when your head hurts and your memory fails
DESCRIPTION
A Presentation by Petros Efthimiou, MD at Lincoln Hospital, Bronx, New YorkTRANSCRIPT
When Your Head Hurts and When Your Head Hurts and Your Memory Fails- Is It Your Memory Fails- Is It
Your Lupus?Your Lupus?
Petros Efthimiou, MD, FACR,Petros Efthimiou, MD, FACR,Lincoln Medical and Mental Health CenterLincoln Medical and Mental Health Center
Assistant Professor of Medicine,Assistant Professor of Medicine,Weill Cornell Medical College,Weill Cornell Medical College,
New York, NYNew York, NY
LUPUSLUPUS
CHRONICCHRONIC
AUTOIMMUNEAUTOIMMUNE
The body’s autoimmune system (“defense")
attacks ITSELF
Skin
Kidney
Lung
Heart
Joints
Blood
Nervous System
Progressive
Long Standing
MULTISYSTEMIC
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
inci
den
ce
1950 2000
10
5
2
Epidemiology of SLEEpidemiology of SLE
T Cell
Abnormal Adhesion Molecule and Chemokine Expression
Tissue Specific PathologyAPC
B7
MHC
FcR
CR RES
AutoAb
DrugsUVInfectious Agents
Genetic Background
Estrogens
B CellIncreased Help
Decreased Cytotoxicity
Altered Cytokine Production
IL-6, IL-10 IL-2
DC
IFN
AutoAg
Apoptosis+ Immune
Complexes
How Does Lupus happen?
American College of Rheumatology American College of Rheumatology Criteria For LupusCriteria For Lupus
Antinuclear Antibody95%
Immunologic Disorder
70%(aDNA, LE prep, aSm,
lupus anticoagulant
Hematologic Disorder
10%
Neurologic Disorder
10%
Renal
Disorder60%
Malar Rash
Serositis
Arthritis
Oral Ulcers
Photosensitivity
Discoid Rash
Neuropsychiatric (NPS) lupusNeuropsychiatric (NPS) lupus
Why does it happen?Why does it happen? NO SINGLE PATHOGENIC MECHANISMNO SINGLE PATHOGENIC MECHANISM
Primary Manifestations Primary Manifestations
of theof the DiseaseDiseaseSecondary Complications Secondary Complications of the Disease or Therapyof the Disease or Therapy
Coincidental
Neuropsychiatric (NPS) lupusNeuropsychiatric (NPS) lupus
NeurologicNeurologic
SeizuresSeizures StrokeStroke HeadacheHeadache Peripheral neuropathyPeripheral neuropathy Movement disordersMovement disorders Transverse myelitisTransverse myelitis Cranial neuropathyCranial neuropathy
PsychiatricPsychiatric
Neurocognitive Neurocognitive dysfunctiondysfunction
Organic brain syndromeOrganic brain syndrome PsychosisPsychosis PsychoneurosisPsychoneurosis
Neuropsychiatric (NPS) lupusNeuropsychiatric (NPS) lupus
SEIZURES
Generalized:whole body affected
Partial: only one part or side
of the body is affected
Complexchange in level
of consciousness
Simple (focal) no change in level of consciousness
May present with:Twitching or shaking
Temporary abnormal sensations Visual disturbances
Neuropsychiatric (NPS) lupusNeuropsychiatric (NPS) lupus
STROKE
May present with:
Sudden numbness or weakness especially on one side of the body with an associated tingling sensation Sudden confusion or trouble speaking or understanding
Sudden trouble seeing
Sudden trouble walking, dizziness, loss of balance or coordination
Sudden severe headache
Neuropsychiatric (NPS) lupusNeuropsychiatric (NPS) lupus
HEADACHE
An organic basis for the headaches in SLE is suggested by the sudden developmentin 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 disturbancesDizziness or vertigo
Tension headachePressing/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
Neuropsychiatric (NPS) lupusNeuropsychiatric (NPS) lupus
PERIPHERAL NEUROPATHY
Polyneuropathy Mononeuropathy
May present as:Temporary numbness, tingling, and pricking sensations (paresthesia) Sensitivity to touch Muscle weakness Burning pain (especially at night) Muscle wasting Paralysis Organ or gland dysfunction. Difficulty digesting food, maintaining safe levels of blood pressure, sweat normally, or experience normal sexual function.
Mononeuritis Multiplex
Neuropsychiatric (NPS) lupusNeuropsychiatric (NPS) lupusNeurocognitive Neurocognitive
DysfunctionDysfunction
Manifested by impairments in mental activities
Memory JudgmentAbstract Thinking
Simple/ ComplexAttention
Language
Psychomotorspeed
Neuropsychiatric (NPS) lupusNeuropsychiatric (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.
Neuropsychiatric (NPS) lupus Neuropsychiatric (NPS) lupus PathogenesisPathogenesis
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
Neuropsychiatric (NPS) lupus Neuropsychiatric (NPS) lupus DiagnosisDiagnosis
STEPS:STEPS:Confirm diagnosis of LupusConfirm diagnosis of Lupus ACR Criteria
History and Physical History and Physical ExaminationExamination
Exclude systemic illness andExclude systemic illness andmedications as confounding variablesmedications as confounding variables
Use of Diagnostic tools for Specific Symptoms or SignsUse of Diagnostic tools for Specific Symptoms or Signs
Neuropsychiatric (NPS) lupus Neuropsychiatric (NPS) lupus DiagnosisDiagnosis
Diagnostic tools for Specific Symptoms or SignsDiagnostic tools for Specific Symptoms or Signs
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 Differentiate
s organic from
psychosocia
l disease
Neuropsychiatric (NPS) lupus Neuropsychiatric (NPS) lupus DiagnosisDiagnosis
Predominantly fixed lesions in the periventricular and Subcortical White Matter
Focal Neurologic DiseaseFocal Neurologic Disease
More Sensitive than CT Scan and T1- Weighted MRI More Sensitive than CT Scan and T1- Weighted MRI for detecting Abnormalities in NP-SLEfor detecting Abnormalities in NP-SLE
T2- Weighted MRIT2- Weighted MRI::
Findings:
Diffuse Neurologic DiseaseDiffuse Neurologic Disease Transient Subcortical White Matter Lesions and patchyHyperintensities in the Gray Matter
Systemic lupus erythematosus: Systemic lupus erythematosus: brain (MRI)brain (MRI)
Systemic lupus erythematosus: Systemic lupus erythematosus: brain (MRI)brain (MRI)
Neuropsychiatric (NPS) lupus Neuropsychiatric (NPS) lupus DiagnosisDiagnosis
CT SCAN
Findings:
Detects structural and focal abnormalities
Brain atrophy
Neuropsychiatric (NPS) lupus Neuropsychiatric (NPS) lupus DiagnosisDiagnosis
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-aspartatereceptor (NMDA)
Organic Brain Syndrome, Cognitive Dysfunction
Treatment of SLE-SummaryTreatment of SLE-Summary
I.I. CorticosteroidsCorticosteroidsII.II. Antimalarials (Plaquenil)Antimalarials (Plaquenil)III.III. Traditional DMARDs (AZA, Methotrexate, etc)Traditional DMARDs (AZA, Methotrexate, etc)IV.IV. CyclophosphamideCyclophosphamideV.V. - + CS: gold standard(changing)- + CS: gold standard(changing)
VI.VI. - best regimen unknown- best regimen unknown
VII.VII. MMF (Cellcept)MMF (Cellcept)
VIII.VIII. -encouraging short term results-encouraging short term results
IX.IX. Anti-B cell strategiesAnti-B cell strategies
X.X. Stem-Cell transplantationStem-Cell transplantation
Neuropsychiatric (NPS) lupus Neuropsychiatric (NPS) lupus ManagementManagement
Chronic AnticoagulationTherapy
STROKE
SEIZURE
Phenytoin & Barbiturates
Carbamazepine – Clonazepan – Valproic Acid - Gabapentin
NEUROPATHY High Doses Corticosteroids
Alternative Approach:Alternative Approach:
Capitalize on information gained Capitalize on information gained from the study of the from the study of the
pathogenesis of the disease.pathogenesis of the disease.
Possible Biologic Interventions in Possible Biologic Interventions in SLESLE
T cell TargetsT cell Targets Anti-CD3Anti-CD3 Anti-CD4Anti-CD4 Anti-CD40LAnti-CD40L CTLA4-IgCTLA4-Ig
B Cell TargetsB Cell Targets Anti-CD20Anti-CD20 Anti-CD22Anti-CD22 Anti-B7Anti-B7 Anti-BlysAnti-Blys TACI-IgTACI-Ig LJP394LJP394
Cytokine TargetsCytokine Targets Anti-IFN (Anti-IFN ( or or )) Anti-TNF Anti-TNF Anti-IL6-RAnti-IL6-R Anti-IL-10Anti-IL-10
Complement TargetsComplement Targets Anti-C5Anti-C5 C3 convertase inhibitor (Crry-Ig)C3 convertase inhibitor (Crry-Ig)
T Regulatory Cell TargetsT Regulatory Cell Targets CD4+CD25+ TcellsCD4+CD25+ Tcells
Stem Cell TransplantationStem Cell Transplantation
The Future in the Treatment of SLEThe Future in the Treatment of SLE
LimitationsLimitations
Lack of Lack of biomarkers/surrogate biomarkers/surrogate endpointsendpoints
Difficulty in Difficulty in conducting trials conducting trials (number of patients)(number of patients)
Heterogeneity of the Heterogeneity of the diseasedisease
Control group Control group Add-on studiesAdd-on studies
ExpectationsExpectations
Develop suitable Develop suitable biomarkersbiomarkers
Increase federal Increase federal funding for multi-funding for multi-center trialscenter trials
Increase Increase industry/angel fundingindustry/angel funding
Better understanding Better understanding of pathogenic of pathogenic processesprocesses
New biologics/drugsNew biologics/drugs