Dyck, Peter James

ABSTRACTAimTo report a novel case of biopsy‐proven, mass spectrometry‐confirmed, wild‐type transthyretin amyloidosis (ATTRwt) in nerve.MethodsThe patient was identified and evaluated in the peripheral nerve clinic. Our nerve laboratory's pathology database and the literature were searched for prior evidence of pathologically confirmed cases of ATTRwt.ResultsA 94‐year‐old man with a history of lumbar spinal stenosis presented to the neurology clinic with subacute‐on‐chronic progressive, upper limb predominant weakness along with numbness and tingling paresthesia. Electromyography (EMG) revealed multiple mononeuropathies involving the right median nerve at the wrist, right ulnar nerve, and right distal radial nerve superimposed upon an 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 and started on diflunisal therapy for neuropathy treatment.ConclusionThis 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 may open up amyloid‐specific treatments for this disease.

Abstract Vasculitic neuropathy is caused by inflammatory destruction of nerve blood vessels resulting in nerve ischaemia. Nerve vasculitis can be divided into two categories based on vessel size: large-arteriole vasculitis (≥75 µm) and microvasculitis (<75 µm). Herein, we characterize the clinical features of nerve large-arteriole vasculitis in comparison to nerve microvasculitis. This is a retrospective cohort study of patients evaluated and biopsied at Mayo sites between 2001 and 2020. We collected clinical and histopathological data from patients whose nerve biopsies were either diagnostic or highly suggestive of nerve vasculitis. Two hundred and seventy-eight cases were identified: 125 cases of large-arteriole vasculitis and 153 cases of microvasculitis. Nerve large-arteriole vasculitis presented with a more acute (50.4% versus 26.8%) versus chronic onset (33.6% versus 57.5%) than nerve microvasculitis (P = 0.0001). Nerve microvasculitis had longer mean time to diagnosis (10.5 versus 4.3 months; P < 0.0001) and longer time to plateau (8.9 versus 3.5 months; P < 0.0001). Nerve large-arteriole vasculitis typically presented as distal asymmetric polyneuropathy (48.0%), whereas nerve microvasculitis typically presented as radiculoplexus neuropathy/polyradiculoneuropathy (more proximal involvement of shoulder and thigh) (43.8%) (P < 0.0001). Systemic autoimmune disease was more common in nerve large-arteriole vasculitis (70.4% versus 22.9%, odds ratio, 8.0; 95% confidence interval, 4.7–13.7; P < 0.0001). Nerve microvasculitis was significantly related to non-systemic vasculitis (71% versus 23%, odds ratio, 7.9; 95% confidence interval, 4.6–13.6; P < 0.0001). Nerve microvasculitis had more autonomic involvement (24.2% versus 7.2%, odds ratio, 4.1; 95% confidence interval, 1.9–8.9; P = 0.0002). Nerve large-arteriole vasculitis and nerve microvasculitis have different but overlapping clinical features. Nerve large-arteriole vasculitis usually presents with acute onset, distal asymmetric polyneuropathy, associated with other autoimmune diseases and systemic involvement. In contrast, nerve microvasculitis usually presents with a subacute/chronic onset, as radiculoplexus neuropathy/polyradiculopathy (distal and proximal pattern) with autonomic involvement, and is more often a form of non-systemic vasculitis.