Clinical,imaging characteristics,and outcomes of neuropsychiatric lupus patient admitted to a referral neurology hospital in Bangladesh: A prospective study

Abstract

Objective

This study aimed to describe the clinical and neuroimaging characteristics and 120-day outcomes in neuropsychiatric systemic lupus erythematosus patients.

Methods

This prospective study involved 32 patients with systemic lupus erythematosus who presented with neuropsychiatric symptoms. The Systemic Lupus Erythematosus Disease Activity Index 2000 was used to evaluate disease activity. Standard treatments were administered, and patients were followed up for 120 days. Outcomes were assessed in terms of remission, partial remission, and mortality.

Results

The most prevalent neuroimaging characteristics were microhemorrhage in eight patients (25%), hemorrhagic infarct in four patients (12%), and ischemic infarct in four patients (12%). Additionally, magnetic resonance angiography of the cerebral artery revealed a beaded appearance in the middle cerebral artery or its branches in nine patients (28%). Magnetic resonance venography showed a filling defect, narrowing, and irregularity of the superior sagittal and transverse sinus in five patients (16%). Upon admission, the mean Systemic Lupus Erythematosus Disease Activity Index 2000 score was 24 (SD = 9). After receiving standard treatment, complete remission occurred in 24 patients (75%) and partial remission in 7 patients (22%), with a median Systemic Lupus Erythematosus Disease Activity Index 2000 score of 2 (interquartile range = 1–4.5) at 120 days, p = 0.02.

Conclusion

Magnetic resonance angiography of cerebral vessels helps confirm vasculitis. Patients generally experience satisfactory outcome with standard treatment at 4 months.

Keywords

Neuropsychiatric lupus imaging characteristics outcome neuropsychiatric systemic lupus erythematosus

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune, immune complex, multisystem chronic inflammatory disease affecting multiple organs, including the central nervous system (CNS). SLE also affects the nervous system through a broad spectrum of clinical manifestations, causing various manifestations in the CNS and peripheral nervous system (PNS). Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication characterized by neurological and psychiatric manifestations of SLE.¹ Neuropsychiatric manifestations occur in the early stages of SLE and occur in 39%–50% of SLE patients.² NPSLE prevalence has been reported in many epidemiological studies, with differences in the prevalence of both NPSLE and SLE based on age, sex, and ethnicity. The incidence of neurological manifestations is higher in women, while seizure risk is more common in men.³ NPSLE is more frequently reported in individuals of African and Asian descent compared with individuals of White ethnicity; however, the severity of NPSLE is reportedly greater in those of White ethnicity.⁴ The incidence of isolated NPSLE remains largely unknown.

NPSLE is one of the catastrophic complications of SLE that may present as stroke, seizure disorder, cranial nerve lesion, altered sensorium, psychosis, and cognitive dysfunction.^1,5 Various pathological mechanisms, such as an immune complex deposition, thrombosis, and accelerated atherosclerosis, lead to ischemia or microhemorrhage in the brain parenchyma and can lead to the NPSLE development.⁶ Establishing a confirmed diagnosis of NPSLE is challenging. There are no specific criteria for diagnosing NPSLE, and it is identified based on the diagnosis of exclusion and expert opinion. Serological tests such as antinuclear antibody (ANA) test or anti-dsDNA commonly guide diagnosis. Thorough clinical assessment involves neurological and psychiatric evaluation. Further evaluation includes assessing the general SLE activity, cardiovascular risk factors, atherosclerotic disease, and thrombotic events. NPSLE diagnosis can be established using different clinical, serological, immunological, electrophysiological, and neuroimaging studies.⁷ Diagnosing neuropsychiatric manifestations in SLE is important as these frequently occur during reproductive years (20–40 years), have high disease severity and poor prognosis, and are difficult to diagnose and treat. Moreover, frequency, clinical presentations, and severity vary according to race and ethnicity. Therefore, it is important to be aware about the neuropsychiatric manifestations among Bangladeshi SLE patients. In Bangladesh, data regarding frequency, clinical pattern, laboratory profile, severity, and outcome of NPSLE are limited. This study aimed to describe the clinical and laboratory profiles, including radio imaging characteristics of intracranial vessels and brain parenchyma, and 120-day outcomes of NPSLE patients admitted to the largest referral center in Bangladesh.

Methods

This comprehensive prospective study was conducted from July 2022 to June 2024 and involved 32 patients with NPSLE admitted to the National Institute of Neurosciences and Hospital in Dhaka. This institute is the largest, super specialized referral neurology hospital that has a specialized stroke unit where thrombolysis, mechanical thrombectomy, emergency coiling or clipping, and neurosurgical interventions are performed on a routine basis. Moreover, it provides comprehensive management for patients with neurological disorders such as demyelinating disorders, movement disorders, lupus and arthritis, epilepsy, sleep disorders, dementia, autism spectrum disorders, and psychiatric illness.

SLE patients initially presented with neuropsychiatric symptoms and were diagnosed according to the 2003 American College of Rheumatology (ACR) nomenclature for CNS lupus¹ and the 2019 ACR/European Alliance of Associations for Rheumatology (EULAR) classification criteria for SLE.⁸ Initially, 102 SLE patients who presented with neurological symptoms were evaluated, and 32 of them were enrolled for the present study according to the inclusion criteria. However, known SLE patients with acute confusional states due to infection, metabolic abnormalities, and malignancy were excluded. Herein, we documented clinical and laboratory parameters, including immunological markers such as ANA, anti-dsDNA, anti-smith antibody, antiphospholipid antibody (anti (aPL)), and complement 3 (C3) and complement 4 as well as neuroimaging characteristics assessed using magnetic resonance imaging (MRI) of the brain and spine and magnetic resonance angiography (MRA) of the brain vasculature (MRI machine resolution power = 3 TESLA). Retinal vessels were evaluated using fluorescent angiography. High-resolution (hr) MRI/vessel wall imaging (VWI), including time of flight (TOF) multiplanar three-dimensional (3D) sequences and contrast-enhanced (gadolinium) T1-weighted dark-blood sequences, was performed to detect concentric vessel wall enhancement and thickening, which is highly suggestive of vasculitis. Luminal stenosis alternating with dilatation, termed the “beading sign” in the small- and medium-sized arteries are typical observation in vasculitis. Contrast-enhanced T1-weighted imaging was performed to distinguish active inflammation from chronic fibrotic changes in the brain parenchyma. Fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) sequences were performed to detect associated ischemic lesions, infarcts, and parenchymal changes, while gradient-recalled echo (GRE) and susceptibility-weighted imaging were performed to detect cerebral microhemorrhage.^9–11 Regarding treatment, every patient received intravenous (IV) methylprednisolone (500 mg to 1 gm for 3 consecutive days) with or without cyclophosphamide (CYC) (750 mg/m²) as pulse therapy, and azathioprine (100 mg per day) or mycophenolate mofetil (1 gm/day) as maintenance therapy. IV CYC was administered every month as maintenance therapy to selected patients (those who presented with seizure, paraparesis, and psychosis). Patients were followed up for 4 months. Disease activity was determined according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores.¹² Outcomes were determined based on remission, relapse, and mortality. Remission was defined based on an SLEDAI-2K score of 0, physician global assessment indicating no disease activity, prednisolone dose <5 mg/day, and stable doses of antimalarial immunosuppressive agents. However, relapse was defined as new onset or aggravation of previous NPSLE symptoms; an increase of >4 points in the SLEDAI-2K score was considered to indicate relapse. For partial remission, we considered improvement in the modified Rankin scale (mRs) score for hemiparetic or paraparetic limbs (mRs score: 0–1 = complete remission and mRs score: 2–4: = partial remission), reduced frequency of seizure, decrease in severity and frequency of headache, and a Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) score of 2 (0–1 = complete remission, 2 = partial remission, and 3–4 = active psychosis).^13,14

Ethical approval was granted by the institutional review board (IRB) of the study institute, the National Institute of Neurosciences and Hospital (NINS & H), with protocol number: IRB/NINS-37-06-2022 (17 June 2022). Written informed consent was obtained from every patient. This study was conducted according to the principles in the Declaration of Helsinki (1975, as revised in 2024). The reporting of this observational study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.¹⁵

Statistical analyses

Continuous data were represented using mean and median values, whereas categorical variables were expressed as frequencies and percentages. Paired student t-test was performed to examine the differences in the SLEDAI-2K scores after treatment.

Results

In total, 32 patients were enrolled. Among them, seven were previously diagnosed with SLE (6 with mucocutaneous and musculoskeletal involvement and 1 with lupus nephritis). Twenty-five (78%) patients initially presented with NPSLE symptoms rather than mucocutaneous or musculoskeletal manifestations. Twenty-eight (87%) patients were women; the male:female ratio was 1:8. The mean age of the study population was 24.8 (8) years, and the median duration since diagnosis of SLE was 3 months (1–4.5). The most common comorbidity was hypothyroidism 4 (12%). Migrainous headache (19, 60%), convulsion (12, 38%), hemiparesis (5, 16%), and psychosis (5, 16%) were the most common presentations. However, blurring of vision due to papillitis was observed in 3 patients. Nevertheless, some atypical presentations were observed, such as paraparesis in 1 patient, chorea in 1, altered level of consciousness in 1, and retinal vasculitis in 2 patients. On admission, the mean SLEDAI-2K score of the study population was 24 (9). After receiving standard treatment, complete remission occurred in 24 (75%) patients, partial remission in 7 (22%) patients, and death in 1 patient; the median SLEDAI-2K score was 2 (1–4.5) at 120 days, p = 0.02. Complications such as infections occurred in 2 patients (Table 1). Laboratory investigations revealed low hemoglobin level, 10.7 (2.2) g/dL; normal neutrophil count, 5418 (1743) mm³; thrombocytopenia, 127,757 (54570) mm³; normal activated partial thromboplastin time (APTT), 35.3 (5.7) s; mildly raised D-dimer level, 1.3(0.4) ng/dL; high anti-ds-DNA, 63.40 (40.1–105.8) IU/mL; low C3, 0.17 (0.06–0.35) g/L; and lupus anticoagulant ratio, 1.2 (0.3) (Table 2). The most prevalent neuroimaging characteristics were microhemorrhage (8, 25%) on susceptibility-weighted imaging (Figure 1(a)) and GRE imaging sequences (Figure 1(b)), hemorrhagic infarct (4, 12%) on GRE, and ischemic infarct (4, 12%) on DWI. Moreover, MRA of the cerebral artery with VWI revealed a beaded appearance both in the anterior cerebral artery and middle cerebral artery (MCA) or their branches (9, 28%) (Figure 2(a)), occlusive thrombus in the distal MCA (5, 16%) (Figure 2(b)), cerebral venous sinus thrombosis (4, 12%), and a dysplastic distal anterior cerebral artery and posterior communicating artery aneurysm in one patient (Figure 3). MR venography showed a filling defect, narrowing, and irregularity of the superior sagittal and transverse sinus in five patients (16%). Optic nerve head and retinal vasculitis were observed in two patients each. Moreover, demyelinating hyperintense lesions in the brain and spinal cord (contrast-enhanced T1 and T2 sequences and FLAIR) were detected in 3 (9%) patients (Table 3).

Table 1.

Clinical characteristics and outcomes of NPSLE patients.

Clinical characteristics and outcomes	Frequency (%)
Age (mean, SD)	24.8 (8) years
Sex
Female	28 (88)
Male	4 (12)
Family history of SLE
1^st degree relatives	4
2^nd degree relatives	2
Comorbidities
Hypothyroidism	4
Diabetes	2
Hypertension	2
Headache	19 (59)
Migrainous	15 (79)
Mixed	3
Thunderclap	1
Convulsion	12 (38)
Focal	9
Generalized	3
Hemiparesis	5 (16)
Psychosis	5 (16)
Blurring of vision	5 (16)
Papillitis	3
Retinal vasculitis	2
Chorea	1
Paraparesis	1
Altered level of consciousness	1
SLE disease activity on admission (Mean, SD)	24 (9)
SLE disease activity at 120 days (Median, IQR)	2 (1–4.5)p = 0.02
Outcome
Complete remission at 120 days	24 (75)
Partial remission at 120 days	7 (22)
Death	1
Complications
Herpes zoster	1
Pneumonia	1

SLE: Systemic lupus erythematosus; IQR: interquartile range; NPSLE: neuropsychiatric systemic lupus erythematosus.

Table 2.

Laboratory characteristics of NPSLE patients.

Trait	Mean (SD) or median (inter quartile range (IQR))
Hemoglobin	10.7 (2.2)
Neutrophil count	5418 (1743)
Platelet count	127757 (54570)
ESR (mm in the 1^st h)	53 (22)
Alanine aminotransferase	38 (11)
Creatinine	0.9 (0.3)
Random glucose	7.3 (3.4)
Activated partial thromboplastin time (APTT)	35.3 (5.7)
D-dimer	1.3 (0.4)
Anti-dsDNA	63.40 (40.1–105.8)
Complement 3	0.17 (0.06–0.35)
Complement 4	0.41 (0.17–0.93)
Lupus anticoagulant ratio	1.2 (0.3)

All patients had ANA (+) with titers >1:80, negative anticardiolipin Ab (IgM and IgG), negative C-ANCA and p-ANCA, negative anti-Sjögren’s syndrome antigen A (SSA)/Ro antibodies, negative anti-Sjögren’s syndrome antigen B (SSA)/Ro antibodies; normal protein C, protein S, and antithrombin III.

IQR: interquartile range; NPSLE: neuropsychiatric systemic lupus erythematosus; ANA: antinuclear antibody; Ab: antibodies; IgM: immunoglobulin M; IgG: immunoglobulin G; C-ANCA: cytoplasmic anti-neutrophil cytoplasmic antibody; p-ANCAA: perinuclear anti-neutrophil cytoplasmic antibody.

Figure 1.

(a) Axial SWI image reveals black dots (microhemorrhages) (yellow arrow) in the right thalamus, internal capsule, and left basal ganglia. (b) Microhemorrhage and acute infarct. Axial GRE-weighted image depicts black dots (microhemorrhages) (yellow arrow) with acute infarct in the right centrum semiovale.

Figure 2.

(a) Beaded appearances (yellow arrow) along the branches of the middle and anterior cerebral arteries. (b) Beaded appearances along the distribution of the middle and posterior cerebral arteries and occlusion of the left middle cerebral artery.

Figure 3.

Digital subtraction angiography shows dysplastic aneurysm in the posterior communicating artery (yellow arrow), distal anterior cerebral artery (green arrow), and branches of the middle cerebral artery (blue arrow).

Table 3.

Neuroimaging and angiographic patterns of the brain and CNS vessels in NPSLE patients.

Trait	Frequency (%)
Micro hemorrhage	8 (25)
Hemorrhagic Infarct	4 (12)
Ischemic infarct	4 (12)
Beaded appearance	9 (28)
Occlusive thrombus in distal MCA	5 (16)
Occlusive thrombus in cerebral venous sinus	4 (12)
Dysplastic aneurysm	1 (3)
Hyperintense lesion (brain and spinal cord)	3 (9)
Optic nerve head vasculitis	2 (6)
Retinal vasculitis	2 (6)
Acute ischemic optic neuropathy	1 (4)

CNS: central nervous system; NPSLE: neuropsychiatric systemic lupus erythematosus; MCA: middle cerebral artery.

Discussion

NPSLE may be the initial presentation of SLE. The most common presentations observed in the present study were migrainous headaches nonresponsive to medications, focal seizures or convulsions, hemiparesis due to stroke, blurry vision due to papillitis or retinal vasculitis, and acute ischemic optic neuropathy. Microhemorrhages, followed by hemorrhagic or ischemic infarcts on MRI brain, and a beaded appearance on MRA in the brain vasculature were the prevalent neuroimaging observations. Complete remission was achieved by most patients who underwent pulse therapy followed by maintenance therapy.

Neuropsychiatric manifestations in SLE are classified as having inflammatory and/or ischemic origin, and MRI is one of the most recognized methods of investigation. When present, vasculitis frequently affects the small vessels of the CNS, and MRA is often normal. Typical findings on MRI are hyperintense white matter (WM) lesions, which represent the collective term referring to small or confluent T2-FLAIR hyperintensities, including the WM, basal ganglia, cerebellum, and brainstem. Involvement of large and medium vessels is less common. Vessel wall analysis is becoming increasingly important as it can identify early vascular changes even before alterations are visible on angiography sequences (e.g. 3D TOF). This enables early treatment initiation, thereby improving the prognosis of patients with inflammatory pathologies.^9–11

Unterman et al.,⁷ Rodrigues et al.,¹⁶ and Kivity et al.¹⁷ have described headache, mood disorders, cognitive dysfunction, seizures, and cerebrovascular diseases such as stroke as initial presentations of SLE. The typical pattern of headache was migrainous and nonresponsive to conventional anti-migraine medications. Interestingly, our patients had migrainous headaches that were nonresponsive to standard treatment. A few of our patients presented with both headaches and seizures. However, one of our patients presented with a thunderclap headache, an unusual presentation in NPSLE. The thunderclap headache was caused by a ruptured dysplastic aneurysm in the anterior communicating arteries, a rare complication of SLE-induced inflammation and ischemia, with abnormal blood flow–induced endothelial remodeling.¹⁸ Although all our patients had negative antiphospholipid and anticardiolipin antibodies and no comorbidities or valvular heart disease, five of them presented with ischemic stroke. MRA revealed an occlusive thrombus in the distal MCA and characteristic beaded appearance of both proximal and distal middle cerebral arteries, most probably due to SLE-induced vasculitis and vasculopathy.¹⁹ It is worthwhile to mention that occlusive thrombus may develop due to antiphospholipid or anticardiolipin, an anti–β2 glycoprotein antibody.^18,19 Psychosis was another important manifestation of NPSLE. We observed that isolated non-enhancing hyperintense lesions were found in the frontal and subcortical areas in patients who presented with cognitive decline and psychosis. We excluded substance abuse, Wilson’s disease, previous history of encephalitis, and metabolic abnormalities in these patients. Other observations included blurred vision due to papillitis, retinal vasculitis, and acute ischemic optic neuropathy.

SLE and retinal vasculitis are autoimmune diseases with a common immunological basis. They can occur concomitantly or alternately. Although the underlying mechanism remains unclear, immune complex deposition and other antibody-related mechanisms, vasculitis, and thrombosis may be responsible for manifestations such as ischemic optic neuropathy, choroidal capillaries, vitreal body, and macula.²⁰ It is noteworthy that ocular manifestations are not a part of the SLE classification criteria; however, one-third of SLE patients exhibit ocular manifestations.⁸

For the primary prevention of major NPSLE manifestations such as cerebrovascular disease, hydroxychloroquine use is recommended. Few controlled trials have been conducted on this subject; therefore, therapy can be targeted toward inflammation reduction and prevention of further ischemic events. Recommended therapies include the administration of high-dose methylprednisolone followed by monthly administration of IV CYC for both ischemic and severe inflammatory varieties, followed by maintenance therapy using azathioprine, mycophenolate mofetil, and cyclosporine. Moreover, anticoagulation is recommended in anti (aPL) syndrome, particularly for patients with atherothrombotic manifestations.^21–24 Most of our patients had ischemic or moderate-to-severe inflammatory disease. We preferred methylprednisolone and monthly IV CYC for the treatment of severe patients. However, azathioprine or mycophenolate mofetil was given as maintenance therapy to patients with mild-to-moderate disease. Antiplatelet therapy was administered to patients presenting with ischemic stroke with negative APS antibodies where the most likely cause was cerebral vasculitis. In our study, we observed that most patients achieved remission. The probable reasons for this include early diagnosis, moderate-to-severe disease activity, absence of multiorgan involvement, early initiation of standard treatment, and regular follow-up. Jönsen et al.²⁵ have reported reduced mortality among NPSLE patients who received early standard treatment, especially glucocorticoid and immunomodulator therapies. However, high disease activity, acute confusional state, low neutrophil counts, cardiac and renal involvement, and more than one NPSLE feature are reportedly associated with higher mortality rates.²⁶

Limitations

Single-center design, small sample size, and short follow-up duration are the major limitations of this study.

Conclusion

NPSLE may be the initial presentation of lupus. Brain MRI with MRA is a useful surrogate tool for identifying vasculitis or vasculopathy, even in patients with negative inflammatory markers. Early initiation of standard treatment may help achieve remission even in cases with high disease activity.

Footnotes

Acknowledgments

We are grateful to Prof. Sharif Uddin Khan, Prof. Badrul Alam, Dr. Rubaed Hossain, Dr. Bazlur Rashid, Dr. Mazharul Islam, Dr. Ashikur Rahman, Dr. Najmun Ruma, and Dr. Subir Chandra Das for their continuous support of the research work. We also thank the Radiology Department of the National Institute of Neurosciences and Hospital (NINS & H) for their support regarding the magnetic resonance (MR) and VWI.

Authors’ contributions

SK Jakaria Been Sayeed conceptualized and formulated the study design, defined intellectual content, and studied the literature and clinical studies related to neuropsychiatric lupus and its imaging characteristics. He obtained the clinical history, performed clinical examinations, and ordered laboratory investigations, prothrombotic markers evaluation, and brain radio imaging. He performed the initial data analyses and interpretation. He was involved in patient management from admission to discharge and provided follow-up care. He was also involved in manuscript preparation, editing, and the review process. He is the guarantor of this study.

Moniruzzaman M defined the intellectual content and studied the literature and clinical studies related to neuropsychiatric lupus and its imaging characteristics. He also obtained the clinical history, performed clinical examinations, and ordered laboratory investigations, prothrombotic markers evaluation, and brain radio imaging. He also performed the initial data analyses and interpretation. He was involved in patient management from admission to discharge and provided follow-up care. He was also involved in manuscript preparation, editing, and the review process.

Reaz Mahmud defined the intellectual content and studied the literature and clinical studies related to neuropsychiatric lupus and its imaging characteristics. He obtained the clinical history, performed clinical examinations, and ordered laboratory investigations, prothrombotic markers evaluations, and brain radio imaging. He performed the initial data analyses and interpretation. He was involved in patient management from admission to discharge and provided follow-up care. He was also involved in manuscript preparation, editing, and the review process.

Sabrina Rahman studied the literature and clinical studies related to neuropsychiatric lupus and its imaging characteristics. She obtained the clinical history, performed clinical examinations, and ordered laboratory investigations, prothrombotic markers evaluations, and brain radio imaging. She performed the initial data analyses and interpretation. She was involved in patient management from admission to discharge and provided follow-up care. She was also involved in manuscript preparation, editing, and the review process.

Tuhfie Jannat studied the literature and clinical studies related to neuropsychiatric lupus and its imaging characteristics. He obtained clinical history, performed clinical examinations, and ordered laboratory investigations, prothrombotic markers evaluations, and brain radio imaging. He was also involved in patient management from admission to discharge and provided follow-up care.

Rahman M M studied the literature and clinical studies related to neuropsychiatric lupus and its imaging characteristics. He performed the initial data analyses and interpretation. He was involved in patient management from admission to discharge and provided follow-up care. He was also involved in manuscript preparation, editing, and the review process.

Availability of data and material

Data will be available upon acceptance of the manuscript for publication.

Declaration of conflicting interests

The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

Ethical consent

Written informed consent was obtained from patients, and ethical approval (IRB/NINS 37-06-22) was also obtained from the institutional review board (IRB) of the National Institute of Neurosciences and Hospital (NINS & H). This study was conducted according to the Declaration of Helsinki (1975, as revised in 2024).

Funding

The authors received no financial support for the research, authorship, and/or publication of this study.

ORCID iDs

S K Jakaria Been Sayeed

Reaz Mahmud

References

Nived

Sturfelt

Liang

, et al. The ACR nomenclature for CNS lupus revisited. Lupus 2003; 12: 872–876.

Hanly

, et al. Psychosis in systemic lupus erythematosus: results from an international inception cohort study. Arthritis Rheumatol 2019; 71: 281–289.

Rastin

Mahmoudi

Sahebari

, et al. Clinical & immunological characteristics in systemic lupus erythematosus patients. Indian J Med Res 2017; 146: 224–229.

González

Toloza

Alarcón

GS.

Impact of race and ethnicity in the course and outcome of systemic lupus erythematosus. Rheum Dis Clin North Am 2014; 40: 433–454, vii–viii.

Monov

Monova

Classification criteria for neuropsychiatric systemic lupus erythematosus: do they need a discussion?

Hippokratia 2008; 12: 103–107.

Cohen

Rijnink

Nabuurs

RJA

, et al. Brain histopathology in patients with systemic lupus erythematosus: identification of lesions associated with clinical neuropsychiatric lupus syndromes and the role of complement. Rheumatology (Oxford) 2017; 56: 77–86.

Unterman

Nolte

Boaz

, et al. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum 2011; 41: 1–11.

Aringer

Costenbader

Daikh

, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 2019; 71: 1400–1412.

Matos

BLD

Borella

LFM

Pereira

, et al. High-resolution vessel wall images and neuropsychiatric lupus: a scoping review. Diagnostics (Basel) 2025; 15: 824.

10.

Mandell

Mossa-Basha

Qiao

; Vessel Wall Imaging Study Group of the American Society of Neuroradiologyet al. Intracranial vessel wall MRI: principles and expert consensus recommendations of the American Society of Neuroradiology. AJNR Am J Neuroradiol 2017; 38: 218–229.

11.

Postal

Lapa

Reis

, et al. Magnetic resonance imaging in neuropsychiatric systemic lupus erythematosus: current state of the art and novel approaches. Lupus 2017; 26: 517–521.

12.

Arora

Isenberg

Castrejon

Measures of adult systemic lupus erythematosus: disease activity and damage. Arthritis Care Res (Hoboken) 2020; 72: 27–46.

13.

Broderick

Adeoye

Elm

Evolution of the modified Rankin scale and its use in future stroke trials. Stroke 2017; 48: 2007–2012.

14.

Park

Lee

Choi

Factor structure of the clinician-rated dimensions of psychosis symptom severity in patients with schizophrenia. Psychiatry Investig 2016; 13: 253–254.

15.

Von Elm

Altman

Egger

; STROBE Initiativeet al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008; 61: 344–349.

16.

Rodrigues

Galego

Costa

, et al. Central nervous system vasculitis in systemic lupus erythematosus: a case series report in a tertiary referral centre. Lupus 2017; 26: 1440–1447.

17.

Kivity

Agmon-Levin

Zandman-Goddard

, et al. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med 2015; 13: 43.

18.

Graffeo

Tanweer

Nieves

, et al. Rapid aneurysm growth and rupture in systemic lupus erythematosus. Surg Neurol Int 2015; 6: 9.

19.

Ota

Srinivasan

Capizzano

, et al. Central nervous system systemic lupus erythematosus: pathophysiologic, clinical, and imaging features. Radiographics 2022; 42: 212–232.

20.

Sivaraj

Durrani

Denniston

, et al. Ocular manifestations of systemic lupus erythematosus. Rheumatology (Oxford) 2007; 46: 1757–1762.

21.

Bertsias

Ioannidis

Aringer

, et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010; 69: 2074–2082.

22.

Hermosillo-Romo

Brey

RL.

Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Best Pract Res Clin Rheumatol 2002; 16: 229–244.

23.

Houssiau

Vasconcelos

D'Cruz

, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis 2010; 69: 61–64.

24.

Magro-Checa

Zirkzee

Huizinga

, et al. Management of neuropsychiatric systemic lupus erythematosus: current approaches and future perspectives. Drugs 2016; 76: 459–483.

25.

Jönsen

Bengtsson

Nived

, et al. Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality. Rheumatology (Oxford) 2002; 41: 1308–1312.

26.

Xiang

Sun

, et al. Prevalence, outcome and prognostic factors of neuropsychiatric systemic lupus erythematosus: a real world single center study. Mod Rheumatol 2020; 30: 321–326.