Primary Neuropsychiatric Systemic Lupus Erythematosus Research Articles

The expanding role of synthetic nucleic acids for diagnosis and treatment.

The presence of autoantibodies is a characteristic and diagnostic index of systemic lupus erythematosus (SLE). Antidouble-stranded DNA (antids-DNA) antibodies are the most frequent autoantibodies found in SLE related to the diagnosis and disease activity of SLE, and are measured by established methods like ELISA as a polyclonal autoantibody. However, there is no reliable data on the relationship between the respective reactivity of these polyclonal antids-DNA antibodies against different epitopes generated from the original antigen and the disease phenotype. Of the complications in SLE, neuropsychiatric SLE (NPSLE) is a troublesome and frequent phenotype of the disease but no specific diagnostic autoantibodies in serum have been found. First in this review, the possibility of antids-DNA antibodies for identifying primary NPSLE in patients with SLE based on the reactivity of different synthetic nucleic acids is described as a diagnostic marker. The purpose of this review is to examine diagnostic and therapeutic opportunities to modulate autoimmune in the central nervous system (CNS) developing the CNS inflammatory disorders. Khatri et al. investigated antids-DNA antibodies in order to develop a reliable method based on the application of synthetic nucleic acids and protein-based antigen arrays to characterize autoreactive antibodies specially for NPSLE. They found autoantibodies in three particular synthetic double stranded antigens and the antinuclear antibody patterns in ordinary lupus and NPSLE. These discoveries are leading to precision medicine in the CNS inflammatory disorders. Verifying the similarity of antids-DNA obtained from patients with NPSLE can be useful as a diagnostic marker. mRNA vaccination can locally suppress autoimmunity in the CNS associated with critical steps for the develop of CNS autoinflammation. Synthetic nuclei acids may provide a diagnostic and therapeutic target in patients with autoimmune CNS inflammatory disorders.

Neuropsychiatric Systemic Lupus Erythematosus: From the Standpoint of Department of Neurology

Neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE), termed neuropsychiatric SLE (NPSLE), encompass a wide variety of neurological and psychiatric characteristics. A neuropsychiatric event may precede an SLE diagnosis; therefore, physicians must screen for SLE in patients presenting with neuropsychiatric symptoms, if they are not already diagnosed with this condition. For assessing patients with SLE who present with neuropsychiatric symptoms, it is important to first determine whether the symptoms are caused by SLE (primary NPSLE), whether they are a complication of a therapy, or whether they are caused by other comorbidities. Accurate attribution of neuropsychiatric symptoms is vital for selecting therapeutic interventions.

Future Perspectives in the Diagnosis of Neuropsychiatric Lupus by Advanced Magnetic Resonance Imaging Techniques.

Neuropsychiatric (NP) syndromes are an important cause of morbi-mortality in patients with Systemic Lupus Erythematosus (SLE). Despite remarkable recent progress, there are no definite methods to diagnose neuropsychiatric SLE (NPSLE) or to differentiate primary NPSLE from secondary causes. NPSLE remains a diagnosis of exclusion, and the clinical judgment is still the main approach to the correct diagnosis. Within this complex context, the Magnetic Resonance Imaging (MRI) has both a diagnostic role, by showing the nervous system involvement on one hand and excluding other causes on the other hand, and a prognostic role, help in assessing the lesions and monitoring the evolution. Conventional MRI shows brain involvement in around half of the patients, although the described findings are rather non-specific and present in many other diseases. However, many advanced MRI techniques are becoming increasingly used over the last period, showing abnormalities even in normal-appearing brains on conventional MRI. These MRI techniques hold promise to have a higher sensitivity and specificity than conventional MRI for NPSLE related changes. This review explores the place and the future perspectives of different advanced MRI techniques in NPSLE.

Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus erythematosus

ObjectivesCerebral perfusion abnormalities have been reported in systemic lupus erythematosus (SLE) but their value in distinguishing lupus from non-lupus-related neuropsychiatric events remains elusive. We examined whether dynamic susceptibility contrast-enhanced perfusion...

Advanced MRI techniques: biomarkers in neuropsychiatric lupus.

Objectives The objective of this study was to determine whether advanced MRI could provide biomarkers for diagnosis and prognosis in neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Our prospective study included 28 systemic lupus erythematosus (SLE) patients with primary central NPSLE, 22 patients without NPSLE and 20 healthy controls. We used visual scales to evaluate atrophy and white matter hyperintensities, voxel-based morphometry and Freesurfer to measure brain volume, plus diffusion-tensor imaging (DTI) to assess white matter (WM) and gray matter (GM) damage. We compared the groups and correlated MRI abnormalities with clinical data. Results NPSLE patients had less GM and WM than controls ( p = 0.042) in the fronto-temporal regions and corpus callosum. They also had increased diffusivities in the temporal lobe WM ( p < 0.010) and reduced fractional anisotropy in the right frontal lobe WM ( p = 0.018). High clinical scores, longstanding disease, and low serum C3 were associated with atrophy, lower fractional anisotropy and higher diffusivity in the fronto-temporal lobes. Antimalarial treatment correlated negatively with atrophy in the frontal cortex and thalamus; it was also associated with lower diffusivity in the fronto-temporal WM clusters. Conclusions Atrophy and microstructural damage in fronto-temporal WM and GM in NPSLE correlate with severity, activity and the time from disease onset. Antimalarial treatment seems to give some brain-protective effects.

Diagnosis and management of neuropsychiatric SLE

Nervous system involvement in systemic lupus erythematosus (SLE) can manifest as a range of neurological and psychiatric features, which are classified using the ACR case definitions for 19 neuropsychiatric syndromes. Approximately one-third of all neuropsychiatric syndromes in patients with SLE are primary manifestations of SLE-related autoimmunity, with seizure disorders, cerebrovascular disease, acute confusional state and neuropathy being the most common. Such primary neuropsychiatric SLE (NPSLE) events are a consequence either of microvasculopathy and thrombosis, or of autoantibodies and inflammatory mediators. Diagnosis of NPSLE requires the exclusion of other causes, and clinical assessment directs the selection of appropriate investigations. These investigations include measurement of autoantibodies, analysis of cerebrospinal fluid, electrophysiological studies, neuropsychological assessment and neuroimaging to evaluate brain structure and function. Treatment involves the management of comorbidities contributing to the neuropsychiatric event, use of symptomatic therapies, and more specific interventions with either anticoagulation or immunosuppressive agents, depending upon the primary immunopathogenetic mechanism. Although the prognosis is variable, studies suggest a more favourable outcome for primary NPSLE manifestations compared with neuropsychiatric events attributable to non-SLE causes.

Markers of acute neuropsychiatric systemic lupus erythematosus: a multidisciplinary evaluation

This study was aimed to assess: (1) the additive diagnostic utility of diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) over conventional MRI in detecting brain lesions in patients with acute primary neuropsychiatric systemic lupus erythematosus (NPSLE), and (2) the relevance of their findings to the associated NP manifestations. Included were 34 patients with acute NPSLE with mean age of 33.26 ± 10.14 years and duration of illness of 3.33 ± 1.71 years. Clinical interviewing and psychiatric and cognitive evaluations were performed by applying the criteria of the diagnostic and statistical manual of mental health disorders criteria (DSM-IV), Stanford Binet Subset Testing, Mini-Mental State Examination and Wechsler Memory Scale-Revised. Serologic tests included looking for antinuclear antibodies, anti-double strand DNA, anti-phospholipid antibodies. Radiologic evaluation included conventional MRI, DWI and MRA. One or more NP manifestations were diagnosed in 28 patients, in which cognitive deficits were reported with headache, psychosis and CVS. Anti-phospholipid antibodies were reported in patients with CVS. Twenty patients (71.43 %) with primary NPSLE (n = 28) had MRI abnormalities in which hyperintense signals at subcortical and periventricular white matter and at the junction between the gray and white matter represented 75 % (n = 15) and with headache (n = 6), psychosis (n = 6) and acute confusional state (n = 3) with and without cognitive deficits, respectively. Moderate-sized infarctions with restricted diffusion in the distribution of middle cerebral arteries were represented in 35 % (n = 7) and with CVS, of them, 71.43 % (n = 5) had beading and focal narrowing of carotid arteries were consistent with vasculitis. Brain atrophy represented 20 % (n = 4) and with psychosis. Compared to those with normal MRI, patients with MRI abnormalities were older (P < 0.050) and had longer duration of illness (P < 0.050). To conclude, although DWI and MRA are helping in more precise etiopathologic diagnosis compared to conventional MRI, but their relevance to the present NP manifestations is still limited.

Prospective Study of Clinical Phenotypes in Neuropsychiatric Systemic Lupus Erythematosus; Multidisciplinary Approach to Diagnosis and Therapy

To describe clinical phenotypes in neuropsychiatric systemic lupus erythematosus (NPSLE). Data were prospectively collected in the Leiden NPSLE referral clinic, where patients suspected of having NPSLE are assessed in a standardized multidisciplinary manner. In consensus meetings, all medical specialists agreed on therapeutic strategy based on the suspected pathogenetic mechanism of NPSLE in the individual patient. An algorithm illustrates the process of decision-making during the consensus meeting. Clinical phenotypes are described, classified by pathogenetic mechanism. One hundred consecutive patients were evaluated, of whom 71 had SLE (29 patients did not fulfill ≥ 4 American College of Rheumatology criteria) and 46 had NPSLE. Primary NPSLE was diagnosed in 38 patients (53%) and could be differentiated in 21 patients (55%) with inflammatory NPSLE who were advised on immunosuppressive therapy, 12 patients (32%) with ischemic NPSLE who were advised on anticoagulant therapy, and 5 patients (13%) with undefined NPSLE who were advised symptomatic treatment only. Cognitive dysfunction and higher level of disease activity were associated with inflammatory NPSLE. Although presence of immunoglobulin G anticardiolipin antibodies and abnormalities on magnetic resonance imaging (MRI) were associated with ischemic NPSLE, abnormalities on MRI lacked specificity to distinguish phenotypes. A history of renal disease and use of corticosteroids were associated with secondary NPSLE. We describe multidisciplinary consensus as a standard for diagnosing and defining phenotypes in NPSLE. These phenotypes show specific characteristics, which can be used to support diagnosis and guide therapeutic decisions. Clinical phenotyping and selection of patients becomes increasingly important when advances in experimental science lead to new targets for therapy in NPSLE.

Multisequence magnetic resonance imaging study of neuropsychiatric systemic lupus erythematosus.

To investigate the relationship between magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), proton magnetic resonance spectroscopy (H-MRS), and T2 relaxometry findings in patients with primary neuropsychiatric systemic lupus erythematosus (NPSLE). The study group consisted of 24 female patients (mean age 36 years [range 23-65]) who had had a variety of neuropsychiatric symptoms that were judged to be due to NPSLE according to the criteria of the American College of Rheumatology. Patients with current active disease were excluded from participation. Quantitative MTI, DWI, H-MRS, and T2 relaxometry data were acquired in all patients, and the correlation coefficients were calculated. MTI results reflecting a decrease in homogeneity of cerebral parenchyma correlated significantly with H-MRS results representing axonal damage. MTI results also correlated significantly with DWI results reflecting increased diffusivity in the cerebral parenchyma. Finally, MTI results reflecting decreased cerebral homogeneity correlated significantly with increased T2 relaxation time, associated with either edema or gliosis. Increased T2 relaxation time correlated significantly with DWI results reflecting increased diffusivity. With the exception of the correlation between H-MRS and MTI findings, there was no significant correlation between H-MRS results and any other parameter. The selected study parameters represent different biologic features in the human brain and can be informative with regard to different pathologic processes in NPSLE. The demonstrated associations between MTI, DWI, H-MRS, and T2 data in patients with a history of NPSLE suggest that there is one pathogenesis and/or common neuropathologic outcome in NPSLE despite differences in clinical presentation.