What is the diagnostic workup and treatment approach for a patient suspected of having Systemic Lupus Erythematosus (SLE) Central Nervous System (CNS) vasculitis?

Workup for SLE CNS Vasculitis

True CNS vasculitis in SLE is exceedingly rare, and the diagnostic workup should prioritize excluding far more common mimics—particularly antiphospholipid antibody-mediated thrombosis, atherosclerotic disease, and infection—before pursuing aggressive immunosuppression. 1, 2

Initial Clinical Assessment

Recognize the rarity: Stroke caused by true vasculitis is very rare in SLE patients; atherosclerotic/thrombotic/embolic cerebrovascular disease is common, making immunosuppressive therapy rarely indicated. 1

Key Clinical Features to Document

• Timing relative to SLE diagnosis: Neuropsychiatric events commonly occur within the first year after SLE diagnosis (50-60% of cases) and often coincide with generalized disease activity (40-50%). 1
• Presence of systemic SLE activity: Generalized disease activity is a strong risk factor (fivefold increase) for neuropsychiatric SLE. 1
• Antiphospholipid antibody status: Persistently positive moderate-to-high titers are strong risk factors for cerebrovascular disease, seizures, and chorea. 1
• Specific neurological manifestations: Focal deficits, encephalopathy, seizures, or progressive cognitive decline over weeks to months. 2, 3

Laboratory Evaluation

Essential Tests

• Antiphospholipid antibody panel: Test for lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies, as these are far more commonly responsible for CNS events than true vasculitis. 1
• ANCA testing: Perform both indirect immunofluorescence and ELISA to exclude ANCA-associated vasculitis. 2
• Inflammatory markers: ESR and CRP, though these are characteristically normal or only minimally elevated in primary CNS vasculitis. 2, 3
• Anti-dsDNA and complement (C3, C4): To assess generalized SLE activity. 1

Cerebrospinal Fluid Analysis

Lumbar puncture should be performed to exclude infection (especially in immunosuppressed patients) and assess for inflammatory markers. 1

• Look for lymphocytic pleocytosis (rarely exceeding 250 cells/mm³), elevated protein, or increased opening pressure. 2
• CSF analysis is critical to exclude septic meningitis before initiating immunosuppression. 1

Neuroimaging Protocol

MRI Brain and Spinal Cord (First-Line)

The recommended MRI protocol includes: 1

• Conventional sequences: T1/T2, FLAIR
• Diffusion-weighted imaging (DWI)
• Gadolinium-enhanced T1 sequences

Expected findings in CNS vasculitis (present in >90% of cases): 2, 3

• Multiple infarcts of variable ages (up to 50% of cases)
• Mass lesions (5%)
• Meningeal enhancement (8%)
• Hemorrhage (9%)
• Enhancement and thickening of vessel walls 4

Vascular Imaging

MR angiography (MRA) or CT angiography (CTA): Noninvasive first-line vascular imaging, though MRA has limited sensitivity (81% in comparative studies) and specificity compared to conventional angiography. 2

Digital subtraction angiography (DSA): Consider when noninvasive imaging is inconclusive, looking for: 2

• Arterial beading with alternating constriction and dilatation
• Segmental arterial narrowing
• Vascular occlusions
• Peripheral aneurysms

Critical caveat: Angiographic findings have low specificity due to significant overlap with atherosclerosis and reversible cerebral vasoconstriction syndrome. 2, 5

Brain Biopsy

Brain biopsy (cortical-leptomeningeal) is the most specific diagnostic test for CNS vasculitis and should be strongly considered when diagnosis remains uncertain after comprehensive workup. 2, 5

Indications for Biopsy

• Imaging findings suggestive of vasculitis without alternative explanation
• Progressive neurological decline despite treatment
• Need to definitively establish diagnosis before committing to prolonged immunosuppression 5

Technical Considerations

• Target abnormal areas identified on MRI or angiography to increase yield. 2
• A negative biopsy does not exclude vasculitis due to the focal nature of the disease. 2
• Biopsy is essential to exclude mimics before initiating aggressive immunosuppression. 6

Differential Diagnosis to Exclude

Before diagnosing CNS vasculitis, systematically exclude: 6

1. Antiphospholipid syndrome (most common in SLE—test for antiphospholipid antibodies) 1
2. Atherosclerotic disease (far more common than vasculitis) 1
3. Infection (septic arteritis, especially in immunosuppressed patients) 1, 6
4. Reversible cerebral vasoconstriction syndrome 2, 5
5. Cardiogenic embolism 6
6. Drug-induced changes 7

Treatment Approach

For Confirmed Inflammatory CNS Vasculitis

Glucocorticoids and immunosuppressive therapy are indicated for neuropsychiatric manifestations reflecting an immune/inflammatory process, following exclusion of non-SLE-related causes. 1

Induction therapy: High-dose glucocorticoids (intravenous methylprednisolone) followed by intravenous cyclophosphamide. 1, 4

Maintenance therapy: Less intensive immunosuppression (azathioprine or mycophenolate mofetil) to prevent recurrence. 1

Alternative for high-risk patients: Intravenous immunoglobulin (IVIG) when cyclophosphamide is contraindicated due to infection risk or prior serious adverse events. 4

For Antiphospholipid-Mediated Disease

Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly in thrombotic cerebrovascular disease. 1

• Long-term anticoagulation for secondary prevention in patients fulfilling antiphospholipid syndrome criteria 1
• Anticoagulation may be superior to antiplatelet therapy for arterial events 1

Common Pitfalls

• Assuming all CNS events in SLE are vasculitis: Most are thrombotic/embolic or atherosclerotic. 1
• Initiating "blind" immunosuppression: This can be catastrophic if infection is the underlying cause. 6
• Over-relying on angiography: Angiographic findings are nonspecific and overlap with multiple conditions. 2, 5
• Ignoring antiphospholipid antibodies: These are far more commonly responsible for CNS events than true vasculitis. 1

Monitoring Response

Imaging improvement should be documented 5-23 days after starting treatment in true vasculitis cases. 4

Repeat MRI to assess response and guide duration of therapy. 4