps. The CFS, the conventional MRI findings and the T2 values were compared before and during steroid therapy. Results None of the patients showed interval change of their CFSs. On conventional MRI, none of the images showed muscle inflammation. During steroid treatment, two boys showed increased fatty infiltration on conventional MRI, and both had an increase of the mean T2 relaxation time (p < 0.05). The remaining nine boys had no increase in fatty infiltration. Of these, three showed an increased mean T2 relaxation time (p < 0.05), two showed no change and four showed a decreased mean T2 relaxation time (p < 0.05). Conclusion T2 mapping is a feasible technique to evaluate the longitudinal muscle changes in those children who receive steroid therapy for DMD. The differences of the mean T2 relaxation time may reflect alterations in disease activity, and even when the conventional MRI and CFS remain stable.