Amyloid Myopathy
ABSTRACT & COMMENTARY
Source: Spuler S, et al. Amyloid myopathy: An underdiagnosed entity. Ann Neurol 1998;43:719-728.
Thirteen patients with muscle weakness demonstrating extracellular deposits of amyloid on muscle biopsy, but with no suspicion of amyloidosis clinically, were retrospectively reviewed. All but one had proximal weakness, the latter having distal weakness, five had extra-muscular symptoms, and three had diarrhea. Easy bruisability, nephrotic syndrome, and nephrosclerosis were seen in one each. Muscle enlargement was seen in only one patient (tongue and masseter) and none had a family history of amyloidosis. CK was elevated up to 70-fold in three, and EMG was myopathic in all patients with denervation potentials in seven. Congo red staining revealed congophilic amyloid deposits in and around the walls of arterioles and venules in all, while in 10 the deposits encased single muscle fibers, particularly in the periphery of fascicles. Immunohistochemistry of the deposits revealed lambda light chain in five, kappa light chain in four, amyloid P in seven, gelsolin in one, beta amyloid precursor protein in six, and ApoE in 10. No patient demonstrated transthyretin, amyloid A, beta 2 microglobulin, ubiquitin, or prion protein. Muscle weakness may be the only presenting symptom of systemic amyloidosis. Routine fluorescent Congo red staining of muscle biopsies is essential for diagnosis.
COMMENTARY
Amyloidosis constitutes a group of diverse protein deposition diseases sharing histologic staining characteristics (Congophilia, apple-green birefringence under polarized light, metachromasia with crystal violet) but differing in the biochemical nature and spectrum of the protein deposits. In the absence of a satisfactory clinical classification, the amyloidoses are categorized by the nature of the amyloid protein and whether deposition is systemic or localized. (See Table.)
Three systemic amyloidoses are recognized. AL (primary) amyloidosis, the most common form in the United States, accompanies plasma cell dyscrasias and neurologically may cause carpal tunnel syndrome, peripheral neuropathy, and autonomic insufficiency. AA (secondary) amyloidosis, occurs in the presence of chronic inflammatory disease and rarely affects the nervous system. Familial amyloidosis, though originally defined as an autosomal dominant peripheral and autonomic neuropathy, is in fact more variable, involving the cardiac, renal, and gastrointestinal systems.
Table
Protein Composition of Amyloidosis
| Systemic amyloidoses | Amyloid protein deposited |
| AL (primary) amyloidosis | Immunoglobulin light chain (Bence Jones protein) |
| AA (secondary) amyloidosis | Serum amyloid A (SAA) |
| ATTR (familial) amyloidosis | Transthyretin (prealbumin) |
| Localized amyloidoses | |
| A ß 2M amyloidosis | ß 2 microglobulin |
| A ß amyloidosis | ß protein |
Several forms of localized amyloidosis are described. Renal dialysis of more than eight years will in most patients result in amyloid deposition in the carpal ligament, causing carpal tunnel syndrome (A ß 2M amyloid). ß protein, a proteolytic degradation product of a larger transmembrane glycoprotein, ß amyloid precursor protein, is deposited in the brain in Alzheimer's disease, Down's syndrome, and amyloid angiopathy.
Muscle fiber deposits of ß protein may be seen in a variety of myopathies, including inclusion body myositis, distal myopathy with rimmed vacuoles, acid maltase deficiency, oculopharyngeal muscular dystrophy, limb girdle muscular dystrophy, and Becker's muscular dystrophy. Within forms of amyloidosis, however, its presence in muscle is limited to the primary amyloidoses where, despite amyloid deposition in the walls of septal vessels, it is only rarely symptomatic. In view of recent findings, however, routine staining for amyloid in myopathic conditions is warranted. -mr
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