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SEULI BOSE BRILL, MDMEDICINE AM REPORT
2/9/10
Neuropsychiatric Lupus
Historical perspective
Initially described by Mortiz Kaposi in 1870s (delirium)
Further description by Osler in early 1903
Prior to this, lupus thought to be primarily cutaneous disease
The term “lupus” used as early as the 13th century to describe a wolf-like rash
25-50% of all patients with SLE have some neuropsychiatric involvement.
Common Clinical Manifestations
Cognitive dysfunction (55-80%)Headache (24-72%)Mood disorders and psychosis (14-57%)Cerebrovascular diseaseAcute confusional statePeripheral nervous system involvement
SLE Related Cognitive Dysfunction
Mild cognitive impairment (detected through neuropsychiatric testing) estimated to be about 80%
Variable presentation Overall cognitive slowing Decreased attention Impaired working memory Executive dysfunction (e.g. difficulty multitasking)
SLE Related Cognitive Dysfunction
More prevalent in those with active compared to inactive SLE
Decline is not inevitableWaxing and waning courseDifficult to distinguish from other causes of
cognitive dysfunctionOften diagnosis of exclusion due to lack of
definitive diagnostic testing
Pathogenesis
• Increased permeability of blood brain barrier– Pro-inflammatory cytokine mediated disruption of
global function
• Vascular injury of small and large caliber vessels– Microangiopathic– Anti-phospholipid antibodies, immune complexes, and
leukoagglutination– May cause focal or global events
Disease Mechanism
Diagnostic Evaluation
Biomarkers
Area of aggressive investigation
Many with low specificity
Many are experimental
Currently with limited clinical application
Implicated Antibodies/ Biomarkers/ Cytokines
Anti-phospholipid
Anti-ribosomal P
Anti-neuronal
Anti-glial fibrillary acidic protein (GFAP)
Anti-endothelial cell
Anti-N-methyl-D-aspartate (NMDA)
Microtubule-associated protein 2 (MAP-2)
Matrix metalloproteinase-9 (MMP-9)
Interleukins (IL) 2, 6, 8, 10
Tumor necrosis factor alpha (TNF-α)
Interferon alpha and gamma
Neuroimaging
Several possible modalities Computerized tomography (CT) Magnetic resonance imaging/angiography (MRI/MRA) Positron electron tomography (PET) Single photon emission computed tomography (SPECT)
Choice depends on focal versus global dysfunction
Supplementation with EEGNormal study does not rule out disease
Cerebral vasculitis generally not detected on MRI/MRA or even autopsy
Treatment
Symptomatic Therapy Anti-epileptics Anti-psychotics Anti-coagulation when anti-phospholipid
antibodies implicatedImmunosuppression (prolonged course)
High dose oral corticosteroids May be coupled with cyclophosphamide or
rituximab Regimens derived from uncontrolled clinical
studies with small numbersCognitive Rehabilitation
In developmental stages
Ongoing NP-SLE Research
Role of auto-antibodies and inflammatory mediators
Long term patient outcomesClinical significance in context of overall
disease activityCorrelation of neuroimaging in patients who
meet diagnostic criteria Controlled trials of treatment modalities
Take Home Points
Neuropsychiatric manifestations of SLE are very common.
Clinical diagnosis can be elusive. Presentations are varied. Diagnostic testing is often unreliable.
Prolonged immune suppression is the mainstay of therapy.
Bibliography
History of Lupus; http://www.lupus.org/
Colasanti T, Delunardo F, Margutti P, Vacirca D, Piro E, Siracusano A, Ortona E. Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus. J Neuroimmunol. 2009 Jul 25;212(1-2):3-9.
Efthimiou P, Blanco M. Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers. Mod Rheumatol. 2009;19(5):457-68.
Hanly JG. Demystifying neuropsychiatric lupus--is it possible? Bull NYU Hosp Jt Dis. 2009;67(3):276-80.
Hanly JG, Harrison MJ. Management of neuropsychiatric lupus. Best Pract Res Clin Rheumatol. 2005 Oct;19(5):799-821.
Hirohata S, Kanai Y, Mitsuo A, Tokano Y, Hashimoto H; Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. A multicenter retrospective study. Clin Rheumatol. 2009 Nov;28(11):1319-23.
Holubar K, Fatović-Ferencić S. Cazenave, Kaposi and lupus erythematosus. A centennial and a sesquicentennial. Dermatology. 2001;203(2).
Kajs-Wyllie M. Lupus cerebritis: a case study. J Neurosci Nurs. 2002 Aug;34(4):176-83.
Muscal E, Brey RL. Neurologic manifestations of systemic lupus erythematosus in children and adults.; Neurol Clin. 2010 Feb;28(1):61-73.
Mallavarapu RK, Grimsley EW. The history of lupus erythematosus. South Med J. 2007 Sep;100(9):896-8.
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