Neuropsychiatric Manifestations in Systemic Lupus Erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses a broad spectrum of neurological and psychiatric disturbances directly attributable to the autoimmune processes of SLE. Clinical presentations range from mild cognitive dysfunction, mood disorders and headache to severe events such as acute confusional state, seizures, cerebrovascular accidents and psychosis. Pathogenic mechanisms include intrathecal autoantibody production, blood–brain barrier disruption, microvascular thrombosis and cytokine‐driven neuroinflammation. Autoantibodies directed against neuronal antigens and proinflammatory mediators such as interleukin‐6 and tumour necrosis factor‐α have been implicated in synaptic dysfunction and glial activation. Neuroimaging studies reveal alterations in functional connectivity, particularly within the default mode network, while neuropsychological testing uncovers deficits in sustained attention, working memory and executive function. Disease attribution remains a challenge, demanding careful correlation of timing, clinical context and exclusion of alternative causes. Early recognition of prodromal neuropsychiatric signs and timely application of immunomodulatory or symptomatic therapies are essential to mitigate long‐term disability and improve quality of life.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Neuropsychiatric Manifestations in Systemic Lupus Erythematosus publication trend

The graph below shows the total number of articles in neuropsychiatric manifestations in systemic lupus erythematosus across all publications each year (not limited to Nature Index journals).

Technical terms

Neuropsychiatric SLE (NPSLE): A subset of SLE manifestations involving central or peripheral nervous system and psychiatric symptoms directly linked to lupus pathology.

Blood–brain barrier (BBB): A specialised endothelial interface that regulates molecular exchange between blood and the central nervous system, whose disruption permits entry of immune mediators.

Interleukin-6 (IL-6): A proinflammatory cytokine elevated in SLE that can activate glial cells and contribute to cognitive dysfunction.

Prodrome: Early or premonitory signs and symptoms indicating impending disease flare or onset of a specific syndrome.

Astrocytosis: Proliferation and activation of astrocytes in the central nervous system in response to inflammation or injury.

References

1. Neuropsychiatric prodromes and symptom timings in relation to disease onset and/or flares in SLE: results from the mixed methods international INSPIRE study. EClinicalMedicine (2024).
2. Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus. Journal of Neuroinflammation (2024).
3. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Medicine (2015).