Replacement Therapy with Imiglucerase Improves Magnetic Resonance Imaging (MRI) Abnormalities in Almost Half Patients with Non-Neuronopathic Form of Gaucher Disease After Twelve Months of Therapy: Results of a Semi-Quantitative MRI Method.

Abstract 2132

Gaucher disease (GD) is a lysosomal storage disease characterized by a genetic disruption in the metabolic breakdown of glucocerebroside caused by a lack of the enzyme beta-glucocerebrosidase. Non-neuronopathic GD form is accompanied by bony complications including osteoporosis, osteonecrosis, lytic lesions, pathological fractures and Erlenmeyer flask deformity. MRI is considered as the most sensitive imaging procedure for assessing skeletal involvement in GD patients. To-date, enzyme replacement therapy with imiglucerase is the standard of care for the treatment of patients with non-neuronopathic GD. Although this treatment has been used for many years, there is limited information for the effect of imiglucerase on bone deformities and MRI findings of GD patients.

To address this issue, we studied 27 adult patients (15M/12F, median age 44.5 years) with non-neuronopathic GD who received replacement therapy with imiglucerase for at least one year. Bisphosphonates were not given in any patient during the study period. MRI of the femoral bones was performed in all patients before the initiation of replacement therapy and 12 months post-imiglucerase treatment. MRI of the femoral bones was also performed in 27, gender and age-matched healthy individuals, who served as controls. We implemented T1-weighted spin echo (T1W) sequences, proton density sequences with fat suppression (PDFS) to further evaluate the detected changes on T1W sequence and short time inversion recovery (STIR) sequences for the evaluation of disease activity. We also performed a thorough comparison of T1W and PDFS images targeting in the detection of the remodeling process of the affected bone. In all patients we evaluated bone infiltration on T1W images in the affected areas as opposed with those of healthy regions and in conjunction with measurements taken from subcutaneous fat of both thighs of the same patients. We followed exactly the same process throughout the whole reevaluation we performed one year after the initiation of replacement therapy with imiglucerase.

The rate of subcutaneous fat of both healthy and affected individuals was fluctuated from 400 up to 880 pixels (GE manufacturer) and those of bony fat tissue from 280 to 340 pixels. On the contrary, the affected values ranged from 80–130 pixels. In order to reduce the possibility of false positive and false negative values we combined all the region of interest (ROI) measurements with the degree of infiltration detected on T1W images. Then, we combined the above MRI findings and introduced the following classification: stage I: ROI 1/2 of normal values and bone infiltration up to 30%; stage II: ROI 1/3 of normal values and bone infiltration from 30 to 60%; stage III: ROI 1/4 of normal values and bone infiltration from 60% to 80% and stage IV: detection of epiphyseal infiltration, osteonecrosis and deformity regardless of the ROI's values. Nevertheless in all patients the ROIs fluctuated from 80–130 pixels.

Before the initiation of replacement therapy, 12 (46%) patients had bone pain, while 3 patients had restrictions in free movement and 2 patients experienced difficulty in walking at the time of study initiation. The majority of the patients (91%) had elevated chitotriosidase levels (median: 1647 nmol/ml/hr, range: 147–18880 nmol/ml/hr) indicating active disease, while 25% of the patients had abnormally high levels of acid phosphatase. All but one patient had abnormal MRI findings: 3 (11%) had stage I MRI abnormalities, 18 (66%) had stage II, 3 (11%) stage III and 2 (7%) had stage IV abnormalities in MRI. Twelve months post-imiglucerase therapy, all patients had reduction in pain and improvement in physical activity. Regarding MRI data, 7 (26%) of patients remained stable (had the same MRI stage), 14 (52%) showed an improvement in MRI stage (at least one stage down in our staging system), while 6 (22%) patients had a deterioration in MRI findings on femoral bones.

Our data suggest that imiglucerase, after one year of therapy, improves symptoms in all patients with bony complications due to non-neuronopathic GD and improves MRI findings in almost half of them. The semi-quantitative MRI method that we used is relatively easy to be performed compared to other available methods for GD and would be useful for the evaluation and follow-up of bone marrow involvement in patients with non-neuronopathic GD.