Electrodiagnostic Features of Vasculitic Neuropathy

By Michael Rubin, MD

Professor of Clinical Neurology, Weill Cornell Medical College

SYNOPSIS: Electrophysiological studies of vasculitic neuropathy indicate that the best discriminators of vasculitis vs. other axonal neuropathies are the side-to-side differences between the same bilateral nerves. When the diagnosis is uncertain, nerve biopsy may be definitive.

SOURCE: Davalos L, Watanabe M, Gallagher GW, et al. Diagnostic characteristics of nerve conduction study parameters for vasculitic neuropathy. Muscle Nerve 2023;67:45-51.

Vasculitis may involve any organ, but when it affects epineurial and endoneurial vessels supplying peripheral nerves, consequent ischemia results in nerve damage, particularly among those systemic vasculitides involving small- or medium-sized arteries, such as granulomatosis with polyangiitis, polyarteritis nodosa, and mixed cryoglobulinemia. Nerve conduction studies (NCS) reveal axonal damage, as opposed to demyelination, involving multiple individual nerves in an asymmetric fashion, and often are performed to support the clinical diagnosis, exclude mimics such as chronic inflammatory demyelinating polyneuropathy (CIDP), and help select a biopsy site where warranted. Which electrodiagnostic features best distinguish vasculitic neuropathy from other axonal neuropathies?

In this retrospective, case-control, University of Michigan, hospital-based study performed between January 2000 and April 2021, records of patients with vasculitic neuropathy who had undergone bilateral NCS were reviewed. Inclusion criteria were age 18 years or older, a diagnosis of vasculitic neuropathy using Peripheral Nerve Society criteria, and, when available, supportive nerve pathology.

Control patients were obtained through EMGPro, an institutional database, who were coded as axonal neuropathy and had undergone NCS between January 2005 and April 2021. Statistical analysis encompassed calculating z-score differences and averaging z-scores, logistic regression modeling, Welch’s t-tests, Fisher’s exact test, and Youden’s J statistics, with P-value < 0.05 considered significant.

Among 92 vasculitic neuropathy cases, 82 had undergone bilateral NCS, with 40 meeting pathologically definite criteria and 42 meeting clinically probable criteria. Of these 82 patients, 62 had systemic vasculitic neuropathy, 58 as the result of connective tissue disorders, including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Sjögren disease, systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, livedoid vasculitis, systemic scleroderma, eosinophilic vasculitis, temporal arteritis, and undifferentiated connective tissue disorder, with mixed cryoglobulins or active cancer in another two each. Among 174 non-inflammatory axonal neuropathy controls, 74 had type 2 diabetes, 35 were prediabetic, 33 were idiopathic, 13 had chemotherapy toxicity, and the remaining cases were attributed to alcohol, type 1 diabetes, critical illness neuropathy, and vitamin B12 or copper deficiency.

Of six parameters of electrophysiology tested, including percent differences or absolute differences of amplitude, conduction velocity, or latency, the amplitude percent difference z-score model showed the best discriminatory capability. Too cumbersome for bedside usage in the electromyography lab, a side-to-side amplitude difference of 50% between at least two bilateral nerves, in either the upper or lower extremity, is a reasonable approximation of the z-score model to diagnose vasculitic neuropathy, best demonstrated using the median and ulnar motor nerves.

COMMENTARY

Does nerve biopsy currently play a role in the diagnosis of neuropathy, given our current advances in neurogenetics, neuroinflammation, and electrophysiology?

A retrospective review of 107 nerve biopsies, performed between April 1998 and June 2021 on patients with peripheral neuropathy presenting to the department of neurology, University of Malaya Medical Centre, Kuala Lumpur, Malaysia, revealed that 63% were diagnostically contributive, 26% were essential, and 37% were helpful, based on Midroni and Bilbao criteria. Among the remainder, 33% were noncontributory and 4% were inadequate.

No definitive pathological diagnosis was obtained in 66% of biopsies, but a diagnosis of vasculitis (18%) or amyloidosis (10%) was made in the remainder. Nerve biopsy is of value in the diagnosis of vasculitis and amyloidosis, but it is of limited value otherwise in the diagnosis of peripheral neuropathy.¹

REFERENCE

1. Lee LY, Tan CY, Wong KT, et al. Diagnostic yield of nerve biopsy in the evaluation of peripheral neuropathies. J Clin Neurosci 2023;107:40-47.