2025 American Academy of Neurology Abstract Website

Objective:

To report a novel case of symptomatic, biopsy proven, mass spectrometry confirmed, wild type transthyretin amyloidosis (ATTRwt) in nerve tissue.

Background:

Transthyretin amyloidosis (ATTR) is a disorder characterized by deposition of insoluble amyloid deposits in organs and connective tissues. ATTR can be due to transthyretin genetic mutations (variant ATTR) or can occur in normal transthyretin genotype (ATTRwt). ATTRwt typically affects older men and was thought only to cause progressive infiltrative cardiomyopathy, although recent evidence has shown deposition in connective tissue causing compressive carpal tunnel syndrome, tenosynovitis, and lumbar stenosis too. While large fiber peripheral neuropathy has also been loosely associated with ATTRwt disease, ATTRwt confirmed deposition directly in nerve tissue causative of neuropathy has not been previously reported, and no amyloid specific treatments are currently approved for the possible associated neuropathy.

Design/Methods:

Case report.

Results:

A 94-year-old man with history of spinal stenosis presented to neurology clinic with a subacute on chronic progressive, upper limb predominant, weakness along with numbness and tingling paresthesia. Electromyography (EMG) revealed multiple mononeuropathies involving bilateral median nerves at the wrists, bilateral ulnar nerves, and bilateral distal radial nerves superimposed upon a mild length-dependent, sensorimotor, axonal predominant, peripheral neuropathy along with multilevel lumbosacral radiculopathies. Extensive serology for causes of neuropathy and multiple mononeuropathies returned unremarkable. A diagnostic right superficial radial nerve biopsy was performed and showed congophilic material within a small epineurial vessel wall in the nerve tissue. Amyloid typing by mass spectrometry was performed and revealed ATTRwt. TTR gene sequencing returned normal. The patient was diagnosed with ATTRwt neuropathy.

Conclusions:

This case confirms the presence of ATTRwt deposition directly in nerve tissue as the likely cause of the patient’s large fiber and multiple mononeuropathies expanding our current understanding of ATTRwt associated disease. Proving the direct association of ATTRwt and neuropathy could open up amyloid specific treatments for this disease.