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  • 1
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 69, No. 10 ( 2010-10-01), p. 1886-1887
    Type of Medium: Online Resource
    ISSN: 0003-4967
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2010
    detail.hit.zdb_id: 1481557-6
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  • 2
    In: Lupus, SAGE Publications, Vol. 28, No. 10 ( 2019-09), p. 1255-1260
    Abstract: C1q is an essential part of the classical pathway of complement activation. Genetic deficiencies, caused by homozygous mutations in one of the C1q genes, are rare and are strongly associated with development of systemic lupus erythematosus (SLE). Here we describe a C1q-deficient patient with a compound heterozygous mutation. Material and methods Serum was analysed with enzyme-linked immunosorbent assay (ELISA) and Western blot for the presence of C1q, and DNA and RNA sequencing was performed to identify the mutations and confirm that these were located on different chromosomes. Results The medical history of the patient includes SLE diagnosis at age 11 years with cerebral involvement at age 13, various infections, osteonecrosis and hemophagocytic syndrome. Using ELISA and Western blot, we confirmed the absence of C1q in the serum of the patient. Using DNA sequencing, two mutations in the C1QC gene were identified: c.100G  〉  A p.(Gly34Arg) and c.205C  〉  T p.(Arg69X). With RNA sequencing we confirmed that the mutations are located on different chromosomes. Discussion The patient described in this case report has a compound heterozygous mutation in C1QC resulting in C1q deficiency.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    RVK:
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2008035-9
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  • 3
    In: Arthritis & Rheumatism, Wiley, Vol. 50, No. 9 ( 2004-09), p. 2877-2881
    Type of Medium: Online Resource
    ISSN: 0004-3591 , 1529-0131
    URL: Issue
    RVK:
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 2014367-9
    detail.hit.zdb_id: 2754614-7
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  • 4
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1491.2-1492
    Abstract: 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 fatigued 1 . 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 Fatigue 10.8 (1.8) 11.1 (1.5) Physical Fatigue 11.4 (2.4) 12.3 (1.9) Reduced Activity 9.6 (2.9) 10.7 (2.2) Reduced Motivation 10.7 (2.6) 11.1 (1.9) Mental Fatigue 9.5 (3.0) 9.8 (2.7) Total score 51.8 (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]Aaronson et al. J Clin Epidemiol. Vol. 51, No. 11, pp. 1055–1068, 1998 Disclosure 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
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
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  • 5
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1514.2-1514
    Abstract: Little is known about mortality in patients with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms. Objectives: We aimed to evaluate all-cause and cause-specific mortality in patients with SLE and NP symptoms. Methods: All patients with the clinical diagnosis of SLE of 18 years and older that visited the tertiary referral NPSLE clinic of the Leiden University Medical Center between 2007-2018 and signed informed consent were included in this study. Patients were classified as NPSLE if NP symptoms were attributed to SLE and immunosuppressive or anticoagulant therapy was initiated, otherwise patients were classified as non-NPSLE. Municipal registries were checked for current status (alive/deceased). Electronical medical files were studied for clinical characteristics and cause of death. Standardized mortality ratios (SMRs) and 95% confidence intervals were calculated using data from the general Dutch population. In addition, a rate ratio (RR) was calculated using direct standardization to compare mortality in NPSLE with non-NPSLE patients. Results: 351 patients with the clinical diagnosis of SLE were included, of which 149 patients were classified as NPSLE (42.5%). Compared with the general population, mortality was increased five times in NPSLE (SMR 5.0, 95% CI: 2.6-8.5) and nearly four times in non-NPSLE patients (SMR 3.7, 95% CI: 2.2-6.0), as shown in Table 1. Risk of death due to cardiovascular disease (CVD) was increased in non-NPSLE patients (SMR 6.2, 95% CI: 2.0-14.6) and an increased risk of death to infections was present in both NPSLE and non-NPSLE patients ((SMR 29.9, 95% CI: 3.5 – 105) and SMR 91.3 (95% CI: 18.8 – 266) respectively). However, mortality did not differ between NPSLE and non-NPSLE patients (RR 1.0, 95% CI: 0.5 – 2.0). Table 1. All-cause mortality in SLE patients presenting with neuropsychiatric symptoms attributed to SLE (NPSLE) or to other causes (non-NPSLE) NPSLE (N = 149) Non-NPSLE (N = 202) Deaths (N, % ) 13 (8.7) 17 (8.4) Age at death (median, range ) 49 (32 – 79) 59 (20 – 89) Follow-up time (years ) 906 1047 Crude mortality rate (per 1000 PY ) 14.3 16.2 All-cause mortality* Female 5.5 (2.8 – 9.6) 3.4 (1.9 – 5.7) Male 2.3 (0.1 - 12.8) 6.2 (1.3 – 18.2) Combined 5.0 (2.6 – 8.5) 3.7 (2.2 – 6.0) * Standardized mortality ratio, ratio of the observed and expected number of deaths Conclusion: Mortality was increased in both NPSLE and non-NPSLE patients in comparison with the general population, but there was no difference in mortality between NPSLE and non-NPSLE patients. Risk of death due to infections was increased in both groups. Disclosure 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, Frits Rosendaal: 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
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
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  • 6
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 606.2-607
    Abstract: Cognitive impairment is common in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms, but the exact underlying structural brain correlates are unknown. Objectives: We aimed to compare cognitive function between groups of patients with different phenotypes of (NP)SLE and assessed the association between brain volumes, white matter hyperintensity (WMH) volume and cognitive function. Methods: Patients who visited the NPSLE clinic of the Leiden University Medical Center between 2007-2015 were included in this study (n=151; 42 ± 13 years, 91% female). In a multidisciplinary consensus meeting, phenotypes were established and neuropsychiatric symptoms were attributed to SLE (NPSLE, inflammatory (n=24) or ischemic (n=12)) or to minor involvement of SLE or other causes (minor/non-NPSLE (n=115)). All patients underwent standardized cognitive assessment of the four cognitive domains: global cognitive functioning (GCF), learning and memory (LM), executive functioning and complex attention (EFCA) and psychomotor speed (PS)). Cognitive dysfunction was defined as a T-score 〈 40, with age, sex, gender and education matched individuals of the Dutch population as reference. In addition, automated volume measurements on brain MRI (white matter, grey matter, white matter hyperintensities (WMH) and total brain volume (TBV)) were performed. Patients with brain infarcts 〉 1.5 cm were excluded. Cognitive function (Z-score) was compared between different NPSLE phenotypes using multiple regression analyses corrected for age, sex and education. Associations between brain volumes, WMH and cognitive function were assessed per phenotype using multiple regression analyses corrected for age, sex and intracranial volume. Results: Global cognitive functioning was impaired in 5%, learning & memory in 46%, and executive functioning & complex attention in 39% and psychomotor speed in 46% of all patients. Patients with inflammatory NPSLE showed the most cognitive impairment and reduced cognitive function compared to ischemic NPSLE (all domains) and minor/non-NPSLE (EFCA) (p 〈 0.05). Lower total brain volume and grey matter volume were associated with lower cognitive functioning in all domains (β: 0.00/0.01 (0.00; 0.01)) and lower white matter volume associated with lower LM, EFCA and PS (β: 0.00/0.01 (0.00; 0.01)) in all patients. Higher WMH volume associated with lower psychomotor speed (β: -0.14 (-0.32; -0.02)), especially in patients with inflammatory NPSLE (β: -0.36 (-0.60; -0.12). Conclusion: Reduced brain volume leads to reduced cognitive function in multiple cognitive domains in all patients with SLE and neuropsychiatric symptoms. Increased WMH volume leads to reduced psychomotor speed, especially in patients with inflammatory NPSLE. Table 1. Prevalence of cognitive impairment in patients with minor/non-NPSLE, inflammatory NPSLE and ischemic NPSLE Global cognitive functioning Learning & memory Executive functioning & complex attention Psychomotor speed All patients (n = 151 ) 8 (5) 70 (46) 57 (39) 69 (46) Inflammatory NPSLE (n = 24 ) 3 (13) 14 (58) 12 (50) 12 (50) Ischemic NPSLE (n = 12 ) 0 (0) 6 (50) 2 (17) 2 (17) Minor/non-NPSLE (n = 115 ) 5 (4) 50 (44) 43 (38) 55 (49) NPSLE = neuropsychiatric systemic lupus erythematosus. Data represent n (%) of patients with cognitive impairment in the mentioned cognitive domain. Cognitive impairment was defined as cognitive function at least 1SD lower than the mean of an age, sex and education matched general Dutch population. The percentages were calculated from total number of patients with available scores: Global functioning: 23/24 inflammatory NPSLE and 113/115 minor/non-NPSLE; psychomotor speed 113/115 minor/non-NPSLE, executive function & complex attention: also 113/115. All tests were available for ischemic NPSLE. Disclosure of Interests: None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1481557-6
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  • 7
    In: Lupus, SAGE Publications, Vol. 26, No. 5 ( 2017-04), p. 543-551
    Abstract: The objective of this study was to assess whether clinical and patient’s reported outcomes are associated with a different pathophysiological origin of neuropsychiatric events presenting in systemic lupus erythematosus. Methods A total of 232 neuropsychiatric events presenting in 131 systemic lupus erythematosus patients were included. Neuropsychiatric systemic lupus erythematosus diagnosis was established per event by multidisciplinary evaluation. All neuropsychiatric events were divided according to a suspected underlying pathophysiological process into one of the following: non-neuropsychiatric systemic lupus erythematosus related, inflammatory and ischaemic neuropsychiatric systemic lupus erythematosus. The clinical outcome of all neuropsychiatric events was determined by a physician-completed four-point Likert scale. Health-related quality of life was measured with the subscales of the patient-generated Short Form 36 (SF-36) health survey questionnaire. The change between scores at paired visits of all domain scores, mental component summary (SF-36 MCS) and physical component summary (SF-36 PCS) scores were retrospectively calculated and used as patient-reported outcome. The association among these outcomes and the different origin of neuropsychiatric events was obtained using multiple logistic regression analysis. Results The clinical status of 26.8% non-neuropsychiatric systemic lupus erythematosus events, 15.8% ischaemic neuropsychiatric systemic lupus erythematosus and 51.6% inflammatory neuropsychiatric systemic lupus erythematosus improved after re-assessment. Almost all SF-36 domains had a positive change at re-assessment in all groups independently of the origin of neuropsychiatric events. Neuropsychiatric systemic lupus erythematosus ( B = 0.502; p  〈  0.001) and especially inflammatory neuropsychiatric systemic lupus erythematosus ( B = 0.827; p  〈  0.001) had better clinical outcome, with change in disease activity being the only important predictor. The change in SF-36 MCS was also independently associated with neuropsychiatric systemic lupus erythematosus ( B = 5.783; p  〈  0.05) and inflammatory neuropsychiatric systemic lupus erythematosus ( B = 11.133; p  〈  0.001). Disease duration and change in disease activity were the only predictors in both cases. The change in SF-36 PCS was only negatively associated with age. Conclusion Inflammatory neuropsychiatric systemic lupus erythematosus events have better clinical outcome and meaningful improvement in SF-36 MCS than ischaemic neuropsychiatric systemic lupus erythematosus or non-neuropsychiatric systemic lupus erythematosus.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    RVK:
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2008035-9
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2014
    In:  Clinical Rheumatology Vol. 33, No. 9 ( 2014-9), p. 1279-1287
    In: Clinical Rheumatology, Springer Science and Business Media LLC, Vol. 33, No. 9 ( 2014-9), p. 1279-1287
    Type of Medium: Online Resource
    ISSN: 0770-3198 , 1434-9949
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
    detail.hit.zdb_id: 1480901-1
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  • 9
    In: Arthritis & Rheumatism, Wiley, Vol. 63, No. 3 ( 2011-03), p. 722-732
    Type of Medium: Online Resource
    ISSN: 0004-3591
    RVK:
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2754614-7
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  • 10
    Online Resource
    Online Resource
    BMJ ; 2010
    In:  BMJ Vol. 340, No. may14 1 ( 2010-05-25), p. c2541-c2541
    In: BMJ, BMJ, Vol. 340, No. may14 1 ( 2010-05-25), p. c2541-c2541
    Type of Medium: Online Resource
    ISSN: 0959-8138 , 1468-5833
    Language: English
    Publisher: BMJ
    Publication Date: 2010
    detail.hit.zdb_id: 1479799-9
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