Complex medical history of a patient with a compound heterozygous mutation in C1QC.

INTRODUCTION: 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.

Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort.

OBJECTIVE: The effect of serum autoantibodies on the brain of systemic lupus erythematosus (SLE) patients remains unclear. We investigated whether serum autoantibodies, individually and assessed in groups, are associated with specific brain-MRI abnormalities or whether these structural changes are associated with other SLE-related or traditional cardiovascular disease risk factors. METHODS: All patients underwent brain 3Tesla-MRI. White matter hyperintensities (WMHs), ischemic lesions, inflammatory-like lesions and cerebral atrophy were scored. Serum autoantibodies analyzed included lupus anticoagulant (LAC), anticardiolipine (aCL) IgG and IgM (first 3 also grouped into antiphospholipid autoantibodies (aPL)), anti-dsDNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm (the latter 5 grouped into SLE-related autoantibodies). Associations were assessed using logistic regression analysis adjusted for potential confounders. Furthermore, a sensitivity analysis including anti-Beta2 glycoprotein-1 antibodies (anti-ß2GP1) in the aPL group was performed and the potential modification role of the neuropsychiatric clinical status in the model was assessed. RESULTS: 325 patients (mean age 42 years (SD 14), 89% female) were included. The following MRI-brain abnormalities were found: WMHs (71%), lacunar infarcts (21%), gliosis (11%), micro-hemorrhages (5%), large hemorrhages (2%), inflammatory-like lesions (6%) and atrophy (14%). No associations were found between individual or total SLE-related autoantibodies and inflammatory-like lesions. A higher number of positive aPL was associated with lacunar infarcts (OR 1.37 (95%CI 1.02-1.99) and gliosis (OR 2.15 (1.37-3.37)). LAC was associated with lacunar infarcts in white matter (OR 3.38 (1.32-8.68)) and atrophy (OR 2.49 (1.01-6.15)), and aCL IgG with gliosis (OR 2.71 (1.05-7.02)). Among other variables, SLE patients with hypertension presented a higher chance for WMHs (OR 5.61 (2.52-12.48)) and lacunar infarcts in WM (OR 2.52 (1.10-5.74)) and basal ganglia (OR 8.34 (2.19-31.70)), while cumulative SLE-damage was correlated with lacunar infarcts in WM (OR 1.43 (1.07-1.90)), basal ganglia (OR 1.72 (1.18-2.51)) and cerebellum (OR 1.79 (1.33-2.41)). These associations were confirmed in the sensitivity analysis. CONCLUSIONS: Brain abnormalities in SLE represent different underlying pathogenic mechanisms. aPL are associated with ischemic brain changes in SLE, while the presence of SLE-related serum autoantibodies is not related to inflammatory-like lesions. Hypertension and cumulative SLE-damage associate with ischemic MRI-brain changes in SLE, suggesting the importance of accelerated atherosclerosis in this process.

Neuropsychiatric symptoms in systemic lupus erythematosus: impact on quality of life.

Objective Assess quality of life in patients with systemic lupus erythematosus (SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE). Methods Quality of life was assessed using the Short-Form 36 item Health Survey (SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow-up. SF-36 subscales and summary scores were calculated and compared with quality of life of the general Dutch population and patients with other chronic diseases. Results At baseline, quality of life was assessed in 248 SLE patients, of whom 98 had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom 64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a significantly reduced quality of life in all subscales of the SF-36. Quality of life at follow-up showed a significant improvement in physical functioning role ( p = 0.001), social functioning ( p = 0.007), vitality ( p = 0.023), mental health ( p = 0.014) and mental component score ( p = 0.042) in patients with neuropsychiatric symptoms not attributed to SLE, but no significant improvement was seen in patients with NPSLE. Conclusion Quality of life is significantly reduced in patients with SLE presenting neuropsychiatric symptoms compared with the general population and patients with other chronic diseases. Quality of life remains considerably impaired at follow-up. Our results illustrate the need for biopsychosocial care in patients with SLE and neuropsychiatric symptoms.

Outcomes of neuropsychiatric events in systemic lupus erythematosus based on clinical phenotypes; prospective data from the Leiden NP SLE cohort.

Objective 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.

Rheumatologists' adherence to a disease activity score steered treatment protocol in early arthritis patients is less if the target is remission.

To compare rheumatologists' adherence to treatment protocols for rheumatoid arthritis (RA) targeted at Disease Activity Score (DAS) ≤2.4 or <1.6. The BeSt-study enrolled 508 early RA (1987) patients targeted at DAS ≤2.4. The IMPROVED-study included 479 early RA (2010) and 122 undifferentiated arthritis patients targeted at DAS <1.6. We evaluated rheumatologists' adherence to the protocols and assessed associated opinions and conditions during 5 years. Protocol adherence was higher in BeSt than in IMPROVED (86 and 70 %), with a greater decrease in IMPROVED (from 100 to 48 %) than in BeSt (100 to 72 %). In BeSt, 50 % of non-adherence was against treatment intensification/restart, compared to 63 % in IMPROVED and 50 vs. 37 % were against tapering/discontinuation. In both studies, non-adherence was associated with physicians' disagreement with DAS or with next treatment step and if patient's visual analogue scale (VAS) for general health was ≥20 mm higher than the physician's VAS. In IMPROVED, also discrepancies between swelling, pain, erythrocyte sedimentation rate, and VASgh were associated with non-adherence. Adherence to DAS steered treatment protocols was high but decreased over 5 years, more in a DAS <1.6 steered protocol. Non-adherence was more likely if physicians disagreed with DAS or next treatment step. In the DAS <1.6 steered protocol, non-adherence was also associated with discrepancies between subjective and (semi)objective disease outcomes, and often against required treatment intensification. These results may indicate that adherence to DAS-steered protocols appears to depend in part on the height of the target and on how physicians perceive the DAS reflects RA activity.

Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: The objective of this paper is to analyse serum levels of anti-C1q, C1q circulating immune complexes (CIC), complement activation and complement components in systemic lupus erythematosus (SLE) patients during the first central nervous system neuropsychiatric (NP) event and to define the possible association between these results and clinical and laboratory characteristics. METHODS: A total of 280 patients suspected of having NP involvement due to SLE were recruited in the Leiden NPSLE-clinic. All SLE patients were classified according to the ACR 1982 revised criteria for the classification of SLE. The clinical disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and NP diagnoses were classified according to the 1999 ACR case definitions for NPSLE. We measured in serum of all patients anti-C1q and C1q CIC levels, the activation capacity of complement (CH50 and AP50) and different complement components (C1q, C3, C4). RESULTS: In 92 patients the symptoms were attributed to SLE. NPSLE patients consisted of 63 patients with focal NPSLE and 34 patients with diffuse NPSLE. Anti-C1q antibodies were significantly higher and CH50, AP50 and C3 were significantly lower in NPSLE patients compared with SLE patients without NPSLE. This association was specially marked for diffuse NPSLE while no differences were found for focal NPSLE. After using potential predictors, decreased C4 remained significantly associated with focal NPSLE, but only when antiphospholipid antibodies (aPL) were included in the model. C3 and AP50 were independently associated with diffuse NPSLE. When SLEDAI-2K was included in the model these two associations were lost. When individual NPSLE syndromes were analysed, psychosis and cognitive dysfunction showed significantly lower values of complement activation capacity and all complement components. No significant associations were seen for other individual NPSLE syndromes. CONCLUSION: The associations between diffuse NPSLE and anti-C1q, C3/AP50 and focal NPSLE and C4 may be explained by disease activity and the presence of aPL, respectively. The role of complement activation and complement components in lupus psychosis and cognitive dysfunction merits further research.

Effectiveness of four dynamic treatment strategies in patients with anticitrullinated protein antibody-negative rheumatoid arthritis: a randomised trial.

OBJECTIVE: To determine the most effective treatment strategy among anticitrullinated protein antibodies (ACPA)-negative patients with early rheumatoid arthritis. METHODS: In the BeSt study, 184 ACPA-negative patients were randomised to: (1) sequential monotherapy, (2) step-up therapy, (3) initial combination including prednisone, (4) initial combination including infliximab. Treatment was targeted at the disease activity score (DAS) ≤2.4. Early response and 10-year outcomes were compared between the four strategy-arms in ACPA-negative patients. RESULTS: ACPA-negative patients achieved more short-term functional improvement from initial combination therapy than when on monotherapy (at month 3, mean Health Assessment Questionnaire (HAQ) 0.71 vs 0.98, p=0.006; at month 6, 0.59 vs 0.87, p=0.004). Functional ability over time was comparable between the strategy-arms (p=0.551) with a mean HAQ of 0.6 at year 10 (p=0.580 for comparison across the strategy-arms). 10-year radiographic progression was negligible (median 0.5) and comparable between the 4 strategy-arms (p=0.082). At year 10, remission was achieved by 11/40 (28%), 9/45 (20%), 17/56 (30%) and 17/43 patients (40%) in strategy-arms 1-4, respectively (p=0.434). Over time, similar remission percentages were achieved in all strategy-arms (p=0.815). 18%, 16%, 20% and 21% in strategy-arms 1 to 4 (p=0.742) were in drug-free remission at year 10, with a median duration of 60 months across the arms. CONCLUSIONS: Initial combination therapy with methotrexate, sulfasalazine and prednisone, or methotrexate and infliximab, is the most effective treatment strategy for ACPA-negative patients, resulting in earlier functional improvement than when on initial methotrexate monotherapy. After 10 years of targeted treatment, in all strategy-arms favourable clinical outcomes were achieved and radiographic progression was limited. TRIAL REGISTRATION NUMBER: NTR262, NTR265.

Health care in systemic lupus erythematosus (SLE): the patient's perspective.

In order to provide more patient-centered care for patients suffering from systemic lupus erythematosus (SLE), we studied their current satisfaction and preferences regarding future health care delivery. We sent questionnaires to all SLE patients visiting the rheumatology outpatient clinic in Leiden, the Netherlands. The questionnaire comprised three topics: (a) health care needs using a modified version of SLE Needs Questionnaire (range 0-38), (b) satisfaction with care per provider (visual analogue scale, range 0 (not at all)-100 (very satisfied)), and (c) preferences for future healthcare (four items). One hundred and two patients (63 % response) reported an average of 16 (±6) health care needs, with all patients reporting a need in the physical domain. More needs were significantly associated with worse physical functioning and a higher educational level. The average satisfaction score was 73 (±19) with a lower overall satisfaction score being associated with younger age and an educational level higher or lower than average. Regarding preferences for future health care delivery, 75 % of patients showed interest in a yearly standardized medical assessment, 57 % in regular, specialized nurse contacts using internet, 50 % in a yearly inventory on the need for self-management support, and 36 % in an education course. The association of age, education level and physical functioning with health care needs, and/or satisfaction suggest that the delivery of care should be better tailored to the needs of subgroups of patients.

Mortality in neuropsychiatric systemic lupus erythematosus (NPSLE).

The standardized mortality ratio (SMR) for systemic lupus erythematosus (SLE) is three; SMR increases to six in case of renal involvement. Up to now data on survival in case of neuropsychiatric involvement in SLE (NPSLE) have been scarce, therefore we calculated an SMR for NPSLE. Furthermore, we identified characteristics that influenced survival by Cox regression analyses. All patients suspected of NPSLE in our center since 1989 were evaluated and included in this study when a diagnosis of primary NPSLE could be established. Patient's life/death status was tracked using the civic registries. Thirty-two (19%) of the 169 included NPSLE patients died within a median follow-up period of six years (range 0.5-24 years). This resulted in a significantly increased mortality rate compared to the general population: SMR 9.5 (95% CI 6.7-13.5). Hazard ratios (HRs) were highest in patients with acute confusional state (HR 3.4) and older age at diagnosis of NPSLE (HR 1.1). A decreased mortality risk was seen with the prescription of antiplatelet therapy (HR 0.22). The time period in which NPSLE was diagnosed did not significantly influence survival. Most frequent causes of death were infection and NPSLE itself.

The relationship between disease activity and depressive symptoms severity and optimism--results from the IMPROVED study.

To assess depressive symptoms severity and dispositional optimism in patients with recent onset arthritis both before and after 4 months treatment. Two hundred twenty-two patients with recent onset RA and undifferentiated arthritis in the IMPROVED study filled out the Beck Depression Inventory (BDI-II) to assess depressive symptoms severity and the Life Orientation Test Revised (LOT-R) to measure optimism before and after 4 months of treatment. All patients were treated with methotrexate 25 mg/week and prednisone 60 mg/day (tapered to 7.5 mg/day in 7 weeks). Linear regression analysis was used to assess the association between the disease activity score (DAS) and its components (tender joint count, general well-being measured with a visual analogue scale (VAS), swollen joint count, and erythrocyte sedimentation rate) with the BDI-II an LOT-R scores. In general, depressive symptoms were mild. The DAS was an independent predictor of depressive symptoms scores both at baseline and after 4 months follow-up, in particular tender joint count and VAS global health. Disease activity was not associated with the level of optimism. Nevertheless, patients who achieved clinical remission improved significantly more in both depression score and optimism score than patients who did not. Patients with early arthritis report improvement in depressive symptoms and optimism with improvement in disease activity and achieving clinical remission. Depression scores are associated with pain and unwell being but not with swollen joint counts and inflammatory parameters.

Health care usage in Dutch systemic lupus erythematosus patients.

As a first step in the improvement of the organization of care for patients with systemic lupus erythematosus (SLE) we studied their health care usage and its determinants. A questionnaire was sent to 161 outpatients of the rheumatology clinic of a Dutch university hospital. The questionnaire comprised questions on health care usage, quality of life and sociodemographic characteristics. Disease characteristics were extracted from the medical record. Among the 102 responders (63% response rate) the proportions of patients reporting contacts with a rheumatologist because of SLE since onset of the disease and over the past 12 months were 100% and 83%, respectively. These proportions were 93% and 68% for all other medical specialists, 88% and 44% for the general practitioner, 78% and 44% for any health professional, 29% and 9% for care at home, 48% and 17% for hospital admissions and 29% and 2% for day-patient care. Younger age, major organ involvement, the use of immunosuppressants and worse physical functioning were found to be significantly associated with greater health care use. This study demonstrated that health care usage by SLE patients is substantial and involves a variety of health care services. Further research should be directed at patients' satisfaction and patients' needs regarding the optimal organization of integrated, multidisciplinary services that are accessible for SLE patients of all ages.

Neuropsychiatric systemic lupus erythematosus: lessons learned from magnetic resonance imaging.

OBJECTIVE: The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE [NPSLE]) are highly diverse, and their etiology is incompletely understood. The aim of this study was to provide an inventory of abnormalities on conventional brain magnetic resonance imaging (MRI) in NPSLE and to interpret the findings in relation to possible underlying pathogenetic mechanisms. METHODS: MR images of the first episode of active NPSLE in 74 patients were retrospectively reviewed. All patients fulfilled the American College of Rheumatology (ACR) 1982 revised criteria for the classification of SLE and were classified according to the 1999 ACR case definitions for NPSLE syndromes. We excluded patients with a history of brain disease and patients in whom other mechanisms unrelated to SLE caused the neuropsychiatric symptoms. RESULTS: The principal findings were: 1) focal hyperintensities in white matter (WM) (49% of all patients) or both WM and gray matter (GM) (5% of all patients), suggestive of vasculopathy or vasculitis; 2) more widespread, confluent hyperintensities in the WM, suggestive of chronic hypoperfusion due to the same mechanisms; 3) diffuse cortical GM lesions (12% of all patients), compatible with an immune response to neuronal components or postseizure changes; and 4) absence of MRI abnormalities, despite signs and symptoms of active disease (42% of all patients). CONCLUSION: Several distinct brain MRI patterns were observed in patients with active NPSLE, suggestive of different pathogenetic mechanisms. To advance our understanding of the various processes leading to NPSLE, the radiographic manifestations may be a good starting point and useful for categorization of patients in further research.

The development of a simple questionnaire to screen patients with SLE for the presence of neuropsychiatric symptoms in routine clinical practice.

AIM: The creation of a physician-administered questionnaire to screen patients with Systemic Lupus Erythematosus (SLE) for the presence of symptoms suggestive of neuropsychiatric involvement (NPSLE). METHODS: The development of the questionnaire followed three phases. First, a list of manifestations was prepared based on the ACR case definitions for NPSLE. A first questionnaire was constructed including 119 items. To reduce their number, a Delphi analysis was carried out and a second questionnaire with 62 questions was developed. This questionnaire was administered to 139 patients with SLE (58 with NPSLE: 29 active, 29 inactive; and 81 without NPSLE: 39 active, 42 inactive). Questions relevant to the screening of patients were selected on the basis of the receiver operating characteristic (ROC) curve analysis. RESULTS: Twenty-seven questions concerning central nervous system and psychiatric manifestations were found to be relevant; the remaining could be eliminated without significantly affecting AUC. The area under the ROC curve (AUC) was 0.69 (95% CI 0.61-0.78). A score above 17 was considered as suggestive of the presence of NPSLE with a sensitivity of 92.9% (95% CI 85.1-97.3 %) and specificity of 25.4% (95% CI 14.7-39.00 %). CONCLUSIONS: This questionnaire could represent a 'core set' of questions that could help in clinical practice to identify patients with neuropsychiatric symptoms requiring further evaluation.

[Psychiatric symptoms in systemic lupus erythematosus]. / Psychiatrische symptomen bij systemische lupus erythematosus.

BACKGROUND: This article focuses on two patients with psychiatric symptoms arising from systemic lupus erythematosus (SLE). Affective and psychotic symptoms frequently occur in SLE, often in combination with cognitive disturbances, and can be a first manifestation of the disorder. The diagnosis and treatment of a possible case of neuropsychiatric SLE should preferably take place in a multidisciplinary setting.

Correlation of magnetization transfer ratio histogram parameters with neuropsychiatric systemic lupus erythematosus criteria and proton magnetic resonance spectroscopy: association of magnetization transfer ratio peak height with neuronal and cognitive dysfunction.

OBJECTIVE: To investigate whether, in neuropsychiatric systemic lupus erythematosus (NPSLE) patients, magnetization transfer ratio (MTR) histogram parameters are related to neurochemical findings obtained using proton magnetic resonance spectroscopy (1H-MRS) and to determine whether MTR histogram changes are linked to specific SLE and NPSLE characteristics. METHODS: Eighteen SLE patients (15 female, 3 male; mean +/- SD age 42.8 +/- 12.8 years), 34 NPSLE patients (32 female, 2 male; mean +/- SD age 35.9 +/- 12.2 years), and 15 healthy controls (14 female, 1 male; mean +/- SD age 44.7 +/- 9.6 years) underwent magnetization transfer imaging and 1H-MRS. Whole-brain MTR histogram parameters were associated with 1H-MRS metabolite ratios, certain SLE criteria, and neuropsychiatric syndromes. RESULTS: No differences were found in the MTR histogram parameters between SLE patients and NPSLE patients. NPSLE patients had a lower MTR histogram peak height than did the healthy controls. The MTR histogram peak height and the mean height were significantly associated with the N-acetylaspartate to creatinine ratio, suggesting neuronal dysfunction. Of all SLE criteria, renal dysfunction and arthritis were associated with MTR histogram parameters. After corrections for age, sex, and these SLE criteria, of the various neuropsychiatric syndromes only cognitive dysfunction was associated with the MTR histogram peak height. CONCLUSION: The MTR peak height is lower in NPSLE patients than in healthy controls. MTR peak height reflects neuronal dysfunction, as detected by 1H-MRS. Furthermore, the MTR peak height is associated with cognitive dysfunction but not with the other neuropsychiatric syndromes evaluated in our study.

Selective gray matter damage in neuropsychiatric lupus.

OBJECTIVE: Damage of brain parenchyma in patients with primary diffuse neuropsychiatric systemic lupus erythematosus (NPSLE) has been indicated by magnetization transfer imaging (MTI). However, the location of MTI abnormalities is unknown. This study was undertaken to assess the distribution of MTI abnormalities over gray matter (GM) and white matter (WM) in SLE patients with a history of NP symptoms without explanatory magnetic resonance imaging (MRI) evidence of focal disease. METHODS: MTI was performed in 24 female SLE patients with a history of diffuse NP symptoms and 24 healthy female controls. Magnetization transfer ratio (MTR) maps were calculated for GM and WM separately, and GM and WM MTR histograms were generated. Univariate and multivariate analyses with age as an additional covariate were performed on the histogram parameters peak location (PL), peak height (PH), and mean MTR. RESULTS: Compared with controls, significantly reduced PH (mean +/- SD 136 +/- 22 arbitrary units versus 151 +/- 13 arbitrary units) and mean MTR (33.3 +/- 1.0 percent units versus 33.6 +/- 0.5 percent units) were found in the GM of NPSLE patients (P = 0.002 and P = 0.033, respectively, in multivariate analyses). No significant differences were observed for WM MTR parameters. CONCLUSION: This is the first study to demonstrate, using MTI, that in SLE patients with a history of NP symptoms and without explanatory focal abnormalities on MRI, the GM is particularly affected. These findings support the hypothesis that neuronal injury may underlie central nervous system manifestations in NPSLE.

A neuroimaging follow up study of a patient with juvenile central nervous system systemic lupus erythematosus.

BACKGROUND: The course of central nervous system systemic lupus erythematosus (CNS-SLE) is largely unknown. New imaging techniques are available to assist in monitoring the disease course. OBJECTIVE: To report a case of juvenile CNS-SLE, in which magnetic resonance imaging (MRI) was used to assess disease activity. CASE REPORT: A 10-year-old female patient with SLE presented with convulsions; MRI and computed tomography (CT) of the cerebrum disclosed abnormalities. Despite adequate treatment, two years later she had a generalised convulsion, and MRI showed new lesions. MR spectroscopy (MRS) indicated neuronal loss, inflammation, and metabolically compromised tissue; magnetisation transfer imaging (MTI) showed an increase in whole brain lesion load. After exclusion of a malignancy, CNS-SLE was the most likely diagnosis, and cyclophosphamide pulses were administered. Initially, multiple sclerosis (MS)-like lesions regressed, but despite maximal immunosuppressive drugs, new lesions formed and disappeared. When immunosuppressive drugs had been stopped for six months MRI showed improved lesions and MTI histograms. DISCUSSION: In this case report, the anatomical substrate, metabolic aspect, neuroimaging, and clinical course of MS-like lesions in a child with CNS-SLE are described. The way in which radiological techniques can support clinical decision making in this young patient with progressive CNS-SLE is illustrated.

Lymphocytic hypophysitis in a 43-year-old woman.

A woman with sarcoidosis and primary hypothyroidism presented with partial hypopituitarism without pituitary gland enlargement. A clinical diagnosis of lymphocytic hypophysitis was established after exclusion of other possibilities, since a definitive diagnosis can only be made after histological studies. This rare form of chronic inflammation and destruction of the anterior pituitary gland is discussed.