Understanding Neuropsychiatric Systemic Lupus Erythematosus (NPSLE): Symptoms, Diagnosis, and Treatment
- Angela Nguyen
- Nov 25
- 3 min read
Introduction
Systemic lupus erythematosus (SLE), commonly known as lupus, occurs when the body’s immune system attacks its own tissues and organs. This chronic condition presents with a complex array of symptoms, such as fatigue, joint pain and stiffness, skin rashes, fever, and hair loss, as well as the characteristic butterfly rash (malar rash). The most common organ manifestation of SLE is in the kidneys, termed “lupus nephritis” (LN).
The second most common organ manifestation is in the central and peripheral nervous systems, termed “Neuropsychiatric Systemic Lupus Erythematosus” (NPSLE). Despite its prevalence and impact, it warrants more public attention.
What Does NSPLE Look Like?
Signs and symptoms of NPSLE can vary depending on which part of the nervous system is involved, but the most common include:
Headaches (sometimes severe or migraine-like)
“Lupus fog” or cognitive effects (memory issues, trouble concentrating, slowed thinking)
Mood changes (depression, anxiety, irritability)
Psychosis (hallucinations and delusions, which are less common but important)
Seizures
Stroke or mini-stroke
Numbness, tingling, or weakness (due to nerve inflammation)
Pathogenesis
The exact cause of NPSLE is unknown. However, research has shown that NPSLE develops when lupus triggers several harmful processes in the brain and nervous system. The immune system produces autoantibodies that mistakenly attack brain tissue or blood vessels, leading to inflammation and damage. Issues with blood flow, such as tiny clots or vessel narrowing, can also reduce oxygen delivery to the brain. In some cases, the protective blood-brain barrier becomes breached, allowing molecules from the bloodstream to enter and disturb normal brain function. Together, these factors explain why people with NPSLE may experience a wide range of symptoms.
Diagnosis
Diagnosing NPSLE can be challenging because its symptoms can also occur in many other conditions. Thus, NPSLE is a diagnosis of exclusion. Healthcare professionals usually combine medical history, physical exam, and special tests to rule out other causes.
Common steps in diagnosing NPSLE include:
Medical history and symptom review: looking at neurological or psychiatric symptoms alongside existing lupus
Neurological exam: checking reflexes, coordination, memory, and mood changes
Blood tests: measuring lupus-related antibodies and checking for clotting disorders
Imaging tests: MRI or CT scans to look for inflammation, blood vessel damage, or small strokes
Cerebrospinal fluid (CSF) tests: to check for inflammation or infection in the brain
Excluding other conditions, as infections, medication side effects, or other illnesses, can present similarly to NPSLE.
Treatment
Treatment for NPSLE focuses on calming the immune system, reducing inflammation, and protecting the brain and nerves. The exact plan depends on which symptoms a person has and how severe they are. Healthcare professionals often combine medication with supportive care.
Common treatments include:
Corticosteroids: to quickly reduce inflammation
Immunosuppressants: to calm the overactive immune system
Blood thinners: to address blood clots or vascular issues if present
Anti-seizure or psychiatric medications: to manage specific symptoms like seizures, depression, or anxiety
Supportive therapies: counseling, physical therapy, or occupational therapy
Living with NPSLE
Helpful strategies include:
Keeping up with check-ups to catch and treat flares early
Taking medications as prescribed, even when symptoms improve
Managing stress and fatigue through rest, gentle exercise, or mindfulness
Seeking mental health support such as counseling, support groups, or talking with loved ones
Avoiding triggers of lupus, such as excessive sun exposure or skipping medications
Living with NPSLE can be difficult, but with the right care, many patients can manage symptoms and improve their quality of life. Because symptoms may come and go, regular follow-up with healthcare providers is essential. Lifestyle choices and support systems also play a big role in daily well-being.
References
Cojocaru, Manole, et al. “Manifestations of Systemic Lupus Erythematosus.” Maedica, U.S. National Library of Medicine, Oct. 2011, pmc.ncbi.nlm.nih.gov/articles/PMC3391953/.
“Lupus.” Mayo Clinic, Mayo Foundation for Medical Education and Research, www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789.
Papachristos, D A et al. “Management of inflammatory neurologic and psychiatric manifestations of systemic lupus erythematosus: A systematic review.” Seminars in arthritis and rheumatism vol. 51,1 (2021): 49-71. doi:10.1016/j.semarthrit.2020.12.004.
Patel, Veena. “The Challenge of Neuropsychiatric Systemic Lupus Erythematosus: From Symptoms to Therapeutic Strategies.” MDPI, Multidisciplinary Digital Publishing Institute, 5 June 2024, www.mdpi.com/2075-4418/14/11/1186.
“Review of Neuropsychiatric Lupus Diagnosis and Management.” Lupus Foundation of America, www.lupus.org/news/review-of-neuropsychiatric-lupus-diagnosis-and-management.
Rodriguez, Tori. “Neuropsychiatric Symptoms in SLE: Diagnosis and Treatment .” Rheumatology Advisor, 6 Aug. 2025, www.rheumatologyadvisor.com/features/neuropsychiatric-lupus-sle-symptoms-diagnosis-and-treatment/.
Sarwar, Sobia, et al. “Neuropsychiatric Systemic Lupus Erythematosus: A 2021 Update on Diagnosis, Management, and Current Challenges.” Cureus, U.S. National Library of Medicine, 14 Sept. 2021, pmc.ncbi.nlm.nih.gov/articles/PMC8516357/.
Sato, Shuzo, et al. “Autoantibodies Associated with Neuropsychiatric Systemic Lupus Erythematosus: The Quest for Symptom-Specific Biomarkers.” Fukushima Journal of Medical Science, U.S. National Library of Medicine, 22 Apr. 2020, pmc.ncbi.nlm.nih.gov/articles/PMC7269884/.
Schwartz, Noa, et al. “Neuropsychiatric Lupus: New Mechanistic Insights and Future Treatment Directions.” Nature Reviews. Rheumatology, U.S. National Library of Medicine, Mar. 2019, pmc.ncbi.nlm.nih.gov/articles/PMC8023338/.
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