Cognitive difficulty in physicians.

Purpose: Remediation of some incompetent physicians has proven difficult or impossible. The authors sought to determine whether physicians with impaired competency had neuropsychological impairment sufficient to explain their incompetence and their failure to improve with remedial continuing medical education (CME).

Method: During a one-year period, 1996-97, all 27 participants in the Physician Review Program (PREP) conducted at McMaster University, a physician competency assessment program, undertook a detailed neuropsychological screening battery.

Cognition and mood in systemic lupus erythematosus. Evaluation and pathogenesis.

Cognitive dysfunction is frequent in SLE, probably related to primary underlying immune/inflammatory mechanisms operating in the brain. Longitudinal studies relating patterns of cognitive impairment to putative pathogenetic factors would provide evidence for this hypothesis. Such studies could also lead to more specific therapeutic interventions to ameliorate or reverse brain compromise in SLE.

The relationship of antiphospholipid antibodies to cognitive function in patients with systemic lupus erythematosus.

Objective: To examine the relationship between antiphospholipid antibody positivity (expressed as the lupus anticoagulant) and cognitive dysfunction in patients with systemic lupus erythematosus (SLE).

Methods: Cross-sectional comparisons of lupus anticoagulant (LA) positive (N = 39) and negative (N = 79) patients and controls (N = 35) on a cognitive test battery; 22 LA-positive and 53 LA-negative patients who had never experienced neuropsychiatric events (never-NP-SLE) were also compared separately.

Results: LA-positive patients were 2 to 3 times more likely than were LA-negative patients to be designated as cognitively impaired.

Neurobehavioral outcomes among farm and nonfarm rural Ecuadorians.

International researchers have urged greater use of simple neurobehavioral batteries in developing country settings where higher levels of exposure and a variety of cultural and demographic factors may both occur. We conducted a cross-sectional survey of 144 farm members and 72 age and education frequency-matched controls from rural Ecuador, using an amplified Neurobehavioral Core Test Battery. Farm members ranged from those with only indirect pesticide contact to applicators regularly applying organophosphate and carbamate insecticides by backpack sprayer.

Psychological aspects of systemic lupus erythematosus: cognitive function, mood, and self-report.

Systemic lupus erythematosus (SLE) is a chronic relapsing/remitting autoimmune disorder with both primary and secondary effects on nervous system integrity and psychological functioning. In addition to the occurrence of clinical psychiatric syndromes such as psychosis, depression, and anxiety, other psychological problems documented with increased frequency in SLE include cognitive deficits and emotional distress. We examine issues related to cognitive function, including its assessment and prevalence, and confounding factors in interpreting cognitive problems as reflecting primary central nervous system involvement in SLE.

Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?

Objective: To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine replacement therapy.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Outpatient clinic.

Cognitive dysfunction in systemic lupus erythematosus is independent of active disease.

Objective: To determine whether disease activity in organ systems other than the central nervous system (CNS) contributes to impaired neurocognitive functioning in patients with systemic lupus erythematosus (SLE) without current major neuropsychiatric problems.

Methods: A cross sectional study of 90 consecutive female patients with SLE. Neuropsychological status was evaluated with a comprehensive 2.

Nervous system lupus: pathogenesis and rationale for therapy.

Several different pathogenic mechanisms appear to be involved in CNS lupus. These include: B-cell/autoantibody-mediated nervous system compromise; immune complex deposition and vasculitis; microthrombosis and vasculopathy; aberrant MHC Class II antigen expression with T-cell mediated disease (multiple-sclerosis model); and, cytokine-induced brain inflammation. These processes are not mutually exclusive: there exist in vitro and in vivo models for each of these.

Disturbed emotionality in autoimmune MRL-lpr mice.

MRL-lpr mice develop symptoms of autoimmune lupus-like disease early in the life and MRL(-)+/+ mice develop it substantially later. The present study examines our previous suggestion that autoimmune MRL-lpr mice show altered emotional reactivity. In addition, it aims to identify the set of measures which best discriminate the behavior of MRL-lpr mice from their congenic controls (MRL +/+).

Corticosteroids and neuropsychological functioning in patients with systemic lupus erythematosus.

Objective: This study was designed to assess the effects of corticosteroids on select aspects of nervous system functioning, specifically, cognition and mood, as well as disease-related symptoms in individual patients with mild systemic lupus erythematosus (SLE) and mild neuropsychiatric (NP) symptoms.

Methods: Ten women who had not been taking corticosteroids for at least 6 months were selected from a referral-based lupus clinic to participate in an N of 1 double-blind, controlled trial consisting of 3 randomly assigned drug/placebo pairings, with a drug dose of 0.5 mg/kg of prednisone daily.

Lymphocyte antigens in neuropsychiatric systemic lupus erythematosus. Relationship of lymphocyte antibody specificities to clinical disease.

Objective: To examine the relationships among specific lymphocyte antigenic reactivities of lupus sera and central nervous system complications of systemic lupus erythematosus (SLE), lymphocytotoxic antibody (LCA) positivity, and specific cognitive impairment.

Methods: Sera from 115 patients with SLE were examined for the presence of IgM- and IgG-class autoantibodies binding to surface target antigens on lymphocytes, by immunoblotting and microdroplet lymphocytotoxicity studies. Seventy-three of these patients also underwent detailed neuropsychological testing within the same time period.

Behavior and immune status of MRL mice in the postweaning period.

The notion that the MRL-lpr substrain is a useful model of behavioral and cognitive deficits found in systemic autoimmune diseases is supported by the recent findings of behavioral dysfunction in autoimmune MRL-lpr mice compared to their congenic control MRL +/+ mice. However, it has not been established whether the altered behavioral profile in MRL-lpr mice is the result of the autoimmune process itself or reflects a subtle difference in genetic background or both. To address the question whether MRL-lpr mice are born with behavioral dysfunction the present study compares the behavior of the two MRL substrains in the early postweaning period, when their immune status does not show detectable difference.

Cognitive deficits in systemic lupus erythematosus.

Several independent studies have now demonstrated the presence of significant cognitive impairment in SLE patients. Such impairment, whether it precedes or follows overt NP events, suggests compromise of the neural substrate, irrespective of overt clinical NP symptomatology. The association between cognitive impairment and brain cross-reactive autoantibodies suggests one mechanism for CNS involvement in SLE that warrants further study; the data relating specific cognitive deficits to the presence of specific antibodies raise the intriguing possibility of system- or structure-specific immune-mediated involvement in the CNS.

Brain-reactive antibodies and behavior of autoimmune MRL-lpr mice.

The hypothesis that brain-reactive autoantibodies (BRA) impair behavior was examined in MRL-lpr mice, which develop spontaneous autoimmune disease. Circulating BRA were measured as in vitro serum reactivity to Neuro-2A neuroblastoma cell line, and behavioral competence was assessed in activity monitors, open field, beam walking, and Morris water maze task. Mice with BRA in serum (BRA positive) exhibited slower spontaneous locomotion in a novel environment, shorter grooming episodes, and less exploration of the open field centre when compared to age-matched 7-11-week-old BRA-negative cagemates.

Spatial learning during the course of autoimmune disease in MRL mice.

The present study examines whether autoimmune MRL-lpr mice develop impairments in learning and memory that correlate with changing severity of lupus-like disease. MRL-lpr mice (n = 20) were tested in the Morris water-maze at 12, 14, 16 and 18 weeks of age. Age-matched controls were congenic MRL +/+ mice (n = 20) that develop the disease much later.

Fluctuating cognitive abnormalities and cerebral glucose metabolism in neuropsychiatric systemic lupus erythematosus.

Brain imaging techniques such as MRI and PET have the potential for identifying central nervous system involvement in SLE. They may also help elucidate the mechanisms giving rise to the widely diverging manifestations of CNS involvement in SLE. This report documents an intensive longitudinal study of three women with neuropsychiatric SLE.

Serum lymphocytotoxic antibodies and neurocognitive function in systemic lupus erythematosus.

The hypothesis that lymphocytotoxic antibodies are associated with neuropsychiatric involvement in systemic lupus erythematosus (NP-SLE) is re-evaluated in this study. In an unselected cohort of 98 women with SLE a cross-sectional study has been performed to analyse associations among standardised clinical, neurological, and neuropsychological assessments and lymphocytotoxic antibodies measured by microcytotoxicity assay. Fifty patients showed objective clinical evidence of continuing or past NP-SLE and 54 patients had cognitive impairment.

The association between sequential changes in serum antineuronal antibodies and neuropsychiatric systemic lupus erythematosus.

To determine the significance of changes in serum antineuronal antibody levels in systemic lupus erythematosus, 9 patients who had a rise and 11 patients who had a fall in neuronal antibody titre over a mean duration of 2.1 years (range 0.25-5.

Neuropsychological correlates of serum lymphocytotoxic antibodies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by frequent neuropsychiatric (NP) manifestations. At least two different pathogenetic mechanisms have been proposed for NP-SLE, including vasculitis and antibodies against neuronal antigens, the latter as expressed by the presence of brain cross-reactive lymphocyte antibodies. We have previously reported a high prevalence of cognitive dysfunction in SLE which can remain subclinical and which cannot be accounted for on the basis of disease activity, general distress, or steroid medication.

Cognitive impairment in systemic lupus erythematosus: a neuropsychological study of individual and group deficits.

Eighty-six females with systemic lupus erythematosus (SLE) were grouped according to present or past history of neuropsychiatric (NP) symptomatology (Active, Inactive, or Never). Performance of these three groups was compared to that of 35 normal women on an extensive battery of neuropsychological tests sampling a wide range of cognitive functions. In addition to making group comparisons, we also devised a system for identifying individual impairment using decision rules for both quantitative and qualitative data.

Neuronal antibodies and cognitive function in systemic lupus erythematosus.

The pathogenesis of neuropsychiatric lupus (NP-SLE) is unclear, but may involve vasculopathy, antibodies against nervous system tissue, or both. A major difficulty in determining the significance of antineuronal antibodies in NP-SLE has been lack of consistent clinical diagnostic approaches. By utilizing a new clinical classification of NP-SLE, neuropsychological assessments, and an assay for IgG antineuronal antibodies, we have found a significant association between antibody-positivity and cognitive impairment or nonfocal NP-SLE.

Prevalence of cognitive impairment in systemic lupus erythematosus.

We administered a battery of neuropsychological tests to 62 female patients with systemic lupus erythematosus (SLE), 12 female patients with rheumatoid arthritis (RA), and 35 normal control subjects. By applying objective decision rules to individual test protocols, an overall prevalence of cognitive impairment of 66% was obtained in the SLE patient sample. Independent clinical, radiological, and laboratory data were used to determine neuropsychiatric (NP) symptomatology and to group SLE patients as 1) "active" (N = 21), 2) "inactive" (N = 15), and 3) "never" (N = 26) NP-SLE.