Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation that primarily targets the joints, leading to pain, swelling, and eventual degradation of cartilage and bone. RA is a multisystem condition whose effects extend far beyond the skeletal system, frequently impacting the nervous system due to persistent, uncontrolled inflammation. This involvement ranges from localized nerve compression to more widespread damage, and neurological complications are a direct consequence of the disease’s underlying pathology.
Systemic Mechanisms Driving Neural Involvement
The inflammation that damages joints also drives neurological complications through several distinct systemic mechanisms. A major factor is the chronic production of pro-inflammatory signaling molecules, known as cytokines, such as Tumor Necrosis Factor-alpha (TNF-a), Interleukin-1 (IL-1), and Interleukin-6 (IL-6). This state of systemic inflammation can directly irritate and damage nerve tissue, which interferes with normal nerve signaling and function.
A particularly aggressive mechanism is rheumatoid vasculitis, which involves the inflammation of blood vessel walls. When small and medium-sized arteries that supply oxygen and nutrients to the nerves become inflamed, their blood flow is restricted. This resulting lack of blood supply, or ischemia, can cause the nerve fibers to die, leading to rapid and severe neurological symptoms. The autoimmune response itself plays a role, as the body produces autoantibodies like Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPAs). These antibodies can form immune complexes that deposit in tissues, including the walls of blood vessels, triggering further inflammation and tissue destruction.
Effects on the Peripheral Nervous System
The nerves outside the brain and spinal cord, collectively known as the peripheral nervous system, are the most common site of neurological involvement in RA. The inflammation and joint swelling characteristic of RA frequently lead to compression of nearby nerves, resulting in entrapment neuropathies.
The most prevalent example is Carpal Tunnel Syndrome, where inflammation of the wrist tendons and joint lining compresses the median nerve as it passes through the wrist tunnel. Similarly, Tarsal Tunnel Syndrome can occur in the ankle, where swelling compresses the tibial nerve, causing pain, numbness, and tingling in the foot. These localized nerve compressions cause focal symptoms that correspond directly to the nerve’s distribution, often affecting the hands and feet.
Beyond localized compression, RA can cause a more generalized condition called symmetrical sensorimotor polyneuropathy. This form of nerve damage is typically axonal, meaning it affects the main body of the nerve cell. Symptoms usually begin subtly in the longest nerves, manifesting as numbness, tingling, or a burning sensation in both feet and hands, often described as a “glove-and-stocking” distribution.
In cases of severe, active disease, particularly when rheumatoid vasculitis is present, patients may develop mononeuritis multiplex. This is a serious condition defined by damage to two or more separate, distinct nerve areas in an asymmetrical pattern. The inflammation of nutrient-supplying blood vessels causes sudden, painful sensory and motor deficits in unrelated parts of the body.
Implications for the Central Nervous System and Spinal Cord
Involvement of the central nervous system (CNS), which includes the brain and spinal cord, is less common but often more severe. One of the most serious complications is cervical spine instability, primarily atlantoaxial subluxation, which affects the first two vertebrae in the neck (C1 and C2). Chronic RA inflammation destroys the ligaments and bone surrounding this junction, leading to joint misalignment and instability.
This instability can cause the upper neck vertebrae to shift, leading to direct compression of the spinal cord, a condition known as myelopathy. Myelopathy can result in weakness, sensory changes, and loss of coordination in the limbs. Continuous monitoring for signs of instability is important, as the likelihood of cervical involvement increases with the duration of RA.
Another less direct but increasingly recognized CNS implication is cognitive dysfunction, often termed “Rheumatoid Fog” by patients. This involves issues with memory, concentration, and processing speed. It is strongly linked to the effect of persistent, high levels of systemic inflammation on brain function.
A rare but potentially devastating CNS complication is cerebral vasculitis, where inflammation affects the blood vessels within the brain. This can lead to a wide range of neuropsychiatric symptoms, including severe headaches, seizures, or stroke-like events due to restricted blood flow.