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Amyloid myopathy presenting with rhabdomyolysis: Evidence of complement activation
Neuromuscular Disorders 16 (2006) 514–517 www.elsevier.com/locate/nmd
Case report
Amyloid myopathy presenting with rhabdomyolysis: Evidence of complement activation C. Rodolico
a,*
a
, A. Mazzeo a, A. Toscano a, C. Pastura a, D. Maimone b, O. Musumeci a, C. Musolino c, G. Vita a
Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy b Neurologic Division, ‘‘Garibaldi’’ Hospital, Catania, Italy c Division of Hematology, Department of Internal Medicine, University of Messina, Messina, Italy Received 10 March 2006; received in revised form 12 June 2006; accepted 14 June 2006
Abstract At age of 57 years, a man experienced an episode of rhabdomyolysis. On that occasion muscle biopsy was not performed, however monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Further he developed a moderate proximal muscle weakness with CK level persistently elevated (1000–1200 U/l). When he came to our observation, at age 67, a muscle biopsy revealed an amyloid myopathy and multiple myeloma was at the same time disclosed. Terminal complement complex C5b9 (membrane attack complex) deposits were found in the vessel walls and muscle fibers surface depicted by amyloid. Our case suggests to keep in mind the possibility that amyloid myopathy may begin as an isolate episode of rhabdomyolysis. The detection of complement complex C5b9 suggests that complement cascade is implicated in the muscular damage of amyloid myopathy. 2006 Elsevier B.V. All rights reserved. Keywords: Rhabdomyolysis; Amyloid myopathy; C5b9
1. Introduction Amyloid myopathy is a rare disorder of the adult age and its diagnosis is often overlooked [1,2]. It is due to the deposition of insoluble amyloid fibrils in skeletal muscle, in most cases as consequence of the secretion of immunoglobulin light chains following a plasma cell dyscrasia (primary or AL amyloidosis) [1–3]. Cases associated with the genetic forms due to transthyretin or gelsolin mutations have been also described [2,3]. In primary amyloidosis amyloid myopathy may be present in the context of a multiorgan impairment, but rarely it constitutes the only clinical manifestation [4–6]. It is *
Corresponding author. Tel.: +39 0902212757; 0902212789. E-mail address: [email protected] (C. Rodolico).
fax:
+39
0960-8966/$ - see front matter 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2006.06.004
characterised by progressive proximal weakness with increased creatine kinase (CK) level, mimicking a polymyositis or a limb-girdle muscular dystrophy; other typical features are muscle pseudohypertrophy and macroglossia [1,2]. Atypical forms with unusual presentation and course have also been described [5,6]. In this report, we present a case of rhabdomyolysis as the presenting symptom of amyloid myopathy due to multiple myeloma (MM). 2. Case report 2.1. Clinical history The patient was a 67-year-old man who at age 57 had had, at rest, an acute episode characterised by diffuse myalgia, ‘‘dark urine’’ and proximal weakness at lower
C. Rodolico et al. / Neuromuscular Disorders 16 (2006) 514–517
limbs with difficulty in walking. History of drugs assumption in the previous weeks was negative and no fever was present. He did not refer other symptoms suggesting a neuromuscular disorder in the previous period of his life. He was admitted, in that occasion, to a Department of Internal Medicine; at examination only a slight weakness of quadriceps muscles was evident. Routine chemistry revealed very elevated serum CK level (98,000 U/l with n.v. < 200); white blood cell and platelet counts were in range, and erytrocite sedimentation rate and C-reactive protein level were normal; serum immunoelectrophoresis evidenced a small k (IgG) M-component only. Renal function was preserved. The patient was submitted to intense hydratation and within 6 days CK decreased to 1418 U/l, muscular pain resolved but the slight proximal weakness at lower limbs still persisted. An electromyography (EMG) showed motor unit potentials of slow amplitude and short duration at proximal sites with presence of at rest activity recordable at quadriceps and deltoid muscles. Neurography, electrocardiography, and echocardiography were normal. The patient did not undergo muscle biopsy and left the hospital with a diagnosis of ‘‘Probable polymyositis in subject with monoclonal gammopathy (IgG lambda) of undetermined significance (MGUS)’’. Therapy with deflazacort (30 mg/day) was started with no benefit. Further the patient developed a moderate proximal muscle weakness at lower limbs with CK level persistently elevated (1000–1200 U/l). When the patient come to our observation, 10 years later, he did not assume any therapy. At examination a pattern of proximal muscle weakness with hypotrophy of periscapular and quadriceps muscles was evident. Tendon reflexes were absent. EMG had a myogenic pattern and neurography was normal. A muscle magnetic resonance study of lower limbs evidenced a diffuse atrophy of thigh muscles, in particular of the posterior compartment, with partial sparing of vastii. 2.2. Muscle biopsy A left vastus lateralis muscle biopsy showed fiber size variability with sclero-adipose substitution, regenerating fibers, and internal nuclei. Focal areas of Congo redpositive material, consistent with amyloid deposition, were identifiable in numerous large and small vessel walls (Figs. 1A–C). The amyloid was also seen surrounding the plasma membrane of some fibers under rhodamine fluorescent optics (Fig. 1D). No infiltrating cells were detectable at immunohistochemistry using antibodies against CD8+, CD4+, CD68+, CD22+, and CD138+ cell lines. No fibres expressing major histocompatibility complex antigens class I and II were present. Terminal complement complex C5b9 (membrane attack complex [MAC]) deposits were found in the same
515
vessel walls and muscle fibers surface, depicted by amyloid (Figs. 1E–H). Immunohistochemistry for dystrophin, sarcoglycans, caveolin and Western blot analysis for calpain and dysferlin were normal. Biochemical analysis for muscle carnitine–palmitoil transferase II, glycolitic, glycogenolytic and myoadenilate deaminase enzymes activities and carnitine level resulted normal. 2.3. Other investigations Serum protein electrophoresis showed M-component which was confirmed as IgG at immunoelectrophoresis (IgG 2390 mg/dl; n.v. 700–1600). IgA level was 27 mg/dl (n.v. 88–410) and IgM < 17 mg/dl (n.v. 34–210). Urine electrophoresis showed Bence–Jones proteinuria with 34.2 mg/l k light chains (n.r. 0–3.9). Bone marrow smears showed a plasma cell population of 40%. Transthoracic ecocardiography evidenced interatrial septum hypertrophy with mild left atrial enlargement. Abdomen ecography was normal; at skull and spinal column X arrays osteolytic areas were not evident. 2.4. Treatment Pulsed oral melphalan (150 lg/Kg/d for 4 days, repeated after 6 weeks) was the therapy chosen. Three boli (1 for month) of intravenous betametasone (40 mg) were also performed. At 3 months, follow-up neuromuscular examination was unchanged and CK level persisted elevated to 1260 U/l. On urine electrophoresis a reduced Bence–Jones proteinuria (24.3 mg/l k light chains) was observed. 3. Discussion Only rare patients with rhabdomyolysis complicating AL amyloidosis due to MM have been reported in the literature [4,7]. In our case, rhabdomyolysis was the presenting feature of amyloid myopathy, which represented even the first manifestation of AL amyloidosis. The relationship between AL amyloidosis and occurrence of rhabdomyolysis is supported by several data: (i) other causes of myoglobinuria were ruled out by biochemistry and immunocytochemistry; (ii) after the episode of rhabdomyolysis, the patient developed a proximal myopathy, which later on resulted to be amyloid in nature. Amyloid myopathy is an underdiagnosed condition and it should be considered in the differential diagnosis of any adult with progressive myopathy [1,2,6]. Our case confirms the utility of Congo red-stained sections viewed under fluorescent light and suggests to keep in mind the possibility that amyloid myopathy may begin as an isolate episode of rhabdomyolysis. The patient experienced an episode of rhabdomyolysis 10 years before our observation; unfortunately in that occasion muscle biopsy was not performed, however, MGUS was diagnosed.
516
C. Rodolico et al. / Neuromuscular Disorders 16 (2006) 514–517
A
B
C
D
E
F
G
H
Fig. 1. Congo red-stained cryosections viewed under rhodamine fluorescent optics demonstrate marked congophilia of large and small blood vessel walls (A–C) as well as at surface of many muscle fibers (D). Serial sections using antibody against C5b9 fragment disclose complement deposits corresponding to amyloid (E–H). (A)–(C) and (E)–(G) 190·; (D) and (H) 130·.
The presence of a monoclonal protein in serum or urine is an important diagnostic clue in this myopathy and immune electrophoresis of serum and urine should be a part of the routine investigation for all myopathies, including isolated iperCKemia and rhabdomyolysis. The importance to make a timely diagnosis resides in the fact that most cases of amyloid myopathy are related to plasma cell dyscrasia or MM which are sometimes responsive to therapy. In our patient a diagnosis ten years before would be crucial.
Different hypotheses have been proposed to explain the clinical features associated with deposition of amyloid in skeletal muscle, such as narrowing of vessel lumina in muscle and peripheral nerves inducing ischemic myopathy or denervation atrophy, or a mechanic interference of amyloid deposits with muscle function [2,3]. Immune-mediated mechanisms have been postulated in two patients with amyloid myopathy and rhabdomyolysis. Autoantibody binding to muscle proteins, or light chain deposition in the membrane of muscle fibers was
C. Rodolico et al. / Neuromuscular Disorders 16 (2006) 514–517
suggested by Ferna`ndez-Sola` et al. [7]. Sundblad et al. reported a 54-year-old man who, in the context of a multiorgan impairment with acute renal failure, developed an episode of rhabdomyolysis with proximal muscular weakness [4]. Immunoblot studies evidenced the presence in the serum of antiskeletal muscle antibody reactivities binding to several muscular proteins. A putative antibody-mediated component was postulated in the pathogenesis of rhabdomyolysis. MAC deposition in vasculature and in necrotic muscle fibres has been reported in a patient with gelsolinamyloidosis [3]. In our case the detection of MAC deposits at surface of nonnecrotic muscle fibres and in vessel walls, in correspondence of amyloid deposition, may indicate a complement-mediated cytotoxicity resulting in injury to microvasculature and sarcolemma and contributing to the pathogenesis of muscular damage. Nevertheless the pathogenetic significance of complement deposits on nonnecrotic muscle fibers, already reported in some patients with muscular dystrophies and rare cases of inflammatory myopathies, remains unclear [8]. Ability of amyloid deposits to trigger complement activation, contributing to injury of axons in their vicinity, has been investigated in acquired and hereditary amyloid neuropathy and in Alzheimer’s disease [9,10]. Probably, MAC deposits, triggered by amyloid precipitation, may induce sarcolemma defects which may render it leaky and thus predispose to fiber necrosis. This mechanism could play a role not only in acute damage leading to rhabdomyolysis but also in chronic amyloid myopathy as seen in our patient. Fur-
517
ther studies will be required to determine the exact consequences of MAC deposits on nonnecrotic muscle fibers in amyloid myopathy. References [1] Chapin JE, Kornfeld M, Harris A. Amyloid myopathy: characteristic features of a still underdiagnosed disease. Muscle and Nerve 2005;31:266–72. [2] Prayson RA. Amyloid myopathy: clinicopathologic study of 16 cases. Hum Pathol 1998;29:463–8. [3] Spuler S, Emslie-Smith A, Engel AG. Amyloid myopathy: an underdiagnosed entity. Ann Neurol 1998;43:719–28. [4] Sundblad A, Porwit A, Ostad M, et al. Antibody reactivities to skeletal muscle proteins in a patient with k light chain secreting multiple myeolma, generalised amyloidosis and rhabdomyolisis. Eur J Haematol 2001;67:189–93. [5] Ashe J, Borel CO, Hart G, Humphrey RL, Derrick DA, Kuncl RW. Amyloid myopathy presenting with respiratory failure. J Neurol Neurosurg Psychiatry 1992;55:162–5. [6] Smestad C, Monstad P, Lindboe CF, Mygland A. Amyloid myopathy presenting with atrophic weakness. Muscle Nerve 2004;29:605–9. [7] Ferna`ndez-Sola` J, Cases A, Monforte R, et al. A possible pathogenetic mechanism for rhabdomyolysis associated with multiple myeloma. Acta Haematol 1987;77:231–3. [8] Spuler S, Engel AG. Unexpected sarcolemmal complement membrane attack complex deposits on nonnecrotic muscle fibers in muscular dystrophies. Neurology 1998;50:41–6. [9] Mazzeo A, Aguennouz M, Messina C, Vita G. Immunolocalization and activation of transcription factor nuclear factor kB in dysimmune neuropathies and familial amyloidotic polyneuropathy. Arch Neurol 2004;61:1097–102. [10] Zanjani H, Finch CE, Kemper C, et al. Complement activation in very early Alzheimer disease. Alzheimer Dis Assoc Disord 2005;19:55–66.
Case report
Amyloid myopathy presenting with rhabdomyolysis: Evidence of complement activation C. Rodolico
a,*
a
, A. Mazzeo a, A. Toscano a, C. Pastura a, D. Maimone b, O. Musumeci a, C. Musolino c, G. Vita a
Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy b Neurologic Division, ‘‘Garibaldi’’ Hospital, Catania, Italy c Division of Hematology, Department of Internal Medicine, University of Messina, Messina, Italy Received 10 March 2006; received in revised form 12 June 2006; accepted 14 June 2006
Abstract At age of 57 years, a man experienced an episode of rhabdomyolysis. On that occasion muscle biopsy was not performed, however monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Further he developed a moderate proximal muscle weakness with CK level persistently elevated (1000–1200 U/l). When he came to our observation, at age 67, a muscle biopsy revealed an amyloid myopathy and multiple myeloma was at the same time disclosed. Terminal complement complex C5b9 (membrane attack complex) deposits were found in the vessel walls and muscle fibers surface depicted by amyloid. Our case suggests to keep in mind the possibility that amyloid myopathy may begin as an isolate episode of rhabdomyolysis. The detection of complement complex C5b9 suggests that complement cascade is implicated in the muscular damage of amyloid myopathy. 2006 Elsevier B.V. All rights reserved. Keywords: Rhabdomyolysis; Amyloid myopathy; C5b9
1. Introduction Amyloid myopathy is a rare disorder of the adult age and its diagnosis is often overlooked [1,2]. It is due to the deposition of insoluble amyloid fibrils in skeletal muscle, in most cases as consequence of the secretion of immunoglobulin light chains following a plasma cell dyscrasia (primary or AL amyloidosis) [1–3]. Cases associated with the genetic forms due to transthyretin or gelsolin mutations have been also described [2,3]. In primary amyloidosis amyloid myopathy may be present in the context of a multiorgan impairment, but rarely it constitutes the only clinical manifestation [4–6]. It is *
Corresponding author. Tel.: +39 0902212757; 0902212789. E-mail address: [email protected] (C. Rodolico).
fax:
+39
0960-8966/$ - see front matter 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2006.06.004
characterised by progressive proximal weakness with increased creatine kinase (CK) level, mimicking a polymyositis or a limb-girdle muscular dystrophy; other typical features are muscle pseudohypertrophy and macroglossia [1,2]. Atypical forms with unusual presentation and course have also been described [5,6]. In this report, we present a case of rhabdomyolysis as the presenting symptom of amyloid myopathy due to multiple myeloma (MM). 2. Case report 2.1. Clinical history The patient was a 67-year-old man who at age 57 had had, at rest, an acute episode characterised by diffuse myalgia, ‘‘dark urine’’ and proximal weakness at lower
C. Rodolico et al. / Neuromuscular Disorders 16 (2006) 514–517
limbs with difficulty in walking. History of drugs assumption in the previous weeks was negative and no fever was present. He did not refer other symptoms suggesting a neuromuscular disorder in the previous period of his life. He was admitted, in that occasion, to a Department of Internal Medicine; at examination only a slight weakness of quadriceps muscles was evident. Routine chemistry revealed very elevated serum CK level (98,000 U/l with n.v. < 200); white blood cell and platelet counts were in range, and erytrocite sedimentation rate and C-reactive protein level were normal; serum immunoelectrophoresis evidenced a small k (IgG) M-component only. Renal function was preserved. The patient was submitted to intense hydratation and within 6 days CK decreased to 1418 U/l, muscular pain resolved but the slight proximal weakness at lower limbs still persisted. An electromyography (EMG) showed motor unit potentials of slow amplitude and short duration at proximal sites with presence of at rest activity recordable at quadriceps and deltoid muscles. Neurography, electrocardiography, and echocardiography were normal. The patient did not undergo muscle biopsy and left the hospital with a diagnosis of ‘‘Probable polymyositis in subject with monoclonal gammopathy (IgG lambda) of undetermined significance (MGUS)’’. Therapy with deflazacort (30 mg/day) was started with no benefit. Further the patient developed a moderate proximal muscle weakness at lower limbs with CK level persistently elevated (1000–1200 U/l). When the patient come to our observation, 10 years later, he did not assume any therapy. At examination a pattern of proximal muscle weakness with hypotrophy of periscapular and quadriceps muscles was evident. Tendon reflexes were absent. EMG had a myogenic pattern and neurography was normal. A muscle magnetic resonance study of lower limbs evidenced a diffuse atrophy of thigh muscles, in particular of the posterior compartment, with partial sparing of vastii. 2.2. Muscle biopsy A left vastus lateralis muscle biopsy showed fiber size variability with sclero-adipose substitution, regenerating fibers, and internal nuclei. Focal areas of Congo redpositive material, consistent with amyloid deposition, were identifiable in numerous large and small vessel walls (Figs. 1A–C). The amyloid was also seen surrounding the plasma membrane of some fibers under rhodamine fluorescent optics (Fig. 1D). No infiltrating cells were detectable at immunohistochemistry using antibodies against CD8+, CD4+, CD68+, CD22+, and CD138+ cell lines. No fibres expressing major histocompatibility complex antigens class I and II were present. Terminal complement complex C5b9 (membrane attack complex [MAC]) deposits were found in the same
515
vessel walls and muscle fibers surface, depicted by amyloid (Figs. 1E–H). Immunohistochemistry for dystrophin, sarcoglycans, caveolin and Western blot analysis for calpain and dysferlin were normal. Biochemical analysis for muscle carnitine–palmitoil transferase II, glycolitic, glycogenolytic and myoadenilate deaminase enzymes activities and carnitine level resulted normal. 2.3. Other investigations Serum protein electrophoresis showed M-component which was confirmed as IgG at immunoelectrophoresis (IgG 2390 mg/dl; n.v. 700–1600). IgA level was 27 mg/dl (n.v. 88–410) and IgM < 17 mg/dl (n.v. 34–210). Urine electrophoresis showed Bence–Jones proteinuria with 34.2 mg/l k light chains (n.r. 0–3.9). Bone marrow smears showed a plasma cell population of 40%. Transthoracic ecocardiography evidenced interatrial septum hypertrophy with mild left atrial enlargement. Abdomen ecography was normal; at skull and spinal column X arrays osteolytic areas were not evident. 2.4. Treatment Pulsed oral melphalan (150 lg/Kg/d for 4 days, repeated after 6 weeks) was the therapy chosen. Three boli (1 for month) of intravenous betametasone (40 mg) were also performed. At 3 months, follow-up neuromuscular examination was unchanged and CK level persisted elevated to 1260 U/l. On urine electrophoresis a reduced Bence–Jones proteinuria (24.3 mg/l k light chains) was observed. 3. Discussion Only rare patients with rhabdomyolysis complicating AL amyloidosis due to MM have been reported in the literature [4,7]. In our case, rhabdomyolysis was the presenting feature of amyloid myopathy, which represented even the first manifestation of AL amyloidosis. The relationship between AL amyloidosis and occurrence of rhabdomyolysis is supported by several data: (i) other causes of myoglobinuria were ruled out by biochemistry and immunocytochemistry; (ii) after the episode of rhabdomyolysis, the patient developed a proximal myopathy, which later on resulted to be amyloid in nature. Amyloid myopathy is an underdiagnosed condition and it should be considered in the differential diagnosis of any adult with progressive myopathy [1,2,6]. Our case confirms the utility of Congo red-stained sections viewed under fluorescent light and suggests to keep in mind the possibility that amyloid myopathy may begin as an isolate episode of rhabdomyolysis. The patient experienced an episode of rhabdomyolysis 10 years before our observation; unfortunately in that occasion muscle biopsy was not performed, however, MGUS was diagnosed.
516
C. Rodolico et al. / Neuromuscular Disorders 16 (2006) 514–517
A
B
C
D
E
F
G
H
Fig. 1. Congo red-stained cryosections viewed under rhodamine fluorescent optics demonstrate marked congophilia of large and small blood vessel walls (A–C) as well as at surface of many muscle fibers (D). Serial sections using antibody against C5b9 fragment disclose complement deposits corresponding to amyloid (E–H). (A)–(C) and (E)–(G) 190·; (D) and (H) 130·.
The presence of a monoclonal protein in serum or urine is an important diagnostic clue in this myopathy and immune electrophoresis of serum and urine should be a part of the routine investigation for all myopathies, including isolated iperCKemia and rhabdomyolysis. The importance to make a timely diagnosis resides in the fact that most cases of amyloid myopathy are related to plasma cell dyscrasia or MM which are sometimes responsive to therapy. In our patient a diagnosis ten years before would be crucial.
Different hypotheses have been proposed to explain the clinical features associated with deposition of amyloid in skeletal muscle, such as narrowing of vessel lumina in muscle and peripheral nerves inducing ischemic myopathy or denervation atrophy, or a mechanic interference of amyloid deposits with muscle function [2,3]. Immune-mediated mechanisms have been postulated in two patients with amyloid myopathy and rhabdomyolysis. Autoantibody binding to muscle proteins, or light chain deposition in the membrane of muscle fibers was
C. Rodolico et al. / Neuromuscular Disorders 16 (2006) 514–517
suggested by Ferna`ndez-Sola` et al. [7]. Sundblad et al. reported a 54-year-old man who, in the context of a multiorgan impairment with acute renal failure, developed an episode of rhabdomyolysis with proximal muscular weakness [4]. Immunoblot studies evidenced the presence in the serum of antiskeletal muscle antibody reactivities binding to several muscular proteins. A putative antibody-mediated component was postulated in the pathogenesis of rhabdomyolysis. MAC deposition in vasculature and in necrotic muscle fibres has been reported in a patient with gelsolinamyloidosis [3]. In our case the detection of MAC deposits at surface of nonnecrotic muscle fibres and in vessel walls, in correspondence of amyloid deposition, may indicate a complement-mediated cytotoxicity resulting in injury to microvasculature and sarcolemma and contributing to the pathogenesis of muscular damage. Nevertheless the pathogenetic significance of complement deposits on nonnecrotic muscle fibers, already reported in some patients with muscular dystrophies and rare cases of inflammatory myopathies, remains unclear [8]. Ability of amyloid deposits to trigger complement activation, contributing to injury of axons in their vicinity, has been investigated in acquired and hereditary amyloid neuropathy and in Alzheimer’s disease [9,10]. Probably, MAC deposits, triggered by amyloid precipitation, may induce sarcolemma defects which may render it leaky and thus predispose to fiber necrosis. This mechanism could play a role not only in acute damage leading to rhabdomyolysis but also in chronic amyloid myopathy as seen in our patient. Fur-
517
ther studies will be required to determine the exact consequences of MAC deposits on nonnecrotic muscle fibers in amyloid myopathy. References [1] Chapin JE, Kornfeld M, Harris A. Amyloid myopathy: characteristic features of a still underdiagnosed disease. Muscle and Nerve 2005;31:266–72. [2] Prayson RA. Amyloid myopathy: clinicopathologic study of 16 cases. Hum Pathol 1998;29:463–8. [3] Spuler S, Emslie-Smith A, Engel AG. Amyloid myopathy: an underdiagnosed entity. Ann Neurol 1998;43:719–28. [4] Sundblad A, Porwit A, Ostad M, et al. Antibody reactivities to skeletal muscle proteins in a patient with k light chain secreting multiple myeolma, generalised amyloidosis and rhabdomyolisis. Eur J Haematol 2001;67:189–93. [5] Ashe J, Borel CO, Hart G, Humphrey RL, Derrick DA, Kuncl RW. Amyloid myopathy presenting with respiratory failure. J Neurol Neurosurg Psychiatry 1992;55:162–5. [6] Smestad C, Monstad P, Lindboe CF, Mygland A. Amyloid myopathy presenting with atrophic weakness. Muscle Nerve 2004;29:605–9. [7] Ferna`ndez-Sola` J, Cases A, Monforte R, et al. A possible pathogenetic mechanism for rhabdomyolysis associated with multiple myeloma. Acta Haematol 1987;77:231–3. [8] Spuler S, Engel AG. Unexpected sarcolemmal complement membrane attack complex deposits on nonnecrotic muscle fibers in muscular dystrophies. Neurology 1998;50:41–6. [9] Mazzeo A, Aguennouz M, Messina C, Vita G. Immunolocalization and activation of transcription factor nuclear factor kB in dysimmune neuropathies and familial amyloidotic polyneuropathy. Arch Neurol 2004;61:1097–102. [10] Zanjani H, Finch CE, Kemper C, et al. Complement activation in very early Alzheimer disease. Alzheimer Dis Assoc Disord 2005;19:55–66.