SLE y học

CENTRAL NERVOUS SYSTEM INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS: MAGNETIC RESONANCE IMAGING AND Simone Appenzeller CEREBROSPINAL FLUID ANALYSIS State University of CampinasUNICAMP, Campinas, Brazil Introduction    Central nervous system (CNS) manifestations occur in up to 70% of SLE patients, depending on criteria applied for diagnosis Symptoms are diverse Secondary causes must be excluded – – – – Hypertension Infections Metabolic abnormalities Drug toxicity Introduction  Pathogenesis: – Autoantibodies and cytokine mediated neuronal dysfunction – Intracranial angiopathy – Coagulopathy Introduction   Magnetic resonance imaging is considered gold standard for diagnosis of anatomic brain abnormalities Findings are diverse – –  Cerebral atrophy White matter lesions Poor clinical correlations Introduction Neuroimage 2007;34(2):694-701 Objective  To evaluate cerebrospinal fluid (CSF) and MRI findings in SLE with active and inactive CNS involvement Inclusion criteria  30 SLE with CNS manifestations (ACR, 1999) – Active – Inactive  Drug free state or stable low doses of immunosuppressive therapy for at least months (10 mg of prednisone or equivalent, 100 mg/day azathioprine)  Controls with similar age and gender distribution – – No chronic disease CSF: mielography CT Exclusion criteria  Not able to undergo MRI exams – Claustrophobia, pacemaker and prosthetic valves  Previous clinical conditions that could influence cerebral atrophy – – – – – – –  history of stroke epilepsy arterial hypertension diabetes mellitus alcohol and drug abuse renal insufficiency and malignancy Patients who fulfilled the ACR criteria for Sjogren syndrome 10 patients excluded CSF  CSF (10 mL) samples: – CSF leukocyte count – IgG synthesis and – oligoclonal IgG bands  Paired samples of serum and CSF were stored at 80º C  All measures were made at a single occasion in order to minimize the intra assay variability  IgG and albumin: – measured by nephelometry (BNII; Dade Behring, Marburg, Germany), and – Blood-brain barrier function: CSF albumin/serum albumin – Intrathecal synthesis: Link Indexes (LI):  CSF IgG/CSF albumin/serum albumin  Oligoclonal IgG bands: – identified by isoelectrofocusing CSF  The IL12, IFNg, TNFa, and IL10: – quantified using commercial kits from Biosource International, Nivelles, Belgium – Intratecal synthesis: serum albumin/CSF albumin*CSF Il12/serum Il12 MRI findings  SLE patients: – Atrophy: (25%) – Hyperintense white matter lesions: 12 (60%) – Demyelinating lesions: (15%) No correlation to clinical findings  Controls: all normal MRIs MRI findings Localization Number of lesions Periventricular 12 Basal ganglia/ internal capsule Callosal/ subcallosal Juxta cortical 22 Brain stem 15 Cerebral cortex 19 578 Cerebral Volume P=0,002 SLE Controls Cerebral Volume 20000 P0,05 15000 10000 5000 0.5 SLE 1.0 w/inactive CNS 1.5SLE w/ 2.0 active CNS CNS 2.5 3.0 Controls 3.5 Serum findings 1500 1500 P