How to manage a patient with Systemic Lupus Erythematosus (SLE) in flare presenting with seizures?

Management of SLE Flare with Seizures

In an SLE patient presenting with seizures during a flare, immediately initiate anti-epileptic drug therapy while simultaneously treating the underlying lupus activity with high-dose glucocorticoids (pulse IV methylprednisolone) combined with immunosuppressive therapy (IV cyclophosphamide) if the seizure is thought to reflect acute inflammatory CNS involvement. 1

Immediate Diagnostic Workup

Before attributing seizures to lupus, you must aggressively exclude other causes—the most dangerous error is assuming seizures are lupus-related without adequately ruling out infection, especially in immunosuppressed patients 2:

• CSF examination is essential to exclude CNS infection, particularly in any patient on immunosuppression 1
• MRI with conventional sequences, diffusion-weighted imaging, and gadolinium-enhanced T1 sequences to identify structural lesions (cerebral atrophy in 40%, white matter lesions in 50-55% of SLE seizure patients) 1, 3
• EEG to identify epileptiform patterns (present in only 24-50% but predictive of recurrence with 73% positive predictive value, 79% negative predictive value) 1
• Antiphospholipid antibody testing as these antibodies confer at least fivefold increased risk for seizures 3
• Exclude metabolic disturbances, drug toxicity, and other precipitants 4

Critical caveat: Normal laboratory values do not exclude active CNS lupus, as neurological involvement can occur independently of systemic disease activity 2

Anti-Epileptic Drug Therapy Decision Algorithm

The decision to start AEDs depends on seizure characteristics and risk factors 1, 5:

Start AED therapy if ANY of these high-risk features are present:

• Two or more unprovoked seizures occurring at least 24 hours apart 1, 5
• Structural brain abnormalities on MRI causally linked to seizures 1, 5
• Focal neurological signs 1, 5
• Partial (complex) seizures 1, 5
• Epileptiform EEG patterns 1, 5
• Serious brain injury 5

AED therapy is NOT necessary for:

• Single isolated seizures without high-risk features 1, 5
• Infrequent seizures in the absence of risk factors 1

Approximately 25% of SLE patients will require a second AED to control seizure activity 1. Generalized tonic-clonic seizures occur in 67-88% of SLE seizure patients, while partial seizures are less common 1, 2.

Immunosuppressive Therapy for Lupus-Related Seizures

If seizures are thought to reflect an acute inflammatory event OR if a concomitant lupus flare is present, treat aggressively with immunosuppression 1, 5:

• Pulse IV methylprednisolone combined with IV cyclophosphamide has demonstrated effectiveness in refractory seizures in the context of generalized lupus activity 1
• Glucocorticoids alone may be used for less severe presentations 1, 5
• Response rates of 60-80% are typical for inflammatory NPSLE manifestations when treated appropriately 3

Important warning: Be aware that cyclophosphamide itself can rarely induce seizures as a paradoxical side effect, though this is uncommon with standard dosing 6

Special Considerations for Antiphospholipid Antibody-Positive Patients

If antiphospholipid antibodies are present 3, 2:

• Consider antiplatelet or anticoagulation therapy, especially if other APS manifestations are present 1
• Triple antibody positivity (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I) indicates highest risk for thrombotic events 2
• Cerebrovascular disease commonly occurs (50-60%) in the context of persistently positive moderate-to-high titers 2

Long-Term Management and AED Discontinuation

For patients seizure-free for 24 consecutive months with resolution of structural lesions on imaging, consider tapering and stopping AEDs 5:

Reconsider discontinuation if:

• Breakthrough seizures occur during taper 5
• Worsening lupus activity with new neuropsychiatric manifestations 5
• Development of new structural brain lesions on repeat imaging 5
• Epileptiform activity appears on EEG 5

Prognostic Factors

Seizures in SLE tend to occur early in disease course, often in younger patients with high disease activity 7, 8:

• Recurrent seizures (epilepsy) occur in 12-22% of SLE seizure patients and significantly impact morbidity and mortality 1
• Predictors of epilepsy include higher baseline disease activity, concurrent multiple NPSLE manifestations, prior strokes, and male gender 8
• Baseline predictors of any seizure include disease activity, psychosis, moderate-to-high titer anti-cardiolipin and anti-Smith antibodies, and damage accrual 8