Elizabeth Kozora

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes

OBJECTIVE To develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE). METHODS An international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests. RESULTS Case definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed. CONCLUSION The American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.

Magnetic resonance imaging abnormalities and cognitive deficits in systemic lupus erythematosus patients without overt central nervous system disease

OBJECTIVE To investigate cerebral magnetic resonance imaging (MRI) abnormalities in relation to cognitive functioning in systemic lupus erythematosus (SLE) patients without a history of central nervous system (CNS) disease. METHODS Ventricle-to-brain ratios (VBRs) and the total number of white matter hyperintensities (WMHIs) were computed in 20 female patients with non-CNS SLE using established MRI computer-generated quantification procedures. Comprehensive neuropsychological test scores across 8 domains were also obtained. RESULTS A mean VBR of 2.83% (SD = 0.7) occurred in the non-CNS SLE patients compared with a VBR of 1.36% in a normative sample. The average number of WMHIs was 4.95 (SD = 6.0). Using a combined rating scale (VBR > 2.25%, WMHIs > 5), 7 of 20 MRI scans (35%) were classified as abnormal. Increased VBRs and larger numbers of WMHIs showed a trend association with longer duration of SLE. Thirty-five percent of the non-CNS SLE patients demonstrated neuropsychological deficits. No significant correlations were found between the VBR, total WMHIs, and cognitive scores. Comparisons of cognitively impaired and nonimpaired patients with non-CNS SLE revealed no significant differences across clinical characteristics or MRI values. CONCLUSION Quantified MRI analyses indicated atypical brain structure and an increased number of WMHIs in a subset of non-CNS SLE patients. However, these MRI abnormalities were not associated with functional abnormalities determined by comprehensive neuropsychological testing. Therefore, MRI analyses are not likely to provide additional clinical information on cognitively impaired SLE patients who have no other evidence of CNS involvement.

Major life stress, coping styles, and social support in relation to psychological distress in patients with systemic lupus erythematosus

The objective of this study was to examine psychological processes in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients in relation to measures of life stress, coping styles, social support and cognitive ability. Fifty-two SLE patients without overt neuropsychiatric symptoms, 29 RA patients and 27 healthy controls completed measures of depression, mood, disease activity, perceived health, stressful life events, coping, and social support. Variables entered into the multiple regression analysis following principal component analysis were: group, major difficult event, major life threatening event, disengaging coping, emotional coping, social support, and cognitive impairment. Depressive symptoms were associated with SLE group status (P, 0.001), major life-threatening events (P, 0.01), disengage coping (P, 0.001) and emotional coping (P, 0.05). SLE group status (P, 0.05), disengage coping (P, 0.05) and emotional coping (P, 0.05) were associated with current distressed mood. SLE patients without overt, major neuropsychiatric symptoms had greater psychological distress compared to RA and control subjects. Increased depressive symptoms and distressed mood state in SLE patients were related to use of disengaging and emotional coping styles. These findings are limited to SLE patients with no overt neuropsychiatric illness and low disease activity, suggesting the need for future studies with a greater variety of SLE patients. Interventions aimed at improving active coping and minimizing emotional response to stress may lower psychological distress in SLE patients with mild disease.

Inflammatory and hormonal measures predict neuropsychological functioning in systemic lupus erythematosus and rheumatoid arthritis patients.

Abnormalities of inflammatory and hormonal measures are common in SLE patients. Although cognitive dysfunction has been documented in SLE patients, the biological mechanism of these deficits has not been clarified. The goal of this study was to explore the relationship between inflammatory and hormonal activity and measures of learning, fluency, and attention in systemic lupus erythematosus patients without neuropsychiatric symptoms (non-CNS-SLE), patients with rheumatoid arthritis (RA), and healthy controls (HC). Fifteen non-CNS-SLE patients, 15 RA patients and 15 HC participants similar in age, education, and gender (female) were compared on tests of cognition, depression, and plasma levels of interleukin-6 (IL-6), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S) and cortisol. Non-CNS-SLE patients demonstrated lower learning and poorer attention. Furthermore, non-CNS-SLE and RA patients had significantly lower levels of DHEA and DHEA-S than HC participants. Hierarchical regression analysis demonstrates that DHEA-S and IL-6 accounts for a unique portion of the variance in subject performance on measures of learning and attention after controlling for depression and corticosteroid treatment. This data highlights the value of hierarchical analyses with covariates, and provides evidence in humans of a relationship between peripheral cytokine levels and cognitive function.

Cognitive and neurologic status in patients with systemic lupus erythematosus without major neuropsychiatric syndromes

OBJECTIVE To examine neuropsychological and neurologic functioning in systemic lupus erythematosus (SLE) patients without histories of overt neuropsychiatric disorders (non-NPSLE patients). METHODS Sixty-seven non-NPSLE patients and 29 healthy controls were administered a standardized neurologic examination and measures of cognition, depression, and self-reported cognitive functioning. RESULTS Non-NPSLE patients scored lower than controls on the total score of the neurologic examination (P < 0.0001). Item analysis indicated that the physicians description of mentation and mood was the only item that differed significantly between patients with SLE and controls (P = 0.004). Compared with controls, non-NPSLE patients had significantly higher rates of impairment on logical reasoning (P = 0.012) and verbal memory (P = 0.03), and trends toward greater impairment on visual attention (P = 0.06) and working memory (P = 0.098). There were no significant differences between non-NPSLE patients and controls on a cognitive impairment index (CII): 20.9% of non-NPSLE patients and 13.8% of controls were impaired. Patients with SLE scored higher on depressive symptoms (P < 0.0001) and perceived cognitive difficulties (P = 0.001) compared with controls. CONCLUSION The utility of a standardized neurologic examination in SLE for excluding overt neurologic dysfunction and assuring a non-NPSLE group selection was demonstrated. In contrast to our earlier study, we did not find differences between non-NPSLE patients and controls on the CII. Slightly lower CII scores in non-NPSLE patients and higher CII scores in controls may have reduced cognitive differences between these groups. Non-NPSLE patients demonstrate specific decline in the areas of attention, memory, and reasoning; continued studies of associated brain regions are warranted.

Benefits of pulmonary rehabilitation in idiopathic pulmonary fibrosis.

BACKGROUND: Information on the benefits of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF) is growing, but PRs effects on certain important outcomes is lacking. METHODS: We conducted a pilot study of PR in IPF and analyzed changes in functional capacity, fatigue, anxiety, depression, sleep, and health status from baseline to after completion of a standard, 6-week PR program. RESULTS: Six-min walk distance improved a mean ± standard error 202 ± 135 feet (P = .01) from baseline. Fatigue Severity Scale score also improved significantly, declining an average 1.5 ± 0.5 points from baseline. There were trends toward improvement in anxiety, depression, and health status. CONCLUSIONS: PR improves functional capacity and fatigue in patients with IPF. (ClinicalTrials.gov registration NCT00692796.)

Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data.

Objective:To correlate cognitive dysfunction with structural and neurometabolic brain findings in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). Background:Over 25% of non-NPSLE patients have cognitive dysfunction, but the cerebral basis of this observation is not well understood. Method:Seven patients with non-NPSLE and seven control subjects were given a series of neuropsychological tests and neuroimaging with magnetic resonance imaging and magnetic resonance spectroscopy. Analyses of cognitive function and structural and neurometabolic measures of the brain were performed. Results:Compared with controls, the non-NPSLE patients were significantly impaired on a global cognitive impairment index (CII). No significant differences between the groups were found in choline/creatine (Ch/Cr), N-acetylaspartic acid/Cr, or hippocampal volumes. Ch/Cr was highly associated with CII across the sample. Conclusions:This is the first study to correlate cognitive impairment with an increase in Ch/Cr ratio among patients with SLE. These results, although preliminary, suggest that changes in cerebral white matter may be important in determining the subtle cognitive impairment that may occur in patients with SLE, even in the absence of neuropsychiatric symptoms.

Neurobehavioral improvement after brief rehabilitation in patients with chronic obstructive pulmonary disease.

PURPOSE Depressive symptoms, physiologic function, and cognition were examined in patients with chronic obstructive pulmonary disease (COPD) after 3 weeks of rehabilitation. METHODS Patients with COPD completed measures of depression, neuropsychological function, exercise, and spirometry before and after a 3-week rehabilitation program. The 30 rehabilitation patients with COPD were compared with 29 untreated patients with COPD and 21 healthy controls similar in age, education, and gender. RESULTS A significant group by time interaction effect was found on the Beck Depression Inventory (BDI). A significant interaction effect was also found on the 6-minute walk. Patients in the COPD rehabilitation program had decreased depressive symptoms and increased 6-minute walk distance compared with the untreated groups. Across the 3 groups, no significant interaction effects were found on neuropsychological tests. However, clinically significant improvement in sustained visual attention, verbal retention, and visuospatial ability were reported in the most impaired patients with COPD in the rehabilitation group. CONCLUSION Compared with control groups, decline in depressive symptoms and increased exercise capacity occurred in patients with COPD after brief rehabilitation. Clinical improvement in visual attention, verbal memory, and visuospatial functions occurred in the impaired patients with COPD participating in treatment. Neurobehavioral improvements after such a brief rehabilitation intervention are relevant for clinical care and warrant continued investigation in well-designed clinical trials.

Cognitive Dysfunction and White Matter Abnormalities in Systemic Lupus Erythematosus

Brain abnormalities have been documented by neuropsychological assessment as well as a variety of neuroimaging techniques in patients with systemic lupus erythematosus (SLE). Conventional neuroimaging in patients with neuropsychiatric disease (NPSLE) typically discloses periventricular white matter (WM) hyperintensities, infarcts, hemorrhages, and cerebral atrophy. In SLE patients with none of these findings, sophisticated neuroimaging techniques have recently supported associations between microstructural WM abnormalities and abnormal attention, executive function, and processing speed. This mild cognitive dysfunction in SLE (MCD-SLE), which may result from early myelinopathy, precedes the more severe cognitive dysfunction of NPSLE, related to more obvious WM and neuronal damage.

White matter microstructure and cognition in non-neuropsychiatric systemic lupus erythematosus.

ObjectiveThis study examined white matter (WM) structural and metabolic alterations in relation to cognition in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). BackgroundSLE can produce cognitive impairment even without overt neuropsychiatric features, but the pathogenesis of this dysfunction is not well understood. Our preliminary study of non-NPSLE found evidence correlating cognitive impairment with increased choline/creatine (Ch/Cr) in frontal lobe WM. MethodsSubjects included 60 non-NPSLE patients and 24 controls. Magnetic resonance imaging and magnetic resonance spectroscopy were performed, and a battery of neuropsychologic tests was administered. Structural and metabolic measures were analyzed and correlated with neuropsychologic data. ResultsNo significant differences were found in total brain, gray matter, and WM volumes, or in frontal WM N-acetylaspartate/Cr, but the non-NPSLE group had significantly increased Ch/Cr in frontal WM. A WM cognitive score (WMCS) that included the Paced Auditory Serial Addition Task, Letter Fluency, and Animal Naming was found to correlate with total WM volume, and lower WMCS correlated with higher left frontal WM Ch/Cr. ConclusionsNon-NPSLE patients had frontal WM metabolic changes that correlated with cognitive impairment, whereas no cerebral atrophy or WM axonal damage was evident. These data confirm and extend our previous observations supporting the role of microstructural WM changes in the cognitive impairment of non-NPSLE patients. The data also suggest that the WMCS may be sensitive to cognitive dysfunction from myelin damage that develops before axonal injury.