Test Catalog

Test ID: LNBAB    
Lyme Central Nervous System Infection IgG with Antibody Index Reflex, Serum and Spinal Fluid

Useful For Suggests clinical disorders or settings where the test may be helpful

Aiding in the diagnosis of neuroinvasive Lyme disease or neuroborreliosis due to Borrelia species associated with Lyme disease (eg, B burgdorferi, B garinii, B afzelli)

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test begins with IgG screening of the spinal fluid (CSF) specimen. If the screen is negative, no additional testing will be performed.

 

If the screen is positive, the paired CSF and serum specimens will be used to establish the antibody index. In order to establish the antibody index, the paired serum and CSF samples (collected within 24 hours of each other) are tested on the same run using quantitative assays to determine levels for the following analytes:

1. Anti-Borrelia species IgG levels in CSF and serum

2. Total IgG in CSF and serum

3. Albumin in CSF and serum

 

These additional tests are necessary in order to normalize the level of anti-Borrelia antibodies to total IgG and albumin in the CSF and establish the antibody index ratio of anti-Borrelia antibodies in CSF-to-serum. This testing is performed at an additional charge.

 

The following algorithms are available in Special Instructions:

-Lyme Neuroborreliosis Diagnostic Algorithm

-Acute Tick-Bourne Disease Testing Algorithm

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Lyme disease is a multisystem and multistage tick-transmitted infection caused by spirochetal bacteria in the Borrelia burgdorferi sensu lato (Bbsl) complex. Nearly all human infections are caused by 3 Bbsl species; B burgdorferi sensu stricto (hereafter referred to as B burgdorferi) is the primary cause of Lyme disease in North America, while B afzelii and B garinii are the primary causes of Lyme disease in Europe and parts of Asia.

 

Lyme disease is the most commonly reported tick-borne infection in North America and Europe, causing an estimated 300,000 cases in the United States each year and 85,000 cases in Europe. The clinical features of Lyme disease are broad and may be confused with various immune and inflammatory disorders. The classic presenting sign of early localized Lyme disease caused by B burgdorferi is erythema migrans (EM), which occurs in approximately 80% of individuals. Other early signs and symptoms include malaise, headache, fever, lymphadenopathy, and myalgia. Arthritis, cardiac disease, and neurological disease may be later stage manifestations.

 

Neuroinvasive Lyme disease (NLD) can affect either the peripheral or central nervous system, with patients classically presenting with the triad of lymphocytic meningitis, cranial neuropathy (especially facial nerve palsy) and radiculoneuritis, which can affect the motor or sensory nerves, or both. These symptoms can occur in any combination or alone. Some patients may present with Bannwarth syndrome, which includes painful radiculoneuritis with variable motor weakness.

 

NLD should be considered in individuals presenting with appropriate symptoms who have had exposure to ticks in a Lyme endemic region of the United States, Europe or Asia. Patients meeting these criteria should be evaluated for the presence of anti-Bbsl antibodies in serum using the standard 2-tiered testing algorithm (LYME / Lyme Disease Serology, Serum ) as recommended by the CDC. Briefly, the LYME test includes testing of serum specimens by an anti-Bbsl antibody ELISA, followed by supplemental testing of all reactive samples using an immunoblot or western blot for detection of IgM- and IgG-class antibodies to Bbsl. Notably, the majority of patients with NLD will be seropositive in serum. Therefore, it is recommended that all patients tested by this assay also have LYME / Lyme Disease Serology, Serum performed. Results from these assays, alongside appropriate exposure history and clinical presentation, may be used to establish a diagnosis of NLD.

 

Spinal fluid (CSF) should not be tested for the presence of antibodies to Bbsl using the current 2-tiered testing algorithm as there are no interpretive criteria for assessment of anti-Bbsl IgM and IgG immunoblot banding patterns in CSF. Additionally, while the presence of antibodies to Bbsl in CSF may be due to true intrathecal antibody synthesis, thus indicating central nervous system (CNS) infection, antibodies may alternatively be present as a result of passive diffusion through the blood-brain barrier or due to blood contamination of CSF during a traumatic lumbar puncture.

 

The Lyme CNS infection antibody index is performed as a reflex and quantitatively measures the level of anti-Bbsl antibodies in CSF and serum, ideally collected within 24 hours of each other, and normalizes those levels to total IgG and albumin in both specimen sources. A positive Lyme CNS AI indicates true intrathecal antibody synthesis of antibodies to Bbsl, which alongside clinical and exposure history can be used to establish a diagnosis of NLD.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Negative

 

Reference values apply to all ages.

Interpretation Provides information to assist in interpretation of the test results

Negative:

No antibodies to Lyme disease causing Borrelia species detected in spinal fluid. A negative result in a patient with appropriate exposure history and symptoms consistent with neuroinvasive Lyme disease should not be used to exclude infection. Testing for antibodies to Lyme disease-causing Borrelia species in serum should be performed.

 

Reactive:

Supplemental testing to determine a Lyme central nervous system antibody index has been ordered. Diagnosis of neuroinvasive Lyme disease should not be established solely based on a reactive screening result.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A single negative result should not be used to exclude the diagnosis of neuroinvasive Lyme disease in a patient with appropriate exposure history and symptoms suggestive of infection. Testing of serum samples using the CDC recommended standard 2-tiered testing algorithm should be performed (LYME / Lyme Disease Serology, Serum).

 

False-negative results may be acquired in patients tested soon after infection, prior to the development of a detectable level of antibodies in the spinal fluid.

 

Falsely reactive results may occur in patients with syphilis or Leptospira infections. Patient management decisions should not be made on a single reactive result.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Wormser GP, Dattwyler RJ, Shapiro 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 2006 Nov 1;43(9):1089-1134

2. Halperin JJ, Shapiro ED, Logigian E, et al: Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2007 Jul 3;69(1):91-102

3. Halperin JJ: Neuroborreliosis. J Neurol 2017;264(6):1292-1297

4. Theel ES: The Past, Present and (Possible) Future of Serologic Testing for Lyme Disease. J Clin Micro 2016;54(5):1191-1196

5. Theel ES, Aguero-Rosenfeld ME, Pritt B, Adem PV, et al: Limitations and confusing aspects of diagnostic testing for neurologic Lyme disease in the United States. J Clin Micro 2018; epub ahead of print. doi: 10.1128/JCM.01406-18

Special Instructions Library of PDFs including pertinent information and forms related to the test