Anne Bolette Tjensvoll

Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjögren syndrome: a comparative population-based study

Objectives: To compare the prevalence and pattern of neuropsychiatric (NP) syndromes observed in systemic lupus erythematosus (SLE) to patients with Primary Sjögren syndrome (PSS) using the American College of Rheumatology (ACR) criteria for the 19 NP syndromes seen in SLE. Methods: A population-based study was conducted including 68 patients with SLE (mean (SD) age 43.8 (13.6) years) and 72 with PSS (age 57.8 (13.0) years). Specialists in internal medicine, neurology and neuropsychology performed standardised examinations. Cerebral MRI scans and neurophysiological studies were performed in all patients. Results: Similar prevalences in SLE and PSS were observed for headaches (87% vs 78%, p = 0.165), cognitive dysfunction (46% vs 50%, p = 0.273), mood disorders (26% vs 33%, p = 0.376), anxiety disorders (12% vs 4%, p = 0.095), cranial neuropathy (1% vs 4%, p = 0.339) and seizure disorders (7% vs 3%, p = 0.208). Cerebrovascular disease was more common in SLE than PSS (12% vs 3%, p = 0.049); but mononeuropathy (0% vs 8%, p = 0.015) and polyneuropathy (18% vs 56%, p<0.001) were less common in SLE than PSS. Other syndromes were rare or absent in both patient groups. Conclusions: Headache, cognitive dysfunction and mood disorders are common in both diseases, but otherwise there are distinct differences in NP involvement, with cerebrovascular diseases more prevalent in SLE and neuropathies more common in PSS. This indicates that some NP disease mechanisms are shared while others differ between the two diseases.

Fatigue in primary Sjögren’s syndrome – A link to sickness behaviour in animals?

Interleukin-1beta (IL-1beta) is involved in the regulation of sickness behaviour in response to infection and inflammation in animals. Human fatigue can be considered an element of sickness behaviour and is a prominent and often disabling phenomenon in autoimmune diseases such as primary Sjögrens syndrome (PSS). The role of the IL-1 system in the fatigue of patients with PSS was explored. A cerebrospinal fluid (CSF) analysis of IL-1beta, IL-1Ra, and IL-1sRII was performed in 54 PSS patients and 53 control subjects. Fatigue was evaluated in the patients using the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (VAS); mood was evaluated using the Beck Depression Inventory (BDI). There were higher CSF levels of IL-1Ra pg/mL in PSS patients vs. controls (median 38.4: range 15.4-81.7 vs. 33.7: 7.3-163.1, p=0.026). Fatigue VAS scores were associated with increasing CSF levels of IL-1Ra in PSS patients (R(2)=0.11, p=0.015). In a subgroup analysis of the non-depressed PSS patients (N=37; 69%), the association between VAS scores and IL-1Ra was even stronger (R(2)=0.20, p=0.006). The positive association between VAS scores and IL-1Ra remained significant in a multiple regression analysis adjusting for age and BDI scores. Increased levels of IL-1Ra in the CSF are associated with increasing fatigue in PSS patients, indicating that the activated IL-1 system is a possible biological factor associated with fatigue.

Fatigue is associated with cerebral white matter hyperintensities in patients with systemic lupus erythematosus

Background: Fatigue is a disabling phenomenon in many patients who have systemic lupus erythematosus (SLE). The pathophysiological processes are unknown, and no known biological disease factors influence the phenomenon. Because depressive mood is consistently associated with fatigue, and drug treatment for SLE does not ameliorate fatigue, a psychological explanation could be an alternative. In search of a somatic basis for fatigue, we looked for alternative markers of biologic activity associated with fatigue. Cerebral white matter hyperintensities (WMHs) represent biochemical changes of brain tissue and are frequently encountered in patients with SLE, and are associated with cognitive impairment in patients with multiple sclerosis. Presence of such an association between fatigue and WMHs in SLE would favour a biological axis to fatigue. Methods: A cross-sectional, case–control study with 62 unselected patients with SLE and 62 age- and gender-matched healthy subjects. Fatigue was evaluated using the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (VAS). WMHs were rated using Scheltens’ method. Results: Greater fatigue and more WMHs appeared in patients with SLE versus healthy subjects. In the full group of patients (n = 62), fatigue VAS was associated with total WMH score (p = 0.009). In subgroup analysis of patients without clinical depression (n = 40), the association with total WMH remained (p = 0.035), whereas this was not the case in the depressed group (n = 18) (p = 0.211). Conclusion: Increased cerebral WMH load is associated with increased fatigue, indicating a biological origin for some portion of fatigue in patients with SLE.

Migraine is frequent in patients with systemic lupus erythematosus: A case-control study

Introduction: The objective of this study was to compare the prevalence of primary headaches in systemic lupus erythematosus (SLE) versus healthy subjects, and to determine whether headaches in SLE are associated with MRI- or cerebrospinal fluid (CSF) abnormalitites. Patients and methods: The case-control study included MRI- and CSF investigations. Headache was classified according to the International Classification of Headache Disorders. Depression and fatigue were measured with Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) respectively. Results: Twenty-four out of 67 SLE patients and 13 out of 67 age- and gender matched healthy subjects had migraine (36% vs 19%, P = 0.03). Nine (13%) SLE patients had migraine with aura vs 4 (6%) in healthy subjects, P = 0.14. The prevalence of tension type headache was equal (60% in patients vs 58% in controls). There was no association between migraine and SLE disease activity, biochemical or immunological markers, cerebral white matter hyperintensities, interleukin-6 in CSF, impairment of the blood-brain barrier, or intrathecal immunoglobulin production. SLE patients had higher BDI- and FSS scores compared with healthy control subjects, and SLE patients with migraine had higher BDI scores than lupus patients without migraine. Conclusions: Migraine is more prevalent in SLE patients, associated with depression like in the general population, but not associated with disease activity or abnormalities detected on cerebral MRI, in CSF, or any SLE characteristics except from SLE photosensitivity. The inclusion of the migraine item in SLE disease activity instruments remains questionable.

Association of hippocampal atrophy with cerebrospinal fluid antibodies against the NR2 subtype of the N-methyl-D-aspartate receptor in patients with systemic lupus erythematosus and patients with primary Sjögren's syndrome.

Cognitive dysfunction is common in both systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (SS). Antibodies against the NR2 subtype of the N‐methyl‐D‐aspartate receptor (anti‐NR2 antibodies) cause hippocampal atrophy and cognitive impairment in mice and have been associated with memory impairment in both patients with SLE and patients with primary SS. In addition, a reduced volume of hippocampal gray matter has been demonstrated in both SLE and primary SS. This study was undertaken to investigate whether there is a connection between the presence of anti‐NR2 antibodies and hippocampal atrophy in human diseases.

Memory Dysfunction in Primary Sjögren's Syndrome Is Associated With Anti‐NR2 Antibodies

OBJECTIVE Our understanding of the etiology and pathogenesis of neuropsychiatric involvement in primary Sjögrens syndrome (SS) is incomplete. In systemic lupus erythematosus, it has been reported that antibodies directed against N-methyl-D-aspartate receptor subtype NR2 (anti-NR2) interfere with memory and learning function, as well as mood. This has not been investigated in primary SS; however, the present study was undertaken to advance our understanding of neuropsychiatric involvement in this disease. METHODS Sixty-six patients with primary SS and 66 age- and sex-matched healthy control subjects underwent clinical examination and neuropsychological evaluation. Anti-NR2 antibodies were measured in serum and cerebrospinal fluid. Hippocampus volume was estimated using software extensions to SPM5. RESULTS Patients with primary SS had smaller hippocampi than healthy subjects (mean ± SD 8.15 ± 0.98 cm(3) versus 8.49 ± 0.88 cm(3); P = 0.01). In patients with primary SS, anti-NR2 antibodies in cerebrospinal fluid were associated with a worse performance in 8 of 10 memory and learning tests, and anti-NR2 antibodies in serum were associated with a worse performance in 6 of those same tests. In addition, a higher proportion of patients with depression than patients without depression had serum anti-NR2 antibody levels above the cutoff value. CONCLUSION Results of this study indicate that anti-NR2 antibodies may represent one of the pathogenetic mechanisms for cognitive disturbances and mood disorders in patients with primary SS.

Cerebral white matter hyperintensities are not increased in patients with primary Sjögren’s syndrome

Background and purpose:  It is frequently thought that cerebral white matter hyperintensities (WMHs) on T‐2 weighted MRI scans are increased in patients with autoimmune diseases. An increased frequency of WHMs has been described in primary Sjögren’s syndrome (PSS), but no controlled studies exist. The aim of this study was therefore to compare WMHs in PSS patients and healthy subjects applying the new European‐American criteria for PSS.

Headache in primary Sjøgren's syndrome: a population‐based retrospective cohort study

We investigated whether the prevalence of primary headaches was higher in patients with primary Sjøgrens syndrome (PSS) than in healthy individuals.

High headache-related disability in patients with systemic lupus erythematosus and primary Sjögren's syndrome.

It is often argued that patients with systemic lupus erythematosus (SLE) have more headaches than healthy subjects, but this association remains controversial. Thus the magnitude and severity of headaches in SLE were evaluated in comparison with another autoimmune disease, namely primary Sjögrens syndrome (pSS).

Loss of cerebral white matter in primary Sjögren's syndrome: a controlled volumetric magnetic resonance imaging study

Although brain involvement is common in primary Sjögrens syndrome (pSS), results from cerebral imaging studies are inconsistent. This study aimed to perform both voxel‐wise and global brain volume analyses in a nearly population‐based pSS cohort to explore whether the patients displayed any focal or diffuse volume differences compared with healthy subjects.