Rheumatoid arthritis: neurologic manifestations

Robert P Lisak MD (

Dr. Lisak of Wayne State University School of Medicine received consultant fees from GLG Consulting, Insight Consulting, Clearview Consulting, Insights Consulting, Haven Consulting, Slingshot Consulting, and Resources Decision Group. He received research support from Alexion, Novartis, Hoffman-LaRoche, Sanofi-Aventis, Argenx and Genzyme and an honorarium from Argenx, Novartis and Mallinckrodt for advisory board membership.

Francesc Graus MD PhD, editor. (Dr. Graus of the University of Barcelona has no relevant financial relationships to disclose.)
Originally released December 4, 2001; last updated January 14, 2020; expires January 14, 2023

This article includes discussion of rheumatoid arthritis: neurologic manifestations, atlantoaxial subluxation, and subaxial subluxation. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Rheumatoid arthritis is a systemic disease that can potentially affect any organ. Neurologic complications in particular are well recognized, causing distinct increase in morbidity and mortality. Multidisciplinary conservative therapies include disease activity control with disease-modifying antirheumatic drugs, glucocorticoids, and new biological agents, in addition to symptomatic treatments such as rest, restriction of activity, moist heat, NSAIDs, gentle massage, etc. Neurologic complications of newer biological therapies and immunosuppressive drugs represent an increasing clinical challenge. Cervical collar, physical therapy, and occupational therapies also have a role. Survival rate is significantly decreased in patients with rheumatoid arthritis and neurologic complications.

Key points


• Patients with rheumatoid arthritis have a reduced survival rate in general.


• Rheumatoid arthritis of the cervical spine is a common complication that is often under-appreciated.


• Neurologic complications related to rheumatoid arthritis affect the central nervous system, peripheral nervous system, muscles, and neuromuscular junction.


• Neurologic complications of newer biological therapies and immunosuppressive drugs are an increasing concern.

Historical note and terminology

Neurologic complications of rheumatoid arthritis have been known for many years. In the 19th century Piters and Villard (Piters and Villard 1886) and later Bannatyne (Bannatyne 1898) described peripheral neuropathy due to rheumatoid arthritis. Bannatyne described infiltration of small round cells in the nerve sheath, in the perivascular region, and among nerve fibers, as well as thickening of intima of blood vessels with encroachment on the vascular luminal wall (Bannatyne 1898). In 1942 Freund and colleagues reviewed the earlier reports on the rheumatoid arthritis neuropathy and reported “perineuritic nodules” in autopsied specimens of rheumatoid arthritis patients (Freund et al 1942). These nodules consisted of chronic inflammatory cells in peripheral nerves. However, the significance of these observations was unknown until Ball described the presence of systemic arteritis that included peripheral neuropathy, which could complicate rheumatoid arthritis (Ball 1954). Three years later, Hart and colleagues reported 10 rheumatoid arthritis patients with peripheral neuropathy and attributed it to diffuse arteritis (Hart et al 1957). Neuropathy, therefore, was considered as an important complication of rheumatoid arthritis. Lastly, Ferguson and Slocumb indicated that development of peripheral neuropathy in rheumatoid arthritis has prognostic values (Ferguson 1961). In their view, rheumatoid arthritis patients with peripheral neuropathy due to vasculitis had decreased survival compared to patients without neuropathy. With introduction of modern neurology in the last 25 years, other neurologic complications of rheumatoid arthritis such as cerebral vasculitis and cervical myelopathy have also been recognized.

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