A Presentation by Petros Efthimiou, MD at Lincoln Hospital, Bronx, New York

1. When Your Head Hurts and Your Memory Fails- Is It Your Lupus? Petros Efthimiou, MD, FACR, Lincoln Medical and Mental Health Center Assistant Professor of Medicine, Weill Cornell Medical College, New York, NY

3. Epidemiology of SLE Incidence : 7.6/100,000/year (pooled from a number of studies) Prevalence: 14.5-50.8/100,000 Hochberg’s Prevalence : 372/100,000 US: close to 1 million people SLE Lupus Foundation: probably 1.5 million incidence 1950 2000 10 5 2

4. How Does Lupus happen? T Cell Abnormal Adhesion Molecule and Chemokine Expression Tissue Specific Pathology APC B7 MHC FcR CR RES AutoAb Drugs UV Infectious Agents Genetic Background Estrogens B Cell Increased Help Decreased Cytotoxicity Altered Cytokine Production IL-6, IL-10 IL-2 DC IFN  AutoAg Apoptosis + Immune Complexes

5. American College of Rheumatology Criteria For Lupus Antinuclear Antibody 95% Immunologic Disorder 70% (aDNA, LE prep, aSm, lupus anticoagulant Hematologic Disorder 10% Neurologic Disorder 10% Renal Disorder 60% Malar Rash Serositis Arthritis Oral Ulcers Photosensitivity Discoid Rash

6. Neuropsychiatric (NPS) lupus Why does it happen? NO SINGLE PATHOGENIC MECHANISM Primary Manifestations of the Disease Secondary Complications of the Disease or Therapy Coincidental

8. Neuropsychiatric (NPS) lupus SEIZURES Generalized: whole body affected Partial: only one part or side of the body is affected Complex change in level of consciousness Simple (focal) no change in level of consciousness May present with: Twitching or shaking Temporary abnormal sensations Visual disturbances

10. Neuropsychiatric (NPS) lupus HEADACHE An organic basis for the headaches in SLE is suggested by the sudden development in someone previously free of headaches, associated with Neurologic changes or changes in personality. Migraine and tension Headaches are the most common type of presentation. Migraine: Throbbing or pounding pain Nausea and vomiting Scalp tenderness Sensitivity to light or sound Worsening of pain with movement Visual disturbances Dizziness or vertigo Tension headache Pressing/tightening (nonpulsating) quality, located on both sides of the head Mild or moderate intensity Not aggravated by routine physical activity No nausea or vomiting Possible sensitivity to light or sound but not both

12. Neuropsychiatric (NPS) lupus Neurocognitive Dysfunction Manifested by impairments in mental activities Memory Judgment Abstract Thinking Simple/ Complex Attention Language Psychomotor speed

13. Neuropsychiatric (NPS) lupus Psychosis Characterized by: Presence of Delusions Presence of Hallucinations False belief despite evidence to the contrary Perceptual experience occurring in the absence of external stimuli.

14. Neuropsychiatric (NPS) lupus Pathogenesis Vascular Abnormalities Noninflamatory Vasculopathy Vasculitis Thrombosis Autoantibodies Inflammatory Mediators Antineuronal antibodies Antiribosomal P antibodies Antiphospholipid antibodies IL-2 IL-6 IL-10 IFN- α TNF- α Matrix Metalloproteinase

17. Neuropsychiatric (NPS) lupus Diagnosis Predominantly fixed lesions in the periventricular and Subcortical White Matter Focal Neurologic Disease More Sensitive than CT Scan and T1- Weighted MRI for detecting Abnormalities in NP-SLE T2- Weighted MRI : Findings: Diffuse Neurologic Disease Transient Subcortical White Matter Lesions and patchy Hyperintensities in the Gray Matter

18. Systemic lupus erythematosus: brain (MRI)

19. Systemic lupus erythematosus: brain (MRI)

20. Neuropsychiatric (NPS) lupus Diagnosis CT SCAN Findings: Detects structural and focal abnormalities Brain atrophy

21. Neuropsychiatric (NPS) lupus Diagnosis SEROLOGIC STUDIES Antiphospholipid ANTIBODIES ASSOCIATION CVA, Vascular Dementia, Seizures, Thromboses, headache, Chorea, Transverse Myelitis Antiribosomal P Psychosis, Severe depression Antineuronal, anti-neural-tissue-specific, anti-N-mrthyl-D-aspartate receptor (NMDA) Organic Brain Syndrome, Cognitive Dysfunction

23. Neuropsychiatric (NPS) lupus Management Chronic Anticoagulation Therapy STROKE SEIZURE Phenytoin & Barbiturates Carbamazepine – Clonazepan – Valproic Acid - Gabapentin NEUROPATHY High Doses Corticosteroids

24. Alternative Approach: Capitalize on information gained from the study of the pathogenesis of the disease.