SLE
Neuropsychiatric Syndromes in Systemic Lupus Erythematosus: A Meta-Analysis

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Objectives

To assess the prevalence of the 19 neuropsychiatric (NP) syndromes in systemic lupus erythematosus (SLE) patients, as defined by the American College of Rheumatology (ACR) in 1999, and better understand the reasons for interstudy variability of prevalence estimates, by performing a meta-analysis of relevant publications.

Methods

A literature search from April 1999 to May 2008 was performed to identify studies investigating NP syndromes in patients with definite SLE, applying the 1999 ACR case definitions and having a sample size of at least 30 patients. Excluded were studies that did not relate to all 19 NPSLE syndromes, presented duplicate data, or were irrelevant.

Results

Seventeen of 112 identified studies matched the inclusion criteria, reporting on a total of 5057 SLE patients, including 1439 NPSLE patients, with 2709 NPSLE syndromes. In a subanalysis of the 10 higher quality prospective and elicited studies (2049 patients) using the random-effects model, the prevalence of NP syndromes in SLE patients was estimated to be 56.3% (95% CI 42.5%-74.7%), and the most frequent NP syndromes were headache 28.3% (18.2%-44.1%), mood disorders 20.7% (11.5%-37.4%), cognitive dysfunction 19.7% (10.7%-36%), seizures 9.9% (4.8%-20.5%), and cerebrovascular disease 8.0% (4.5%-14.3%), although significant between-study heterogeneity was present (P < 0.05). Autonomic disorder and Guillain-Barré syndrome carried a prevalence of less than 0.1%. No case of plexopathy was reported.

Conclusions

NP syndromes were estimated to exist in more than half of SLE patients. The most prevalent manifestations were headache, mood disorders, and cognitive dysfunction. A major limitation of the study was the significant heterogeneity of prevalence estimates between studies.

Section snippets

Methods

This study was conducted according to the guidelines outlined by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group (20).

Results

Our search identified 112 articles (Fig. 1), of which 17 met the inclusion criteria and were incorporated in the final analysis (Table 1). The final cohort comprised of 5057 SLE patients. Of these, 1439 patients (28.5%, range: 12.2%-94.7%) had 2709 NP syndromes (mean of 1.88 syndromes per NPSLE patient, range: 1.0-3.48). Most studies were single-center (13/17 studies) and reported on an adult population (8/17, N = 3782 patients), although some studies reported on either pediatric (5/17, N =

Methodologic Differences Between Studies

We identified 2 major methodologic approaches used in the 17 studies. The first (applied in 7/17 studies) was purely a retrospective, chart-driven one and therefore prone to biases such as low-quality patient records and underestimation of the subjective manifestations (eg, headache). The second approach (used in 10/17 studies) combined a retrospective chart review with either a prospective follow-up or additional elicited information (eg, questionnaires about past medical history, additional

Conclusion

Ours is the first study to compile the body of data on NPSLE prevalence using the 1999 ACR case definitions, a decade after their publication. NP syndromes were estimated to exist in more than half of SLE patients, making it one of the most common and significant manifestations of SLE. Many of the NP syndromes, such as cognitive dysfunction and autonomic disorders, may be difficult to detect and may require careful testing of all patients to avoid underdiagnosis.

Determining the prevalence of

Acknowledgment

We would like to thank Dr. Yedidya Dotan for his important remarks and assistance with the statistical analysis.

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    The authors have no conflicts of interest to disclose.

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