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When Your Head Hurts And Your Memory Fails


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

Published in: Health & Medicine
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When Your Head Hurts And Your Memory Fails

  1. 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
  2. 2. LUPUS <ul><li>CHRONIC </li></ul><ul><li>AUTOIMMUNE </li></ul>The body’s autoimmune system (“defense&quot;) attacks ITSELF Skin Kidney Lung Heart Joints Blood Nervous System Progressive Long Standing MULTISYSTEMIC
  3. 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. 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. 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. 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
  7. 7. Neuropsychiatric (NPS) lupus <ul><ul><li>Neurologic </li></ul></ul><ul><li>Seizures </li></ul><ul><li>Stroke </li></ul><ul><li>Headache </li></ul><ul><li>Peripheral neuropathy </li></ul><ul><li>Movement disorders </li></ul><ul><li>Transverse myelitis </li></ul><ul><li>Cranial neuropathy </li></ul><ul><ul><li>Psychiatric </li></ul></ul><ul><li>Neurocognitive dysfunction </li></ul><ul><li>Organic brain syndrome </li></ul><ul><li>Psychosis </li></ul><ul><li>Psychoneurosis </li></ul>
  8. 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
  9. 9. Neuropsychiatric (NPS) lupus STROKE <ul><li>May present with: </li></ul><ul><li>Sudden numbness or weakness especially on one side of the body </li></ul><ul><li>with an associated tingling sensation </li></ul><ul><li>Sudden confusion or trouble speaking or understanding </li></ul><ul><li>Sudden trouble seeing </li></ul><ul><li>Sudden trouble walking, dizziness, loss of balance or coordination </li></ul><ul><li>Sudden severe headache </li></ul>
  10. 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
  11. 11. Neuropsychiatric (NPS) lupus PERIPHERAL NEUROPATHY Polyneuropathy Mononeuropathy <ul><li>May present as: </li></ul><ul><li>Temporary numbness, tingling, and pricking sensations (paresthesia) </li></ul><ul><li>Sensitivity to touch </li></ul><ul><li>Muscle weakness </li></ul><ul><li>Burning pain (especially at night) </li></ul><ul><li>Muscle wasting </li></ul><ul><li>Paralysis </li></ul><ul><li>Organ or gland dysfunction. </li></ul><ul><li>Difficulty digesting food, maintaining safe levels of blood pressure, sweat normally, or experience normal sexual function. </li></ul>Mononeuritis Multiplex
  12. 12. Neuropsychiatric (NPS) lupus Neurocognitive Dysfunction Manifested by impairments in mental activities Memory Judgment Abstract Thinking Simple/ Complex Attention Language Psychomotor speed
  13. 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. 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
  15. 15. Neuropsychiatric (NPS) lupus Diagnosis <ul><li>STEPS: </li></ul>Confirm diagnosis of Lupus ACR Criteria History and Physical Examination Exclude systemic illness and medications as confounding variables Use of Diagnostic tools for Specific Symptoms or Signs
  16. 16. Neuropsychiatric (NPS) lupus Diagnosis <ul><li>Diagnostic tools for Specific Symptoms or Signs </li></ul>STROKE CT Scan MRI Echocardiogram Blood tests (to assess for coagulopathy) Carotids Ultrasonography SEIZURE EEG NEUROPATHY EMG COGNITIVE ABNORMALITIES Psychometric Testing Differentiates organic from psychosocial disease MRI EEG Blood tests (to assess for coagulopathy) ANXIETY / DEPRESSION Psychometric Testing Differentiates organic from psychosocial disease
  17. 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. 18. Systemic lupus erythematosus: brain (MRI)
  19. 19. Systemic lupus erythematosus: brain (MRI)
  20. 20. Neuropsychiatric (NPS) lupus Diagnosis CT SCAN Findings: Detects structural and focal abnormalities Brain atrophy
  21. 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
  22. 22. Treatment of SLE-Summary <ul><li>Corticosteroids </li></ul><ul><li>Antimalarials (Plaquenil) </li></ul><ul><li>Traditional DMARDs (AZA, Methotrexate, etc) </li></ul><ul><li>Cyclophosphamide </li></ul><ul><li>- + CS: gold standard(changing) </li></ul><ul><li>- best regimen unknown </li></ul><ul><li>MMF (Cellcept) </li></ul><ul><li>-encouraging short term results </li></ul><ul><li>Anti-B cell strategies </li></ul><ul><li>Stem-Cell transplantation </li></ul>
  23. 23. Neuropsychiatric (NPS) lupus Management Chronic Anticoagulation Therapy STROKE SEIZURE Phenytoin & Barbiturates Carbamazepine – Clonazepan – Valproic Acid - Gabapentin NEUROPATHY High Doses Corticosteroids
  24. 24. Alternative Approach: Capitalize on information gained from the study of the pathogenesis of the disease.
  25. 25. Possible Biologic Interventions in SLE <ul><li>T cell Targets </li></ul><ul><li>Anti-CD3 </li></ul><ul><li>Anti-CD4 </li></ul><ul><li>Anti-CD40L </li></ul><ul><li>CTLA4-Ig </li></ul><ul><li>B Cell Targets </li></ul><ul><li>Anti-CD20 </li></ul><ul><li>Anti-CD22 </li></ul><ul><li>Anti-B7 </li></ul><ul><li>Anti-Blys </li></ul><ul><li>TACI-Ig </li></ul><ul><li>LJP394 </li></ul><ul><li>Cytokine Targets </li></ul><ul><li>Anti-IFN (  or  ) </li></ul><ul><li>Anti-TNF  </li></ul><ul><li>Anti-IL6-R </li></ul><ul><li>Anti-IL-10 </li></ul><ul><li>Complement Targets </li></ul><ul><li>Anti-C5 </li></ul><ul><li>C3 convertase inhibitor (Crry-Ig) </li></ul><ul><li>T Regulatory Cell Targets </li></ul><ul><li>CD4+CD25+ Tcells </li></ul><ul><li>Stem Cell Transplantation </li></ul>
  26. 26. The Future in the Treatment of SLE <ul><li>Limitations </li></ul><ul><li>Lack of biomarkers/surrogate endpoints </li></ul><ul><li>Difficulty in conducting trials (number of patients) </li></ul><ul><li>Heterogeneity of the disease </li></ul><ul><li>Control group </li></ul><ul><li>Add-on studies </li></ul><ul><li>Expectations </li></ul><ul><li>Develop suitable biomarkers </li></ul><ul><li>Increase federal funding for multi-center trials </li></ul><ul><li>Increase industry/angel funding </li></ul><ul><li>Better understanding of pathogenic processes </li></ul><ul><li>New biologics/drugs </li></ul>