Amyloid Myopathy Research Articles

Monoclonal gammopathy with both nemaline myopathy and amyloid myopathy

Monoclonal gammopathies due to plasma cell dyscrasias can induce diverse rare neuromuscular disorders. Deposition of monoclonal antibody light chains in skeletal muscle causes amyloid myopathy. Monoclonal gammopathy is occasionally associated with sporadic late-onset nemaline myopathy. Here we report a monoclonal gammopathy patient with both sporadic late-onset nemaline myopathy and amyloid myopathy. The diagnoses were based on immunofixation electrophoresis of urine, and serum for free light chain assay, Congo red staining and Thioflavin S staining of muscle biopsies, as well as immunohistochemical staining and electron-microscopic observation. Nemaline myopathy and amyloid myopathy can present in the same patient with monoclonal gammopathy.

Amyloid Myopathy With and Without Systemic Amyloidosis (S54.006)

Amyloid Myopathy With and Without Systemic Amyloidosis (S54.006)

Amyloid Myopathy as an Inclusion Body Myositis Mimic (P2.127)

Amyloid Myopathy as an Inclusion Body Myositis Mimic (P2.127)

Amyloid Myopathy Presenting with Dysphagia and an Inclusion Body Myositis Phenotype (P2.119)

Amyloid Myopathy Presenting with Dysphagia and an Inclusion Body Myositis Phenotype (P2.119)

Amyloid myopathy as the presenting feature of lymphoplasmacytic lymphoma.

Amyloid myopathy as the presenting feature of lymphoplasmacytic lymphoma.

Systemic Immunoglobulin Light Chain Amyloidosis–Associated Myopathy: Presentation, Diagnostic Pitfalls, and Outcome

ObjectiveTo characterize the natural history of immunoglobulin light chain amyloidosis–associated myopathy and to provide guidelines for recognition. Patients and MethodsFifty-one patients with systemic immunoglobulin light chain amyloidosis and biopsy-confirmed muscle amyloid deposition diagnosed between January 1, 1995, and December 31, 2015, were included in this study. ResultsCommon presenting symptoms were muscle weakness in 49 patients (96%), dysphagia in 23 (45%), myalgia in 17 (33%), macroglossia in 17 (33%), jaw claudication in 13 (25%), and hoarseness in 9 (18%). The median time from the onset of symptoms to diagnosis was almost 2 years. Less than two-thirds of the patients with an outside muscle biopsy (16 of 27) had an established pathologic confirmation of amyloidosis due to failure to routinely incorporate Congo red staining. Moreover, 12 patients were incorrectly treated before diagnosis of amyloid myopathy. More than half of the patients had normal creatine kinase levels at diagnosis. Cardiac troponin T levels were elevated above the reference range in 5 of 12 patients who lacked evidence of cardiac involvement. Median overall survival was 32 months. Factors associated with inferior survival were involvement of more than 2 organs (median survival, 13 months), cardiac involvement (median survival, 15 months), and absence of stem cell transplant (median survival, 18 months). With the exclusion of patients treated with stem cell transplant, no improvement in survival was seen over the 1995-2004 and 2005-2015 decades. ConclusionImmunoglobulin light chain amyloidosis–associated myopathy is rare. Delay in diagnosis is common, and there is a high rate of pathologic and clinical misdiagnosis. Awareness of elevation of cardiac troponin T levels in the absence of cardiac disease may be a clue to diagnosis.

Whole Exome Sequencing Leading to the Diagnosis of Dysferlinopathy with a Novel Missense Mutation (c.959G>C).

Dysferlinopathy is an uncommon, progressive muscular dystrophy that has a wide phenotypic variability and primarily supportive management (Nguyen et al., 2007; Narayanaswami et al., 2014). Amyloid myopathy is a distinct, rare disorder that can present similarly to inflammatory myopathies and requires a high clinical suspicion for early intervention to prolong survival. Amyloid myopathy is typically associated with other systemic manifestations of amyloidosis, but rare cases of isolated amyloid myopathy have been described (Mandl et al., 2000; Hull et al., 2001). Positive Congo red stains on tissue biopsy remain the gold standard for diagnosis (Spuler et al., 1998; Karacostas et al., 2005). A high clinical suspicion and meticulous diagnostic workup that includes novel techniques are necessary for identifying these rare disorders. We report a middle-aged man with progressive leg muscle weakness who was initially treated as having amyloid myopathy but was later diagnosed as having dysferlinopathy by Whole Exome Sequencing (WES) analysis. We also report a novel missense mutation (c.959G>C) to help correlate in any patient with presumed dysferlinopathy and to add to the already known genotype of this disorder.

Teaching Neuro Images : Dyspnea as a presenting manifestation of amyloid myopathy

Teaching Neuro <i>Images</i> : Dyspnea as a presenting manifestation of amyloid myopathy

Teaching Neuro Images : Dyspnea as a presenting manifestation of amyloid myopathy

A 69-year-old man had dyspnea followed by slowly progressive proximal leg weakness over 2 years. He had macroglossia (figure 1). Creatine kinase was 1,378 U/L. A deltoid biopsy revealed myopathy, denervation atrophy, and congophilic deposits around perimysial vessels, indicating amyloid (figure 2). Further workup revealed serum monoclonal lambda protein, bone marrow amyloid, and cardiomyopathy. Amyloid myopathy, an underrecognized entity, predominantly presents with progressive proximal weakness in primary amyloidosis.(1) Dyspnea results from cardiomyopathy or respiratory muscle weakness (our patient had both). Macroglossia due to amyloid deposition is a helpful clinical clue. The patient is on chemotherapy with cyclophosphamide, dexamethasone, and bortezomib, which improves prognosis in amyloidosis.(2.)

Chronic myopathy due to immunoglobulin light chain amyloidosis

Amyloid myopathy associated with a plasma cell dyscrasia is a rare cause of muscle hypertrophy. It can be a challenging diagnosis, since pathological findings are often elusive. In addition, the mechanism by which immunoglobulin light-chain deposition stimulates muscle overgrowth remains poorly understood. We present a 53-year old female with a 10-year history of progressive generalized muscle overgrowth. Congo-red staining and immunohistochemistry revealed perivascular lambda light chain amyloid deposits, apparent only in a second muscle biopsy. The numbers of central nuclei and satellite cells were increased, suggesting enhanced muscle progenitor cell formation. Despite the chronicity of the light chain disease, the patient showed complete resolution of hematologic findings and significant improvement of her muscle symptoms following autologous bone marrow transplantation. This case highlights the importance of early diagnosis and therapy for this treatable cause of a chronic myopathy with muscle hypertrophy.

Clinical Significance of Amyloid Myopathy (P01.113)

Clinical Significance of Amyloid Myopathy (P01.113)

Expanding the spectrum of monoclonal light chain deposition disease in muscle

The diagnosis of amyloid myopathy is delayed when monoclonal gammopathies are not detected on initial testing and muscle biopsies are nondiagnostic, and the EMG and symptoms can mimic an inflammatory myopathy. Case report of a patient presenting with severe progressive muscle weakness of unclear etiology despite an extensive workup including two nondiagnostic muscle biopsies. Directed by MRI, a third biopsy revealed amyloid angiopathy and noncongophilic kappa light chain deposition in scattered subsarcolemmal rings and perimysial regions. A serum free light chain (FLC) assay revealed a kappa monoclonal gammopathy, which was not detected by multiple immunofixations. The spectrum of immunoglobulin deposition in muscle is similar to other organs. It comprises a continuum that includes parenchymal amyloid deposition, amyloid angiopathy, and noncongophilic Light Chain Deposition Disease (LCDD). We recommend including the FLC assay in the routine investigation for monoclonal gammopathies. This case also highlights the value of MRI-guided muscle biopsy.

骨格筋でのみアミロイドの沈着を確認しえたアミロイドーシスの1例

A 75-year-old man was admitted to our hospital with progressive weakness in the lower extremities for 7 months. Immunoelectrophoresis of serum detected IgA λ type M protein and bone marrow examination detected an increase in monoclonal plasma cells, thus leading to a diagnosis of IgA λ type multiple myeloma. Subsequent muscular CT scan showed severe fatty infiltration of vastus lateralis muscles, and histopathological examinations of biopsied muscle specimens an abundance of abnormal "ring-fiber-like" appearance, positive staining by Congo red and the presence of anti-λ light chain antibody. This led to a diagnosis of amyloid myopathy. No depositions were seen in rectal mucosa, cardiac muscle, or sural nerve. The results of double immunohistochemical staining using anti-dystrophin antibody and anti-λ light chain antibody suggested the possibility of direct injury by amyloid to muscle fibers. The case presented here was thus amyloidosis confirmed by deposition of amyloid only in muscles. In conclusion, when amyloidosis is suspected and there is evidence of muscle injury, muscle biopsy should be performed.

Bence-Jones Protein–Type Myeloma With Amyloid Myopathy Presenting as Amyloidomas and Extensive Amyloid Deposits in the Muscularis Propria

This study reports a 59-year-old man who suffered from multiple skeletal muscle amyloidomas and showed a rapidly fatal course. He noticed left inguinal pain and gait disturbance due to muscle weakness of the left leg. Protein in urine (3.3 g/d) and Bence-Jones protein of the κ type (2.3 g/d) were detected. Bone marrow aspiration showed 11.6% monoclonal plasma cells in nucleated cells. A core needle-biopsied and resected left inguinal tumor showed the deposition of eosinophilic amorphous materials positive for Congo red stain and the κ-light chain. He was diagnosed with plasma cell myeloma with AL (amyloid light chain) amyloidosis. Multiple soft-part tumors developed, grew rapidly, and he died 3 months after admission. At autopsy, 3 large amyloidomas were observed in the skeletal muscles, and prominent amyloid deposits were also seen in the diaphragm, intercostal muscle, iliopsoas muscle, and cervical skeletal muscles examined. Massive amyloid materials deposited diffusely in the propria muscularis of the gastrointestinal tract: the tongue to the rectum.

Amyloid myopathy: a therapeutic trial for the rare and underdiagnosed myopathy with bortezomib

A 69-year-old woman was referred to our clinic because of a 6-month history of progressive muscle weakness. Five years previously, when she was diagnosed as having nephrotic syndrome, the renal biopsy showed deposition of AL-amyloid. Subsequent investigations revealed multiple myeloma with k-type Bence-Jones protein at stage 3 according to the international staging system. A course of vincristine, doxorubicin and dexamethasone (VAD) and an additional course of cyclophosphamide were administered, followed by another course of melphalan (L-PAM) at age 67. The proteinuria slightly improved but persisted for 5 years, when proximal weakness developed. Neurological examination revealed proximally dominant weakness with MRC scale 4 in the deltoid and 3 in the iliopsoas muscles and she was unable to stand up from a full squat. Serum creatine kinase (CK) elevated to 3,399 U/L. Electromyography showed a myogenic pattern with small motor unit potentials, fibrillation potentials and early recruitment pattern. Muscle biopsy revealed a variation of fiber size, little infiltration of inflammatory cells, and homogeneous accumulations beneath the muscle membrane (Fig. 1a). Congo red-positive materials were noted both in vessel walls and in muscle fibers (Fig. 1b, c, d) with fluorescence for rhodamine, consistent with amyloid deposition, the hallmark of amyloid myopathy. We were not able to identify whether the deposits were located beneath the basal lamina or the plasmalemma due to lack of electron microscopic preparation. Five years ago, the serum CK value was 110 U/L (Fig. 2). Two years later, when her nephrotic syndrome deteriorated, the CK elevated to 2,336 IU/L without overt weakness. Interestingly, after she received L-PAM, the CK decreased to 120 U/L just 1 month after the treatment. When girdle weakness developed 6 months ago, the CK again soared to 3,378 U/L. The fluctuation of CK and the amyloid deposition in the muscle led us to the diagnosis of amyloid myopathy due to multiple myeloma. We then administered two consecutive courses of bortezomib (1.3 mg/m on days 1, 4, 8, and 11 for the first course and 1.0 mg/m on days 1, 4, 8, and 11 for the second course). The treatment reduced the proportion of myeloma cells from 16.8 to 1.2%. The CK started to fall a few weeks after the first course and eventually fell to 187 U/L 1 month after the second course, when she was able to rise from a sitting position more easily. However, multiple myeloma deteriorated in the following months and the CK again elevated to 694 U/L. She was not able to receive additional treatment because of her poor general status. Amyloid myopathy, a progressive myopathy in a proximally dominant fashion, is caused by a variety of primary amyloidoses, such as familial amyloidosis, AL-amyloidosis and multiple myeloma [1–3]. Postulated mechanisms include impaired muscle metabolism or failed electrical conduction by amyloid deposition beneath the muscle membrane [4, 5]. Therapeutic trials have included plasmapheresis, administration of corticosteroid, and high-dose K. Shiga (&) R. Mizutani R. Isayama T. Tokuda M. Nakagawa Department of Neurology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Hirokoji-agaru, Kawaramachi-dori, Kamigyo-ku, Kyoto 602-0841, Japan e-mail: kenshiga@koto.kpu-m.ac.jp

A case of amyloid myopathy masquerading as inflammatory myopathy

A case of amyloid myopathy masquerading as inflammatory myopathy

Amyloid myopathy: a diagnostic challenge

Amyloid myopathy (AM) is a rare manifestation of primary systemic amyloidosis (AL). Like inflammatory myopathies, it presents with proximal muscle weakness and an increased creatine kinase level. We describe a case of AL with severe, rapidly progressive myopathy as the initial symptom. The clinical manifestation and muscle biopsy were suggestive of inclusion body myositis. AM was not suspected until amyloidosis was seen in the gastric mucosal biopsy. The muscle biopsy was then re-examined more specifically, and Congo red staining eventually showed vascular and interstitial amyloid accumulation, which led to a diagnosis of AM. The present case illustrates the fact that the clinical picture of AM can mimic that of inclusion body myositis.

424: Amyloid myopathy: An unusual but important cause of muscle weakness

Purpose: Unlike neuropathy secondary to amyloid deposition, myopathy is infrequently described. We report the clinical, electrophysiological and pathological findings of two patients with distinct forms of this disease. We review the literature to determine the common presentations of amyloid myopathy and possible clues to the diagnosis.

Axial myopathy due to primary amyloidosis

A 74-year-old man presented with progressive weakness involving only his back muscles. Serum protein electrophoresis revealed the presence of a monoclonal gammopathy. Muscle biopsy of affected muscles demonstrated amyloid light chain deposition surrounding individual muscle fibers as well as in the walls of blood vessels in association with vasculitis. Selective involvement of axial muscles in isolated amyloid myopathy has not been previously described. We report the occurrence of axial myopathy with associated vasculitis as a presenting feature of primary (AL) amyloidosis. Amyloidosis should be considered in the differential diagnosis of focal myopathies, since the condition may be responsive to chemotherapy.

G.P.7 02 Amyloid myopathy presenting with rhabdomyolysis: Evidence of complement activation

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 isolated episode of rhabdomyolysis. The detection of complement complex C5b9 suggests that complement cascade is implicated in the muscular damage of amyloid myopathy.