CASE-OF-THE-MONTH Section Editors Robert C. Griggs, MD Rochester, New York Jerry R. Mendell, MD Columbus, Ohio
Robert G. Miller, MD San Francisco, Caitforflia
A 29-year-old female with type I diabetes mellitus developed pain, focal tenderness, and swelling in the posterior left thigh. Subsequent evaluation included a muscle biopsy, which revealed large confluent areas of necrosis and edema, compatible with a diagnosis of diabetic muscle infarction (DMI). Diabetic muscle infarction (DMI) is an unusual neuromuscular complication of diabetes mellitus. DMI begins with the acute onset of focal pain and swelling in the thigh. The anterior compartment (quadriceps muscle group) or posterior compartment (hamstring muscle group) are most frequently involved. The focal region of muscle damage can be noninvasively viewed by magnetic resonance imaging and radionuclide scans. Muscle biopsy demonstrates large confluent regions of muscle necrosis and edema. DMI needs to be differentiated from other processes that can cause leg pain in a diabetic patient. Key words: diabetes mellitus muscle infarction MUSCLE & NERVE 15:850-855 1992
CASE=OF=THE=MONTH: PAINFUL THIGH MASS IN A YOUNG WOMAN: DIABETIC MUSCLE INFARCTION RICHARD J. BAROHN, MD, and JOHN T. KISSEL, MD
Most of the neuromuscular complications of diabetes mellitus involve the peripheral nerve. Distal symmetric polyneuropathy, autonomic neuropathy, mononeuropathy, and lumbosacral radioculoplexopathy are all well-recognized complications of diabetes. Diabetic syndromes in which muscle is the primary site of pathology are much less common.1,2.4v8- 10 In this report, the clinical, electrophysiologic, radiologic, and muscle biopsy findings in a typical case of diabetic muscle infarction (DMI) in the thigh will be presented and several controversial aspects of the diagnosis, pathogenesis, and management of this condition will be discussed (a brief report of this case has previously been published in a different format).’ CASE REPORT
A 29-year-old female with type 1 diabetes mellitus since age 9, and a history of nephropathy and retinopathy, developed sudden
Clinical History.
From the Department of Medicine, Division of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr. Barohn); and Department of Neurology, Ohio State University, Columbus, Ohio (Dr. Kissel) Address reprint requests to Richard J. Barohn, MD, Department of Medicine (Neurology), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284. Accepted for publication September 5, 1991
CCC 0148-639X/92/070850-06 $04 00 Q 1992 John Wiley
850
8, Sons, Inc.
Diabetic Muscle Infarction
pain, focal tenderness, and swelling in the posterior aspect for her left thigh. There was no associated skin erythema and no fever. The pain did not begin during physical activity, and there was no history of trauma. The patient denied numbness, paresthesias, or back pain. The symptoms worsened over the next 2 weeks and the thigh swelling extended to the knee. An arthrocentesis was normal. She was placed on a 2-week course of antibiotics, but the symptoms did not improve. Eight weeks after the onset of symptoms, a limited muscle biopsy of the biceps fenioris was performed adjacent to the painful mass through a 2-cm incision. Histologic examination revealed only slight muscle fiber size variability and a few scattered necrotic fibers without inflammatory cells. The thigh pain and swelling seemed to improve slightly over the next several weeks. Twelve weeks after the onset-of the pain, however, she had a sudden recurrence of symptoms with enlargement of the mass, and she became unable to walk without assistance. When the mass and pain persisted, she was admitted to the hospital for a more extensive muscle biopsy, 16 weeks after the initial symptoms began. Physical Examination. onadmission she was afebrile. There was a firm, tender 12 X 10 cm mass in the left posterior-medial thigh. There was no erythema or warmth in the skin overlying the tender region. There was some extension of the
MUSCLE & NERVE
July 1992
edema to the knee. Muscle strength in the proximal left leg, including knee extension, was normal. Knee flexion was difficult to assess because of pain, but there was full antigravity motion with some resistance. Strength in the arms, right leg, and distal left leg was normal. There was a mild loss of vibratory sensation in the toes with decreased pinprick and light touch to the ankles bilaterally. Muscle stretch reflexes were normal in the arms, hypoactive at the knees, and absent at the ankles. She had difficulty walking, as minimal pressure on the left leg produced severe pain. Laboratory Evaluation. The white blood count was 8000 cells/mm3 with a normal differential. The erythrocyte sedimentation rate was 119 mm/h prior to the initial biopsy, and remained elevated throughout her course. The fasting blood glucose was 110 mg/dL. Serum creatine kinase was 144 IU/L (normal < 215 IU/L) at the time of the first biopsy, and 126 lU/L just before the second muscle biopsy. Radiologic investigations included a normal venogram without evidence of deep venous thrombosis. A 3-phase technetium-99 monophosphate bone scan (done prior to the first muscle biopsy) showed increased blood flow to the left posterior thigh on the flow images (Fig. l), but
FIGURE 2. Sagittal view of left thigh by TPweighted MRI scan. There is diffuse high signal in the biceps femoris, semimembranosus and semitendinosus muscles while the bone and anterior compartment muscles appear normal.
no increased radionuclide uptake in the bone on delayed static images. Magnetic resonance imaging scans (MRI) of the left thigh were obtained prior to both muscle biopsies. These showed an area of high signal in the posterior comparment muscles (biceps femoris, semimembranosus, semitendinosus) on the T2-weighted images (Fig. 2). The same area had low signal characteristics on the T1weighted image. ELECTRODIAGNOSTIC EXAMINATION
L
FIGURE 1. Technetium-99 monophosphate bone scan; left posterior oblique view. On this flow image, an increased radionuclide collection is seen in the posterior aspect of the left thigh.
Diabetic Muscle Infarction
T h e electrodiagnostic studies were done before the first muscle biopsy (6 weeks after the onset of symptoms). Motor and sensory nerve conduction studies (NCS) were performed using surface electrode recordings and standard methods. Median and ulnar motor and sensory NCS were normal. Peroneal and tibia1 motor NCS and sural NCS had conduction velocities at the lower limit of normal bilaterally; compound motor and sensory action potential amplitudes were slightly reduced in both legs. These NCS findings were interpreted as showing a mild distal symmetric polyneuropathy. Electromyopathy (EMG) was performed using a 50-mm monopolar needle. Fibrillation potentials were graded on a 0 to 4+ system. Insertional activity was increased and 3+ fibrillation potentials were present in the left biceps femoris muscle, in the region where the patient was most tender in
MUSCLE & NERVE
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651
the mid- and distal-posterior thigh. Very few motor unit potentials (MUP) could be recruited in this region, and some areas were devoid of voluntary MUPs. Where MUPs were recruited, they were brief (3 to 5 ms) and of small amplitude (50 to 200 mV), with 50% of the MUPs being polyphasic. The firing rate of early-recruited motor units was less than 10 Hz, and the number of MUPs recruited with a minimal contraction was not increased (i.e., normal recruitment). EMG of the iliacus, gluteus medius, vastus lateralis, gastrocnemius, and anterior tibialis muscles in the left and right lower extremities were normal. HISTOPATHOLOGY
An extensive open muscle biopsy (through a 20-cm incision) was performed on the biceps femoris muscle at the site of maximal swelling and tenderness. The open biopsy revealed large areas of muscle necrosis with a dramatic loss of muscle fibers and extensive endomysial edema (Fig. 3). Scattered necrotic and ghost fibers were present in these confluent areas of fiber loss, as well as occasional regenerating fibers. In several areas, there was infiltration by mononuclear inflammatory cells, both in the endomysial and perimysial spaces, and rarely around blood vessels. There was no necrosis of the blood vessel walls o r obliteration of the lumen. Surrounding the large areas of infarction, the muscle fibers had a more normal-appearing architectural pattern. COURSE
After the second biopsy, the pain and swelling slowly improved, with complete resolution of all symptoms and signs by 6 months. The patient subsequently developed worsening nephropathy and died of diabetic complications 1 year after onset of her thigh symptoms. DISCUSSION
Diabetic muscle infarction in the thigh is an unusual neuromuscular complication of diabetes mellitus. However, it may be more common than previously reco nized. Eleven prior cases have been reported'*f428-10(Table l), and we have observed 2 other young female diabetics with DMI over the past year (unpublished data). The case reported here illustrates most of the typical features of the syndrome. DMI begins with the abru t onset of thigh pain, tenderness, and swelling.Fz24Over a period of days, a firm mass develops. The muscles most frequently involved
852
Diabetic Muscle Infarction
FIGURE 3. (A) Low-power view of biceps femoris muscle biopsy. There is a large central area of muscle fiber loss and endomysial edema bordering on an area of more normal appearing (B)Higher-power field from fibers (hematoxylin and eosin, ~50). the same biopsy showing scattered necrotic and regenerating fibers, marked endomysial edema, and a small collection of inflammatory cells surrounding individual muscle fibers (hematoxylin and eosin, ~ 1 4 0 ) .
are the vastus lateralis, thigh adductors, and biceps femoris. It is not uncommon for the edema to extend to the knee and mimic a joint effusion.' DMI tends to occur in younger, poorly controlled diabetic patients with other end-organ complications (retinopathy, nephropathy, neuropathy). There are no associated systemic symptoms or signs indicative of infection and no skin discoloration suggesting cellulitis or thrombophlebitis. The painful mass persists for weeks, occasionally with exacerbation of symptoms, and then spontaneously resolves over several months. Contralateral involvement of the other thigh, absent in this case, can occur after the initial episode resolves, and
MUSCLE 8, NERVE
July 1992
Table 1. Diabetic muscle infarction: Literature review. Authorlyear Angervall et al. (1965) Banker et
al. (1973)
No. patients
MIF
Age
Muscle
Elevated CK
Biopsy proven
2
M M F F F
52 30 28 50 28
NR NR Yes NR Yes
+ + + +
M F F F F M
54 29 34 34 35 57
BF VUADD VL VL VC, VM IL ADD IL, VL, VM, BF G VL, RF VL, VM, RF VM
2
Levinsohn et a1 (1976)
1
Reich et al. (1985)
2
Chester et al. (1986)
Ratliff (1987)
3* 1
V L = vastus lateralis; VM = vastus medialis; BF - = No
NR No No
No No NR
= biceps fernoris; ADD = adductor; IL = iliacus;
+
Worsening after Bx
Contralateral recurrence
-
No
-
No Yes (4 wk) Yes (10 mo) No
+ + -
No Yes (7 mo) Yes (24 mo) Yes (5 wk) ? No
-
+ + + t
t
t t
-
G = gastrocnemius; NR = not recorded;
+ = yes;
*.Six patients are discussed, but patients I and 2 are also reported in Banker et a/.z and patient 6 is reporfed in Reich et a/.'O Tone of these 3 patients (not specified by the authors) had a needle biopsy and did not worsen, 2 had an open biopsy and did worsen.
has occurred in nearly half of the reported cases weeks to months after the first episode (Table 1). Three of the previously reported cases134died of complications of diabetes within a year after the episode of DMI. The creatine kinase levels (CK) have been normal in most cases in which it has been reported (including our own), a finding that may help distinguish DMI from focal polymyositis. However, exactly when the CKs were obtained in the disease course is unclear for the cases in the literature. In the present case, there was a delay of several weeks from the onset of symptoms to the time the initial CK was obtained. It is possible that an elevated CK would be found more often if obtained within the first several days after the acute muscle infarct (we have observed this in 1 unpublished case). The electrodiagnostic features of DMI have not been discussed in any of the prior reports. Nerve conduction studies in this case revealed a generalized distal symmetric polyneuropathy. Needle EMG (performed 6 weeks after the acute infarct), demonstrated fibrillation potentials in the involved muscles, with a loss of voluntary MUPs in the most involved areas. T h e remaining MUPs were brief and polyphasic, but the recruitment pattern was not increased at minimal effort, probably because of the extensive loss of functional muscle fibers in the involved thigh muscles. Arteriographic studies have revealed either atherosclerosis in medium- and large-size vessels, or a faint collection of dye in the region of the swelling.' More recently, attention has been fo-
Diabetic Muscle Infarction
cused on newer radiographic techniques to diagnose D M I . ~ , * - ~ ~ Computed tomography and sonography of the thigh have demonstrated enlargement of the quadriceps muscles.* Reich et all0 described 2 cases in which MRI revealed high signals on T2 images in the involved thigh muscles (adductor muscles in 1 patient and vastus lateralis, medialis, rectus femoris, and iliopsoas in the other). Computed tomography also demonstrated swelling in these muscles, but the T2-weighted sequences on sagittal MRI delineated the abnormal regions in greater detail. Radionuclide imaging of the same cases with Tc-99 demonstrated radiopharmaceutical accumulation in the region of the mass (but not in bone), due to increased vascular permeability at the site of infarction. The patients were not biopsied in this report, however, and the thigh lesions spontaneously resolved over weeks to several months. These authors suggested that a diagnostic muscle biopsy was not necessary in patients with a characteristic clinical presentation and typical bone scan or MRI findings." Banker and Chester have even stated that biopsy of the masses could actually worsen symptoms and delay recovery in these patients.' Of their 5 biopsied patients, all developed some increase in symptoms after the procedure, except 1 who underwent needle biopsy (Table l).4 Our patient did experience an increase in the thigh mass size and worsening of pain after the first limited biopsy. However, whether the biopsy was the cause of the exacerbation, versus increased ambulation, is unclear. Indeed, after the second more
MUSCLE & NERVE
July 1992
853
extensive biopsy and resection of the infarcted muscle there was gradual and sustained improvement. Others have not reported postbiopsy worsening.’ We believe it is reasonable to delay biopsy in those patients who have the typical clinical presentation for DMI, a focally abnormal EMG as noted above and an MRI scan showing increased T2 signal-weighted images in the clinically suspected muscles. However, a muscle biopsy may OCcasionally be needed for diagnosis, particularly in patients with atypical clinical or radiologic features or in those patients in whom recovery is delayed (as in the present case). The histologic features of DMI consist of large confluent areas of muscle necrosis and edema. The normal architectural pattern,of the muscle in these areas is obliterated. Early observers of DMI commented that the lesions probably reflected areas of vascular ischemia to large areas of muscle.lS2Multifocal areas of hemorrhage have also been reported. Regenerating muscle fibers are usually present, often at the periphery of the infarcted areas. Inflammatory cells may infiltrate the confluent necrotic areas. This inflammation can be striking, as in our case. Arterioles and capillaries may be occluded by fibrin and the capillary walls can be thickened. Autopsy has revealed atherosclerosis of the iliac and renal arteries with muscle infarction not only in the clinically involved vastus lateralis and medialis, but also in the rectus femoris muscle.* The muscle infarcts are thought to be due to the occlusion or blood vessels in the distribution of the femoral artery and its branches.’-3 Emboli to more distal vessels may also play a role.* The differential diagnosis of DMI includes diabetic lumbosacral radiculoplexopathy (DLSRP), also referred to a diabetic “amyotrophy,” or Bruns- Garland syndrome.3 Both syndromes begin with the abrupt onset of lower extremity pain that can ultimately involve the opposite side. In DLSRP, however, the pain is usually localized to the low back, hip, or buttocks, with radiation into the thigh; while, in DMI, the pain is more focal and associated with swelling and a firm mass. DLSRP patients develop dramatic weakness and atrophy in proximal, and often distal lower extremity muscles. Sensory symptoms (numbness/ paresthesias) do not result from DMI, unless there is a prior distal symmetric polyneuropathy, while they can occur in DLSKP. T h e ESR may be nonspecifically elevated in both disorders. Whereas the MRI, CT, and radionuclide images will be abnormal in DMI, they should be normal in DLSRP. ‘r2
’,*
854
Diabetic Muscle Infarction
The EMG in DSLRP is also different and characterized by widespread fibrillations in many muscles (usually including the paraspinous muscles), with long-duration, polyphasic MUPs, and decreased recruitment pattern. NCS may not be helpful in distinguishing the disorders, as both may show evidence of a distal symmetric polyneuropathy. T h e abrupt onset in both syndromes, and pathologic evidence for probable focal ischemia in the muscle (DMI) or nerve (DLSRP),3 supports the theory that both entities have a primary vascular etiology. DMI also needs to be distinguished from other disorders not necessarily associated with diabetes mellitus. Polymyoisitis can rarely present with focal swelling and pain6 and, while it often then progresses to a more diffuse process, it can remain i ~ o l a t e d However, .~ these cases typically have an elevated CK and significant weakness, and they rarely spontaneously recover without treatment. The muscle biopsy in focal polymyositis will not show the large zonal areas of muscle necrosis and architectural obliteration as in DMI, but instead will have diffuse endomysial inflammatory cells and necrotic muscle fibers singly or in small groups. Other disorders which need to be considered are thrombophlebitis, abscess, osteomyelitis, primary tumor of the muscle, and septic arthritis. The associated systemic symptoms, radiologic imaging (MRI, radionuclide scan), EMG, and if necessary, muscle biopsy, should help distinguish these disorders from DMI. The treatment of DMI is supportive. Analgesics are necessary for pain reduction. Banker and Chester have suggested that physical therapy and even routine dail activity, may exacerbate the pain and ~welling!,~ They have advocated immobilization until the symptoms begin to improve. While it certainly is often painful for patients to move the involved leg and to walk, we have not found that such activity actually delays recovery. T o our knowledge, no other investigators have advocated immobilization as a form of therapy in DMI patients. This issue, therefore, remains unresolved until more patients are carefully followed. In summary, diabetic muscle infarction is a neuromuscular disorder that should be in the differential diagnosis of leg pain and weakness in a diabetic patient. While there have been only a small number of cases reported, DMI may be mistaken for other disorders and is probably underrecognized. Careful consideration of the clinical, radiologic and, if necessary, biopsy features of the syndrome will distinguish it from the other neuro-
MUSCLE & NERVE
July 1992
muscular complications of diabetes and other cases of leg pain.
6. 7.
REFERENCES 1. Angervall L, Stener B: Tumoriform focal muscular degen-
2. 3. 4. 5.
eration in two diabetic patients. Diabetologza 1965; 1:39-42. Banker B, Chester S: Infarction of the thigh muscle in the diabetic patient. Neurology 1973;23:667- 677. Barohn RJ, Sahenk Z, Warmolts JR, Mendell J R : l h e Bruns-Garland syndrome (“Diabetic Amyotrophy”): Revisited 100 years later. Arch Neurol 1991;48: 1130- 1135. Chester S, Banker B: Focal infarction of muscle in diabetes. Diabetic Care 1986;9:623-630. Cumming WK, Weiser R, Teoh R, et al: Localized nodular
Diabetic Muscle Infarction
8. 9. 10.
myositis: A clinical and pathological variant of polymyositis. Q J Med 1977;184:531-546. Heffner RR, Barron SA: Polymyositis beginning as a focal process. Arch Neurol 1981;38:439-442. Lauro GR, Kissel JT, Simon SR: Idiopathic muscle infarction in a diabetic patient. J EoneJoznt Surg 1991;73A:301304. Levinsohn EM, Bryan PJ: Computed tomography in unilateral extremity swelling of unusual cause. J Cornput A~sist Tornogr 1979;3:67-70. Ratliff J , Matthews J, Blalock J, et al: Infarction of the quadriceps muscle: A complication of diabetic vasculopathy. South Med J 1986;79: 1595. Reich S, Wiener SN, Chester S, et al: Clinical and radiologic features of spontaneous muscle infarction in the diabetic. Clzn Nucl Med 1985;10:876-879.
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855
Robert G. Miller, MD San Francisco, Caitforflia
A 29-year-old female with type I diabetes mellitus developed pain, focal tenderness, and swelling in the posterior left thigh. Subsequent evaluation included a muscle biopsy, which revealed large confluent areas of necrosis and edema, compatible with a diagnosis of diabetic muscle infarction (DMI). Diabetic muscle infarction (DMI) is an unusual neuromuscular complication of diabetes mellitus. DMI begins with the acute onset of focal pain and swelling in the thigh. The anterior compartment (quadriceps muscle group) or posterior compartment (hamstring muscle group) are most frequently involved. The focal region of muscle damage can be noninvasively viewed by magnetic resonance imaging and radionuclide scans. Muscle biopsy demonstrates large confluent regions of muscle necrosis and edema. DMI needs to be differentiated from other processes that can cause leg pain in a diabetic patient. Key words: diabetes mellitus muscle infarction MUSCLE & NERVE 15:850-855 1992
CASE=OF=THE=MONTH: PAINFUL THIGH MASS IN A YOUNG WOMAN: DIABETIC MUSCLE INFARCTION RICHARD J. BAROHN, MD, and JOHN T. KISSEL, MD
Most of the neuromuscular complications of diabetes mellitus involve the peripheral nerve. Distal symmetric polyneuropathy, autonomic neuropathy, mononeuropathy, and lumbosacral radioculoplexopathy are all well-recognized complications of diabetes. Diabetic syndromes in which muscle is the primary site of pathology are much less common.1,2.4v8- 10 In this report, the clinical, electrophysiologic, radiologic, and muscle biopsy findings in a typical case of diabetic muscle infarction (DMI) in the thigh will be presented and several controversial aspects of the diagnosis, pathogenesis, and management of this condition will be discussed (a brief report of this case has previously been published in a different format).’ CASE REPORT
A 29-year-old female with type 1 diabetes mellitus since age 9, and a history of nephropathy and retinopathy, developed sudden
Clinical History.
From the Department of Medicine, Division of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr. Barohn); and Department of Neurology, Ohio State University, Columbus, Ohio (Dr. Kissel) Address reprint requests to Richard J. Barohn, MD, Department of Medicine (Neurology), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284. Accepted for publication September 5, 1991
CCC 0148-639X/92/070850-06 $04 00 Q 1992 John Wiley
850
8, Sons, Inc.
Diabetic Muscle Infarction
pain, focal tenderness, and swelling in the posterior aspect for her left thigh. There was no associated skin erythema and no fever. The pain did not begin during physical activity, and there was no history of trauma. The patient denied numbness, paresthesias, or back pain. The symptoms worsened over the next 2 weeks and the thigh swelling extended to the knee. An arthrocentesis was normal. She was placed on a 2-week course of antibiotics, but the symptoms did not improve. Eight weeks after the onset of symptoms, a limited muscle biopsy of the biceps fenioris was performed adjacent to the painful mass through a 2-cm incision. Histologic examination revealed only slight muscle fiber size variability and a few scattered necrotic fibers without inflammatory cells. The thigh pain and swelling seemed to improve slightly over the next several weeks. Twelve weeks after the onset-of the pain, however, she had a sudden recurrence of symptoms with enlargement of the mass, and she became unable to walk without assistance. When the mass and pain persisted, she was admitted to the hospital for a more extensive muscle biopsy, 16 weeks after the initial symptoms began. Physical Examination. onadmission she was afebrile. There was a firm, tender 12 X 10 cm mass in the left posterior-medial thigh. There was no erythema or warmth in the skin overlying the tender region. There was some extension of the
MUSCLE & NERVE
July 1992
edema to the knee. Muscle strength in the proximal left leg, including knee extension, was normal. Knee flexion was difficult to assess because of pain, but there was full antigravity motion with some resistance. Strength in the arms, right leg, and distal left leg was normal. There was a mild loss of vibratory sensation in the toes with decreased pinprick and light touch to the ankles bilaterally. Muscle stretch reflexes were normal in the arms, hypoactive at the knees, and absent at the ankles. She had difficulty walking, as minimal pressure on the left leg produced severe pain. Laboratory Evaluation. The white blood count was 8000 cells/mm3 with a normal differential. The erythrocyte sedimentation rate was 119 mm/h prior to the initial biopsy, and remained elevated throughout her course. The fasting blood glucose was 110 mg/dL. Serum creatine kinase was 144 IU/L (normal < 215 IU/L) at the time of the first biopsy, and 126 lU/L just before the second muscle biopsy. Radiologic investigations included a normal venogram without evidence of deep venous thrombosis. A 3-phase technetium-99 monophosphate bone scan (done prior to the first muscle biopsy) showed increased blood flow to the left posterior thigh on the flow images (Fig. l), but
FIGURE 2. Sagittal view of left thigh by TPweighted MRI scan. There is diffuse high signal in the biceps femoris, semimembranosus and semitendinosus muscles while the bone and anterior compartment muscles appear normal.
no increased radionuclide uptake in the bone on delayed static images. Magnetic resonance imaging scans (MRI) of the left thigh were obtained prior to both muscle biopsies. These showed an area of high signal in the posterior comparment muscles (biceps femoris, semimembranosus, semitendinosus) on the T2-weighted images (Fig. 2). The same area had low signal characteristics on the T1weighted image. ELECTRODIAGNOSTIC EXAMINATION
L
FIGURE 1. Technetium-99 monophosphate bone scan; left posterior oblique view. On this flow image, an increased radionuclide collection is seen in the posterior aspect of the left thigh.
Diabetic Muscle Infarction
T h e electrodiagnostic studies were done before the first muscle biopsy (6 weeks after the onset of symptoms). Motor and sensory nerve conduction studies (NCS) were performed using surface electrode recordings and standard methods. Median and ulnar motor and sensory NCS were normal. Peroneal and tibia1 motor NCS and sural NCS had conduction velocities at the lower limit of normal bilaterally; compound motor and sensory action potential amplitudes were slightly reduced in both legs. These NCS findings were interpreted as showing a mild distal symmetric polyneuropathy. Electromyopathy (EMG) was performed using a 50-mm monopolar needle. Fibrillation potentials were graded on a 0 to 4+ system. Insertional activity was increased and 3+ fibrillation potentials were present in the left biceps femoris muscle, in the region where the patient was most tender in
MUSCLE & NERVE
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651
the mid- and distal-posterior thigh. Very few motor unit potentials (MUP) could be recruited in this region, and some areas were devoid of voluntary MUPs. Where MUPs were recruited, they were brief (3 to 5 ms) and of small amplitude (50 to 200 mV), with 50% of the MUPs being polyphasic. The firing rate of early-recruited motor units was less than 10 Hz, and the number of MUPs recruited with a minimal contraction was not increased (i.e., normal recruitment). EMG of the iliacus, gluteus medius, vastus lateralis, gastrocnemius, and anterior tibialis muscles in the left and right lower extremities were normal. HISTOPATHOLOGY
An extensive open muscle biopsy (through a 20-cm incision) was performed on the biceps femoris muscle at the site of maximal swelling and tenderness. The open biopsy revealed large areas of muscle necrosis with a dramatic loss of muscle fibers and extensive endomysial edema (Fig. 3). Scattered necrotic and ghost fibers were present in these confluent areas of fiber loss, as well as occasional regenerating fibers. In several areas, there was infiltration by mononuclear inflammatory cells, both in the endomysial and perimysial spaces, and rarely around blood vessels. There was no necrosis of the blood vessel walls o r obliteration of the lumen. Surrounding the large areas of infarction, the muscle fibers had a more normal-appearing architectural pattern. COURSE
After the second biopsy, the pain and swelling slowly improved, with complete resolution of all symptoms and signs by 6 months. The patient subsequently developed worsening nephropathy and died of diabetic complications 1 year after onset of her thigh symptoms. DISCUSSION
Diabetic muscle infarction in the thigh is an unusual neuromuscular complication of diabetes mellitus. However, it may be more common than previously reco nized. Eleven prior cases have been reported'*f428-10(Table l), and we have observed 2 other young female diabetics with DMI over the past year (unpublished data). The case reported here illustrates most of the typical features of the syndrome. DMI begins with the abru t onset of thigh pain, tenderness, and swelling.Fz24Over a period of days, a firm mass develops. The muscles most frequently involved
852
Diabetic Muscle Infarction
FIGURE 3. (A) Low-power view of biceps femoris muscle biopsy. There is a large central area of muscle fiber loss and endomysial edema bordering on an area of more normal appearing (B)Higher-power field from fibers (hematoxylin and eosin, ~50). the same biopsy showing scattered necrotic and regenerating fibers, marked endomysial edema, and a small collection of inflammatory cells surrounding individual muscle fibers (hematoxylin and eosin, ~ 1 4 0 ) .
are the vastus lateralis, thigh adductors, and biceps femoris. It is not uncommon for the edema to extend to the knee and mimic a joint effusion.' DMI tends to occur in younger, poorly controlled diabetic patients with other end-organ complications (retinopathy, nephropathy, neuropathy). There are no associated systemic symptoms or signs indicative of infection and no skin discoloration suggesting cellulitis or thrombophlebitis. The painful mass persists for weeks, occasionally with exacerbation of symptoms, and then spontaneously resolves over several months. Contralateral involvement of the other thigh, absent in this case, can occur after the initial episode resolves, and
MUSCLE 8, NERVE
July 1992
Table 1. Diabetic muscle infarction: Literature review. Authorlyear Angervall et al. (1965) Banker et
al. (1973)
No. patients
MIF
Age
Muscle
Elevated CK
Biopsy proven
2
M M F F F
52 30 28 50 28
NR NR Yes NR Yes
+ + + +
M F F F F M
54 29 34 34 35 57
BF VUADD VL VL VC, VM IL ADD IL, VL, VM, BF G VL, RF VL, VM, RF VM
2
Levinsohn et a1 (1976)
1
Reich et al. (1985)
2
Chester et al. (1986)
Ratliff (1987)
3* 1
V L = vastus lateralis; VM = vastus medialis; BF - = No
NR No No
No No NR
= biceps fernoris; ADD = adductor; IL = iliacus;
+
Worsening after Bx
Contralateral recurrence
-
No
-
No Yes (4 wk) Yes (10 mo) No
+ + -
No Yes (7 mo) Yes (24 mo) Yes (5 wk) ? No
-
+ + + t
t
t t
-
G = gastrocnemius; NR = not recorded;
+ = yes;
*.Six patients are discussed, but patients I and 2 are also reported in Banker et a/.z and patient 6 is reporfed in Reich et a/.'O Tone of these 3 patients (not specified by the authors) had a needle biopsy and did not worsen, 2 had an open biopsy and did worsen.
has occurred in nearly half of the reported cases weeks to months after the first episode (Table 1). Three of the previously reported cases134died of complications of diabetes within a year after the episode of DMI. The creatine kinase levels (CK) have been normal in most cases in which it has been reported (including our own), a finding that may help distinguish DMI from focal polymyositis. However, exactly when the CKs were obtained in the disease course is unclear for the cases in the literature. In the present case, there was a delay of several weeks from the onset of symptoms to the time the initial CK was obtained. It is possible that an elevated CK would be found more often if obtained within the first several days after the acute muscle infarct (we have observed this in 1 unpublished case). The electrodiagnostic features of DMI have not been discussed in any of the prior reports. Nerve conduction studies in this case revealed a generalized distal symmetric polyneuropathy. Needle EMG (performed 6 weeks after the acute infarct), demonstrated fibrillation potentials in the involved muscles, with a loss of voluntary MUPs in the most involved areas. T h e remaining MUPs were brief and polyphasic, but the recruitment pattern was not increased at minimal effort, probably because of the extensive loss of functional muscle fibers in the involved thigh muscles. Arteriographic studies have revealed either atherosclerosis in medium- and large-size vessels, or a faint collection of dye in the region of the swelling.' More recently, attention has been fo-
Diabetic Muscle Infarction
cused on newer radiographic techniques to diagnose D M I . ~ , * - ~ ~ Computed tomography and sonography of the thigh have demonstrated enlargement of the quadriceps muscles.* Reich et all0 described 2 cases in which MRI revealed high signals on T2 images in the involved thigh muscles (adductor muscles in 1 patient and vastus lateralis, medialis, rectus femoris, and iliopsoas in the other). Computed tomography also demonstrated swelling in these muscles, but the T2-weighted sequences on sagittal MRI delineated the abnormal regions in greater detail. Radionuclide imaging of the same cases with Tc-99 demonstrated radiopharmaceutical accumulation in the region of the mass (but not in bone), due to increased vascular permeability at the site of infarction. The patients were not biopsied in this report, however, and the thigh lesions spontaneously resolved over weeks to several months. These authors suggested that a diagnostic muscle biopsy was not necessary in patients with a characteristic clinical presentation and typical bone scan or MRI findings." Banker and Chester have even stated that biopsy of the masses could actually worsen symptoms and delay recovery in these patients.' Of their 5 biopsied patients, all developed some increase in symptoms after the procedure, except 1 who underwent needle biopsy (Table l).4 Our patient did experience an increase in the thigh mass size and worsening of pain after the first limited biopsy. However, whether the biopsy was the cause of the exacerbation, versus increased ambulation, is unclear. Indeed, after the second more
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extensive biopsy and resection of the infarcted muscle there was gradual and sustained improvement. Others have not reported postbiopsy worsening.’ We believe it is reasonable to delay biopsy in those patients who have the typical clinical presentation for DMI, a focally abnormal EMG as noted above and an MRI scan showing increased T2 signal-weighted images in the clinically suspected muscles. However, a muscle biopsy may OCcasionally be needed for diagnosis, particularly in patients with atypical clinical or radiologic features or in those patients in whom recovery is delayed (as in the present case). The histologic features of DMI consist of large confluent areas of muscle necrosis and edema. The normal architectural pattern,of the muscle in these areas is obliterated. Early observers of DMI commented that the lesions probably reflected areas of vascular ischemia to large areas of muscle.lS2Multifocal areas of hemorrhage have also been reported. Regenerating muscle fibers are usually present, often at the periphery of the infarcted areas. Inflammatory cells may infiltrate the confluent necrotic areas. This inflammation can be striking, as in our case. Arterioles and capillaries may be occluded by fibrin and the capillary walls can be thickened. Autopsy has revealed atherosclerosis of the iliac and renal arteries with muscle infarction not only in the clinically involved vastus lateralis and medialis, but also in the rectus femoris muscle.* The muscle infarcts are thought to be due to the occlusion or blood vessels in the distribution of the femoral artery and its branches.’-3 Emboli to more distal vessels may also play a role.* The differential diagnosis of DMI includes diabetic lumbosacral radiculoplexopathy (DLSRP), also referred to a diabetic “amyotrophy,” or Bruns- Garland syndrome.3 Both syndromes begin with the abrupt onset of lower extremity pain that can ultimately involve the opposite side. In DLSRP, however, the pain is usually localized to the low back, hip, or buttocks, with radiation into the thigh; while, in DMI, the pain is more focal and associated with swelling and a firm mass. DLSRP patients develop dramatic weakness and atrophy in proximal, and often distal lower extremity muscles. Sensory symptoms (numbness/ paresthesias) do not result from DMI, unless there is a prior distal symmetric polyneuropathy, while they can occur in DLSKP. T h e ESR may be nonspecifically elevated in both disorders. Whereas the MRI, CT, and radionuclide images will be abnormal in DMI, they should be normal in DLSRP. ‘r2
’,*
854
Diabetic Muscle Infarction
The EMG in DSLRP is also different and characterized by widespread fibrillations in many muscles (usually including the paraspinous muscles), with long-duration, polyphasic MUPs, and decreased recruitment pattern. NCS may not be helpful in distinguishing the disorders, as both may show evidence of a distal symmetric polyneuropathy. T h e abrupt onset in both syndromes, and pathologic evidence for probable focal ischemia in the muscle (DMI) or nerve (DLSRP),3 supports the theory that both entities have a primary vascular etiology. DMI also needs to be distinguished from other disorders not necessarily associated with diabetes mellitus. Polymyoisitis can rarely present with focal swelling and pain6 and, while it often then progresses to a more diffuse process, it can remain i ~ o l a t e d However, .~ these cases typically have an elevated CK and significant weakness, and they rarely spontaneously recover without treatment. The muscle biopsy in focal polymyositis will not show the large zonal areas of muscle necrosis and architectural obliteration as in DMI, but instead will have diffuse endomysial inflammatory cells and necrotic muscle fibers singly or in small groups. Other disorders which need to be considered are thrombophlebitis, abscess, osteomyelitis, primary tumor of the muscle, and septic arthritis. The associated systemic symptoms, radiologic imaging (MRI, radionuclide scan), EMG, and if necessary, muscle biopsy, should help distinguish these disorders from DMI. The treatment of DMI is supportive. Analgesics are necessary for pain reduction. Banker and Chester have suggested that physical therapy and even routine dail activity, may exacerbate the pain and ~welling!,~ They have advocated immobilization until the symptoms begin to improve. While it certainly is often painful for patients to move the involved leg and to walk, we have not found that such activity actually delays recovery. T o our knowledge, no other investigators have advocated immobilization as a form of therapy in DMI patients. This issue, therefore, remains unresolved until more patients are carefully followed. In summary, diabetic muscle infarction is a neuromuscular disorder that should be in the differential diagnosis of leg pain and weakness in a diabetic patient. While there have been only a small number of cases reported, DMI may be mistaken for other disorders and is probably underrecognized. Careful consideration of the clinical, radiologic and, if necessary, biopsy features of the syndrome will distinguish it from the other neuro-
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muscular complications of diabetes and other cases of leg pain.
6. 7.
REFERENCES 1. Angervall L, Stener B: Tumoriform focal muscular degen-
2. 3. 4. 5.
eration in two diabetic patients. Diabetologza 1965; 1:39-42. Banker B, Chester S: Infarction of the thigh muscle in the diabetic patient. Neurology 1973;23:667- 677. Barohn RJ, Sahenk Z, Warmolts JR, Mendell J R : l h e Bruns-Garland syndrome (“Diabetic Amyotrophy”): Revisited 100 years later. Arch Neurol 1991;48: 1130- 1135. Chester S, Banker B: Focal infarction of muscle in diabetes. Diabetic Care 1986;9:623-630. Cumming WK, Weiser R, Teoh R, et al: Localized nodular
Diabetic Muscle Infarction
8. 9. 10.
myositis: A clinical and pathological variant of polymyositis. Q J Med 1977;184:531-546. Heffner RR, Barron SA: Polymyositis beginning as a focal process. Arch Neurol 1981;38:439-442. Lauro GR, Kissel JT, Simon SR: Idiopathic muscle infarction in a diabetic patient. J EoneJoznt Surg 1991;73A:301304. Levinsohn EM, Bryan PJ: Computed tomography in unilateral extremity swelling of unusual cause. J Cornput A~sist Tornogr 1979;3:67-70. Ratliff J , Matthews J, Blalock J, et al: Infarction of the quadriceps muscle: A complication of diabetic vasculopathy. South Med J 1986;79: 1595. Reich S, Wiener SN, Chester S, et al: Clinical and radiologic features of spontaneous muscle infarction in the diabetic. Clzn Nucl Med 1985;10:876-879.
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