Amyloid Mimics Chronic Inflammatory Demyelinating Polyneuropathy

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: Amyloidosis may present with the clinical and electrophysiologic features of chronic inflammatory demyelinating polyneuropathy. Nerve biopsy may be necessary to make an accurate diagnosis.

Source: Mathis S, et al. Amyloid neuropathy mimicking chronic inflammatory demyelinating polyneuropathy. Muscle Nerve DOI: 10.1002/mus.22229.

Chronic inflammatory demyelinating polyneuropathy (CIDP) presents as a slowly progressive (for more than 8 weeks), symmetric, motor greater than sensory polyneuropathy, with both proximal and distal muscle weakness, large fiber more than small fiber, distally predominant sensory impairment, and depressed or absent deep tendon reflexes. Electrodiagnostic studies are characteristic, demonstrating conduction block, conduction velocity slowing, prolonged distal motor latencies, delayed or absent F waves, and dispersion of compound motor action potentials (CMAP). Intravenous immunoglobulin (IVIG), steroids, and plasma exchange are the mainstays of treatment, with two-thirds responding initially. Approximately 10-15% will be refractory to therapy. Some of these patients may in fact have amyloid neuropathy.

Among patients undergoing sural nerve biopsy at the Universities of Poitiers and Limoges, France, over a 5-year period, five patients (four men and one woman) with suspected CIDP with onset in the late seventh or early eighth decade, were shown to have biopsy-proven amyloidosis. All demonstrated weakness, sensory loss, and generalized areflexia, with four having elevated cerebrospinal fluid protein, ranging from 50-90 mg/dL. Electrodiagnostic studies were typical of acquired demyelinating polyneuropathy, with prolonged or absent F responses and distal motor latencies, slowed motor conduction velocity, and decreased or normal CMAP amplitudes. Prior to referral, four patients had failed to respond to steroids or IVIG, or both, with one patient receiving no previous therapy. Three patients had underlying small fiber involvement, based on a history of alternating episodes of constipation and diarrhea, or postural hypotension, or both. All sural nerve biopsies demonstrated Congo red staining. Only occasional onion bulb formation was evident. Direct sequencing of the transthyretin gene revealed a V30M mutation in three patients, with two patients having primary amyloid polyneuropathy. In those with the V30M mutation, amyloid deposits were seen around endoneural blood vessels. When otherwise typical CIDP patients are refractory to immunosuppressive therapy, amyloid should be suspected and sural nerve biopsy and sequencing of the transthyretin gene should be performed.

Commentary

Formerly called prealbumin and encoded on chromosome 18, more than 100 dominant mutations have now been identified in the transthyretin gene, resulting in the most frequent form of hereditary amyloidosis, transthyretin (TTR) amyloidosis. Pathology results from extracellular amyloid deposition in multiple organ systems, and carpal tunnel syndrome or a slowly progressive sensorimotor and autonomic neuropathy are its characteristic neurologic presentations, with motor function usually preserved in the latter until the sensory neuropathy is considerably advanced. Motor neuropathy, mimicking anterior horn cell disease also has been reported¹ highlighting the heterogeneity of this disease entity. Amyloid should be suspected as an alternative diagnosis in these instances, particularly if cataracts, vitreous opacities, renal, heart, or skin involvement are also found. Periumbilical fat pad biopsy may be negative, and muscle or nerve biopsy must be performed with specific staining for amyloid should the question arise.

Reference

1. Riboldi G, et al. Tyr78Phe transthyretin mutation with predominant motor neuropathy as the initial presentation. Case Rep Neurol 2011;3:62-68.