Lyme Neuroborreliosis

Transcription

1 Lyme Neuroborreliosis Presenter: Elitza S. Theel, Ph.D., D(ABMM) Director of Infectious Diseases Serology Co-Director, Vector-Borne Diseases Service Line Department of Laboratory Medicine and Pathology at Mayo Clinic, Rochester, Minnesota MFMER 2 1

2 Disclosures None MFMER 3 Utilization Message As you view this presentation, consider the following important points regarding testing: How is the testing going to be used in your practice? When should the tests be used? How will results impact patient management? MFMER 4 2

3 Lyme Neuroborreliosis (LNB) Background 1,2,3 Borrelia burgdorferi sensu lato members (>15 species) B. brugdorferi sensu stricto, B. garinii, B. afzellii and ~4 others Transmitted through Ixodes sp. ticks Lyme disease can progress through multiple stages LNB is seen in ~3%-15% of untreated patients Symptoms develop 4-6 (range 1-12) weeks post infection Most common manifestations: Meningoradiculitis Lymphocytic meningitis Cranial nerve palsy ~35,000 cases reported ~300,000 cases estimated neurologic manifestations are too nonspecific to warrant a purely clinical diagnosis [of LNB]; laboratory support [for diagnosis] is required IDSA Guidelines MFMER 5 Diagnostic Testing Considerations for LNB Consider risk of infection first! Exposure history (eg, travel to a Lyme disease endemic area) Time of year (eg, lack of tick activity in winter) CSF findings Lymphocytic pleocytosis Mildly elevated protein Glucose levels are typically normal Testing for CXCL13 B-cell attractive chemokine Elevated in patients with LNB and in patients with other neuroinflammatory diseases Not recommended as an aid for diagnosis of LNB MFMER 6 3

4 Diagnostic Testing for LNB 4 Direct detection of Lyme Borrelia <10% of CSF cultures for B. burgdorferi are positive Culture no longer performed in hospital or reference laboratories RT-PCR for Lyme Borrelia Most PCR assays are laboratory developed tests and methods vary Clinical Specimen No. of studies % Median Sensitivity (range) % Specificity (range) Synovial Fluid (23 100) 100 Photo Credit: J. Haney Carr; Public Health Image Library EM Biopsy (30 89) CSF (5 100) Blood (0 100) Low Bacterial Burden Serology MFMER 7 Serologic Testing for Lyme Disease IgM Positive: Ab to 2/3 Bb proteins IgG positive: Ab to 5/10 Bb proteins MFMER 8 4

5 Challenges with Standard Serologic Testing for LNB 5,6 Limitations of testing for anti-b. burgdorferi serum antibodies only: Up to 15% of patients with LNB will be seronegative Background seropositivity rate is ~5% Standard two-tiered testing algorithm developed for evaluation of serum, not CSF Important to differentiate intrathecal antibody synthesis in the CNS versus passive diffusion of serum antibodies into the CSF across a compromised blood-csf barrier Intrathecal Antibody Synthesis CNS Blood CNS Passive Diffusion Blood MFMER 9 Use of a Lyme Antibody Index (AI) as an Aid for Diagnosis of LNB Normalizes the level of Borrelia-specific antibodies in CSF versus serum to total IgG in both specimen sources Lyme Disease Antibody Index :Summary of Formulas Quotient Bb IgG in Formula CSF Corrects for blood-csf permeability and U/mL (CSF) dilution factor(csf) CSQ abnormally elevated intrathecal Ab synthesis Borrelia (IgG) Bb IgG in serum AI = CSQ CSF & serum collected concurrently total (IgG) Total IgG in CSF Total IgG in serum Total IgG in CSF CSQ alb albumin in CSF albumin in serum Lyme AI is recommended by both the IDSA Total IgG in serum AI using CSQ total (IgG) CSQ Borrelia (IgG) CSQ total (IgG) and EFNS for diagnosis of LNB AI using CSQ lim. (IgG) CSQ Borrelia (IgG) CSQ lim. (IgG) Methods and AI criteria vary between labs Lyme Borrelia AI Interpretation: EFNS criteria for definite LNB: < 0.6 Invalid Neurologic symptoms consistent with LNB : Negative CSF pleocytosis (> 5 cells/µl) : Equivocal 1.6: Positive Elevated anti-borrelia AI U/mL (serum) dilution factor(serum) CSQ lim. (IgG) 0.93 [(CSQ alb ) ] 1/ MFMER 10 5

6 General Performance Characteristics of the Lyme AI 6,7,8 General performance characteristics Sensitivity: Disease Duration Sensitivity Specificity <6 weeks 70% 90% 6 weeks >95% >95% Remains positive post-treatment! Specificity: >95% False positives (e.g., neurosyphilis, other Borrelia spp., etc.) MFMER 11 Resources 1. Knudtzen FC, Andersen NS, Jensen TG, Skarphédinsson S: Characteristics and clinical outcome of Lyme neuroborreliosis in high endemic area, : a retrospective cohort study in Denmark. Clin Infect Dis Oct 16;65(9): Wormser GP, Dattwyler RJ, Shapior ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis Nov 1;43(9): Hinkley A, Connally N, Meek J, et al. Lyme disease testing by large commercial laboratories in the United States. Clin Infect Dis Sep 1;56(5) Ružić-Sabljić E, Cerar T: Progress in the molecular diagnosis of Lyme disease. Expert Rev Mol Diagn Jan;17(1):19-30 MFMER 12 6

7 Resources Continued 5. Halperin J, Logigian E, Finkel M, Pearl R: Practice parameters for the diagnosis of patients with nervous system Lyme borreliosis (Lyme disease). Quality Standards Subcommittee of the American Academy of Neurology. Neurology Mar; 46(3): Blanc F, Jaulhac B, Fleury M, et al. Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology Sep 4;69(10): Shah A, O Horo J, Wilson J, et al. An unusual cluster of neuroinvasive Lyme disease cases presenting with bannwarth syndrome in the Midwest United States. Open Forum Infect Dis Jan;5(1) 8. Mygland A, Ljøstad U, Fingerle V, et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol Jan;17(1)8-16, e1-4 MFMER 13 Questions or requests to: MMLHotTopics@mayo.edu For more information Visit MayoMedicalLaboratories.com or call Mayo Laboratory Inquiry at