Dissociation in SLE: A part of lupus fog?

INTRODUCTION: Lupus fog is ill-defined. We aimed to study whether lupus fog is the result of dissociation by studying the prevalence of dissociation and dissociative fog in patients with SLE and neuropsychiatric manifestations of inflammatory and non-inflammatory origin. METHODS: Patients visiting the tertiary referral center for neuropsychiatric systemic lupus erythematosus (NPSLE) of the LUMC between 2007-2019 were included. Patients were classified as having neuropsychiatric symptoms of inflammatory or non-inflammatory origin. Dissociation was studied using the Dissociative Experience Scale-II (DES), in which the presence of 28 dissociative symptoms is rated (0-100% of the time), of which one question assesses the presence of a dissociative fog directly. Average scores are calculated and scores ≥ 25 are considered indicative of a dissociative disorder. A score of ≥ 30 on question 28 (dissociative fog) was considered indicative for the presence of a fog. Summary scores in the general adult population range from 4.4 to 14. Multiple regression analysis (MRA) was performed to study the association between inflammatory neuropsychiatric symptoms and dissociation. DES results are presented as median (range) and MRA as B and 95% confidence interval (CI). RESULTS: DES questionnaires were available for 337 patients, of which 69 had an inflammatory NPSLE phenotype (20%). Mean age in the total study population was 43 ± 14 years and the majority was female (87%). The median dissociation score was 7.1 (0-75) and did not differ between patients with neuropsychiatric symptoms of inflammatory or non-inflammatory origin (B: -0.04 (95% CI: -0.17; 0.09)). 35 patients (10%) had a score indicative of a dissociative disorder. The most common type of dissociation was absorption/imagination. 43 patients (13%) reported a dissociative fog. DISCUSSION: In most patients with SLE and neuropsychiatric symptoms, dissociative symptoms are within normal range, regardless of underlying etiology. Dissociative fog is present, but uncommon. Lupus fog is most likely not associated with dissociation.

Fatigue in patients with systemic lupus erythematosus and neuropsychiatric symptoms is associated with anxiety and depression rather than inflammatory disease activity.

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 (ß: 0.8 (95% CI -4.8; 6.1) and there was less fatigue in patients with an inflammatory phenotype on the MFI and VAS (ß: -3.7 (95% CI: -6.9; -0.5) and ß: -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.

Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy.

Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77-9.50]mm2/s × 10-4) compared with presymptomatic mutation-carriers (2.62 [1.96-3.43]mm2/s × 10-4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16-0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08-0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22-0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13-0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = -0.42 [-0.69-0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.