A Case of Cerebral Large-Vessel Vasculitis Concomitant Fahr Syndrome in Systemic Lupus Erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogenous, devastating autoimmune inflammatory disease with multiorgan involvement. A variety of neurological and psychiatric symptoms may be caused by nervous system involvement, termed neuropsychiatric systemic lupus erythematosus. CASE REPORT: We describe a young man newly diagnosed with SLE who had a stroke as an initial symptom and was found to have cerebral large-vessel vasculitis and Fahr syndrome. CONCLUSIONS: The novelties of this report are the extensive cerebral calcification demonstrated on head computerized tomography in a patient with SLE, and the depiction of an underlying vasculitis on high-resolution magnetic resonance vessel wall imaging. It is our aim to describe this atypical form of neuropsychiatric systemic lupus erythematosus onset and to make known the usefulness of the new magnetic resonance imaging techniques for the diagnosis of cerebral large-vessel vasculitis.

Systemic lupus erythematosus with diffuse intracranial calcification: A case report and review of literature.

OBJECTIVE: to investigate the clinical characteristics of systemic lupus erythematosus with diffuse intracranial calcification. METHODS: The clinical characteristics of one case of systemic lupus erythematosus with diffuse intracranial calcification were analyzed, and 12 cases in related literatures were reviewed by searching Medline and Wanfang database. RESULTS: Our case and 12 cases reviewed were all female. With the exception of one case, the course of SLE was more than 5 years. The clinical manifestations of the nervous system are diverse, including epilepsy, hemiplegia, cognitive impairment, and mental abnormalities. In the presence of neuropsychiatric manifestations, this case and six cases reviewed had SLE activity. Cerebrospinal fluid (CSF) examination was performed in seven patients, including four patients with CSF protein elevation, two patients with IL-6 elevation, and one patient with anti-ribosomal p antibody elevation. This case and 10 of 12 cases reviewed had bilateral basal ganglia calcification. Intracranial calcification was very high density on CT and showed high T1WI and low T2WI signal on MRI. CONCLUSION: Systemic lupus erythematosus with intracranial calcification is a rare and severe manifestation of SLE, which is not completely parallel to SLE activity. The clinical manifestations of the nervous system are diverse, and bilateral basal ganglia calcification is the most common in imaging. High T1WI signal and low T2WI signal may be used as one of the imaging features to identify intracranial calcification.

Brain MRI in patients with acute confusional state of diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus.

OBJECTIVE: The objective of this study is to explore the characteristics of brain MRI abnormalities in acute confusional state (ACS) in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Thirty-six patients with ACS admitted to our institutions from 1992 to 2015 were exhaustively enrolled. Their medical charts and brain MRI scans were reviewed. RESULTS: Eighteen of 36 ACS patients had MRI abnormalities, mostly high-intensity lesions of various sizes in the cerebral white matter. MRI abnormalities improved after treatment in 12 of 14 patients in follow-up studies. MRI abnormalities were not correlated with ages at the onset of ACS, disease durations of SLE, the presence of anti-DNA, anti-phospholipid or anti-ribosomal P antibodies, or IL-6 levels in sera or cerebrospinal fluid. Notably, MRI abnormalities were significantly associated with the presence of serum anti-Sm antibodies (p = 0.0067). Finally, eight of the 18 patients with MRI abnormalities, but none of the other 18 patients without MRI abnormalities, died from active SLE. Thus, MRI abnormalities significantly increased the mortality in ACS (p = 0.0013, HR =10.36 [95% CI: 2.487-43.19]). CONCLUSION: These results demonstrate that patients with ACS with MRI abnormalities have more severe diseases, resulting in poorer prognoses. The data also indicate that anti-Sm is involved in the development of MRI abnormalities in ACS.

Brain histopathology in patients with systemic lupus erythematosus: identification of lesions associated with clinical neuropsychiatric lupus syndromes and the role of complement.

OBJECTIVES: Neuropsychiatric (NP) involvement is a poorly understood manifestation of SLE. We studied post-mortem histopathology in relation to clinical NPSLE syndromes and complement deposition in brains of NPSLE and SLE patients and controls. Furthermore, we investigated the correlation between cerebral post-mortem histopathology and ex vivo 7 T MRI findings in SLE and NPSLE. METHODS: A nationwide search for autopsy material yielded brain tissue from 16 NPSLE and 18 SLE patients. Brains obtained from 24 patients who died of acute cardiac events served as controls. Apart from a histopathological evaluation, paraffin-embedded cortical tissue was stained for components of the classical, lectin and terminal complement pathways. RESULTS: Diffuse vasculopathy, microinfarction, macroinfarction, vasculitis and microthrombi occurred significantly more often in NPSLE than SLE patients and were absent in controls. Focal vasculopathy was found in both SLE patients and controls. Complement deposition was strongly associated with both SLE and NPSLE, but not with controls (P < 0.001). Microthrombi were found uniquely in NPSLE and were associated with C4d and C5b-9 deposits (P < 0.05). A 7 T MRI was unable to detect most small vessel injury that was visible histopathologically. CONCLUSION: Our study demonstrates that histopathological lesions in NPSLE represent a continuum, ranging from non-specific lesions such as focal vasculopathy, to more specific lesions including C4d- and C5b-9-associated microthrombi and diffuse vasculopathy related to clinical syndromes defining NPSLE. Complement deposition may be a key factor in the interaction between circulating autoantibodies and thromboischaemic lesions observed in NPSLE. Therefore, complement inhibition may have novel therapeutic potential in NPSLE.

Neuropsychiatric Lupus in clinical practice / Lúpus neuropsiquiátrico na prática clínica

ABSTRACT Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs, characterized by the production of autoantibodies and the development of tissue injury. The etiology of SLE is partially known, involving multiple genetic and environmental factors. As many as 50% of patients with SLE have neurological involvement during the course of their disease. Neurological manifestations are associated with impaired quality of life, and high morbidity and mortality rates. Nineteen neuropsychiatric syndromes have been identified associated with SLE, and can be divided into central and peripheral manifestations. This article reviews major neuropsychiatric manifestations in patients with SLE and discusses their clinical features, radiological findings and treatment options.

RESUMO Lúpus eritematoso sistêmico (LES) é uma doença autoimune crônica que envolve múltiplos órgãos e sistemas, caracterizada pela produção de auto anticorpos e lesão tecidual. A etiologia do LES é parcialmente conhecida e envolve interação entre fatores genéticos e ambientais. Até 50% dos pacientes com LES apresentam envolvimento neurológico no decorrer da doença. Manifestações neurológicas estão associadas a prejuízo na qualidade de vida e altas taxas de mortalidade e morbidade. Foram identificadas 19 síndromes neuropsiquiátricas em pacientes com LES, divididas entre manifestações do sistema nervoso central e periférico. O objetivo deste artigo é revisar as manifestações neuropsiquiátricas mais importantes. Serão abordadas as características clínicas, os aspectos radiológicos e opções de tratamento dos eventos neuropsiquiátricos.

Tumor-like cerebral perivasculitis in a pediatric patient with systemic lupus erythematosus.

Nervous system manifestations are present in up to 70% of patients with systemic lupus erythematosus (SLE). The spectrum of clinical symptoms varies widely, from severe, life-threatening symptoms at presentation, such as transverse myelitis, to symptoms of more subtle and subclinical abnormalities of neurocognitive function. We report the case of a 14-year-old patient with SLE and lupus nephritis under regular steroid therapy, who had a sudden onset of consciousness change. Brain magnetic resonance imaging showed a huge mass lesion. After surgical decompression and corticosteroid pulse therapy, the patient's neurologic symptoms improved dramatically. Brain biopsy revealed perivasculitis of the brain with marked perivascular infiltration of eosinophils, macrophages, and neutrophils. Microhemorrhage was also evident. The patient recovered without obvious neurologic sequelae.

Voxel-based morphometry of brain SPECT can detect the presence of active central nervous system involvement in systemic lupus erythematosus.

OBJECTIVE: To determine the value of voxel-based morphometry (VBM) of brain SPECT (single-photon emission computed tomography) images (BSI) in discriminating active central nervous system (CNS) manifestations in systemic lupus erythematosus (SLE) patients. PATIENTS AND METHODS: Forty SLE patients (mean age 33 yrs) and 33 normal volunteers were submitted to BSI. SLE patients were screened for the presence of CNS involvement following the American College of Rheumatology (ACR) case definition. Patients with CNS infections, uraemia, diabetes and previous ischaemic or haemorrhagic stroke were excluded. Magnetic resonance imaging (MRI) scans were obtained in a 2T scanner (Elscint Prestige) with T1- and T2-weighted images. BSI were performed after injection of 1110 MBq (30 mCi) of (99m)Tc-ECD (ethyl-cysteinate-dimer). BSI were analysed using the statistical parametric mapping. After normalization, segmentation and smoothing the groups of SLE patients with active and inactive CNS manifestations and healthy volunteers were compared using VBM. Post-processed images were compared voxel-by-voxel using t-test in order to determine differences of intensity between groups. This analysis included grand mean scaling, proportional threshold masking (set to 0.4) and implicit masking. A P-value of 0.001 and cluster size of 32 were taken into consideration. RESULTS: VBM analyses of BSI did not show any differences between SLE patients with inactive CNS involvement and normal controls. However, the group of SLE patients with active CNS involvement had a global hypoperfusion, more intense in the frontal, dorsolateral and medial temporal lobe when compared with SLE patients without CNS involvement (P = 0.001) and healthy volunteers (P = 0.001). CONCLUSION: VBM of BSI is a useful and objective method for detecting perfusion abnormalities in SLE patients, which is indicative of active CNS involvement. However, it is not helpful in differentiating the clinical sub-types of CNS involvement according to the ACR classification.

Elimination of anticardiolipin antibodies and cessation of cognitive decline in a UV-A1-irradiated systemic lupus erythematosus patient.

In the first patient with high levels of anticardiolipin antibodies (aCL) treated with ultraviolet-A1 (UV-A1; 320-400 nm) radiation, eight months of twice-weekly low-dose (10 J/cm(2)) irradiation was accompanied by the decrease of aCL levels to normal, cessation of clinical and positron emission tomographic (PET) scanning evidence of cognitive decline, and reversal of livedo reticularis. All occurred within the framework of an improving Revised Systemic Lupus Activity Measure (SLAM-R) score. Further studies in systemic lupus erythematosus (SLE) patients with elevated aCL are indicated.

Reversal of brain dysfunction with UV-A1 irradiation in a patient with systemic lupus.

Low-dose ultraviolet A-1 (UV-A1; 340-400 nm) bodily irradiation significantly reduces clinical manifestations of systemic lupus erythematosus (SLE). As neuropsychiatric-like symptoms respond prominently, a single patient was selected to undergo positron emission tomography (PET) before and after therapy to determine the effects of the therapy on the brain. The functional changes in 18F-deoxyglucose uptake as determined by PET imaging in this SLE patient indicated that improvement in brain function paralleled the reversal of cognitive deficits noted after the administration 160 kJ of bodily UV-A1 irradiation administered three times a week. Also of interest is that the UV-A1 irradiation, for the first time, ameliorated discoid lupus rashes, presumably due to a systemic action, as the lesions were for the first time covered during therapy.

Objective evidence of abnormal regional cerebral blood flow in patients with systemic lupus erythematosus on Tc-99m ECD brain SPECT.

Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 78 SLE patients with neuropsychiatric manifestations. These patients were separated into two subgroups: group 1 including 48 cases with definite neuropsychiatric symptoms/signs and group 2 with 30 cases having no neuropsychiatric symptoms/signs. Tc-99m ECD brain SPECT demonstrated hypoperfusion brain lesions in 90% and 20% of patients in groups 1 and 2, respectively. In both groups, parietal lobe and cerebellum are the most and least common areas with hypoperfusion lesions, respectively. This study suggests that Tc-99m ECD brain SPECT may provide objective information for detection of hypoperfusion brain lesions in SLE patients.

Early and delayed Tc-99m ECD brain SPECT in SLE patients with CNS involvement.

We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lobe in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients.