From the Guidelines
Neuropsychiatric lupus, or neurolupus, is caused by the autoimmune disease systemic lupus erythematosus (SLE) affecting the central nervous system, with mechanisms involving autoantibodies, blood vessel inflammation, and microclots forming in cerebral blood vessels, as supported by the 2019 update of the EULAR recommendations for the management of SLE 1. The exact mechanisms of neurolupus involve:
- Autoantibodies attacking neural tissues
- Blood vessel inflammation (vasculitis) in the brain
- Microclots forming in cerebral blood vessels These processes lead to neuronal damage and dysfunction. Genetic factors predispose some individuals to develop neurolupus, while environmental triggers like infections, stress, and certain medications can initiate or worsen symptoms. The blood-brain barrier becomes compromised, allowing inflammatory cells and antibodies to enter the central nervous system. Specific antibodies implicated include anti-ribosomal P, anti-NMDA receptor, and antiphospholipid antibodies, which directly damage neurons or disrupt their function. Cytokines and other inflammatory mediators released during lupus flares also contribute to neurological symptoms. Treatment typically involves immunosuppressive medications like corticosteroids, hydroxychloroquine, and sometimes cyclophosphamide or rituximab, depending on symptom severity, as recommended by the EULAR guidelines 1. Addressing neurolupus requires a multidisciplinary approach with rheumatologists and neurologists working together to manage this complex manifestation of lupus. The diagnostic work-up aims to exclude causes unrelated to SLE, and investigations include cerebrospinal fluid analysis, EEG, neuropsychological tests, nerve conduction studies, and MRI, as outlined in the EULAR recommendations 1. Glucocorticoids and immunosuppressive therapy are indicated when neurolupus is thought to reflect an inflammatory process, and antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, as stated in the EULAR guidelines 1.
From the Research
Causes of Neurolupus
The exact causes of neurolupus, also known as neuropsychiatric systemic lupus erythematosus (NPSLE), are not fully understood. However, several factors are thought to contribute to its development, including:
- Neuroinflammation, which is a complex process that contributes to the pathogenesis of immune-mediated and neurodegenerative pathologies 2
- Ischemic and inflammatory mechanisms, which have an important input on NPSLE pathogenesis 2
- Damage to the blood-brain barrier (BBB), local and systemic production of autoantibodies, and neuronal injury and apoptosis, which can lead to diffuse cerebral events, such as cognitive dysfunction and psychotic disorder 2
- Systemic inflammation, which can lead to aberrant brain-resident immune cell activation, leakage of the blood-brain barrier, and the production of circulating antibodies that cross-react with brain antigens 3
Pathogenesis of Neurolupus
The pathogenesis of neurolupus is thought to involve a complex interplay between the immune system, the nervous system, and other factors, including:
- Genetic predisposition, environmental triggers, and hormonal milieu, which can contribute to the development of systemic lupus erythematosus (SLE) 4
- Autoantibodies and immunocomplexes, which can engage the complement system and disrupt the clearance of nucleic acids after cell death 4
- Dysregulation of cytokines, including type I interferons, which can contribute to the development of NPSLE 4
Clinical Manifestations of Neurolupus
The clinical manifestations of neurolupus can vary widely, and may include: