Seuli Bose Brill, MD

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Neuropsychiatric Lupus

• Seuli Bose Brill, MD
• Medicine AM Report
• 2/9/10

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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

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25-50 of all patients with SLE have some
neuropsychiatric involvement.
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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

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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)

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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

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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

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Disease Mechanism
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Diagnostic Evaluation
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Biomarkers

• Area of aggressive investigation
• Many with low specificity
• Many are experimental
• Currently with limited clinical application

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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

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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

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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

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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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Bibliography

• History of Lupus http//www.lupus.org/
• Colasanti T, Delunardo F, Margutti P, Vacirca D,
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• Efthimiou P, Blanco M. Pathogenesis of
  neuropsychiatric systemic lupus erythematosus and
  potential biomarkers. Mod Rheumatol.
  200919(5)457-68.
• Hanly JG. Demystifying neuropsychiatric lupus--is
  it possible? Bull NYU Hosp Jt Dis.
  200967(3)276-80.
• Hanly JG, Harrison MJ. Management of
  neuropsychiatric lupus. Best Pract Res Clin
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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
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• Holubar K, Fatovic-Ferencic S. Cazenave, Kaposi
  and lupus erythematosus. A centennial and a
  sesquicentennial. Dermatology. 2001203(2).
• Kajs-Wyllie M. Lupus cerebritis a case study. J
  Neurosci Nurs. 2002 Aug34(4)176-83.
• Muscal E, Brey RL. Neurologic manifestations of
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  adults. Neurol Clin. 2010 Feb28(1)61-73.