Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder defined by inflammation that primarily targets the joints, leading to pain and structural damage. While RA is typically associated with musculoskeletal symptoms, it is a whole-body disease with the potential to affect various organ systems, including the nervous system. The occurrence of seizures in a patient with RA is a rare complication, usually stemming from either the systemic effects of the disease itself or from the treatments used to manage it.
Direct Link: How RA Inflammation Affects the Central Nervous System
The body-wide inflammation characteristic of RA can, in rare instances, extend directly to the central nervous system (CNS) and trigger neurological events like seizures. The primary direct cause is a severe, extra-articular manifestation of RA known as rheumatoid meningovasculitis. This condition involves the inflammation of the blood vessels and membranes (meninges) covering the brain and spinal cord, which can restrict blood flow and lead to localized tissue irritation that sparks seizure activity.
Another direct pathway involves rheumatoid meningitis, which is inflammation of the meninges. Seizures are a known, though uncommon, symptom of this rare complication, which can cause symptoms like headache and altered mental status. The inflammation itself creates an excitatory environment in the brain, lowering the threshold for electrical disturbances that result in a seizure.
In rarer cases, the characteristic rheumatoid nodules that usually form under the skin can develop within the CNS. These intracranial rheumatoid nodules act as space-occupying lesions, and their presence can put pressure on brain tissue. This localized irritation can disrupt normal electrical signaling, leading to focal or generalized seizures. When RA directly causes a seizure, it is typically a sign of severe, active, and uncontrolled systemic disease requiring immediate, aggressive treatment.
Indirect Risk Factors: The Role of RA Medications
The treatment regimen for RA is a more frequent, though still uncommon, source of seizure risk, often through the side effects of medications that can lower the seizure threshold. Glucocorticoids, such as high-dose prednisone, are potent anti-inflammatory drugs used to manage disease flares and have known neurological side effects. These can include anxiety, insomnia, and confusion, and in some patients, particularly with high or rapidly changing doses, they can increase the likelihood of a seizure.
Certain disease-modifying antirheumatic drugs (DMARDs) also carry warnings regarding neurological complications. Methotrexate (MTX), a common RA treatment, can cause neurotoxicity in a small percentage of patients, particularly when given at high doses or intrathecally. This neurotoxicity can manifest as headaches, stroke-like symptoms, or seizures, often temporally related to the dose.
Hydroxychloroquine (HCQ) is another medication that can affect the nervous system, with its labeling noting a potential to lower the seizure threshold. Biologic therapies, such as TNF inhibitors, are also associated with rare inflammatory central nervous system events, including demyelinating disorders, which can be related to seizure onset. These medication-related events are important to identify, as stopping the causative drug usually resolves the neurological symptoms.
Co-occurring Conditions and Differential Diagnosis
A seizure in a patient with RA is frequently not a direct result of the arthritis but a consequence of co-existing or secondary conditions common in this patient population. Systemic inflammation in RA is linked to accelerated atherosclerosis and an increased risk of stroke, which is itself a major cause of seizures. RA patients have a significantly higher risk of stroke compared to the general population.
RA frequently overlaps with other autoimmune conditions that have a direct and established link to seizures. The co-existence of RA with systemic lupus erythematosus (SLE) is known as Rhupus syndrome, and SLE is strongly associated with neuropsychiatric manifestations, including seizures, which occur in an estimated 15% to 20% of patients with SLE. Secondary Sjögren’s syndrome, which often overlaps with RA, can also cause neurological complications that may lead to seizures.
Infection and metabolic disturbances represent another layer of seizure risk. RA patients, especially those on immunosuppressive therapy, have a higher susceptibility to severe infections, which can lead to sepsis and subsequent sepsis-associated encephalopathy. The systemic inflammation associated with severe infection can trigger seizures. Metabolic imbalances, such as severe hypoglycemia or electrolyte disturbances, can also provoke seizures and are more likely in a person with RA due to disease-related complications or medication effects.
The diagnostic process for a seizure in an RA patient is complex, requiring a neurologist and rheumatologist to work together to rule out the most likely causes first. This involves testing for infection, checking for metabolic issues, reviewing the drug regimen for potential neurotoxicity, and using imaging like MRI and EEG to look for signs of stroke or the rare direct CNS inflammation seen in RA. Distinguishing between a drug side effect, a secondary condition, or a direct RA complication is essential for determining the correct and most effective treatment strategy.