Cytoarchitectureal changes in hippocampal subregions of the NZB/W F1 mouse model of lupus.

Over 50% of clinical patients affected by the systemic lupus erythematosus disease display impaired neurological cognitive functions and psychiatric disorders, a form called neuropsychiatric systemic lupus erythematosus. Hippocampus is one of the brain structures most sensitive to the cognitive deficits and psychiatric disorders related to neuropsychiatric lupus. The purpose of this study was to compare, layer by layer, neuron morphology in lupus mice model NZB/W F1 versus Wild Type mice. By a morphometric of cells identified on Nissl-stained sections, we evaluated structural alterations between NZB/W F1 and Wild Type mice in seven hippocampal subregions: Molecular dentate gyrus, Granular dentate gyrus, Polymorph dentate gyrus, Oriens layer, Pyramidal layer, Radiatum layer and Lacunosum molecular layer. By principal component analysis we distinguished healthy Wild Type from NZB/W F1 mice. In NZB/W F1 mice hippocampal cytoarchitecture, the neuronal cells resulted larger in size and more regular than those of Wild Type. In NZB/W F1, neurons were usually denser than in WT. The Pyramidal layer neurons were much denser in Wild Type than in NZB/W F1. Application of principal component analysis, allowed to distinguish NZB/W F1 lupus mice from healthy, showing as NZBW subjects presented a scattered distribution and intrasubject variability. Our results show a hypertrophy of the NZB/W F1 hippocampal neurons associated with an increase in perikaryal size within the CA1, CA2, CA3 region and the DG. These results help advance our understanding on hippocampal organization and structure in the NZB/W F1 lupus model, suggesting the hypothesis that the different subregions could be differentially affected in neuropsychiatric systemic lupus erythematosus disease. Leveraging an in-depth analysis of the morphology of neural cells in the hippocampal subregions and applying dimensionality reduction using PCA, we propose an efficient methodology to distinguish pathological NZBW mice from WT mice."

Neurolupus como manifestación de primer brote psicótico Reporte de caso / Neurolupus as a manifestation of the first psychotic episode: case report

Resumen Antecedentes: El lupus eritematoso sistémico (LES) es una enfermedad auto inmunitaria crónica multisistémica con diversas manifestaciones clínicas. Siendo las mujeres la pobla ción vulnerable y con mayor afectación a nivel neurológico, al presentar mayor riesgo de convulsiones. Las manifestaciones neuropsiquiátricas ocurren en etapas tempranas de la enfermedad y del diagnóstico, ya que pueden presentarse junto con manifestaciones sistémicas o no. La frecuencia de manifestaciones neuropsiquiátricas en el lupus eritematoso sistémico se ha descrito del 14 al 75%, siendo las alteraciones cognitivas uno de los grandes síntomas a destacar1. La cual puede ir acompañada de trastornos afectivos de tipo depresión y ansiedad. Ya que la psicosis secundaria a LES se remarca por su baja prevalencia (10%)2, los estudios de laboratorio nos suelen orientar hacia el diagnóstico definitivo, siendo los anticuerpos ribosomales P los que se han relacionado más específicamente con la psicosis lúpica. La resonancia magnética es la prueba de elección y las lesiones cerebrales están dominadas por hiperintensidades de materia blanca en forma de punción3. En el siguiente reporte de caso, presentamos a una paciente de 20 años, la cual contaba con antecedentes de esteatosis hepática diagnosticado, diabetes tipo MODY y resección de ovario derecho por teratoma maduro de 9 años de evolución, pero sin antecedentes psiquiátricos de importancia para el momento de su valoración. Sin embargo, de forma aguda presentó un brote psicótico caracterizado por ideas delirantes de grandiosidad y referencia, así como alteraciones conductuales, cognitivas y afectivas. Por las que tuvieron que acudir a hospital de 3er nivel durante el periodo de contingencia sanitaria en el 2020. Tras el antecedente de presentar infección por SARS-CoV-2 tres meses antes de su patología neuropsiquiátricas. Se sospechó en síntomas neurológicos secundarios a infección por COVID-19, así como patología psiquiátrica aislada. Por lo que se realizó abordaje de estudio de primer brote psicótico, diagnosticándose lupus eritematoso sistémico con manifestaciones neuropsiquiátricas. El tratamiento se basó en un bolo de metilprednisolona y antipsicóticos, luego modificada por terapia con corticoesteroides orales y antipsicótico de depósito. Conclusión: El lupus eritematoso sistémico con manifestaciones neuropsiquiátricas es una presentación poco frecuente del padecimiento, por la amplia variación en la aparición de este, los pacientes con síntomas psiquiátricos en contexto de hospital general deben de ser tomados en cuenta para abordajes extensos4. De la misma forma, el tener este conocimiento del caso podrá ampliar nuestro conocimiento sobre las complicaciones de esta patología reumatológica. Y una de sus complicaciones más graves como la psicosis lúpica para poder realizar un mejor abordaje del primer brote psicótico en hospitales generales, donde la valoración de un especialista puede ser más complicada para mejorar las condiciones médicas de estos pacientes.

Abstract Background: Systemic lupus erythematosus is a chronic multisystemic autoimmune disease with diverse clinical manifestations. Women are the most vulnerable population and have the greatest neurological involvement with a higher risk of seizures. Neuropsychiatric manifestations occur in early stages of the disease and diagnosis since they can occur together with systemic manifestations or not. The frequency of neuropsychiatric manifestations in systemic lupus erythematosus has been described from 14 to 75%; being cognitive alterations one of the major symptoms to highlight. Which, in the same way can be accompanied by affective disorders such as depression and anxiety. Since psychosis, secondary to SLE, stands out for its low prevalence (10%), laboratory studies usually guide us towards a definitive diagnosis, being ribosomal P antibodies the ones that have been more specifically related to lupus psychosis. MRI is the test of choice and brain lesions are dominated by punctate white matter hyperintensities. In the following case report, we present a 20-year-old patient who had a history of diagnosed hepatic steatosis, MODY type diabetes and resection of the right ovary for mature teratoma of 9 years of evolution; but with no psychiatric history of importance at the time of her evaluation. However, she acutely presented a psychotic outbreak characterized by delusions of grandiosity and reference; as well as behavioral, cognitive, and affective alterations. For which she had to go to a 3rd level hospital during the period of health contingency in 2020. After a history of SARS-CoV-2 infection three months before her neuropsychiatric pathology, neurological symptoms secondary to COVID-19 infection were suspected, as well as isolated psychiatric pathology. Therefore, a study approach of the first psychotic outbreak was performed, diagnosing systemic lupus erythematosus with neuropsychiatric manifestations. Treatment was based on a bolus of methylprednisolone and antipsychotics; later modified by therapy with oral corticosteroids and depot antipsychotic. Conclusion: Systemic lupus erythematosus with neuropsychiatric manifestations is an infrequent presentation of the disease, because of the wide variation in its appearance, patients with psychiatric symptoms in a general hospital setting should be considered for extensive approaches. In the same way, having this knowledge of this case may broaden our knowledge about the complications of this rheumatologic pathology. And one of its most serious complications such as lupus psychosis to be able to make a better approach to the first psychotic outbreak in general hospitals, where the assessment of a specialist can be more complicated.

[Neuropsychiatric manifestations in patients with systemic lupus erythematosus: about 108 cases in Cameroon]. / Manifestations neuropsychiatriques au cours du lupus érythémateux systémique: à propos de 108 cas au Cameroun.

Few data on neuropsychiatric disorders in systemic lupus erythematosus (NPSLE) are available in sub-Saharan Africa. The purpose of this study was to determine their frequency and describe their features in Cameroon. We conducted a retrospective study collecting all the medical records of patients with systemic lupus erythematosus (SLE) hospitalized in the department of rheumatology of 3 hospitals in Cameroon from 2009 to 2019. Lupus activity was assessed using the SLE activity index (SLEDAI). A total of 108 records of patients with a mean age of 40.2 ± 13.7 years were included in the study. The frequency of NPSLE was 55.5% (n=60). Neuropsychiatric disorders were diagnosed concomitantly with SLE (37.0%; n = 40) while in 20 patients with SLE (18.5%) they occurred during the first year. When NPSLE were inaugural, central nervous system involvement was dominant, with demyelinating syndrome 27.8% (n=30) and headaches 21.3% (n=23). Mononeuropathy was the most frequent peripheral nervous system involvement (15.7%; n=17). Factors associated with NPSLE occurrence were malar rash (p=0.024), alopecia (p=0.024), very high lupus activity (p=0.011), arthralgia (p<0.001), anti-nuclear factor (p=0.002). NPSLE did not appear to influence either lupus activity (log rank p=0.227) or the probability of new onset lupus (log rank p=0.233). More than half of patients had NPSLE during the first year. The presence of cutaneous and articular signs, high lupus activity, and anti-nuclear factor were associated with the occurrence of NPSLE.

Cognitive changes mediated by adenosine receptor blockade in a resveratrol-treated atherosclerosis-prone lupus mouse model.

Background and aim: Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Prior work showed that resveratrol's anti-atherogenic properties are mediated in part through the adenosine A2A receptor. The present study explores the potential contribution of adenosine A2A receptor activation to neuroprotective action of resveratrol on cognitive deficits in a model of atherosclerosis-prone systemic lupus erythematosus. Experimental procedure: Using behavioral analysis (open field, static rod, novel object recognition) and QRT-PCR, this study measured working memory, anxiety, motor coordination, and expression of mRNA in the brain. Results and conclusion: Data indicate that resveratrol increases working memory, on average but not statistically, and shows a trend towards improved motor coordination (p = 0.07) in atherosclerosis-prone lupus mice. Additionally, resveratrol tends to increase mRNA levels of SIRT1, decrease vascular endothelial growth factor and CX3CL1 mRNA in the hippocampus. Istradefylline, an adenosine A2A receptor antagonist, antagonizes the effects of resveratrol on working memory (p = 0.04) and the expression of SIRT1 (p = 0.03), vascular endothelial growth factor (p = 0.04), and CX3CL1 (p = 0.03) in the hippocampus.This study demonstrates that resveratrol could potentially be a therapeutic candidate in the modulation of cognitive dysfunction in neuropsychiatric lupus, especially motor incoordination. Further human studies, as well as optimization of resveratrol administration, could confirm whether resveratrol may be an additional resource available to reduce the burden of cognitive impairment associated with lupus. Additionally, further studies need to address the role of A2A blockade in cognitive function among the autoimmune population. Section: 3. Dietary therapy/nutrients supplements. Taxonomy classification by EVISE: autoimmunity, inflammation, neurology.

Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus.

BACKGROUND: The aim was to evaluate the diagnostic potential of serum neurofilament light chain (sNfL) measurements in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: sNfL levels were determined by single molecule array assay in a retrospective cross-sectional cohort of 144 patients with systemic lupus erythematosus (SLE). After log-transformation of sNfL levels, mean sNfL levels were compared between NPSLE patients and SLE patients without neuropsychiatric disease using Student's t test. Furthermore, the association of different neuropsychiatric manifestations with sNfL levels was assessed using a one-way analysis of variance (ANOVA) with post hoc analysis. Associations of sNfL with clinical and laboratory parameters were assessed by correlation and multiple linear regression analysis. RESULTS: NPSLE patients (n = 69) had significantly higher sNfL levels than SLE patients without neuropsychiatric disease manifestations (n = 75; mean difference: 0.13, 95% CI: 0.04-0.22, p = 0.006). With regard to the category of NPSLE manifestation, mean sNfL levels were only increased in NPSLE patients with focal central nervous system (CNS) involvement (n = 45; mean difference: 0.16, 95% CI: 0.02-0.30, p = 0.019), whereas mean sNfL levels of NPSLE patients with diffuse CNS and peripheral nervous system involvement did not differ from those of SLE patients without neuropsychiatric manifestations. Age and serum creatinine concentrations were identified as relevant contributors to sNfL levels. CONCLUSION: sNfL is a promising, easily accessible biomarker for neuropsychiatric involvement in SLE patients and might therefore complement the diagnostic workup of SLE patients with suspected involvement of the nervous system.

[Spontaneous intracranial hypotension: A rare cause of headache in systemic lupus erythematosus]. / Hypotension intracrânienne : une cause rare de céphalées au cours du lupus systémique.

INTRODUCTION: Spontaneous intracranial hypotension (SIH), a rare cause of headache, may be idiopathic or secondary, in particular to Systemic Lupus Erythematosus (SLE) where it remains exceptionally evoked or documented. CASE REPORT: A 36-year-old woman presented with postural headache, recurrent nausea and vomiting. The discovery of a nephrotic syndrome led to the diagnosis of SLE with lupus nephropathy (class IV-G-(A)). A brain MRI showed signs of intracranial hypotension with tonsil ptosis and a left parietal hypersignal, and leading to a diagnosis of neurolupus with SIH. Treatment with prednisone, cyclophosphamide, and then mycophenolate mofetil allowed a rapid complete response of all systemic, renal and neurological manifestations, including the iconographic signs of intracranial hypotension. CONCLUSION: Headaches are frequent and often unexplained during SLE. Their orthostatic character should, if appropriate, suggests a SIH and lead to perform a brain MRI, even in the absence of other neurological signs.

Lupus neuropsiquiátrico. A propósito de tres casos y revisión de la literatura / Neuropsychiatric lupus Regarding three cases and review of the literature / Lúpus neuropsiquiátrico Em relação a três casos e revisão da literatura

Resumen: Las manifestaciones neuropsiquiátricas del lupus eritematoso sistémico (LES) constituyen un amplio espectro clínico con compromiso del Sistema Nervioso Central y Periférico por parte de esta enfermedad. Afecta aproximadamente a un 56% de los pacientes con LES, frecuentemente próximo al diagnóstico. Constituye un desafío diagnóstico, especialmente en pacientes sin antecedentes de la enfermedad. El diagnóstico es de exclusión. Se encuentra en revisión el rol de algunos auto-anticuerpos y técnicas de neuroimágen en la estrategia diagnóstica de esta afección. Se presentan tres casos clínicos y realizamos una revisión de la literatura.

Abstract: The neuropsichiatric manifestations of systemic lupus erythematosus are very wide, involving central and peripheral nervous system. Affecting approximately 56% of lupus patients, with higher incidence previous or next to the diagnosis. It is a challenge for phisicians, specially for patients without previous diagnostic of the desease. Diagnostic is of exclussion, because there are not specific test. There are in disccussion the role of some autoantibodies and neuroimagenological tecniques for this purpose. We present 3 case report and review of the literature.

Resumo: As manifestações neuropsiquiátricas do lúpus constituem um amplo espectro clínico com comprometimento do Sistema Nervoso Central e Periférico por esta doença. Afeta aproximadamente 56% dos pacientes com LES, quase sempre próximos ao diagnóstico. Constitui um desafio diagnóstico, principalmente em pacientes sem histórico da doença. O diagnóstico é exclusão. O papel de alguns autoanticorpos e técnicas de neuroimagem na estratégia de diagnóstico dessa condição está sendo analisado. Três casos clínicos são apresentados e revisamos a literatura.

Prevalence of neurolupus in a Colombian cohort / Prevalencia de neurolupus en una cohorte colombiana

ABSTRACT Background: Systemic lupus erythematosus (SLE) can affect the nervous system and present a variety of neurological and psychiatric syndromes but the prevalence of neuropsychiatric manifestations in Colombia is unknown. Methods: Cross-sectional study. Patients were assessed by the department of rheumatology between 2010 and 2013 and included randomly chosen subjects over 18 years of age. Prevalence of neurological manifestations was calculated using a confidence interval of 95%. SLE disease activity index was used as baseline to compare statistically with activity, neurological manifestations and fatality. Mann-Whitney U test was used for quantitative variables, while chi-square test was used for qualitative variables. Results: 306 subjects initially entered into the study, 274 were analyzed, 89.1% were women with a median age of 43 years (interquartile range: 23). Prevalence of neuropsychiatric manifestations was 26.2% (95% CI: 21.2-31%). The most common symptoms were headache (13.1%; 95% CI: 9.1-17.2%), cerebrovascular disease (8%; 95% CI: 5.1-11.3%), acute confusional state (6.6%; 95% CI: 4-9.1%), seizure disorders (4.7%; 95% CI: 2.6-7.3%), and aseptic meningitis (2.2%; 95% CI: 0.7-4%); autonomic neuropathy, polyneuropathy, and myelopathy each occurred at 0.7% (95% CI: 0-1.8%). Patients with neuropsychiatric manifestations had severe disease activity (45.8%) and (31.9%) had moderate disease activity. Conclusions: In hospitalized patients diagnosed with SLE, NPS manifestations can occur in up to 26% of cases, the most frequent being headache, cerebrovascular disease, acute confusional state, seizures, and aseptic meningitis and the most frequent treatment being systemic steroids. Prospective studies are required to determine their prognostic implications in this group of patients.

Resumen Antecedentes: El lupus eritematoso sistémico (LES) puede afectar el sistema nervioso con una amplia variedad de síndromes psiquiátricos y neurológicos. La prevalencia de manifestaciones neuropsiquiátricas en Colombia es desconocida. Métodos: Estudio de cohorte transversal. A partir de la revisión del sistema de información del hospital se obtuvieron datos de los pacientes con diagnóstico de LES, mayores de 18 años, que fueron valorados por reumatología entre 2010 y 2013. Se utilizó un muestreo aleatorio del listado de sujetos con diagnóstico de lupus en el hospital, se calculó la prevalencia de manifestaciones neurológicas con IC 95%, se realizaron cruces exploratorios entre la actividad de la enfermedad por SLEDAI y las manifestaciones neurológicas, y desenlace de fallecimiento. Resultados: De 306 sujetos ingresados al estudio se llevaron al análisis final 274 individuos, de los cuales el 89,1% fueron mujeres; la mediana de edad fue de 43 años (RIQ: 23); la prevalencia de manifestaciones neuropsiquiátricas fue del 26,2% (IC 95%: 21,2-31). Los síntomas neurológicos en orden descendente incluyen cefalea (13,1%; IC 95%: 9,1-17,2), enfermedad cerebrovascular (8%; IC 95%: 5,1-11,3), estado confusional agudo (6,6%; IC 95%: 4-9,1), trastornos convulsivos (4,7%; IC 95%: 2,6-7,3), meningitis aséptica (2,2%; IC 95%: 0,7-4), neuropatía autonómica, polineuropatía y mielopatía (presentes en el 0,7%; IC 95%: 0-1,8). Dentro de la población con manifestaciones neuropsiquiátricas se encontró que el 45,8% tenía actividad severa de la enfermedad y el 31,9% actividad moderada. Conclusiones: En pacientes hospitalizados con diagnóstico de LES las manifestaciones neuropsiquiátricas pueden ocurrir hasta en el 26% de los casos; las más frecuentes son cefalea, enfermedad cerebrovascular, estado confusional agudo, convulsiones y meningitis aséptica, y el tratamiento más frecuente son los esteroides sistémicos. Se requieren estudios prospectivos para determinar sus implicaciones pronósticas en este grupo de pacientes.

Distinct regional brain atrophy pattern in multiple sclerosis and neuropsychiatric systemic lupus erythematosus patients.

Differentiation of systemic lupus erythematosus (SLE) from multiple sclerosis (MS) can be challenging, especially when neuropsychiatric (NP) symptoms are accompanied by white matter lesions in the brain. Given the lack of discriminative power of currently applied tools for their differentiation, there is an unmet need for other measures that can aid in distinguishing between the two autoimmune disorders. In this study we aimed at exploring whether brain atrophy measures could serve as markers differentiating MS and SLE. Thirty-seven relapsing-remitting MS and 38 SLE patients with nervous system manifestations, matched according to age and disease duration, underwent 1.5 Tesla magnetic resonance imaging (MRI), including volumetric sequences, and clinical assessment. Voxelwise analysis was performed using ANTS-SyN elastic registration protocol, FSL Randomise and Gamma methods. Cortical and subcortical segmentation was performed with Freesurfer 5.3 pipeline using T1-weighted MPRAGE sequence data. Using MRI volumetric markers of general and subcortical gray matter atrophy and clinical variables, we built a stepwise multivariable logistic diagnostic model to identify MRI parameters that best differentiate MS and SLE patients. We found that the best volumetric predictors to distinguish them were: fourth ventricle volume (sensitivity 0.86, specificity 0.57, area under the curve, AUC 0.77), posterior corpus callosum (sensitivity 0.81, specificity 0.57, AUC 0.68), and third ventricle to thalamus ratio (sensitivity 0.42, specificity 0.84, AUC 0.65). The same classifiers were identified in a subgroup analysis that included patients with a short disease duration. In MS brain atrophy and lesion load correlated with clinical disability, while in SLE age was the main determinant of brain volume. This study proposes new imaging parameters for differential diagnosis of MS and SLE with central nervous system involvement. We show there is a different pattern of atrophy in MS and SLE, and the key structural volumes that are differentially affected include fourth ventricle and posterior section of corpus callosum, followed by third ventricle to thalamus ratio. Different correlation patterns between volumetric and clinical data may suggest that while in MS atrophy is driven mainly by disease activity, in SLE it is mostly associated with age. However, these results need further replication in a larger cohort.

Neurological Disease in Lupus: Toward a Personalized Medicine Approach.

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials.

Polyspecific antibodies without persisting antigen in multiple sclerosis, neurolupus and Guillain-Barré syndrome: immune network connectivity in chronic diseases / Anticorpos poliespecíficos sem antígeno persistente em esclerose múltipla, neurolupus e síndrome de Guillain-Barré: conectividade imunológica em doenças crônicas

ABSTRACT The polyspecific antibody synthesis in multiple sclerosis (MS) gained diagnostic relevance with the frequent combination of measles-, rubella- and varicella zoster antibodies (MRZ-antibody reaction) but their pathophysiological role remains unknown. This review connects the data for intrathecal polyspecific antibody synthesis in MS and neurolupus with observations in the blood of patients with Guillain-Barré syndrome (GBS). Simultaneously increased antibody and autoantibody titers in GBS blood samples indicate that the polyspecific antibodies are based on a general property of an immune network, supported by the deterministic day-to-day concentration variation of antibodies in normal blood. Strongly correlated measles- and rubella- antibody variations point to a particular connectivity between the MRZ antibodies. The immune network, which provides serological memory in the absence of an antigen, implements the continuous change of the MRZ pattern in blood, not followed by the earlier immigrated B cells without corresponding connectivity in the brain. This may explain the different antibody patterns in cerebrospinal fluid, aqueous humor and blood of the individual MS patient. A complexity approach must implement a different view on causation in chronic diseases and causal therapies.

RESUMO A síntese de anticorpos poliespecíficos em esclerose múltipla (EM) ganhou relevância diagnóstica com a combinação frequente de anticorpos contra sarampo, rubéola e varicela-zoster (reação de anticorpos MRZ), mas seu papel fisiopatológico permanece desconhecido. Esta revisão relaciona os dados da síntese intratecal de anticorpos poliespecíficos em EM e Neurolupus com observações no sangue de pacientes com síndrome de Guillain Barré (SGB). Simultaneamente, os títulos aumentados de anticorpos e autoanticorpos em amostras de sangue de SGB indicam que os anticorpos poliespecíficos se baseiam numa propriedade geral de uma rede imunitária, suportada pela variação determinística da concentração diária de anticorpos no sangue normal. As variações fortemente correlacionadas de anticorpos contra sarampo e rubéola apontam para uma conectividade particular entre os anticorpos MRZ. A rede imunitária, que fornece memória sorológica na ausência de um antígeno, implementa a mudança contínua do padrão MRZ no sangue, não seguida pelas células B que imigraram anteriormente sem conectividade no cérebro. Isto pode explicar os diferentes padrões de anticorpos no LCR, humor aquoso e sangue do paciente individual de EM. Uma abordagem complexa deve implementar uma visão diferente sobre a causalidade em doenças crônicas e terapias causais.

Neurological Manifestations in Systemic Lupus Erythematosus: A Single Centre Study from North East India.

INTRODUCTION: Neurological manifestations although common in Systemic Lupus Erythematosus (SLE), are often not recognized due to their diversed and varied presentation. Therefore, the study was planned to highlight the pattern of neurological involvement in SLE to help in early recognition. AIM: To study the pattern of neurological involvement in SLE and its correlation with disease activity and different investigation. MATERIALS AND METHODS: This hospital based prospective observational study was carried out from August 2009 to July 2010. Diagnosed cases of SLE [based upon American Rheumatism Association (ARA) criteria] who presented with neurological manifestations at the time of diagnosis or develop during the course of the disease were included in the study. They were assessed clinically and investigated with neuroimaging and neurophysiological tests as applicable. RESULTS: In total, 52 consecutive patients with SLE were evaluated, 92% were female. The most common age group was 21 to 25 years. Nervous system involvement was found in 19 (36.54%) patients. Cognitive impairment was the most frequent manifestation, present in 11 (57.89%) patients followed by seizure disorder in eight patients (42.1%). Peripheral neuropathy was diagnosed in eight (42.1%), acute confusional state in six (31.57%) and headache and depression was diagnosed in five (26.31%) patients each. Less common manifestations were psychosis, movement disorder and aseptic meningitis. Percentage of neurological manifestations directly correlated with disease activity. A significant difference was found in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score between the patients with Neuro Psychiatric Systemic Lupus Erythematosus (NPSLE) and those without NPSLE (32.42±16.34 Vs 17.3±10.6). CONCLUSION: Neurological involvement in SLE is seen relatively early in the course of the disease with cognitive impairment being the most common manifestation and correlate with disease activity.

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients.

OBJECTIVE: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly understood. Damage within the CNS is driven by the autoimmune response; however, immunopathophysiology of neuropsychiatric (NP) SLE is multifactorial. Immune cell neurotrophin production could be neuroprotective against autoimmunity-driven CNS damage, as has been shown in multiple sclerosis. The aim of this study was to establish whether immune cell neurotrophin production is associated with damage severity in NPSLE. METHODS: Selected neurotrophins (BDNF, NGF, NT-3, and NT-4/5) were measured with ELISA within peripheral blood mononuclear cells (PBMCs) isolated from 38 NPSLE patients matched with 39 healthy controls. Subcortical and cortical structure volumes were segmented with the Freesurfer 5.3 pipeline on T1-weighted isotropic images acquired on a 1.5-T MRI scanner. RESULTS: BDNF and NGF levels in PBMCs were reduced in NPSLE compared to the healthy population. The PBMC BDNF level was associated with reduced thalamus, caudate, and putamen volumes. The NGF level correlated with lateral ventricles enlargement and thalamic volume loss. CONCLUSIONS: In NPSLE, immune cell BDNF and NGF levels are linked with subcortical atrophy. Higher BDNF levels are associated with higher midsagittal atrophy, which may reflect compensatory mechanisms, upregulating BDNF when neuroprotection is needed. These data require further confirmation.

Encephalopathy with upper body hypertonia and myoclonus in patient with systemic lupus erythematosus and anti-CASPR2.

Systemic lupus erythematosus (SLE) may involve the nervous system but there are no specific biomarkers of neuroSLE. Limbic encephalitis has been rarely associated with SLE. We present a case of a 22-year-old black woman where typical SLE psychosis evolved to an encephalopathy with atypical features, normal MRI, electroencephalogram slowing and frontal and occipito-temporal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG PET).Memory deficits, bizarre behaviour, psychosis, neuromyotonia and movement disorders have been described in autoimmune central nervous system disorders and associated with specific antibodies. Brain MRI may be normal and cortical brain hypometabolism on FDG PET scans has been reported. We have not found any report of limbic encephalitis or other SLE neurological manifestation associated to positive titres of anti-CASPR2 antibodies and this may warrant systematic investigation. In the rare cases of limbic encephalitis associated with SLE no specific antibodies were documented. Anti-CASPR2 antibodies have been associated not only with limbic encephalitis but also with neuromyotonia and Morvan syndrome. Although our patient had a specific pattern of tone abnormalities with an impressive cervical and upper limb hypertonicity and flaccid lower limbs, no myotonic discharges were found. We did not find any association between myoclonus and anti-CASPR2 antibodies. We cannot exclude that a non determined autoantibody could have played a role; however, clinical and FDG PET improvement supports an antibody-mediated injury, in this case of neuroSLE.