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Skeletal complications of type I gaucher disease: The magnetic resonance features
ClinicalRadiology (1990) 41, 244-247
Skeletal Complications of Type I Gaucher Disease" The Magnetic Resonance Features B. J. C R E M I N * , H. D A V E Y * and J. G O L D B L A T T t . ~
*Paediatric Radiology, Red Cross Children's Hospital, University of Cape Town, South Africa and tDepartment of Human Genetics and Inherited Skeletal Disorders, University of Cape Town Medical School, Cape Town, South Africa 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.
There are three phenotypic forms of Gaucher disease. The common form Type I, spares the central nervous system but progressively involves the visceral and osseous systems. Types II and IiI are much rarer childhood forms with neurological manifestations. Type I Gaucher disease is an autosomal recessively inherited metabolic storage disorder resulting from a deficiency of the lysosomal enzyme glucocerebrosidase (Brady et al., 1965). The undegraded glycosphingolipid accumulates specifically in cells of the monocyte-macrophage system producing hepatosplenomegaly and skeletal complications consequent on bone marrow infiltration. Bone problems occurred in 80% of patients (Beighton et al., 1982; Goldblatt and Beighton, 1979) and are responsible for significant pain and disability. Clinical and radiographic assessment of disease severity is inadequate unless the disease is advanced (Myers et al., 1975). Nuclear medicine studies with 99Tcmsulphur colloid will show increased uptake in the early stages of marrow expansion (Cheng and Holman, 1978; H e r m a n n et al., 1986; Israel et al., 1986). This will decrease with bone infarction and necrosis from decreased blood flow. Better results are obtained by a combined computed tomography (CT) and scintigraphic approach (Hermann et al., 1986). M R I currently offers the best evaluation of bone marrow involvement (Lanir et al., 1986; Rosenthal et al., 1986).
imaging which might have reduced partial volume effects. D a t a was collected on a 256 x 256 matrix interpolated on to 512 x 512 for display. Spin echo pulse sequences were used exclusively and are characterised below by their repetition time (TR) and time to echo (TE) in milliseconds. T1 weighted images were obtained using a T R 500 ms and TE of 30 ms, and T2 weighted images were acquired using a T R of 1700 ms and double echo sequence with TEs of 30 and 100 ms. Image slice widths were 5 or 6 mm and the images made in the coronal plane were reconstructed on a 256 x 256 matrix. PATIENTS AND RESULTS The six patients in this study had the typical clinical features of Type I Gaucher disease with the diagnosis confirmed by the finding of deficient leucocyte glucocerebrosidase activity and Gaucher cells on histological examination of bone marrow biopsies. Brief clinical descriptions are presented specifically in relation to the region of interest investigated with MRI. CASE R E P O R T S Case 1. A male (I.H.) born in 1934, had Gaucher disease diagnosed following investigations for thrombocytopenia. This necessitated sple-
METHOD The magnetic resonance examinations were performed on a Gyrex 5000 superconducting imager (Elscint) operating at 0.5 Tesla. Initially we were relatively inexperienced in the use of M R I . We lacked a suitable coil for the limbs and did not use techniques such as inclined plane Correspondence to: Dr B. J. Cremin. Present address: Princess Margaret Children's Hospital, Perth, Australia.
Fig. 1 Moderatelyadvanced case. T1 image (TR600 TE30) showing uneven loss or signal intensity in distal femora with modelling deformity. There is also irregular loss of signal in the distal epiphyses (arrows).
245
MRI OF TYPE I G A U C H E R DISEASE
Fig. 2 - Avascular necrosis. T1 image (TR600 TE30) showing early to intermediate avascular necrosis of femora1 capital epiphyses. Bony contour remains normal but there is segmental loss of signal (arrows). Patchy marrow replacement is also evident in pelvic bones.
nectomy at the age of 45 years. Ten years later he had no limb or joint pains and on skeletal survey the only radiological abnormality was moderate Erlenmeyer flask deformities of both lower femora. The MRI appearances of both femora (Fig. 1) showed extensive but incomplete marrow infiltration. Case 2. A female (Z.B.) born in 1958, had Gaucher disease diagnosed at the age of 28 years after investigations for her abdominal distension and splenomegaly. She presented with a low-grade chronic ache in the right hip and passive range of movement of the joint was mildly limited by pain. At this stage the radiographs were normal but the MRI showed changes of avascular necrosis in both femoral capital epiphyses (Fig. 2). Case 3. A male (T.K.) born in 1978 had Gaucher disease diagnosed after investigations for hepatosplenomegaly. He presented with severe pain in the left thigh with associated pyrexia, leucocytosis and a raised erythrocyte sedimentation rate. Radiographs of the femora showed mild periosteal reactions along the medial margins of the shafts, more marked on the left. The MRI during the acute phase showed an inhomogeneous decreased intensity of marrow signals on a T1 weighed image (Fig. 3a) and increased signal intensity on T2 weighted images (Fig. 3b) in both mid femora. Bilateral periosteal elevation was evident with soft tissue swelling on the left. The MRI, repeated 2 weeks later, after all clinical signs had abated on bed-rest and analgesics without antibiotics showed reduction in these features (Fig. 3c). Case 4. A female (S.C.) born in 1960 had Gaucher disease diagnosed at the age of 25 when hepatosplenomegaly was detected at a routine medical examination. She required a splenectomy because of severe pancytopenia due to hypersplenism. Imaging studies w~re performed to determine the effect of splenectomy on the progression of bone changes. Radiographs were unhelpful in this assessment and only showed a minor modelling defect of the lower femora producing a mild Erlenmeyer flask deformity. M R I of the legs before the splenectomy showed mild marrow involvement in lower femora. The study was repeated 15 months after splenecfomy and this showed that the changes had become slightly more extensive. She had experienced no bone or joint symptoms during this period and the radiographs were unchanged. Case 5. A female (N.K.) born in 1969 had Gaucher disease diagnosed at the age of four years following investigations for splenomegaly. She had repeated episodes of bone and joint pain particularly involving the right hip and both lower femoral regions. These attacks were disabling and associated with warmth, redness and swelling of the involved regions. They resolved after approximately 2 weeks bed-rest and analgesia. Radiographs during a remission showed generalised osteopenia, mild modelling deformities of long bones, cortical thinning and endosteat scalloping and marked expansion of the lower femora producing Erlenmeyer flask deformities. MRI (Fig. 4a) of the distal femora showed modelling deformity with mild marrow replacement. Case 6. A female (L.K.) born in 1970 is the sister of Case 5. Gaucher disease was diagnosed during a family study after the condition was confirmed in her sister at 11 years of age. She had a splenectomy and
subsequently experienced recurrent episodes of discomfort in her hips, knees and thighs. The painful attacks were similar to her sister's and also resolved without antibiotic therapy. Compared with Case 5, the radiographs revealed more severe Erlenmeyer flask deformities of the lower femora. The MRI changes (Fig. 4b) were also of greater severity.
DISCUSSION The majority of patients with Type I Gaucher disease have significant morbidity from skeletal involvement ( B e i g h t o n et al., 1982; G o l d b l a t t a n d B e i g h t o n , 1979).
Fig. 3 - (a)
246
CLINICAL RADIOLOGY
(a)
(b)
(b) Fig. 4 - Familial comparison. (a) T1 image (TR600 TE30) showing flask deformity of lower femora and mild reduction in marrow signal intensity in distal femora (arrows). (The impaired quality of this image was due to lack of a suitable coil at the time of the examination.) (b) T1 image (TR600 TE30) showing deformity and more severe marrow involvement in the younger sister. The left femoral shaft shows signals
from patchy marrow remnants (arrows).
(c) Fig. 3 - 'Pseudo-osteomyelitis'. (a) T1 image (TR600 TE30) showing'a diffuse loss of marrow signal in femora. The distal epiphyses are spared. (b) T2 weighted image (TR1700 TE 100)demonstrates increased signal from diaphyses of both femora. Associated periosteal reaction and soft
tissue swellingon medialaspect of left femur is seen (arrows).(c) Partial resolution two weeks later.
MR1 estimates the extent of the bone marrow replacement and the cell infiltrate results in a diffuse loss of marrow signal in both the T 1 and T2 weighted series with marked shortening of T2 values.
In two previous communications, Lanir et al. (1986) examined five patients and found a homogeneous marrow replacement, whilst Rosenthal et al. (1986) examined 24 patients and found the replacement was inhomogeneous. In all our six patients the marrow replacement was distinctly inhomogeneous with streaky marrow remnants remaining. This is exemplified by the appearances seen in the long term follow up o f Case 1. The six patients in this study had skeletal complications that were inadequately demonstrated by conventional radiographs. MRI showed the extent of the bony involvement and complications from disturbed blood flow. MRI showed that the bony epiphyses were relatively spared unless there was extensive marrow involvement. M R I is a sensitive method of detecting avascular necrosis (Powers, 1986) and any localised loss of signal intensity should arouse the suspicion of osteonecrosis (Sartoris and Resnick, 1987). This is well shown in Case 2. It is a particularly disabling complication of Gaucher that occurs in about 50% of affected individuals (Beighton et al., 1982). In the early stages there may be no radiographic changes and the finding of MRI changes in the femoral heads alerts the clinician to impending ischaemic changes.
MRI OF TYPE I GAUCHER DISEASE
Case 3 had a severe episode of bone pain which clinicoradiographically had the features of either pseudoosteomyelitis or a true osteomyelitis. Differentiation of these conditions is important because therapeutic bone drilling during an aseptic crisis may produce chronic intractable bone sinuses (Beighton et al., 1982). The MRI changes detected during the acute attack, which had mostly resolved on the subsequent study two weeks later, supported the diagnosis of pseudo-osteomyelitis. The clinical course with spontaneous resolution without antibiotic therapy confirmed this diagnosis particularly as the changes were bilateral and diaphyseal. Similar changes may occur in T2 images during osteomyelitis (Quinn et aL, 1988; Unger et al., 1987) so MRI on its own cannot differentiate between the two. In both conditions the high T2 weighted signals received from both marrow and adjacent soft tissue appear to represent an increase of fluid content in the structures. There is controversy as to the role of splenectomy in the natural course of the bone infiltrate in Gaucher disease (Beighton et al., 1982). Theoretically, removal of the splenic storehouse of accumulating material should increase the load on the liver and bone marrow. Case 1, apart from Erlenmeyer flask deformities of lower femora, had no clinico-radiographic evidence of increased bone disease 10 years after splenectomy and the MRI only showed moderately severe bone marrow involvement. Case 4, however, demonstrated some increased marrow involvement on a repeat study after a 15 month period. Comparison of the MRI features in the siblings, Cases 5 and 6, does not resolve the issue. The younger sister, Case 6, had a splenectomy 6 years previously and subsequent MRI showed evidence of more severe Gaucher infiltration of her marrow than her older sibling. However, this could also reflect intrafamilial clinical variability and be an expression of genetic heterogenicity. Further studies of the bone marrow are required to see if it is more affected after splenectomy and also to assess the differing degree of affection that may occur in members of the same family.
CONCLUSION Magnetic resonance imaging has important applications for the study, follow-up and management of patients with Type I Gaucher disease. MRI has been shown to be a particularly sensitive and helpful modality in the following situations.
247
1 The early ascertainment of avascular necrosis, especially of femoral heads. 2 The assessment of bone crises in the long bones. The possibility of a bone infection needs clinical evaluation. 3 The long-term monitoring of marrow infiltration to assess the role of therapeutic interventions in the natural course of the disorder. Acknowledgements. This research was supported by grants from the South African Medical Research Council, the Mauerberger Foundation, the Harry Crossley Foundation and the University of Cape Town Staff Research Fund.
REFERENCES Beighton P, Goldblatt J & Sacks S (1982). Bone involvement in Gaucher disease. In: Gaucher Disease: A Century of Delineation and Research. pp-103 107. Alan R Liss Inc, New York. Brady RO, Kanfer, JN & Shapiro D (1965). Metabolism of glucocerebrosides II. Evidence of an enzymatic deficiency in Gaucher's disease. Biochemical and Biophysical Research Communications, 18, 221-225. Cheng TH & Holman BL (1978). Radionuclide assessment of Gaucher's disease. Journal of Nuclear Medicine, 19, 1333-1336. Goldblatt J & Beighton P (1979). Gaucher Disease in South Africa. Journal of Medical Genetics, 16, 302-305. Hermann G, Goldblatt J, Levy RN, Goldsmith SJ, Desnick RJ & Gr'abowski GA (1986). Gauchers disease Type I: Assessment of bone involvement by CT and scintigraphy. American Journal of Roentgenology, 147, 943-948. Israel O, Jerushalmi J & Front D (1986). Scintigraphic findings in Gaucher's disease. Journal of Nuclear Medicine, 27, 1557 1563. Lanir A, Hadar H, Cohen I, Tal Y, Benmair J, Schreiber R & Clouse ME (1986). Gaucher disease: Assessment with MR Imaging. Radiology, 161, 239-244. Myers HS, Cremin BJ, Beighton P & Sacks S (1975). Chronic Gaucher's disease: radiological findings in 17 South Africa cases. British Journal of Radiology, 48, 465-469. Powers JA (1986). Magnetic resonance imaging in marrow disease. Clinical Orthopedics & Related Research, 206, 79-85. Quinn SF, Murray W, Clark RA & Chochran C (1988). MR imaging of chronic osteomyelitis. Journal of Computer Assisted Tomography, 12, 113-117. Rosenthal DI, Scott JA, Barraner J, Mankin H J, Saini S, Brady T J, Osier LK & Doppelt S (1986). Evaluation of Gaucher disease using magnetic resonance imaging. Journal of Bone & Joint Surgery, 68-A, 802 808. Sartoris DJ & Resnick D (1987). MRI imaging of the musculoskeletal system: current and future status. American Journal of Roentgenology, 149, 457-467. Unger E, Moldofsky P, Gatenby R, Hartz W & Broder G (1987). Diagnosis of osteomyelitis by MR imaging. American Journal of Roentgenology, 150, 605-610
Skeletal Complications of Type I Gaucher Disease" The Magnetic Resonance Features B. J. C R E M I N * , H. D A V E Y * and J. G O L D B L A T T t . ~
*Paediatric Radiology, Red Cross Children's Hospital, University of Cape Town, South Africa and tDepartment of Human Genetics and Inherited Skeletal Disorders, University of Cape Town Medical School, Cape Town, South Africa 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.
There are three phenotypic forms of Gaucher disease. The common form Type I, spares the central nervous system but progressively involves the visceral and osseous systems. Types II and IiI are much rarer childhood forms with neurological manifestations. Type I Gaucher disease is an autosomal recessively inherited metabolic storage disorder resulting from a deficiency of the lysosomal enzyme glucocerebrosidase (Brady et al., 1965). The undegraded glycosphingolipid accumulates specifically in cells of the monocyte-macrophage system producing hepatosplenomegaly and skeletal complications consequent on bone marrow infiltration. Bone problems occurred in 80% of patients (Beighton et al., 1982; Goldblatt and Beighton, 1979) and are responsible for significant pain and disability. Clinical and radiographic assessment of disease severity is inadequate unless the disease is advanced (Myers et al., 1975). Nuclear medicine studies with 99Tcmsulphur colloid will show increased uptake in the early stages of marrow expansion (Cheng and Holman, 1978; H e r m a n n et al., 1986; Israel et al., 1986). This will decrease with bone infarction and necrosis from decreased blood flow. Better results are obtained by a combined computed tomography (CT) and scintigraphic approach (Hermann et al., 1986). M R I currently offers the best evaluation of bone marrow involvement (Lanir et al., 1986; Rosenthal et al., 1986).
imaging which might have reduced partial volume effects. D a t a was collected on a 256 x 256 matrix interpolated on to 512 x 512 for display. Spin echo pulse sequences were used exclusively and are characterised below by their repetition time (TR) and time to echo (TE) in milliseconds. T1 weighted images were obtained using a T R 500 ms and TE of 30 ms, and T2 weighted images were acquired using a T R of 1700 ms and double echo sequence with TEs of 30 and 100 ms. Image slice widths were 5 or 6 mm and the images made in the coronal plane were reconstructed on a 256 x 256 matrix. PATIENTS AND RESULTS The six patients in this study had the typical clinical features of Type I Gaucher disease with the diagnosis confirmed by the finding of deficient leucocyte glucocerebrosidase activity and Gaucher cells on histological examination of bone marrow biopsies. Brief clinical descriptions are presented specifically in relation to the region of interest investigated with MRI. CASE R E P O R T S Case 1. A male (I.H.) born in 1934, had Gaucher disease diagnosed following investigations for thrombocytopenia. This necessitated sple-
METHOD The magnetic resonance examinations were performed on a Gyrex 5000 superconducting imager (Elscint) operating at 0.5 Tesla. Initially we were relatively inexperienced in the use of M R I . We lacked a suitable coil for the limbs and did not use techniques such as inclined plane Correspondence to: Dr B. J. Cremin. Present address: Princess Margaret Children's Hospital, Perth, Australia.
Fig. 1 Moderatelyadvanced case. T1 image (TR600 TE30) showing uneven loss or signal intensity in distal femora with modelling deformity. There is also irregular loss of signal in the distal epiphyses (arrows).
245
MRI OF TYPE I G A U C H E R DISEASE
Fig. 2 - Avascular necrosis. T1 image (TR600 TE30) showing early to intermediate avascular necrosis of femora1 capital epiphyses. Bony contour remains normal but there is segmental loss of signal (arrows). Patchy marrow replacement is also evident in pelvic bones.
nectomy at the age of 45 years. Ten years later he had no limb or joint pains and on skeletal survey the only radiological abnormality was moderate Erlenmeyer flask deformities of both lower femora. The MRI appearances of both femora (Fig. 1) showed extensive but incomplete marrow infiltration. Case 2. A female (Z.B.) born in 1958, had Gaucher disease diagnosed at the age of 28 years after investigations for her abdominal distension and splenomegaly. She presented with a low-grade chronic ache in the right hip and passive range of movement of the joint was mildly limited by pain. At this stage the radiographs were normal but the MRI showed changes of avascular necrosis in both femoral capital epiphyses (Fig. 2). Case 3. A male (T.K.) born in 1978 had Gaucher disease diagnosed after investigations for hepatosplenomegaly. He presented with severe pain in the left thigh with associated pyrexia, leucocytosis and a raised erythrocyte sedimentation rate. Radiographs of the femora showed mild periosteal reactions along the medial margins of the shafts, more marked on the left. The MRI during the acute phase showed an inhomogeneous decreased intensity of marrow signals on a T1 weighed image (Fig. 3a) and increased signal intensity on T2 weighted images (Fig. 3b) in both mid femora. Bilateral periosteal elevation was evident with soft tissue swelling on the left. The MRI, repeated 2 weeks later, after all clinical signs had abated on bed-rest and analgesics without antibiotics showed reduction in these features (Fig. 3c). Case 4. A female (S.C.) born in 1960 had Gaucher disease diagnosed at the age of 25 when hepatosplenomegaly was detected at a routine medical examination. She required a splenectomy because of severe pancytopenia due to hypersplenism. Imaging studies w~re performed to determine the effect of splenectomy on the progression of bone changes. Radiographs were unhelpful in this assessment and only showed a minor modelling defect of the lower femora producing a mild Erlenmeyer flask deformity. M R I of the legs before the splenectomy showed mild marrow involvement in lower femora. The study was repeated 15 months after splenecfomy and this showed that the changes had become slightly more extensive. She had experienced no bone or joint symptoms during this period and the radiographs were unchanged. Case 5. A female (N.K.) born in 1969 had Gaucher disease diagnosed at the age of four years following investigations for splenomegaly. She had repeated episodes of bone and joint pain particularly involving the right hip and both lower femoral regions. These attacks were disabling and associated with warmth, redness and swelling of the involved regions. They resolved after approximately 2 weeks bed-rest and analgesia. Radiographs during a remission showed generalised osteopenia, mild modelling deformities of long bones, cortical thinning and endosteat scalloping and marked expansion of the lower femora producing Erlenmeyer flask deformities. MRI (Fig. 4a) of the distal femora showed modelling deformity with mild marrow replacement. Case 6. A female (L.K.) born in 1970 is the sister of Case 5. Gaucher disease was diagnosed during a family study after the condition was confirmed in her sister at 11 years of age. She had a splenectomy and
subsequently experienced recurrent episodes of discomfort in her hips, knees and thighs. The painful attacks were similar to her sister's and also resolved without antibiotic therapy. Compared with Case 5, the radiographs revealed more severe Erlenmeyer flask deformities of the lower femora. The MRI changes (Fig. 4b) were also of greater severity.
DISCUSSION The majority of patients with Type I Gaucher disease have significant morbidity from skeletal involvement ( B e i g h t o n et al., 1982; G o l d b l a t t a n d B e i g h t o n , 1979).
Fig. 3 - (a)
246
CLINICAL RADIOLOGY
(a)
(b)
(b) Fig. 4 - Familial comparison. (a) T1 image (TR600 TE30) showing flask deformity of lower femora and mild reduction in marrow signal intensity in distal femora (arrows). (The impaired quality of this image was due to lack of a suitable coil at the time of the examination.) (b) T1 image (TR600 TE30) showing deformity and more severe marrow involvement in the younger sister. The left femoral shaft shows signals
from patchy marrow remnants (arrows).
(c) Fig. 3 - 'Pseudo-osteomyelitis'. (a) T1 image (TR600 TE30) showing'a diffuse loss of marrow signal in femora. The distal epiphyses are spared. (b) T2 weighted image (TR1700 TE 100)demonstrates increased signal from diaphyses of both femora. Associated periosteal reaction and soft
tissue swellingon medialaspect of left femur is seen (arrows).(c) Partial resolution two weeks later.
MR1 estimates the extent of the bone marrow replacement and the cell infiltrate results in a diffuse loss of marrow signal in both the T 1 and T2 weighted series with marked shortening of T2 values.
In two previous communications, Lanir et al. (1986) examined five patients and found a homogeneous marrow replacement, whilst Rosenthal et al. (1986) examined 24 patients and found the replacement was inhomogeneous. In all our six patients the marrow replacement was distinctly inhomogeneous with streaky marrow remnants remaining. This is exemplified by the appearances seen in the long term follow up o f Case 1. The six patients in this study had skeletal complications that were inadequately demonstrated by conventional radiographs. MRI showed the extent of the bony involvement and complications from disturbed blood flow. MRI showed that the bony epiphyses were relatively spared unless there was extensive marrow involvement. M R I is a sensitive method of detecting avascular necrosis (Powers, 1986) and any localised loss of signal intensity should arouse the suspicion of osteonecrosis (Sartoris and Resnick, 1987). This is well shown in Case 2. It is a particularly disabling complication of Gaucher that occurs in about 50% of affected individuals (Beighton et al., 1982). In the early stages there may be no radiographic changes and the finding of MRI changes in the femoral heads alerts the clinician to impending ischaemic changes.
MRI OF TYPE I GAUCHER DISEASE
Case 3 had a severe episode of bone pain which clinicoradiographically had the features of either pseudoosteomyelitis or a true osteomyelitis. Differentiation of these conditions is important because therapeutic bone drilling during an aseptic crisis may produce chronic intractable bone sinuses (Beighton et al., 1982). The MRI changes detected during the acute attack, which had mostly resolved on the subsequent study two weeks later, supported the diagnosis of pseudo-osteomyelitis. The clinical course with spontaneous resolution without antibiotic therapy confirmed this diagnosis particularly as the changes were bilateral and diaphyseal. Similar changes may occur in T2 images during osteomyelitis (Quinn et aL, 1988; Unger et al., 1987) so MRI on its own cannot differentiate between the two. In both conditions the high T2 weighted signals received from both marrow and adjacent soft tissue appear to represent an increase of fluid content in the structures. There is controversy as to the role of splenectomy in the natural course of the bone infiltrate in Gaucher disease (Beighton et al., 1982). Theoretically, removal of the splenic storehouse of accumulating material should increase the load on the liver and bone marrow. Case 1, apart from Erlenmeyer flask deformities of lower femora, had no clinico-radiographic evidence of increased bone disease 10 years after splenectomy and the MRI only showed moderately severe bone marrow involvement. Case 4, however, demonstrated some increased marrow involvement on a repeat study after a 15 month period. Comparison of the MRI features in the siblings, Cases 5 and 6, does not resolve the issue. The younger sister, Case 6, had a splenectomy 6 years previously and subsequent MRI showed evidence of more severe Gaucher infiltration of her marrow than her older sibling. However, this could also reflect intrafamilial clinical variability and be an expression of genetic heterogenicity. Further studies of the bone marrow are required to see if it is more affected after splenectomy and also to assess the differing degree of affection that may occur in members of the same family.
CONCLUSION Magnetic resonance imaging has important applications for the study, follow-up and management of patients with Type I Gaucher disease. MRI has been shown to be a particularly sensitive and helpful modality in the following situations.
247
1 The early ascertainment of avascular necrosis, especially of femoral heads. 2 The assessment of bone crises in the long bones. The possibility of a bone infection needs clinical evaluation. 3 The long-term monitoring of marrow infiltration to assess the role of therapeutic interventions in the natural course of the disorder. Acknowledgements. This research was supported by grants from the South African Medical Research Council, the Mauerberger Foundation, the Harry Crossley Foundation and the University of Cape Town Staff Research Fund.
REFERENCES Beighton P, Goldblatt J & Sacks S (1982). Bone involvement in Gaucher disease. In: Gaucher Disease: A Century of Delineation and Research. pp-103 107. Alan R Liss Inc, New York. Brady RO, Kanfer, JN & Shapiro D (1965). Metabolism of glucocerebrosides II. Evidence of an enzymatic deficiency in Gaucher's disease. Biochemical and Biophysical Research Communications, 18, 221-225. Cheng TH & Holman BL (1978). Radionuclide assessment of Gaucher's disease. Journal of Nuclear Medicine, 19, 1333-1336. Goldblatt J & Beighton P (1979). Gaucher Disease in South Africa. Journal of Medical Genetics, 16, 302-305. Hermann G, Goldblatt J, Levy RN, Goldsmith SJ, Desnick RJ & Gr'abowski GA (1986). Gauchers disease Type I: Assessment of bone involvement by CT and scintigraphy. American Journal of Roentgenology, 147, 943-948. Israel O, Jerushalmi J & Front D (1986). Scintigraphic findings in Gaucher's disease. Journal of Nuclear Medicine, 27, 1557 1563. Lanir A, Hadar H, Cohen I, Tal Y, Benmair J, Schreiber R & Clouse ME (1986). Gaucher disease: Assessment with MR Imaging. Radiology, 161, 239-244. Myers HS, Cremin BJ, Beighton P & Sacks S (1975). Chronic Gaucher's disease: radiological findings in 17 South Africa cases. British Journal of Radiology, 48, 465-469. Powers JA (1986). Magnetic resonance imaging in marrow disease. Clinical Orthopedics & Related Research, 206, 79-85. Quinn SF, Murray W, Clark RA & Chochran C (1988). MR imaging of chronic osteomyelitis. Journal of Computer Assisted Tomography, 12, 113-117. Rosenthal DI, Scott JA, Barraner J, Mankin H J, Saini S, Brady T J, Osier LK & Doppelt S (1986). Evaluation of Gaucher disease using magnetic resonance imaging. Journal of Bone & Joint Surgery, 68-A, 802 808. Sartoris DJ & Resnick D (1987). MRI imaging of the musculoskeletal system: current and future status. American Journal of Roentgenology, 149, 457-467. Unger E, Moldofsky P, Gatenby R, Hartz W & Broder G (1987). Diagnosis of osteomyelitis by MR imaging. American Journal of Roentgenology, 150, 605-610