Skeletal Radio1 (1992) 21:463465

Skeletal Radiology

MRI evaluation of amyloid myopathy J.P. Metzler, M.D. 1, J.L. Fleckenstein, M.D. 1, C.L. White III, M.D. 2, R.G. Hailer, M.D. 3, E.P. Frenkel, M.D. 4, and R.G. Greenlee Jr., M.D. 3 Departments of 1 Radiology, 2 Neuropathology, 3 Neurology, 4 Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, and Department of Neurology, Veterans Affairs Medical Center, Dallas, Texas, USA

Abstract. A m y l o i d m y o p a t h y is a rare c o m p l i c a t i o n of

A m y l o i d o s i s is characterized b y the d e p o s i t i o n o f a m y loid p r o t e i n fibrils w i t h i n v a r i o u s tissues [7]. P r i m a r y amyloidosis includes b o t h i d i o p a t h i c a m y l o i d o s i s a n d that associated with p l a s m a cell dyscrasia such as m u l t i ple m y e l o m a . S e c o n d a r y a m y l o i d o s i s is associated with m a n y c h r o n i c diseases. We r e p o r t the m a g n e t i c reson a n c e i m a g i n g ( M R I ) f i n d i n g s in two p a t i e n t s with prim a r y a m y l o i d o s i s w h o p r e s e n t e d with clinical findings of a m y l o i d " p s e u d o h y p e r t r o p h y " o f the extremities, a feature characteristic o f a l n y l o i d m y o p a t h y [10].

culty standing from a kneeling position. She also complained of a tingling sensation in her hands when sleeping on her side, hoarseness, and dysphagia. A deltoid muscle biopsy performed at another institution 7 years previously reportedly showed mild, nonspecific abnormalities. She was treated with glucocorticoids for a presumptive diagnosis of polymyositis. Symptoms initially improved but eventually recurred. A second muscle biopsy performed at an outside institution 4 years later was also interpreted as being nonspecific. Results of Congo red staining were not reported for either biopsy specimen. The remarkable finding on physical examination at our institution was a hard, wood-like texture upon palpation of the trunk and extremities. Mild macroglossia was evident. The patient had proximal weakness in her upper and lower extremities. Sensation was intact, reflexes were brisk but symmetric, and her muscles resisted passive movement. MRI examination was performed at 0.35 T on a Toshiba America MRI, Inc. (South San Francisco) device. Images were obtained at the mid-thigh level using spin echo (500/30, 2000/30,60) as well as short z (TI) inversion recovery (STIR) (1500/30/100) technique. Relaxation times were calculated from thigh images as previously described [5]. The vastus lateralis had a T1 time of 885 ms and a T2 time of 43 ms while the rectus femoris had a T1 of 850 ms and T2 of 30 ms (Fig. 1). These contrast with normal muscle relaxation times using the same sevice (T1 = 590 -t-49 ms and T2 = 28 + 1 ms) [2]. Open biopsy of the left quadriceps showed amyloid deposits within the walls of the perimysial and endomysiat blood vessels and small amounts in the perineurium of intramuscular nerve twigs (Fig. 2). Serum protein electrophoresis demonstrated hypogammaglobulinemiabut no monoclonal abnormality. Bone marrow aspiration and biopsy relealed increased numbers of plasma cells, some of which were in small sheets and clusters. The patient was treated with cyclic courses of melphalan and prednisone for a malignant plasma cell dyscrasia. Although her symptoms did not regress, over a period of 2.5 years there was little progression.

Case reports

Case 2

Case 1

A 45-year-old woman was referred with a 3-4 year history of muscle stiffness and fatigability. Inability to completely dorsiflex her left foot caused a gait disturbance. On examination, extremities were diffusely enlarged and hard to palpation. Range of motion of all extremities was decreased but sensation was intact. Macroglossia was absent. Past history included surgery for bilateral carpal tunnel syndrome 8 years previously. A quadriceps muscle biopsy at another institution 8 months prior to referral was reportedly

p r i m a r y a m y l o i d o s i s. The m a g n e t i c r e s o n a n c e i m a g i n g ( M R I ) features of two p a t i e n t s with a m y l o i d m y o p a t h y were studied. Slight p r o l o n g a t i o n of muscle T1 a n d T2 r e l a x a t i o n times was e v i d e n t b u t the striking a b n o r m a l i t y was m a r k e d r e t i c u l a t i o n o f the s u b c u t a n e o u s fat. T h e clinical findings o f i n d u r a t e d extremities far exceeds the m i n i m a l signal i n t e n s i t y a l t e r a t i o n seen i n the muscles. The M R a p p e a r a n c e o f a m y l o i d m y o p a t h y differs f r o m t h a t o f other n e u r o m u s c u l a r c o n d i t i o n s in the m i n i m a l changes f o u n d in muscle, b u t the striking a b n o r m a l i t y seen in s u b c u t a n e o u s fat m a k e s it distinct f r o m m a n y neuromuscular conditions.

Key words: M a g n e t i c r e s o n a n c e i m a g i n g - A m y l o i d o s i s - Myopathy - Amyloid pseudohypertrophy - Abnormal s u b c u t a n e o u s fat

A 57-year-old woman presented with an 8-year history of progressive muscle weakness and stiffness that initially manifested as diffiCorrespondence to: James L. Fleckenstein, M.D., Algur H. Meadows Diagnostic Imaging Center, 5171 Harry Hines Boulevard, Dallas, TX 75235-8896, USA

9 1992 International Skeletal Society

464

J.P. Metzler et al. : MRI of amyloid myopathy

Fig. 1 a-d. Axial MRI at the mid-thigh level in case 1 in the area of induration. Minimally increased signal intensity of the vastus muscles (v) compared to the rectus femoris muscle (r) is visible on 2000/30 (a), 2000/60 (b) and STIR (d). A coarse reticular pattern of decreased signal intensity within the subcutaneous tissue is visible, particularly on the 500/ 30 sequence (e, arrow)

Fig. 2. Amorphous deposits of congophilic proteinaceous material are present within the walls of perimysial blood vessels (arrow). These deposits demonstrated green birefringence when viewed with cross-polarizing light and were metachromatic on crystal violet-stained preparations, both characteristic of amyloid. No amyloid is visible inside myofibers. (Congo red, x 375)

Fig. 3. Axial 2000/60 image through thighs in case 2. Note reticular pattern of subcutaneous fat (large arrow). The image fails to demonstrate focal abnormality of muscles but lack of distinct muscle boundaries is striking (for example, between arrowheads) near the site of prior biopsy of left rectus femoris muscle (small arrow)

J.P. Metzler et al. : MRI of amyloid myopathy nonspecific and the diagnosis of polymyositis was entertained. Review of the biopsy specimen demonstrated slight amorphous hyaline thickening of perimysial connective tissue which was subsequently shown by Congo red staining to be amyloid deposits. Evidence of recent denervation and some reinnervation was also shown to be present upon histochemical analysis. MRI was performed with the same device as in case 1 using the same sequences (Fig. 3). Relaxation times were not calculated but the muscles of the thigh showed only minimal subjective signal abnormality. Marked hypointense reticulation of the subcutaneous fat was again evident on all sequences.

Discussion Progressive muscle weakness, stiffness, generalized enlargement o f muscles, and a woody consistency of the limbs are classical clinical findings of a rare manifestattion of primary amyloidosis. This condition has been referred to as " a m y l o i d m y o p a t h y " or " a m y l o i d pseud o h y p e r t r o p h y " . The pattern and extent of amyloid deposition vary but primarily involve interstitial connective tissue and small blood vessels and nerves [10]. The MRI findings in a patient with a focal nasopharyngeal accumulation of amyloid included decreased signal intensity on both T1- and T2-weighted images [3]. M R I of amyloid deposits which were clearly identifiable in bone have also been shown to have decreased signal intensity on Tl-weighted [6, 8] and mildly T2-weighted [6] images. Other reports of abdominal viscera involved with amyloid describe variably altered T1 and T2 relaxation times [1, 9, 11]. However, calculation of relaxation times in abdominal viscera is often difficult and so the significance of these findings is unclear. The only other report o f the M R appearance o f skeletal muscles presumed to be infiltrated with amyloid described a patient with primary amyloidosis who developed ophthalmoplegia [4]. This patient's extraocular muscles were enlarged but the signal intensities were subjectively not altered. This is consistent with our findings as adjustments in photographic settings can make small but significant relaxation time abnormalities manifest as only subtle or nonvisible signal intensity alterations. The M R I appearance of muscles in amyloid myopathy, both in our cases and in the case of ophthalmoplegia is remarkable for the minimal signal intensity alterations. This is in contrast to a wide variety of other myopathies in which the presence o f focal fat and/or edema contribute to a remarkable appearance on M R I [2]. This has practical significance in that amyloidosis does not appear to be justifiably included in the differential diagnosis o f patients whose M R I scans show markedly edematous or fatty changes of muscle. The etiology of the prolonged relaxation times determined in case 1 is unknown. In view of reports of amyloid deposits in bone and nasopharynx being hypointense on T1- and T2-weighted images, the prolonged relaxation times of the infiltrated muscle might not be a direct manifestation of the amyloid itself but could

465 conceivably be a secondary finding [3, 6, 8]. We speculate that denervation, which was suggested histochemically in case 2, might contribute [2]. Another possibility is an increased total water or free water content of the muscles. The paucity of M R I changes in involved muscles prompts speculation that the clinically firm and stiff extremities may not be due to abnormal muscles but rather are due to amyloid deposited in the subcutaneous tissues. This speculation is based on the strikingly reticulated and hypointense appearance o f the subcutaneous fat in both patients on T1- and T2-weighted images. Amyloidosis of the fat is supported by the fact that fat biopsy is a frequent test used to diagnose amyloidosis. Amyloid is deposited in rings around fat cells [12]. In summary, the markedly abnormal physical findings in the soft tissue of patients with amyloid myopathy are out of proportion to the degree of MRI changes in the muscle. A hypointense streaky appearance to the subcutaneous fat may be the only striking visible abnormality. Acknowledgements. We thank Dennis Burns, M.D., for help in coordinating the review of pathology. We also thank Dorothy Gutekunst, Virginia Reed Vaughn, Alison Russell, Joe Reyes and Tommie Hall. This effort was supported by the Nasher Family Cancer Research Program.

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