Systemic lupus erythematosus (SLE) is a chronic autoimmune disease where the immune system mistakenly attacks its own healthy tissues and organs. Because this systemic attack can affect virtually any part of the body, including the central nervous system, lupus can cause seizures. Seizures are recognized as one of the most serious neurological manifestations of the disease. They can occur at any point in the disease course, sometimes even before a lupus diagnosis is established. Managing lupus-related seizures involves treating both the seizure event and the underlying autoimmune activity causing the inflammation.
Lupus and Central Nervous System Involvement
When lupus affects the brain, spinal cord, or peripheral nerves, the condition is classified under the term Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Seizures are a major manifestation of NPSLE. The frequency of seizures in SLE patients can range from about 9% to as high as 58% in reported studies, highlighting the variability of the disease.
Seizures are part of a wider spectrum of symptoms that can arise from NPSLE, including headaches, cognitive dysfunction, mood disorders, and stroke. The most common type of seizure associated with lupus is the generalized tonic-clonic seizure, which involves loss of consciousness and muscle jerking. Seizures often occur during periods of high lupus disease activity.
Biological Mechanisms Causing Seizures
The seizure activity in lupus is caused by inflammation, autoantibodies, and vascular damage within the brain.
One primary mechanism is vascular insult, where the blood vessels supplying the brain become damaged or blocked, leading to a lack of oxygen or micro-infarctions. Antiphospholipid antibodies, which are sometimes present in SLE, can increase the risk of blood clots (thrombosis). These clots obstruct blood flow and cause focal regions of ischemia, potentially triggering a seizure.
A second major mechanism involves the penetration of specific autoantibodies into the central nervous system. When the blood-brain barrier is compromised by inflammation, autoantibodies can cross into the brain tissue and directly interfere with neuronal function. For instance, anti-ribosomal P antibodies and anti-neuronal antibodies are thought to target and disrupt nerve cells, increasing neuronal excitability and lowering the seizure threshold.
Systemic inflammation also plays a role through the release of pro-inflammatory cytokines, such as interleukin-6. These chemical messengers can contribute to overall brain irritation, which further lowers the threshold at which a seizure may be triggered. This combination of vascular damage, antibody attack on neurons, and generalized neuroinflammation creates a seizure-prone environment in the lupus brain.
Diagnosing Lupus-Related Seizure Activity
Attributing a seizure to lupus can be a diagnostic challenge because many factors can cause seizures in a patient with SLE, including infection, metabolic imbalances, or medication side effects. The first step in the diagnostic process is to rule out these secondary causes, such as uremia from kidney disease, electrolyte disturbances, or central nervous system infections like meningitis.
Magnetic Resonance Imaging (MRI) of the brain is used to look for signs of inflammation, lesions, or ischemic damage specific to lupus. An Electroencephalogram (EEG) is performed to confirm abnormal electrical activity and classify the type of seizure. A lumbar puncture may be performed to collect Cerebrospinal Fluid (CSF) for analysis. Elevated white blood cell counts or specific inflammatory markers in the CSF provide supportive evidence for active NPSLE as the cause of the seizure.
Treatment and Management Strategies
The management of lupus-related seizures requires a two-pronged approach: immediate control of the seizure event and long-term suppression of the underlying autoimmune disease activity.
Standard anti-epileptic drugs (AEDs), such as levetiracetam or valproic acid, are used acutely to stop and prevent future seizures. However, AEDs alone do not address the root cause of the problem.
To prevent recurrence, the primary treatment focuses on suppressing the systemic autoimmune inflammation that is attacking the brain. This typically involves high-dose corticosteroids, such as intravenous methylprednisolone, which are powerful anti-inflammatory agents. For more severe or persistent cases, stronger immunosuppressive medications like cyclophosphamide or azathioprine may be used to bring the overall lupus activity under control. Treating the underlying lupus helps stabilize the central nervous system environment and reduces the long-term risk of future neurological events.