VOL. 1, No. 2 / 3, July 2004

I. I. Ali, et al. [2004] Med Hypotheses Res 1: 111-119.

Possible Role of the Hippocampus in the Pathogenesis
of Cognitive Dysfunction in Neuropsychiatric Systemic
Lupus Erythematosus

Imran I. Ali, Edward Savolaine, Noor A. Pirzada, Michiyo Tomita
and Thomas J Santoro*

Departments of Neurologyy (IIA, NAP) and Radiology (ES), Medical College of Ohio,
Toledo, Ohio; Department of Internal Medicine (MT, TJS), University of North Dakota
School of Medicine and Health Sciences, Fargo, ND; and Research Service (TJS), Veterans
Affairs Medical Center, Fargo, ND, USA.

Abstract.  Neuropsychiatric disease, manifested in part by cognitive dysfunction, is
increasingly recognized as a major cause of morbidity in systemic lupus erythematosus
(SLE), a prototypic autoimmune disease.  Cognitive deficits in SLE include impaired
short-term memory, suggesting potential involvement of the hippocampus and temporal
lobe in the development of these aberrations. Similarly, mice that spontaneously manifest
lupus-like illnesses exhibit behavioral disturbances which map to the hippocampus. To
explore the possibility that cognitive dysfunction in SLE is associated with structural
lesions in the hippocampus, five consecutive patients with SLE and subjective complaints
of short-term memory impairment underwent neuroimaging of the brain. A qualitative
loss of hippocampal volume on high-resolution magnetic resonance imaging was found in
all such patients compared with age- and sex-matched controls. The results suggest the
hypothesis that the hippocampus is pathogenetically linked to cognitive impairment in

*Address all correspondence to: Dr. Thomas J. Santoro, Department of Internal
Medicine, University of North Dakota School of Medicine and Health Sciences, 1919 Elm
Street, Fargo, ND 58102. Phone: 701-293-4137; Fax: 701-293-4145. E-Mail:

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