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Nerve Symptoms

RA complications affecting the nervous system (both the central and peripheral nervous systems) can occur from inflammation of the small blood vessels (vasculitis) that feed the nerves, with immune system cells and chemicals causing nerve damage (demyelination), or from compression of the nerves by damaged joints and related structures. Examples of the latter include carpal tunnel syndrome, with nerve symptoms affecting the hand and fingers, and cervical spine involvement resulting in compression of the spinal cord, causing pain and sensory loss in the hands and feet.1

An estimated 20% of RA patients may experience clinically significant symptoms affecting the peripheral nerves (those nerves outside of the brain and the spinal cord). However, many more RA patients (65% to 85%) experience subclinical nerve involvement (where symptoms are not serious enough to satisfy any specific diagnosis).2

Additionally, nerve symptoms can result as side effects from the many medications that are used to treat RA, including glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs), including newer biologic treatments.2 Patients diagnosed with demyelinating diseases, such as multiple sclerosis, cannot use any of the TNF-inhibitor drugs which are known to cause demyelination as a rare side effect.

Non-compressive nerve symptoms

Non-compressive nerve symptoms result from inflammation that affects the nerve directly, resulting in demyelination, a process where the outer protective layer of the nerve (myelin) is damaged, and damage to the axon (the part of the nerve cell that transmits electrical nerve impulses). Demyelination and axonal damage can result in symptoms including pain, abnormal sensations, such as  tingling and “pins-and-needles”, and muscle weakness. The most common manifestations of this non-compressive nerve damage include loss of the ability to extend the wrist (wrist drop) or move the toes or ankle upward (foot drop), as in the motion used for walking.2


Compressive nerve symptoms

Nerve compression (also called entrapment) can occur early in the course of RA, as changes take place in joints, resulting in direct pressure on nerves located in proximity to joint structures. The most common example of this is carpal tunnel syndrome, a condition that affects as many as two-thirds of RA patients. In carpal tunnel syndrome, inflammation affects the tendons and ligaments that surround the median nerve, which runs through the carpal tunnel in the wrist into the thumb side of the hand. Inflamed tendons and ligaments compress the nerve producing stinging pain, numbness, and tingling, affecting the first three fingers and the thumb side of the hand. Pain and abnormal sensations are made worse by repetitive movements and nerve symptoms may even involve the forearm and upper arm.2

Nerve entrapment disorders similar to carpal tunnel syndrome may also occur with the ulnar nerve in the elbow (called cubital tunnel syndrome) and the tibial nerve that runs along the inner leg near the ankle (called tarsal tunnel syndrome). Tarsal tunnel syndrome can result in numbness and other abnormal sensations (burning, tingling, and electrical sensations) in the foot, affecting the big toe, first three toes, and the heel.2


Central nervous system symptoms

RA-related inflammation may affect the cervical spine, causing swelling in the joints between vertebra (specifically the atlas and the axis), which can cause compression of the spinal cord. Compression of the spinal cord may result in a range of symptoms, including neck pain (on movement), headache, weakness, abnormal reflexes, loss of normal sensation in various parts of the body, and changes in blood pressure and breathing.2


Nervous system effects of RA medications

Common medications used to treat RA, including NSAIDs, glucocorticoids, and DMARDs, may be associated with side effects that affect the nervous system. While these effects may only occur in a minority of patients, they may explain certain nerve symptoms experienced by patients with RA. For example, corticosteroid treatment can be associated with cognitive dysfunction, hypomania, and depression and the DMARD methotrexate can be associated with headache and impairment of the ability to concentrate.2 Some DMARDs, such as sulfasalazine or leuflunomide, can lead to peripheral neuropathy and TNF-inhibitors, such as are known to lead to demyelinating disorders, such as multiple sclerosis or Gullian-Barré syndrome.


Possible nervous system side effects with RA medications

Side effects
  • Hypomania, mania, depression, psychosis, myopathy, cognitive dysfunction
  • Aseptic meningitis, psychosis, cognitive dysfunction
  • Headache, impaired ability to concentrate
  • Headache, peripheral neuropathy, vertigo
  • Peripheral neuropathy, headache
Gold salts
  • Peripheral neuropathy, Guillain-Barré-type syndrome, cranial nerve palsies, encephalopathy
TNF inhibitors
  • Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, multiple sclerosis

Adapted from Ramos-Remus C, Duran-Barragan S, Castillo-Ortiz JD. Beyond the joints: neurological involvement in rheumatoid arthritis. Clin Rheumatol 2012;31:1-12.


Treatment of RA-related nerve symptoms

Treatment of RA-related nerve symptoms depends on the nature, location, and severity of the symptom. Initial treatment options may include medications used to control RA-related inflammation and pain, including NSAIDs, glucocorticoids, and DMARDs, a group of drugs which includes newer biologic treatments.3

In cases where inflammation of joints in the cervical spine is causing nerve compression, interventions that may be useful in controlling pain include use of a neck brace or collar and application of heat or cold. Spinal manipulation should not be used in patients with RA-related involvement in the cervical spine. Additionally, surgical intervention (including fusion of vertebra) may used to address nerve symptoms.4,5 In cases of nerve entrapment in the wrist, elbow, or ankle/foot, treatment options include bracing to restrict movement, exercise and physical therapy, alternative approaches (eg. acupuncture), and surgical options to relieve nerve compression.6

Written by: Jonathan Simmons | Last reviewed: September 2013.
1. Prete M, Racanelli V, Digiglio L, Vacca A, Dammacco F, Perosa F. Extra-articular manifestations of rheumatoid arthritis: An update. Autoimmun Rev 2011;11:123-31. 2. Ramos-Remus C, Duran-Barragan S, Castillo-Ortiz JD. Beyond the joints: neurological involvement in rheumatoid arthritis. Clin Rheumatol 2012;31:1-12. 3. Venables PJW. Patient information: Rheumatoid arthritis treatments (beyond the basics). In: O'Dell JR, Greene JM, eds. UptoDate. Wolters Kluwer Health. Accessed at: 2013. 4. Wasserman BR, Moskovich R, Razi AE. Rheumatoid arthritis of the cervical spine--clinical considerations. Bull NYU Hosp Jt Dis 2011;69:136-48. 5. Schur PH, Currier BL. Cervical subluxation in rheumatoid arthritis. In: Maini RN, Romain PR, eds. UptoDate. Wolters Kluwer Health. Accessed at: 2013. 6. Carpal tunnel syndrome fact sheet. Available at: Accessed 032513.