Cognitive Dysfunction in Neuropsychiatric Systemic Lupus Erythematosus

Melanie J. Harrison, MD, MS, Lisa D. Ravdin, PhD


Curr Opin Rheumatol. 2002;14(5) 

In This Article

Neuropsychiatric Disease Classification

In 1999, the American College of Rheumatology (ACR) convened an ad hoc committee to devise nomenclature and case definitions for neuropsychiatric lupus syndromes.[11**] This was in response to the recognition that there were no universally accepted criteria for identifying and describing the multitude of neuropsychiatric manifestations of SLE. In fact, terms like "lupus cerebritis" and "CNS lupus" were common wastebaskets into which were grouped many of these syndromes, which clinicians could not better explain. The ACR Nomenclature provides a framework for identifying and evaluating 19 neuropsychiatric syndromes seen in SLE, and includes diagnostic criteria with special attention to relevant associated conditions as well as exclusion criteria. The committee also provided specific recommendations for evaluating these conditions (ie, laboratory tests, imaging techniques, neuropsychological test battery).

Cognitive dysfunction is one of the 19 SLE-associated neuropsychiatric syndromes outlined by the ACR criteria. Given the frequency of cognitive complaints in SLE patients, many researchers have attempted to quantify cognitive dysfunction with neuropsychological testing. The disease itself presents with a great deal of within and between subject variability, and the profile of neuropsychological dysfunction mirrors this unstable pattern. The ACR recommends a 1-hour neuropsychological test battery that includes measures of premorbid verbal abilities, complex attention, information processing, and psychomotor speed, cognitive flexibility, and verbal and figural memory ( Table 1 ).

In 2001, Ainiala et al.,[12] conducted a population-based study in southern Finland to determine the prevalence of neuropsychiatric syndromes using the ACR Nomenclature. Patients (ages 16-65 years) underwent a comprehensive evaluation, including a complete medical history, physical examination focused on detecting neurologic disorders, and a 3 to 4 hour battery of neuropsychological tests. This investigation reported that 81% of SLE patients had evidence of at least one of the 19 ACR-defined neuropsychiatric conditions, while many patients were classified as having multiple syndromes (as many as six). The most frequently identified neuropsychiatric manifestation was cognitive dysfunction (81%). Of those 37 subjects with abnormal neuropsychological test results, only 14 (38%) were considered to have clinically important cognitive symptomatology. Objective memory testing abnormalities were the most frequently observed deficit in this population (43%), followed by deficits in simple attention, visuospatial processing, and psychomotor speed (26% each).

In a follow-up validation study[13] of the ACR nomenclature, these same investigators compared the SLE subjects to non-SLE controls matched for demographic variables. Interestingly, all neuropsychiatric syndromes were found in both the SLE and control populations, but with greater frequency among the SLE subjects. The odds of manifesting one of these neuropsychiatric syndromes was 9.5 times greater in SLE subjects than in controls. More specifically, cognitive dysfunction had the highest prevalence rate of all neuropsychiatric syndromes among SLE subjects who were nine times more likely than controls to present with this condition. When eliminating the "milder" syndromes from the analysis (ie, headache), prevalence rates decreased significantly for both groups, and the overall odds decreased from 9.5 to 7. The authors attributed this higher prevalence rate of neuropsychiatric syndromes to the inclusion of minor manifestations in the nomenclature, (ie, headache and mood disorders), concluding that the nomenclature lacks specificity for SLE. However, while these findings are noteworthy, the intent of the ACR Nomenclature was to facilitate research in this area by developing uniform means of reporting, so that multicenter trials and comparisons between studies could be made. They were not intended for clinical or diagnostic purposes, or to discriminate SLE patients from the non-SLE population. Furthermore, the neuropsychological methods used by the investigators were only partly consistent with the ACR recommendations.


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