Limited preventive effect of prednisone on neuropsychiatric symptoms in murine systemic lupus erythematosus

Introduction We aimed to investigate risk factors for fatigue in patients with systemic lupus erythematosus (SLE) and neuropsychiatric symptoms in order to identify potential interventional strategies. Methods Patients visiting the neuropsychiatric SLE (NPSLE) clinic of the Leiden University Medical Center between 2007–2019 were included. In a multidisciplinary consensus meeting, SLE patients were classified as having neuropsychiatric symptoms of inflammatory origin (inflammatory phenotype) or other origin (non-inflammatory phenotype). Fatigue was assessed with the SF-36 vitality domain (VT) since 2007 and the multidimensional fatigue inventory (MFI) and visual analogue scale (VAS) since 2011. Patients with a score on the SF-36 VT ≥1 standard deviation (SD) away from the mean of age-related controls of the general population were classified as fatigued; patients ≥2 SD away were classified as extremely fatigued. Disease activity was measured using the SLE disease activity index-2000. The influence of the presence of an inflammatory phenotype, disease activity and symptoms of depression and anxiety as measured by the hospital anxiety and depression scale (HADS) was analyzed using multiple regression analyses corrected for age, sex and education. Results 348 out of 371 eligible patients filled in questionnaires and were included in this study . The majority was female (87%) and the mean age was 43 ± 14 years. 72 patients (21%) had neuropsychiatric symptoms of an inflammatory origin. Fatigue was present in 78% of all patients and extreme fatigue was present in 50% of patients with an inflammatory phenotype vs 46% in the non-inflammatory phenotype. Fatigue was similar in patients with an inflammatory phenotype compared to patients with a non-inflammatory phenotype on the SF-36 VT (β: 0.8 (95% CI −4.8; 6.1) and there was less fatigue in patients with an inflammatory phenotype on the MFI and VAS (β: −3.7 (95% CI: −6.9; −0.5) and β: −1.0 (95% CI −1.6; −0.3)). There was no association between disease activity and fatigue, but symptoms of anxiety and depression (HADS) associated strongly with all fatigue measurements. Conclusion This study suggests that intervention strategies to target fatigue in (NP)SLE patients may need to focus on symptoms of anxiety and depression rather than immunosuppressive treatment.

Download Full-text

Pattern and prevalence of neuropsychiatric lupus: a retrospective study from a tertiary level hospital in Bangladesh

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00334-z ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Fahima Hossain ◽

Mohammad Delwer Hossain Hawlader ◽

Dipak Kumar Mitra ◽

Mohammad Hayatun Nabi ◽

Md. Mujibur Rahman

Keyword(s):

Systemic Lupus Erythematosus ◽

Retrospective Study ◽

Cognitive Dysfunction ◽

Lupus Erythematosus ◽

Neuropsychiatric Symptoms ◽

Tertiary Care ◽

Care Hospital ◽

Systemic Lupus ◽

Case Definitions ◽

American College Of Rheumatology

Abstract Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is well known for its varying presentations and poor outcomes, but little is evident about its distribution and characteristics among the Bangladeshi population. This study aimed to assess the pattern and prevalence of neuropsychiatric symptoms in female systemic lupus erythematosus (SLE) patients of Bangladesh. A retrospective study was conducted at a tertiary care hospital in Dhaka, Bangladesh, between January and December 2018. One hundred female SLE patients were included in the study purposively. Data were collected on sociodemographic and clinical characteristics of diagnosed SLE cases visiting the SLE clinic and indoor medicine department. Neuropsychiatric (NP) syndromes were defined according to the widely accepted American College of Rheumatology (ACR) nomenclature and case definitions. Results A total of 244 NP events were identified in fifty-five patients. Headache was the most frequent symptom (55%), followed by cognitive dysfunction (50%), anxiety (49%), psychosis (43%), seizure (23%), depression (17%), and cerebrovascular disease (ischemic type, 7%). The NP manifestations were more prevalent among urban residents (58.2%), younger patients (41.8%), and patients with graduate-level education (34.5%). Besides, young age at diagnosis (p = 0.038), Raynaud’s phenomenon (p = 0.015), other organ involvement (p < 0.001), and time of NPSLE development (p < 0.001) were found to be significantly associated with the development of these manifestations. Conclusion NP damage is prevalent among Bangladeshi female SLE patients (55%) with headache and cognitive dysfunction being the most common symptoms. Routine screening for neuropsychiatric symptoms among suspected SLE cases and further evaluation with a larger population are warranted.

Download Full-text

Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus (NPSLE): Can They Be Used as Biomarkers for the Differential Diagnosis of This Disease?

Clinical Reviews in Allergy & Immunology ◽

10.1007/s12016-021-08865-2 ◽

2021 ◽

Author(s):

Elias Manca

Keyword(s):

Systemic Lupus Erythematosus ◽

Central Nervous System ◽

Nervous System ◽

Differential Diagnosis ◽

Human Body ◽

Lupus Erythematosus ◽

Neuropsychiatric Symptoms ◽

Systemic Lupus ◽

Neuropsychiatric Systemic Lupus Erythematosus ◽

The Central Nervous System

AbstractSystemic lupus erythematosus is a complex immunological disease where both environmental factors and genetic predisposition lead to the dysregulation of important immune mechanisms. Eventually, the combination of these factors leads to the production of self-reactive antibodies that can target any organ or tissue of the human body. Autoantibodies can form immune complexes responsible for both the organ damage and the most severe complications. Involvement of the central nervous system defines a subcategory of the disease, generally known with the denomination of neuropsychiatric systemic lupus erythematosus. Neuropsychiatric symptoms can range from relatively mild manifestations, such as headache, to more severe complications, such as psychosis. The evaluation of the presence of the autoantibodies in the serum of these patients is the most helpful diagnostic tool for the assessment of the disease. The scientific progresses achieved in the last decades helped researchers and physicians to discover some of autoepitopes targeted by the autoantibodies, although the majority of them have not been identified yet. Additionally, the central nervous system is full of epitopes that cannot be found elsewhere in the human body, for this reason, autoantibodies that selectively target these epitopes might be used for the differential diagnosis between patients with and without the neuropsychiatric symptoms. In this review, the most relevant data is reported with regard to mechanisms implicated in the production of autoantibodies and the most important autoantibodies found among patients with systemic lupus erythematosus with and without the neuropsychiatric manifestations.

Download Full-text

POS0709 LUPUS FOG IS NOT DISSOCIATIVE FOG

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.424 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 604.1-604

Author(s):

R. Monahan ◽

A. Blonk ◽

H. Middelkoop ◽

M. Kloppenburg ◽

T. Huizinga ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Neuropsychiatric Symptoms ◽

Adult Population ◽

Systemic Lupus ◽

Tertiary Referral Center ◽

Neuropsychiatric Systemic Lupus Erythematosus ◽

Dissociative Symptoms ◽

Dissociative Experience ◽

Dissociative Experience Scale

Background:The presence of a ‘fog’ is frequently reported by patients with systemic lupus erythematosus (SLE). However, little is known about this lupus fog: it is thought to be a result of cognitive dysfunction, but fogs can also be the result of dissociation. The Dissociative Experience Scale-II (DES) is a standardized tool to study dissociation. In the general adult population, scores range from 4.4-14.1-3Objectives:We aimed to study the prevalence of dissociative symptoms including dissociative fog in patients with SLE and neuropsychiatric symptoms.Methods:Patients visiting the tertiary referral center for neuropsychiatric systemic lupus erythematosus (NPSLE) of the LUMC between 2007-2019 were included. All patients underwent a standardized multidisciplinary assessment. Patients were classified as NPSLE if neuropsychiatric symptoms were attributed to SLE and immunosuppressive or anticoagulant therapy was initiated, otherwise patients were classified as minor/non-NPSLE. Dissociation was studied using the DES. The DES separates different types of dissociative symptoms: amnesia, absorption/imagination and derealization/depersonalization. It also contains one question regarding evaluating the presence of a dissociative fog: “Some people sometimes feel as if they are looking at the world through a fog, so that people and objects appear far away or unclear”. All statements (n = 28) regarding dissociative symptoms are rated from ‘none of the time’ to ‘all of the time’ (0-100%); scores >25 are considered abnormal. A multiple regression analysis (MRA) were performed to compare dissociation in patients with and without NPSLE. DES results are presented as median (range) and MRA as odds ratio (OR) and 95% confidence interval (CI).Results:DES questionnaires were available for 337 patients, of which 97 had the diagnosis NPSLE (29%). Mean age in patients with NPSLE was 41 ± 13 years and 84% was female. In minor/non-NPSLE, median age was 44 ± 14 years and 87% was female.Median dissociation was 7 (0-75) and did not differ between patients with minor/non-NPSLE and NPSLE (OR: 1.0 (95% CI: -0.9; 1.1)). The most common type of dissociation was absorption/imagination (median: 12, range 0-75) and depersonalization/derealization was infrequent (median: 1, range 0-84). 43 patients (13%) had an abnormal score (>25) on the dissociative fog question.Conclusion:Dissociative symptoms are within normal range in patients with SLE and neuropsychiatric symptoms, regardless of underlying etiology. Dissociative fog seems uncommon and therefore lupus fog is most likely not the result of dissociation.References:[1]Bernstein EM and Putnam FW. Development, reliability, and validity of a dissociation scale. J Nerv Ment Dis 1986; 174: 727-735. 1986/12/01. DOI: 10.1097/00005053-198612000-00004.[2]Maaranen P, Tanskanen A, Honkalampi K, et al. Factors associated with pathological dissociation in the general population. Aust N Z J Psychiatry 2005; 39: 387-394. 2005/04/30. DOI: 10.1080/j.1440-1614.2005.01586.x.[3]van IJzendoorn MH and Schuengel C. The measurement of dissociation in normal and clinical populations: Meta-analytic validation of the Dissociative Experiences Scale (DES). Clinical Psychology Review 1996; 16: 365-382. DOI: 10.1016/0272-7358(96)00006-2.Table 1.Presence of dissociation in patients with SLE and neuropsychiatric symptomsTotal cohort(n = 337)Minor/non-NPSLE(n = 240)NPSLE(n = 97)DES (median, range)Total questionnaire7 (0 - 75)8 (0 - 66)6 (0 – 75)Amnesia5 (0 - 76)5 (0 - 68)4 (0 - 76)Absorption/imagination12 (0 – 75)13 (0 – 75)10 (0 – 73)Depersonalization/derealization1 (0 – 84)1 (0 – 73)1 (0 – 84)Dissociative fog* 0 (0-100)0 (0-100)0 (0-100)DES = Dissociative Experience Scale NPSLE = neuropsychiatric systemic lupus erythematosus.*Dissociative fog is question 28 of the DES-IIDisclosure of Interests:None declared

Download Full-text

AB0383 EXTREME FATIGUE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND NEUROPSYCHIATRIC SYMPTOMS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.941 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1491.2-1492

Author(s):

R. Monahan ◽

R. Fronczek ◽

J. Eikenboom ◽

H. Middelkoop ◽

L. J. J. Beaart- van de Voorde ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Nervous System ◽

Standard Deviation ◽

Lupus Erythematosus ◽

Neuropsychiatric Symptoms ◽

Systemic Lupus ◽

System Involvement ◽

Vas Score ◽

Age Related ◽

Sf 36

Background:Fatigue is commonly described in chronic illnesses, especially auto-immune disorders such as systemic lupus erythematosus (SLE).Objectives:We aim to study the prevalence of fatigue in SLE patients with NP symptoms and compare fatigue in SLE patients with NP symptoms attributed to major organ involvement due to SLE (NPSLE) with SLE patients with NP symptoms not caused by major nervous system involvement (non-NPSLE).Methods:All patients visiting the tertiary referral center for NPSLE in the LUMC between 2007-2019 with the clinical diagnosis of SLE and age >18 years that signed informed consent were included in this study. Patients underwent a standardized multidisciplinary assessment, including two questionnaires: SF-36 (2007-2019) and multidimensional fatigue index (MFI, 2011-2019). Patients were classified as NPSLE in this study if NP symptoms were attributed to SLE and immunosuppressive or anticoagulant therapy was initiated, otherwise patients were classified as non-NPSLE. The vitality (VT) domain of the SF-36 domain was used to assess fatigue, which generates a score from 0-100, 100 representing the complete absence of fatigue. Patients with a score more than 1 standard deviation (SD) removed from age-related controls of the Dutch general population were classified as fatigued; patients more than 2 SD removed were classified as extremely fatigued1. The MFI was also used, which consists of 5 subdomain scores between 0-20, leading to a total score between 0-100, 100 representing the most extreme fatigue. All scores are presented as mean and standard deviation.Results:373 patients fulfilled the inclusion criteria and SF-36 questionnaires of 328 patients were available (88%). The majority of these patients was female (87%) and 98 were classified as NPSLE (30%). In NPSLE patients, average age was 41 ± 13 years and in non-NPSLE the average age was 45 ± 14 years. The average score of the SF-36 vitality domain was 36.0 ± 20.7 in NPSLE vs 33.9 ± 18.8. in non-NPSLE. Overall, 73.5% of the patients were fatigued and 46.9% extremely fatigued in NPSLE vs 77.8% fatigued and 45.7% extremely fatigued in non-NPSLE.The MFI questionnaire and VAS score were available for 222 patients, of which 65 patients were classified as NPSLE (29.3%). Table 1 depicts the scores of NPSLE and non-NPSLE patients on the MFI subdomains and the VAS score.Table.Patient characteristics at registry entry.NPSLE(N = 65)Non-NPSLE (N = 157)MFI(mean, sd)General Fatigue10.8 (1.8)11.1 (1.5)Physical Fatigue11.4 (2.4)12.3 (1.9)Reduced Activity9.6 (2.9)10.7 (2.2)Reduced Motivation10.7 (2.6)11.1 (1.9)Mental Fatigue9.5 (3.0)9.8 (2.7)Total score51.8 (9.9)54.9 (6.9)SF-36 Vitality (mean, sd)35 (20.7)32.7 (18.2)Conclusion:Nearly half of patients with SLE and NP symptoms are as extremely fatigued as only 2.5% of the general Dutch population. Extreme fatigue is not influenced by major nervous system involvement.References:[1]Aaronsonet al.J Clin Epidemiol. Vol. 51, No. 11, pp. 1055–1068, 1998Disclosure of Interests:Rory Monahan: None declared, Rolf Fronczek: None declared, Jeroen Eikenboom: None declared, Huub Middelkoop: None declared, L.J.J. Beaart- van de Voorde: None declared, Gisela Terwindt: None declared, Nic van der Wee: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Margreet Kloppenburg: None declared, G.M. Steup-Beekman: None declared

Download Full-text

NEUROPSYCHIC POLYMORPHISM OF JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS

Clinical Medicine and Pharmacology ◽

10.12737/2409-3750-2021-7-3-28-34 ◽

2021 ◽

Vol 7 (3) ◽

pp. 28-34

Author(s):

Yu. Minakova ◽

M. Silenko ◽

O. Ivanova

Keyword(s):

Systemic Lupus Erythematosus ◽

Nervous System ◽

Lupus Erythematosus ◽

Neuropsychiatric Symptoms ◽

Clinical Manifestations ◽

Pathogenetic Mechanism ◽

Systemic Lupus ◽

Juvenile Systemic Lupus Erythematosus ◽

Wide Range ◽

Prognostic Criterion

Damage to the nervous system (neurolupus) is one of the most common clinical manifestations of systemic lupus erythematosus (SLE) in childhood, and is also considered as an unfavorable prognostic criterion for the course of this disease. Neurolupus is characterized by a wide range of clinical manifestations in both children and adult patients, which is due in most cases to a common pathogenetic mechanism - the formation of systemic microvasculitis. The non-specificity and variability of neuropsychiatric symptoms, which may appear already at the onset of the disease, significantly complicate the early diagnosis of SLE and necessitate a close acquaintance of the pediatrician with neurolupus polymorphism in children.

Download Full-text