Transcript Neuropsychiatric Lupus - UNC School of Medicine

Neuropsychiatric Lupus
SEULI BOSE BRILL, MD
MEDICINE AM REPORT
2/9/10
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 disease
 Acute confusional state
 Peripheral nervous system involvement
SLE Related Cognitive Dysfunction
 Mild cognitive impairment (detected through
neuropsychiatric testing) estimated to be about 80%
 Variable presentation
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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
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inactive SLE
Decline is not inevitable
Waxing and waning course
Difficult to distinguish from other causes of cognitive
dysfunction
Often 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
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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 EEG
 Normal study does not rule out disease
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Cerebral vasculitis generally not detected on MRI/MRA or even
autopsy
Treatment
 Symptomatic Therapy
 Anti-epileptics
 Anti-psychotics
 Anti-coagulation when anti-phospholipid antibodies
implicated
 Immunosuppression (prolonged course)
 High dose oral corticosteroids
 May be coupled with cyclophosphamide or rituximab
 Regimens derived from uncontrolled clinical studies with
small numbers
 Cognitive Rehabilitation
 In developmental stages
Ongoing NP-SLE Research
 Role of auto-antibodies and inflammatory mediators
 Long term patient outcomes
 Clinical significance in context of overall disease
activity
 Correlation 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.
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Presentations are varied.
Diagnostic testing is often unreliable.
 Prolonged immune suppression is the mainstay of
therapy.
Bibliography
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History of Lupus; http://www.lupus.org/
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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.
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Efthimiou P, Blanco M. Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers. Mod Rheumatol.
2009;19(5):457-68.
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Hanly JG. Demystifying neuropsychiatric lupus--is it possible? Bull NYU Hosp Jt Dis. 2009;67(3):276-80.
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Hanly JG, Harrison MJ. Management of neuropsychiatric lupus. Best Pract Res Clin Rheumatol. 2005 Oct;19(5):799-821.
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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.
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Holubar K, Fatović-Ferencić S. Cazenave, Kaposi and lupus erythematosus. A centennial and a sesquicentennial. Dermatology. 2001;203(2).
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Kajs-Wyllie M. Lupus cerebritis: a case study. J Neurosci Nurs. 2002 Aug;34(4):176-83.
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Muscal E, Brey RL. Neurologic manifestations of systemic lupus erythematosus in children and adults.; Neurol Clin. 2010 Feb;28(1):61-73.
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Mallavarapu RK, Grimsley EW. The history of lupus erythematosus. South Med J. 2007 Sep;100(9):896-8.