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Abstract Number: 1261

The Usefulness Of Traditional Neurocognitive Testing and N-Methyl-D-Aspartate Receptor Antibodies In Pediatric Lupus Patients

Natasha M. Ruth1, Mary C. Kral2, Tamara K. Nowling3, Stephanie Slan4, Murray H. Passo5 and Gary S. Gilkeson4, 1Pediatric Rheumatology, Medical University of South Carolina, Charleston, SC, 2Genetics and Developmental Pediatrics, MUSC, Charleston, SC, 3Medicine/Rheumatology, Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston, SC, 4Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, SC, 5Pediatrics, Medical University of South Carolina, Charleston, SC

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Lupus, neuropsychiatric disorders and pediatrics

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Session Information

Session Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects II: Pediatric Systemic Lupus Erythematosus, Pediatric Vasculitis and Pediatric Myositis

Session Type: Abstract Submissions (ACR)

Background/Purpose: In order to identify lupus patients at risk for CNS disease, and specifically, cognitive dysfunction, the ACR recommended a standard battery of tests for use in individuals with SLE.  This led to the use of formal neurocognitive testing as the gold standard when measuring cognitive function in SLE.  Almost all studies when measuring neurocognitive function in SLE use a standardized battery of traditional psychometric tests.  These tests have been used to assess which areas of cognition are most affected in patients with SLE and also to help assess the validity of other tools that are thought to be useful in measuring cognitive function in SLE.  Anti-NMDA receptor antibodies are anti-double stranded DNA antibodies that cross-react with the NMDA receptors NR2a and NR2b. The activation of the NMDA receptor is critical in learning and memory and is expressed on neurons throughout the hippocampus and cortex. To measure the prevalence of anti-NMDA receptor antibodies in pediatric patients with SLE and JIA and to assess the association between elevated anti-NMDA receptor antibodies and neurocognitive dysfunction in these populations.

Methods:   Patients diagnosed with SLE prior to age of 18 were recruited.  Each underwent formal neurocognitive testing. The test battery included a comprehensive assessment of cognitive domains. The patients also underwent NMDA receptor-NR-2 subunit antibody testing by ELISA. 

Results: 21 pediatric lupus and 9 JIA patients were enrolled in the study. Independent samples t-tests comparing group means on the cognitive data revealed statistically significant group differences for full scale IQ (t=-3.173, p<.01), auditory working memory (t=-2.180, p<.05), single word reading skills (t=-3.001, p<.01), math calculation skills (t=-2.805, p<.01). There were trends toward significance in verbal memory (t=-1.997, p=.056), inattention [omission errors on the CPT-II] (t=2.025, p-.053) and reading fluency (t=-1.968, p=.059).  In all cases above, the JIA group outperformed the cSLE group.  There was not a significant group difference for the NMDA receptor antibody levels.  There was a significant correlation between the NMDA receptor antibody level and the CPT-II reaction time (r=.542, p<.01) ie. the higher the antibody value, the slower the reaction time for all participants (including JIA patients and SLE patients).

Conclusion: Patients with SLE appear to have multiple areas of cognition that are affected as determined by traditional neurocognitive testing.  NMDA receptor antibodies do not appear to correlate well with the formal testing except in the area of reaction time.  Although promising in mouse models, this antibody may not prove to be a good biomarker for assessing cognition in pediatric patients with SLE.


Disclosure:

N. M. Ruth,
None;

M. C. Kral,
None;

T. K. Nowling,
None;

S. Slan,
None;

M. H. Passo,

Pfizer Inc,

5;

G. S. Gilkeson,
None.

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