Application Study of Brain Structure and Functional Magnetic Resonance Imaging in Patients with Systemic Lupus Erythematosus and Cognitive Dysfunction.

Objective: This study was aimed to investigate the application value of brain magnetic resonance imaging (MRI) technique, including arterial spin labeling (ASL) and diffusion tensor imaging (DTI) in patients with systemic lupus erythematosus (SLE) and cognitive dysfunction (CDF). Methods: A total of 50 patients with SLE admitted to the hospital from September 2020 to December 2022 were selected and divided into the group with CDF (n = 21) and the group without CDF (n = 29) according to the score of Montreal Cognitive Assessment Scale (MoCA). Additionally, 10 healthy individuals who underwent physical examinations during the same period were recruited as controls. After the conventional MRI, DTI and ASL data of all subjects were collected, statistical parametric mapping software combined with voxel morphology is applied for gray matter volume, white matter and gray matter cerebral blood flow (CBF) analysis among different groups. Results: There is a statistically significant difference in conventional MRI findings between the SLE group and the control group (P < .05). However, There was no significant difference in white matter fractional anisotropy (FA) values between the two groups (P > .05). The apparent diffusion coefficients (ADC) of the right precuneus and the right Brodmann's area 21 and 6 in SLE patients with CDF were significantly higher than SLE patients without CDF (P < .05). In comparison to the non-CDF group, the CDF group exhibited reduced gray matter volume, primarily in the anterior cingulate gyrus, left frontal lobe, and right insula (P < .05). Meanwhile, the white matter and gray matter cerebral blood flow (CBF) of SLE patients with CDF were significantly lower than those without CDF. (P < .05). Correlation analysis showed that the MoCA score was positively associated with the volume of gray matter in the right insula, bilateral frontal lobe, left temporal lobe, and cingulate gyrus (P < .05). Additionally, MoCA score was also found to be positively associated with the CBF of white matter and gray matter (P < .05). Conclusions: Alterations in gray matter volume and CBF in SLE patients are closely associated with combined CDF and can be observed by DTI and ASL techniques.

Quantitative susceptibility mapping in the thalamus and basal ganglia of systemic lupus erythematosus patients with neuropsychiatric complaints.

Systemic lupus erythematosus (SLE) is an auto-immune disease characterized by multi-organ involvement. Although uncommon, central nervous system involvement in SLE, termed neuropsychiatric SLE (NPSLE), is not an exception. Current knowledge on underlying pathogenic mechanisms is incomplete, however, neuroinflammation is thought to play a critical role. Evidence from neurodegenerative diseases and multiple sclerosis suggests that neuroinflammation is correlated with brain iron accumulation, making quantitative susceptibility mapping (QSM) a potential hallmark for neuroinflammation in vivo. This study assessed susceptibility values of the thalamus and basal ganglia in (NP)SLE patients and further investigated the in vivo findings with histological analyses of postmortem brain tissue derived from SLE patients. We used a 3T MRI scanner to acquire single-echo T2*-weighted images of 44 SLE patients and 20 age-matched healthy controls. Of the 44 patients with SLE, all had neuropsychiatric complaints, of which 29 were classified as non-NPSLE and 15 as NPSLE (seven as inflammatory NPSLE and eight as ischemic NPSLE). Mean susceptibility values of the thalamus, caudate nucleus, putamen, and globus pallidus were calculated. Formalin-fixed paraffin-embedded post-mortem brain tissue including the putamen and globus pallidus of three additional SLE patients was obtained and stained for iron, microglia and astrocytes. Susceptibility values of SLE patients and age-matched controls showed that iron levels in the thalamus and basal ganglia were not changed due to the disease. No subgroup of SLE showed higher susceptibility values. No correlation was found with disease activity or damage due to SLE. Histological examination of the post-mortem brain showed no increased iron accumulation. Our results suggest that neuroinflammation in NPSLE does not necessarily go hand in hand with iron accumulation, and that the inflammatory pathomechanism in SLE may differ from the one observed in neurodegenerative diseases and in multiple sclerosis.

Degraded microarchitecture by low trabecular bone score is associated with prevalent vertebral fractures in patients with systemic lupus erythematosus.

PURPOSE: Recently, trabecular bone score (TBS) has emerged as an important supplementary assessment tool in osteoporosis diagnosis and management. The high incidence of fragility fracture within the non-osteoporotic range of bone mineral density (BMD), among systemic lupus erythematosus (SLE) patients, highlights the crucial role of bone microarchitecture in osteoporosis. This study aimed to evaluate whether TBS identified existing vertebral fractures (VF) more accurately than BMD in SLE patients. METHODS: This study enrolled 147 SLE patients from the Asia Pacific Lupus Collaboration (APLC) cohort, who had BMD and TBS assessed from January 2018 until December 2018. Twenty-eight patients sustaining VF and risk factors associated with increased fracture occurrence were evaluated. Independent risk factors and diagnostic accuracy of VF were analyzed by logistic regression and ROC curve, respectively. RESULT: The prevalence of vertebral fracture among SLE patients was 19%. BMD, T-score, TBS, and TBS T-score were significantly lower in the vertebral fracture group. TBS exhibited higher positive predictive value and negative predictive value than L spine and left femur BMD for vertebral fractures. Moreover, TBS had a higher diagnostic accuracy than densitometric measurements (area under curve, 0.811 vs. 0.737 and 0.605). CONCLUSION: Degraded microarchitecture by TBS was associated with prevalent vertebral fractures in SLE patients. Our result suggests that TBS can be a complementary tool for assessing vertebral fracture prevalence in this population.

Subcortical gray matter atrophy is associated with cognitive deficit in multiple sclerosis but not in systemic lupus erythematosus patients.

Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.

Prevalence of and risk factors for low bone mineral density in Japanese female patients with systemic lupus erythematosus.

To examine the prevalence of and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in Japanese female patients with systemic lupus erythematosus (SLE). We performed BMD measurements by dual X-ray absorptiometry at the lumbar spine and the hip and collected basic and lifestyle-related, clinical and treatment characteristics among 58 SLE patients. Odds ratios (ORs) and their 95% confidence intervals (CIs) were assessed for associations between low BMD and selected factors among SLE patients. The mean BMD ± SD was 0.90 ± 0.17 g/cm(2) at the lumbar spine and 0.76 ± 0.17 g/cm(2) at the hip. The prevalence of osteopenia (2.5 SD < T score < 1 SD) was 50.0% and that of osteoporosis (T score < 2.5 SD) was 13.8% in our SLE patients. After adjustment for age and disease duration, we found the number of deliveries (OR = 5.58, 95% CI = 1.31-26.06; P = 0.02) to be a risk factor for overall low BMD (T score < 1 SD) and a maximal dosage of >50 mg/day of oral corticosteroids (OR = 0.25, 95% CI = 0.07-0.91; P = 0.035) as a preventive factor for low BMD at the lumbar spine. Reduced BMD, especially in spinal trabecular bone, was pronounced in Japanese female patients with SLE, particular in those with a history of delivery. A history of high-dose oral corticosteroids was associated with the preservation of BMD at the lumbar spine, however, further study is needed considering the limited sample size.

Calcinosis cutis in systemic lupus erythematosus: a case report and review of the published work.

Calcinosis cutis is a common clinical feature of dermatomyositis and scleroderma but rarely reported in association with systemic lupus erythematosus (SLE). Calcinosis cutis in SLE occurs without calcium and phosphorus metabolic abnormalities and may be localized or generalized. The pathophysiology remains unclear and no effective therapy is currently available. We report a 30-year-old woman with a 13-year history of SLE who developed multiple calcinosis cutis around both knees and we review the relevant published work.

Targeting Notch signaling in autoimmune and lymphoproliferative disease.

Patients with autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosis (SLE) have T-cell dysregulation and produce abnormal, activated T lymphocytes and an atypical peripheral T-cell population, termed double negative T cells (DNTs). T-cell functions, including DNT transition in T-cell development and T-cell activation, are critically dependent on Notch signaling. We hypothesized that inhibiting Notch signaling would be effective in ALPS and SLE by reducing the production of abnormal DNTs and by blocking aberrant T-cell activation. We tested this hypothesis using murine models of ALPS and SLE. Mice were randomized to treatment with the notch pathway inhibitor (gamma-secretase inhibitor), N-S-phenyl-glycine-t-butyl ester (DAPT), or vehicle control. Response to treatment was assessed by measurement of DNTs in blood and lymphoid tissue, by monitoring lymph node and spleen size with ultrasound, by quantifying cytokines by bead-array, by ELISA for total IgG and anti-double-stranded DNA (dsDNA) specific antibodies, and by histopathologic assessment for nephritis. We found a profound and statistically significant decrease in all disease parameters, comparing DAPT-treated mice to controls. Using a novel dosing schema, we avoided the reported toxicities of gamma-secretase inhibitors. Inhibiting the Notch signaling pathway may thus present an effective, novel, and well-tolerated treatment for autoimmune and lymphoproliferative diseases.

Abnormal regional cerebral blood flow in systemic lupus erythematosus patients with psychiatric symptoms.

OBJECTIVE: Single-photon emission computed tomography (SPECT) studies have demonstrated decreased regional cerebral blood flow (rCBF) in systemic lupus erythematosus (SLE) patients. However, no study has done voxel-based analysis using statistical parametric mapping (SPM) that can evaluate rCBF objectively, and the relationship between rCBF and psychiatric symptoms has not been well investigated. Using L,L-ethyl cysteinate dimer (99mTc ECD) SPECT and SPM, we aimed to clarify the association of rCBF changes with psychiatric symptoms in SLE patients whose magnetic resonance imaging (MRI) showed no morphological abnormalities. METHOD: Twenty SLE patients and 19 healthy volunteers underwent 99mTc ECD SPECT. Data were collected from August 2000 to March 2003. SLE was diagnosed according to American College of Rheumatology criteria, and psychiatric symptoms were diagnosed according to ICD-10 criteria. On the basis of the modified Carbotte, Denburg, and Denburg method, the patients were classified into 3 groups: a group with major psychiatric symptoms (hallucinosis, delusional disorder, and mood disorder), a group with minor psychiatric symptoms (anxiety disorder, dissociative disorder, and emotionally labile disorder), and a group without psychiatric symptoms. Gross organic lesions were ruled out by brain MRI. Group comparisons of rCBF were performed with analysis using SPM99. RESULTS: SLE patients without MRI lesions showed decreased rCBF in the posterior cingulate gyrus and thalamus. The reduction in rCBF was overt in patients with major psychiatric symptoms. CONCLUSION: Our study indicated that SLE patients may have dysfunction in the posterior cingulate gyrus and thalamus and that this may be associated with the severity of psychiatric symptoms.

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.

Does bowel preparation improve the quality of abdominal gallium scintigraphy?

Physiological accumulation of gallium in the intestine is a major weakness of gallium scintigraphy in evaluating the abdomen. In this study, we used two different cathartics to evaluate the efficacy of bowel cleansing in improving the quality of abdominal gallium imaging. One hundred and fifty patients underwent gallium scintigraphy and were randomly divided into three groups. Group A received no bowel preparation, Group B received 30 ml of castor oil the night before imaging, and Group C received bisacodyl the night before imaging. Gallium activity in the intestine was rated on a three-point scale from 0 to II based on the anterior view of a delayed 48-h gallium image. Our data showed that the incidence of gallium accumulation in the small intestine was low. On the contrary, there was high prevalence of gallium activity in the colon. Forty-eight percent of Group A patients had obvious gallium activity in the colon. The percentage decreased significantly to 28% and 22% in Groups B and C, respectively. No significant difference was noted between Group B and Group C. In conclusion, our data suggest that the application of either castor oil or bisacodyl significantly improves the quality of 48-h abdominal gallium scintigraphy. There were no significant differences in the efficacy of bowel cleansing on gallium activity between these two laxatives.

Diffuse central nervous system lupus involving white matter, basal ganglia, thalami and brainstem.

We described an 11-year-old girl with acute central nervous system lupus showing diffuse lesions. She developed generalized convulsions followed by prolonged coma, and her psychomotor ability recovered fully after 3 months of steroid therapy. Cranial magnetic resonance imaging (MRI) showed high signal intensity in the cerebral deep white matter, bilateral basal ganglia, thalami, and brainstem on T2-weighted image. These lesions resolved over 1 month with residual atrophic change in the heads of the caudate nucleus on MRI. Acute SLE leukoencephalopathy may be recognized as a subtype of CNS lupus.

Central nervous system vasculopathy in neonatal lupus erythematosus.

Central nervous system involvement in neonatal lupus erythematosus (NLE) has not been previously reported. We report four patients with NLE, all with complete congenital heart block and three with cerebral ultrasound and color Doppler flow imaging (CDFI) studies demonstrating evidence of associated vasculopathy in the gangliothalamic vasculature. CDFI confirmed blood flow through the affected vessels, indicating that blood flow was not compromised at this early stage. Short-term follow-up revealed no signs of progression of the vasculopathy, focal ischemia, gangliothalamic atrophy, or neurological impairment. Nevertheless, the implications of this finding with respect to the natural history of NLE remain to be defined, particularly in cases in which the disease develops into systemic lupus erythematosus later in life. Besides specific diagnostic studies for NLE, cerebral ultrasound, and CDFI studies are mandatory in all cases of complete congenital heart block, regardless of whether mothers are diagnosed as having connective-tissue disease or not. Neonates with signs of vasculopathy in the gangliothalamic region should be examined for NLE.

Sonographic lenticulostriate vasculopathy in infants: some associations and a hypothesis.

PURPOSE: To describe the causes of infantile lenticulostriate vasculopathy (LSV) as demonstrated by sonography and propose the pathogenesis of these findings. METHODS: Five hundred eighty-six infants were examined via echoencephalography because of seizures, psychomotor retardation, dysmorphism, congenital malformation, microcephaly, macrocephaly, bulging of anterior fontanel, consciousness disturbance, or prematurity. We directed our attention on the sonographic study to the basal ganglionic and thalamic areas. Twenty-eight of the 586 patients underwent color Doppler studies. RESULTS: In 34 infants with gray-scale neurosonographic findings of LSV, 16 were associated with various causes that have been reported before. In 8 patients entities not previously associated with LSV were found: neonatal lupus, neonatal hypoglycemia, uncomplicated prematurity, encephalitis, and head injury. In the remaining 10 cases, a specific cause could not be found. The LSV was found in 16 (40%), 5 (14%), and 13 (3%) patients with perinatal, acquired, and nonspecific causes, respectively. Generally, this is an uncommon finding because it was observed in only 34 (5.8%) of the study infants; 24 of these 34 had a documented cause of the vasculopathy. With LSV associated with perinatal causes there was a greater chance of sonographic LSV's developing than with that of acquired causes. CONCLUSIONS: We suggest that sonographic LSV is a nonspecific marker of a previous insult to the developing brain, and the special hemodynamics of the fetal brain plays an important role in its pathogenesis.

[The importance of osteoscintigraphy for the early detection of rheumatic joint lesions]. / Znachenie osteostsintigrafii dlia rannego vyiavleniia revmaticheskikh porazhenii sustavov.

The scintigraphic semeiotics was investigated of involvement of osteoarticular system in rheumatoid polyarthritis in 186 patients (79 of them suffered of rheumatoid arthritis, 62 of systemic lupus erythematosus, 34 of systemic scleroderma, 11 of dermatomyositis). Roentgenological examination was supplemented by consecutive local scintigraphy of axial skeleton and peripheral joint by of gamma rays with labeled 99mTc phosphate complexes. Isoactive zones with subsequent quantitative evaluation of the information were obtained as a result of computerized processing of the scintigraphic images of the joints. The results were compared with those obtained in patients with rheumatoid arthritis. It was established that inspite of the similarity of the scintigraphic manifestations, each of them has its regularities due to differences of the pathomorphological processes in the joints.

Transient thalamic hypodensity in lupus erythematosus with generalized seizures.

Computerized tomography revealed extensive bilateral hypodensity of the thalamus after an episode of severe arterial hypertension and convulsions in a patient with systemic lupus erythematosus. Radiologic and neurologic abnormalities were substantially resolved 1 week later. The unusual radiologic findings are discussed in relation to possible unique characteristics of vascular permeability in the thalamus.