Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis: Primary systemic amyloidosis is often complicated by painful, sensory, and autonomic neuropathy.
Source: Matsuda M, et al. Peripheral nerve involvement in primary systemic AL amyloidosis: A clinical and electrophysiological study. Eur J Neurol 2011;18:604-610.
What is the extent and nature, clinically and elec-trophysiologically, of peripheral nerve involvement in primary systemic AL amyloidosis? To address these questions, a retrospective review was undertaken of 43 such patients, previously untreated, admitted between April 2002 and June 2008 to the Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan. Diagnosis was based on tissue biopsy confirmation of amyloid deposition using Congo red and immunohistochemical staining. Records reviewed included the neurological examination, electrodiagnostic studies, past medical history, and blood and urine studies. Statistical analysis was provided by Student's t-test and Mann–Whitney's U test with P < 0.05 considered statistically significant.
Neuropathic involvement, either mononeuropathy, polyneuropathy, or autonomic neuropathy, was evident in 15 patients (34.9%), including nine men and six women, with a mean age of 57.9 years and a mean disease duration of 14.7 months. Polyneuropathy was diagnosed in 11; in two of these it was the presenting symptom. Bilateral carpal tunnel syndrome was present in four, including one with polyneuropathy. Autonomic symptoms, encompassing orthostatic hypotension, hypohydrosis, impotence, urinary incontinence, and alternating diarrhea and constipation, were present in eight, only one of whom had neither polyneuropathy nor carpal tunnel syndrome. In all, sensory symptoms were predominant, with muscle weakness in the distal legs present in only three elderly patients. None had cranial nerve involvement. Electrodiagnostically, the polyneuropathy was predominantly axonal in nature, with decreased motor and sensory amplitudes but only minimal prolongation of terminal motor latencies and mild slowing of motor and sensory nerve conduction velocities compared to normal controls. Neuropathy is common in primary systemic AL amyloidosis and resembles that seen with the late-age-onset transthyretin-type of familial amyloid polyneuropathy.
Primary systemic AL amyloidosis is a lymphoproliferative plasma cell or B-cell disorder in which fibrils of monoclonal light chains, derived from intact monoclonal light chains, fragments of light chains, or heavy chains, are deposited in multiple organs including the liver, kidney, heart, gastrointestinal tract, and peripheral nervous system. Characteristic clinical findings include macroglossia, restrictive cardiomyopathy, proteinuria, the presence of a serum or urine monoclonal protein, and amyloid deposition in affected tissue, the last being the confirmatory test. Peripheral neuropathy is caused by amyloid fibril deposition within the walls of nerve vessels with resultant ischemia or autoantibody interaction. Usually progressive, distal, symmetric, predominantly sensory, and often painful in nature, neuropathy also affects autonomic nerves as well as individual mixed nerves due to localized amyloid deposition (amyloidoma). Cranial nerves may also be affected, though almost always in association with peripheral neuropathy.1
1. Sadek I, et al. Primary systemic amyloidosis presenting with asymmetric multiple mononeuropathies. J Clin Oncology 2010;28:e429-e432.