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
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 • 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 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
Biomarkers • Area of aggressive investigation • Many with low specificity • Many are experimental • Currently with limited clinical application
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 EEG • Normal 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 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. • Presentations are varied. • Diagnostic testing is often unreliable. • Prolonged immune suppression is the mainstay of therapy.
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