From the Guidelines
Neuropsychiatric lupus (neuro lupus) is caused by inflammation affecting the central nervous system in people with systemic lupus erythematosus (SLE), resulting from the immune system mistakenly attacking healthy tissues in the brain, spinal cord, and nerves. This occurs through several mechanisms, including autoantibodies that cross the blood-brain barrier and directly damage neural tissue, blood vessel inflammation (vasculitis) that disrupts blood flow to the brain, and the formation of blood clots that can cause strokes or other neurological problems 1. Cytokines, which are inflammatory molecules released during immune responses, can also directly damage brain tissue. Risk factors that increase the likelihood of developing neuro lupus include having severe systemic lupus, previous neurological symptoms, high levels of antiphospholipid antibodies, and uncontrolled high blood pressure.
Key Mechanisms and Risk Factors
- Autoantibodies crossing the blood-brain barrier
- Blood vessel inflammation (vasculitis)
- Formation of blood clots
- High levels of antiphospholipid antibodies
- Uncontrolled high blood pressure
- Previous neurological symptoms
- Severe systemic lupus Certain medications used to treat lupus, such as high-dose corticosteroids, can occasionally cause neuropsychiatric symptoms that mimic neuro lupus.
Diagnosis and Treatment
Treatment typically involves immunosuppressive medications like cyclophosphamide, rituximab, or mycophenolate mofetil, along with corticosteroids to reduce inflammation, and sometimes anticoagulants if blood clots are involved 1. The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis, EEG, neuropsychological tests, nerve conduction studies, and MRI. Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process, and antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.
From the Research
Causes of Neuro Lupus
The exact causes of neuro lupus, a condition characterized by the effects of systemic lupus erythematosus (SLE) on the central nervous system (CNS), are complex and multifactorial. Some key factors include:
- Autoantibodies, particularly anti-dsDNA and anti-Sm, which are highly specific to SLE and participate in immune complex formation and inflammatory damage on multiple end-organs, including the CNS 2
- Immune complex deposition and complement activation, which can lead to thrombo-ischemic injury and small vasculopathic changes in the brain 3
- Genetic predisposition, environmental triggers, and hormonal factors, which can contribute to the development and activity of SLE 4
- Dysregulation of cytokines, including type I interferons, and disruption of the clearance of nucleic acids after cell death, which can also play a role in the pathogenesis of SLE 4
Pathological Mechanisms
The pathological mechanisms underlying neuro lupus involve:
- Thrombo-ischemic injury and small vasculopathic changes, which are the most common neuropathological features of SLE 3
- Immune complex deposition on cortical vessels, which can lead to cerebral lupus vasculopathy 3
- Activation of the complement system and engagement of immune cells, which can contribute to tissue damage and inflammation 2, 4
- Release of pro-inflammatory cytokines, such as interleukin-6 (IL-6), which can exacerbate disease activity 5
Biomarkers and Disease Activity
Several biomarkers have been identified as potential predictors of disease activity in SLE, including:
- Anti-dsDNA and complement levels (C3 and C4) 5
- Circulating immune complexes (CIC) and IL-6, which have been shown to correlate with disease activity and can be used in combination to improve prediction of active clinical SLE 5
- Erythrocyte sedimentation rate (ESR), which can also be elevated in active SLE 5