氢质子磁共振波谱在轻度认知障碍中的诊断价值

目的探讨氢质子磁共振波谱分析（1H．MRS）在轻度认知功能障碍（MCI）诊断中的应用价值。方法回顾性分析22例MCI患者接受’H．MRS检查的资料,并与18例年龄、性别、受教育程度相匹配的认知功能正常的健康体检者进行对照。所有受检者均为右利手,采用激励回波采样模式检测,计算双侧大脑额中回皮质下白质区和双侧海马的N-乙酰天冬氨酸／肌酸（NAA／Cr）、肌醇／肌酸（mI／Cr）,肌醇／NAA（mI／NAA）等的比值,并比较各组比值间的差异。结果①MCI组的左额中回皮质下白质、左海马、右海马NAA／Cr比值分别为（1．29±0．18）、（1．30±0．18）、（1．20±0．23）,均低于对照组的（1．83±0．14）、（1．54±0．22）、（1．37±0．16）,差异均有统计学意义（P〈0．05）;MCI组的右额中回皮质下白质NAA／Cr比值为（1．32±0．19）,低于对照组的（1．35±0．24）,差异无统计学意义（P〉0．05）。②MCI组的左额中回皮质下白质、左海马、右海马mI／Cr比值分别为（0．66±0．12）、（1．02±0．14）、（0．68±0．06）,均高于对照组的（0．56±0．09）、（0．89±0．09）、（0．52±0．05）,差异均有统计学意义（P〈0．05）;MCI组的右额中回皮质下白质mI／Cr比值为（0．56-4-0．08）,低于对照组（O．58±0．07）,差异无统计学意义（P〉0．05）。⑧MCI组的左额中回皮质下白质、左海马、右海马mI／NAA比值分别为（0．52±0．12）,（0．80-t-O．15）,（0．59±0．13）,均高于正常对照组的（0．30±0．04）,（0．59±0．10）,（0．39±0．06）,差异均有统计学意义（P〈0．05）;MCI组的右额中回皮质下白质mI／NAA比值为0．44±0．09,与正常对照组的0．44±0．11比较,差异无统计学意义（P〉0．05）。结论1H－MRS检测MCI患者的左额中回皮质下白质、双侧海马NAA／Cr比值低于正常对照组,mI／Cr和mI／NAA比值高于正常对照组。这些指标的变化可为MCI的早期诊断提供依据。     

Relationship between clinical factors and neuropsychiatric manifestations in systemic lupus erythematosus

Neuropsychiatric symptoms are often seen in patients with systemic lupus erythematosus (SLE). To investigate the relationship between involvement of the nervous system and clinical factors, including autoantibodies and the activity of SLE, we retrospectively reviewed 25 patients with neuropsychiatric SLE (NPSLE, mean age: 35.2±12.2 years). As controls 37 SLE patients without neuropsychiatric manifestations (mean age: 31.8±15.8 years) were employed in this study. At the onset no significant differences were seen in any clinical factors between the patients and the controls except for serum antinuclear antibodies. In relapse, the patients with NPSLE showed significantly lower levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores without neuropsychiatric evaluation (p<0.0001), erythrocyte sedimentation rate (ESR, p<0.005), and antinuclear and anti-double-stranded DNA antibodies (p<0.005) and higher WBC values (p<0.05) than at the onset. Also in the patients with relapsing NPSLE similar significant differences were seen in these parameters between onset and relapse (p<0.005). Despite a lack of significant differences, the cerebrospinal fluid showed lower values in cell counts, total protein, and IgG in relapse than at onset. These results suggest that there are no clinical factors that predict the development of NPSLE and that relapse can occur with low disease activity in the nervous system even with an inactive state of other organ involvement. Since NPSLE may suddenly relapse with a slight change in common disease activation markers, including inflammatory reactions, autoantibodies, and complements in serum and CSF findings, adequate corticosteroid and/or immunosuppressive agents should be given at the onset and gradually be tapered after recovery, while looking out for recurrence.     

Neuropsychiatric manifestations in pediatric systemic lupus erythematosus: a 20-year study

The objective of this study was to investigate the manifestations, treatment and outcome of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (SLE) patients. The charts of 185 pediatric patients with SLE diagnosed between 1985 and 2005 in a tertiary referral hospital were retrospectively reviewed. NPSLE were defined using the American College of Rheumatology NPSLE case definitions. NPSLE developed in 34.6% (64/185) of the patients. The mean onset age was 15.2 years. Fourteen patients (21.9%) had NP manifestations on initial diagnosis of SLE. The median duration from the onset of SLE to NP manifestation was 11 months. The most frequent NP manifestations were seizure disorder (84.4%), ischemic stroke (28.1%) and psychosis (21.9%). However, the prevalence of manifestations of NPSLE might be underestimated by the retrospective design of our study. Higher mean C3/C4 levels, less percentage of anti-dsDNA antibodies elevation and higher percentage of elevated anticardiolipin antibodies were observed in NPSLE events than in non-NPSLE events (P < 0.05). The mortality rate of NPSLE patients decreased from 52.2% in 1985-1994 cohort to 27.8% in 1995-2005 cohort. In the past 10 years, the leading cause of death in NPSLE patients was NPSLE itself. NPSLE is common in pediatric SLE patients. It has diverse manifestations and a high mortality.     

The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus

OBJECTIVE: To determine the incidence and prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) and glomerulonephritis in ethnically diverse pediatric onset SLE inpatient and outpatient populations. METHODS: Seventy-five pediatric onset patients with SLE including Native American, Asian, Black, Spanish-American, and Caucasian subjects were evaluated prospectively and cross sectionally. During the 6 year study, 55 patients became inpatients. Subjects underwent medical interview, physical examination, laboratory review, neuropsychiatric inventory, and chart review. Classification of NPSLE was accomplished with the 1999 ACR NPSLE case definitions. RESULTS: Prospectively, NPSLE occurred in 95% of pediatric SLE patients and was more common than glomerulonephritis (55%; p < or = 0.0001). NPSLE prevalence (%) and incidence (event/person/yr) were as follows: headache 72%, 95; mood disorder 57%, 0.41; cognitive disorder 55%, 0.49; seizure disorder 51%, 0.94; acute confusional state 35%, 0.6; anxiety disorder 21%, 0.28; peripheral nervous system disorder 15%, 0.16; cerebrovascular disease 12%, 0.32; psychosis 12%, 0.16; chorea 7%, 0.01; demyelinating syndrome 4%, 0.01; and myelopathy 1%, 0.001. Cross sectionally, active NPSLE was present in 93% of inpatients and 69% of outpatients. When only serious forms of NPSLE were considered (stroke, seizures, major cognitive disorder, chorea, psychosis, major depression, acute confusional state), serious or life-threatening NPSLE occurred in 76% of all SLE subjects prospectively, and in 85% and 40% of inpatients and outpatients cross sectionally, which in each instance was more common than glomerulonephritis (p < or = 0.001). CONCLUSION: NPSLE is one of the most common serious complications of pediatric SLE, and is particularly increased in pediatric inpatients.     

Lymphocytotoxic antibodies in systemic lupus erythematosus are associated with disease activity irrespective of the presence of neuropsychiatric manifestations

OBJECTIVES: To evaluate the association of the presence of lymphocytotoxic, anti-beta2-glycoprotein I (anti-beta2-GPI) and anti-ribosomal P (anti-P) antibodies in patients with systemic lupus erythematosus (SLE), presenting or not neuropsychiatric (NP) manifestations, stratified according to the activity of the disease. METHODS: A total of 138 patients with SLE (59 with active NPSLE, 49 with active non-NPSLE, and 30 with inactive disease) and 57 healthy controls were studied. Disease activity was assessed by the SLE Disease Activity Index (SLEDAI). The presence of lymphocytotoxic antibodies was assessed using a complement-dependent lymphocytotoxicity assay. The presence of anti-beta2-GPI and anti-P antibodies was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Lymphocytotoxic antibodies were detected primarily in patients with active disease, that is in 35 out of 59 (59.3%) NPSLE and 23 out of 49 (46.9%) non-NPSLE patients, whereas only four out of 30 (13.3%) inactive SLE patients and none of the healthy controls exhibited the autoantibody. The frequency of lymphocytotoxic antibodies in active SLE patients, considered as a whole or stratified into NPSLE or non-NPSLE, was significantly increased in relation to inactive SLE patients (p<0.001 for each comparison). No significant difference was observed when comparing active NPSLE with non-NPSLE patients. No associations were observed between the presence of anti-beta2-GPI or anti-P antibodies and the activity of SLE or the presence of lymphocytotoxic antibodies. CONCLUSIONS: Lymphocytotoxic antibodies occurred more frequently in patients with active SLE than in patients with inactive disease, irrespective of the presence of NP manifestations, a finding that is similar to classical biomarkers of lupus activity (anti-dsDNA and complement). These results indicate that the assessment of the presence of lymphocytotoxic antibodies may be an additional useful tool for the evaluation of SLE activity.     

Anti-ribosomal P protein antibodies influence mortality of patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematous involving a severe form of the disease

Abstract

Objectives: The aim of this study is to clarify the effect of various autoantibodies on overall mortality in patients with diffuse psychiatric/neuropsychological syndromes in SLE (diffuse NPSLE).

Methods: Fifty-five patients with diffuse NPSLE admitted from 1992 to 2017 had met inclusion criteria and were recruited for this study. The relationship of various serum autoantibodies with mortality was retrospectively analyzed based on the medical charts.

Results: Of 55 patients, 14 patients [25.5%] had died during the observation period (2728 [22-8842] days (median [range])). The 5-year, 10-year, 15-year and 20-year mortality rates were 18.8%, 21.9%, 36.9% and 47.4%, respectively. Among various serum autoantibodies at the onset of diffuse NPSLE, only the presence of anti-ribosomal P protein antibodies (anti-ribo P) significantly increased the risk for death (relative risk 2.262, 95% confidence interval 1.276–4.417, p?=?0.005). Of 14 fatal patients, 10 patients had died within 1 y after the onset of diffuse NPSLE. Remarkably, 7 of 10 patients with positive anti-ribo P had died of the severe complication primarily attributed to SLE except for one patient.

Conclusions: The presence of anti-ribo P is a significant risk factor for overall poor prognosis in patients with diffuse NPSLE, involving a fatal complication by SLE.     

神经相关性自身抗体检测在神经精神性狼疮中的意义

目的 探讨神经相关性自身抗体在系统性红斑狼疮(SLE)和神经精神性狼疮(NPSLE)患者血清或脑脊液中的敏感性和特异性,评价其在NPSLE诊断中的意义.方法 利用间接免疫荧光法分别以成神经瘤细胞株(SK-N-SH)、神经胶质瘤细胞株(U251)以及C57BL/10小鼠的大脑及脊髓切片为底物检测121例SLE患者、34例疾病对照组和34名健康对照组的血清及24例NPSLE患者和22例疾病对照组的脑脊液中抗神经元细胞抗体、抗神经胶质细胞抗体、抗脑抗体及抗脊髓抗体.结果 SLE患者血清中抗神经元细胞抗体、抗脑抗体及抗脊髓抗体的阳性率(17.4%、25.6%和29.8%)明显高于类风湿关节炎(RA)患者以及正常对照组(P＜0.05或P＜0.01),在SLE诊断中的特异性分别为98.5%、95.6%和100%;抗神经元细胞抗体、抗脑抗体及抗脊髓抗体均与SLE疾病活动性指数(SLEDAI)积分呈正相关,并与NPSLE患者的癫痫发作、头痛、急性意识障碍以及情绪失调、焦虑等症状的发生有关;NPSLE患者血清的抗神经元细胞抗体、抗脑抗体和抗脊髓抗体的阳性率(27.8%、38.9%和61.1%)明显高于无中枢神经系统受累的SEE患者(P＜0.05或P＜0.01);NPSLE患者的脑脊液中抗脑抗体、抗脊髓抗体的阳性率均为29.2%,与疾病对照组比较,差异具有统计学意义(P＜0.05或P＜0.01);在NPSLE诊断中的特异性分别为100%和95.5%.结论 抗神经元细胞抗体、抗脑抗体及抗脊髓抗体对SLE诊断的特异性较高,但敏感性偏低;3种抗体均与SLE疾病活动性相关;血清中抗神经元细胞抗体、抗脑抗体及抗脊髓抗体是NPSLE诊断的较特异性抗体,抗脊髓抗体可能是诊断NPSLE较敏感的指标之一;脑脊液中的抗脑抗体、抗脊髓抗体对NPSLE的诊断更具有特异性.     

The metabolic alterations within the normal appearing brain in patients with Hashimoto’s thyroiditis are correlated with hormonal changes

Hashimoto’s thyroiditis (HT) is the most common autoimmune disease in humans usually associated with subsequent hypothyroidism. The purpose of the study was to assess metabolic alterations within the normal appearing brain in subjects with HT using MR spectroscopy (MRS) and to correlate MRS measurements with hormonal concentrations. Fifty-five HT patients (mean age 43.5 yrs) and 30 healthy controls (mean age 42.5 yrs) were examined with the use of a 1.5 T MR scanner. There were no signs of central nervous system involvement in the studied group. The MRS examinations were performed using the single voxel method. The voxels were placed in the left parietal white matter (PWM) and the posterior cingulate gyrus (PCG). The NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated. The correlations between metabolite ratios and hormonal concentrations (TSH, fT3, fT4) as well as anti-TG and anti-TPO levels were also assessed. We found significantly (p?<?0.05) decreased NAA/Cr ratios in PCG and PWM in HT subjects compared to the control group. There were no other significant differences in metabolite ratios. We observed significant positive correlations between the NAA/Cr ratio in PCG as well as the PWM and fT3 level. There was also a significant negative correlation between the Cho/Cr ratio in the PCG and fT4 level. MRS could be a sensitive biomarker capable of depicting early cerebral metabolic disturbances associated with HT. Our findings may indicate the reduction of neuronal activity within the normal appearing brain in patients with HT as well as suggesting that there is a possible biological association between thyroid dysfunction and cerebral metabolic changes.

     

IP-10/MCP-1 ratio in CSF is an useful diagnostic marker of neuropsychiatric lupus patients

SIR, Neuropsychiatric syndromes of systemic lupus erythematosus(NPSLE) is one of the major causes of morbidity and mortalityin patients with systemic lupus erythematosus (SLE). NPSLE hasbeen reported to occur in 14–75% of SLE patients and symptomsare extremely diverse, including seizures, stroke, depressionand psychosis [1, 2]. Due to the multiple pathogenic mechanismsthat evoke the diverse clinical manifestations of NPSLE, nosingle test is available     

Apolipoprotein E polymorphism in patients with neuropsychiatric SLE

The aim of this study was to investigate a relationship between neuropsychiatric SLE (NPSLE), characterized by many different neurological and psychiatric disorders, and the polymorphism of apoE as a neurobiologically important molecule conferring increased risk and a worse prognosis of a variety of CNS diseases. One hundred and forty-six SLE patients and 93 healthy controls were studied. Out of the SLE cohort, 48 patients (32.8%) were diagnosed with NPSLE and further classified according to criteria of onset, extent, relapsing tendency and type of neuropsychiatric impairment. Apolipoprotein E (apoE) polymorphism was determined by PCR-RFLP and confirmed by isoelectrofocusing. The frequency of the 4 allele was significantly higher in the NPSLE group than in the non-NPSLE group (17.7% vs. 3.1%, ²=19.05, p<0.0001). Distribution of apoE genotypes was significantly different between NPSLE and non-NPSLE groups (²=80.95, p<0.0001). Both 4 allele frequency (17.7% vs 8.6%, ²=5.082, p<0.024) and genotype distribution (²=7.202, p<0.027) were significantly different between NPSLE group and the controls. The allele 4 was also associated with earlier disease onset (Fishers test, p<0.036) and peripheral nervous system involvement (²=8.242, p<0.0041), but not with relapse frequency (p<0.37) or major/minor subtype of the disease (p<0.90). The 4 allele carriers did not develop significantly more neuropsychiatric syndromes than non- carriers (1.75±0.23 sy (mean ± SD) in 4 vs 1.85±0.19 sy (mean ± SD) in non-4 carriers, Mann–Whitney test, p<0.78). In conclusion, the data suggest an association between apoE polymorphism and NPSLE.Abbreviations apoE Apolipoprotein E - NPSLE Neuropsychiatric SLE - SLE Systemic lupus erythematosus     

Hyperglycaemia is associated with changes in the regional concentrations of glucose and myo-inositol within the brain

Aims/hypothesis  The aim of the study was to assess the effect of hyperglycaemia on regional concentrations of glucose and other substrates within the brain in non-diabetic individuals and in patients with type 1 diabetes. Methods  The brain metabolites of 17 men with type 1 diabetes and 12 age-matched non-diabetic men (22–43 years old) were studied after an overnight fast (plasma glucose 9.2 ± 3.0 vs 4.8 ± 0.5 mmol/l, respectively). N-Acetylaspartate (NAA), creatine, choline, myo-inositol (mI) and glucose in the frontal cortex, frontal white matter and thalamus were quantified with proton magnetic resonance spectroscopy. Results  In the non-diabetic participants, the glucose level was 47% higher (p < 0.01) in the frontal cortex than in the frontal white matter. In contrast, this regional variation was not observed in the diabetic participants, in whom the glucose level in the frontal white matter was 64% higher (p < 0.001) and in the frontal cortex 25% higher (p = 0.033) than that of the non-diabetic participants. In the diabetic participants, the glucose level in each of the three regions studied correlated with fasting plasma glucose (r = 0.88–0.67, p < 0.01). In addition, in the diabetic participants, mI was 20% higher (p < 0.001) and NAA 6% lower (p = 0.037) in the frontal white matter, and mI was 8% higher (p = 0.042) in the frontal cortex, than in the non-diabetic participants. Conclusions/interpretation  In type 1 diabetes, hyperglycaemia is associated with accumulation of glucose and mI in the cortex and in the white matter. The results of this study were presented in abstract form at the 17th Annual Meeting of the Diabetic Neuropathy Study Group (NEURODIAB) of the EASD in Utrecht, the Netherlands, 14–16 September 2007.     

Association of anti-ribosomal P protein antibodies with neuropsychiatric and other manifestations of systemic lupus erythematosus

The objective of our study was to determine the prevalence of neuropsychiatric manifestations and anti-ribosomal P antibodies (aRP) in SLE and to examine the diagnostic utility and associations of aRP with neuropsychiatric and other disease manifestations. Thirty two consecutive SLE patients, diagnosed according to the updated 1997 ACR criteria, were studied. A full medical history, rheumatological, neurological, psychiatric examination, and psychometric evaluation, including a battery of tests for cognitive dysfunction and the Symptom Checklist-90-Revised depression and anxiety scales were administered to all patients. Disease activity was scored using the SLEDAI. Neuropsychiatric manifestations were diagnosed and categorized according to the 1999 ACR case definitions for 19 NPSLE syndromes. Laboratory and serologic tests including ANA, anti-ds DNA, anti-cardiolipin antibodies (aCL) and aRP (ELISA) were also carried out. Twenty six (81.2%) patients had one or more NP manifestations. Depression (59.4%), headache (46.9%) and cognitive dysfunction (37.5%) were the commonest NPSLE syndromes. Other less commonly detected manifestations included seizures, anxiety, acute confusional state, stroke, and psychosis. aRP was positive in seven (21.9%) patients, all of whom had one or more NPSLE syndromes. Patients with psychiatric manifestations in general and mood disorders in particular had significantly higher mean titers of aRP than patients without these disorders (p < 0.05). aRP were found to be significantly associated with a younger age at the onset of SLE, with more severe articular manifestations and with the presence but not the severity of depression. aRP were highly specific for NPSLE and depression, and they were highly sensitive for psychosis. Neuropsychiatric manifestations are found in 81.2% of unselected Egyptian SLE patients. The presence of aRP antibodies positively predicts patients with psychiatric manifestations in general and mood disorders in particular, for which aRP is specific, but not sensitive. However, aRP is sensitive for psychosis, so that its absence in patients with SLE may help exclude Lupus psychosis. The authors have no conflicts of interest or disclosures.     

Neuropsychiatric manifestations and antiphospholipid antibodies in pediatric onset lupus: 14?years of experience from a tertiary center of North India

The objective is to study the neuropsychiatric (NP) manifestations in pediatric onset systemic lupus erythematosus (SLE) at a tertiary care hospital of northwestern India applying American College of Rheumatology (ACR) case definitions in the context of occurrence of antiphospholipid antibodies (APLA). Data of 53 children with SLE were analyzed for NP syndromes. Tests for detection of APLA were performed as per international standards for quality control. Twenty-seven of the 53 (50.94%) children with lupus had at least one NP manifestation. The male to female ratio of our cohort of pediatric lupus was 1:2.8. However, there was significant male preponderance in patients with NPSLE as compared to patients without NPSLE (1:1.25 vs. 1:12; P < 0.0001). Majority of children with NPSLE (15/27, 55.5%) already had NP manifestations at the time of diagnosis and most of them (81.5%) had experienced more than one NP symptom. Headache was the commonest NP manifestation and was seen in 39.6% children with SLE followed by seizure disorder (35.8%) and cognitive dysfunction (16.9%). Tests for APLA were carried out in 37 of 53 (69.8%) patients with SLE and in 24 of 27 (88.8%) patients with NPSLE. While anticardiolipin antibodies were seen more frequently in children with NPSLE as compared to those without NPSLE (57.8 vs. 23%), lupus anticoagulant was more frequent in children without NPSLE (53.8 vs. 34.7%). However, these differences were statistically not significant. Eleven of the 27 children with NPSLE succumbed to their illness, primarily due to uncontrolled disease activity. Mean duration of follow-up of patients with NPSLE who are alive was 65.4 ± 36.9 months. NP manifestations are common in pediatric onset lupus and contribute to significant morbidity. As compared to previously published literature, a significantly greater proportion of boys were affected. APLA were frequently detected in children with NPSLE. There is paucity of literature pertaining to NP manifestations of pediatric lupus in the context of APLA, especially with regard to antibodies to beta-2 glycoprotein I. To the best of our knowledge, this is the first detailed study on NP manifestations in childhood lupus from a developing country applying ACR case definitions.     

系统性红斑狼疮患者认知功能障碍的分析

目的 调查系统性红斑狼疮（SLE）患者认知功能障碍的发生率，并分析认知功能与临床指标的相关性。方法 对18例神经精神性狼疮（NPSLE）、30例无神经精神症状的SLE（nSLE）患者、20名对照分别使用韦氏成人智力量表（WAIS—RC）中的分测验进行认知功能的评估，同时使用焦虑自评量表（SDS）、抑郁自评量表（SAS）进行抑郁、焦虑方面的评估。所有SLE患者都详细记录了病程、疾病活动性、目前糖皮质激素的用量。结果 认知功能不全在NPSLE组及nSLE组的发生率分别为33％和20％。两组的认知功能状况在领悟、相似性、木块图分测验中与对照组相比差异均有统计学意义。两组之间在WAIS—RC的5个分测验中比较差异无统计学意义。通过多元回归分析发现，受教育年限、病程、既往无神经精神症状3项指标与SIE患者的认知功能存在相关性，且对认知功能影响大小的顺序依次为病程、受教育年限、既往无神经精神症状。结论 SLE患者的认知功能较正常人群减退。SIE患者的认知功能与受教育年限呈正比，与病程及既往有过神经精神症状呈反比。常规对SIE患者进行标准化的认知功能评估，可早期诊断认知功能障碍。     

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.     

Antineurofilament antibody evaluation in neuropsychiatric systemic lupus erythematosus

We used Western blot analysis to examine the occurrence and titer of antibody to cytoskeletal neurofilament protein antigens in patients with neuropsychiatric manifestations of systemic lupus erythematosus (SLE) and in controls. Twenty-two patients with neuropsychiatric SLE (NPSLE) had an increased incidence of antineurofilament antibody (ANFA) compared with 34 patients with SLE without neuropsychiatric symptoms, 78 patients with other disease processes, and 22 healthy controls. ANFA were found to be directed against the 205,000- and 160,000-dalton proteins of the neurofilament triplet. Patients with a diffuse NPSLE clinical presentation had the greatest frequency of serum ANFA (7 of 12, 58%) compared with all other groups examined. Magnetic resonance imaging and serum anticardiolipin antibody testing were also performed in selected patients with NPSLE. Patients with a focal clinical presentation of NPSLE, positive magnetic resonance imaging findings, and negative serum ANFA had significantly elevated levels of anticardiolipin antibody.     

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.     

Factors and comorbidities associated with central nervous system involvement in systemic lupus erythematosus: a retrospective cross-sectional case–control study from a single center

To evaluate, by a retrospective cross-sectional case–control study from a single center, the distribution of a number of factors and comorbidities potentially related to central nervous system involvement in SLE Italian patients, a number of “generic” (i.e. not strictly SLE related) and “specific” (i.e. SLE related) risk factors were checked and their distribution analyzed in SLE patients with (NPSLE) and without (SLE) neuropsychiatric (NP) involvement. One hundred and fifty-three SLE patients with NP involvement observed from 1999 to 2008 and 247 SLE patients without NP manifestations, matched for sex, age and disease duration were included in the study. A neuropsychiatric (NP) event represented the heralding symptom of the disease in 40.5% of NPSLE. Headache, cerebrovascular events, mood disorders and seizures were the most frequent NP manifestations. NPSLE patients had a major cumulative number of the investigated factors than controls without NP involvement. Antiphospholipid antibodies (aPL), lupus anticoagulant (LA), Antiphospholipid antibodies syndrome (APS), Raynaud’s phenomenon, smoke, assumption of contraceptives and higher cumulative dose of glucocorticosteroids (GC) were significantly more commonly observed among NPSLE. APS and systemic arterial hypertension were more frequently detected among patients with focal NP manifestations, especially cerebrovascular events. aPL, LA, APS, Raynaud’s phenomenon, smoke, contraceptives intake and higher cumulative dose of GC did prove more frequently detected in NPSLE patients than in controls. In particular, overall, arterial hypertension should be regarded as a potential independent “risk factor” for focal involvement, especially for cerebrovascular events.     

MHC class II, tumour necrosis factor alpha, and lymphotoxin alpha gene haplotype associations with serological subsets of systemic lupus erythematosus

OBJECTIVE: To conduct a case-control study to investigate whether there are independent tumour necrosis factor alpha (TNFalpha) or lymphotoxin alpha (LTalpha) haplotype associations with SLE or with any of the major serological subsets of SLE. METHODS: 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFalpha, and LTalpha alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFalpha, six single nucleotide polymorphisms (SNPs) at positions -1031, -863, -857, -308, -238, and +488 and for LTalpha three SNPs at positions +720, +365, and +249 were studied to assign six TNFalpha haplotypes (TNF1-6) and four LTalpha haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples. RESULTS: The most significant association with SLE overall was with HLA-DR3 (p<0.001; odds ratio (OR) = 2.5 (95% confidence interval, 1.6 to 3.8)) and the extended haplotype HLA-DQB1*0201;DRB1*0301;TNF2;LTA2 (p<0.001; OR = 2.3 (1.4 to 3.7)). Associations were strongest in the anti-La positive group (13%) of SLE patients (HLA-DR3, OR = 71 (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro in the absence of anti-La (p<0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended haplotype (HLA-DQB1*0303;DRB1*0701/2;TNF5;LTA3) was decreased in SLE overall (p<0.02; OR = 0.2 (0.05 to 0.8)). CONCLUSIONS: The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFalpha alleles on an extended DR3 haplotype.     

Spin-spin relaxation of brain tissues in systemic lupus erythematosus

Objective. To correlate the spin-spin relaxation time (T2) of brain tissue in neuropsychiatric systemic lupus erythematosus (NPSLE) with the patient's clinical condition. Methods. T2 values were determined in 54 SLE patients and 45 non-SLE controls at 1.5 Tesla, using intensity from multi-echo magnetic resonance (MR) images fitted to an exponential decay curve with rateconstant T2. Results. The T2 of white matter was increased in SLE patients compared with controls (P = 0.01) and was increased in those patients who had previously experienced major NPSLE. Patients with acute diffuse neurologic manifestations (seizures, psychosis, coma) demonstrated a longer T2 of the gray matter (mean ± SD 92.75 ± 6.35 ms, n = 10) than did other SLE patients (mean ± SD 79.61 ± 5.04 ms, n = 44) (P = 0.02 by t-test), which suggests acute cerebral edema. The mean T2 values of reversible and nonreversible focal lesions were significantly different (P < 0.02), indicating different microenvironments and micropathology. Conclusion. Quantitative T2 measurement extends the utility and sensitivity of conventional MR imaging for evaluating NPSLE.