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

Ordering Guidance

This test should be ordered in patients with suspected neuroinvasive Lyme disease. It is preferred for diagnosis of neuroinvasive Lyme disease over testing of spinal fluid (CSF) by immunoblot for IgM and IgG class antibodies to Borrelia species associated with Lyme disease. This test can help distinguish true intrathecal synthesis of antibodies to Lyme disease in the CSF, indicating neuroinvasive infection, versus antibody presence due to passive diffusion through the blood-brain barrier or, possibly, due to blood contamination of the CSF as a result of a traumatic lumbar puncture.


For Lyme testing on serum, order LYME / Lyme Disease Serology, Serum.

Additional Testing Requirements

Although a small percentage of patients with neuroinvasive Lyme disease may be seronegative, it is recommended that all patients tested by this assay also have standard 2-tiered testing for Lyme disease performed (LYME / Lyme Disease Serology, Serum).

Specimen Required

Both spinal fluid (CSF) and serum are required for this test. CSF and serum must be collected within 24 hours (maximum) of each other.


Specimen Type: Spinal fluid

Container/Tube: Sterile vial

Specimen Volume: 1.2 mL

Collection Instructions:

1. A spinal fluid (CSF) sample of 1.2 mL needs to be collected within 24 hours of the serum specimen, preferably at the same time.

2. Label vial as spinal fluid or CSF.

3. CSF aliquot should be from the second, third, or fourth CSF vial collected during the lumbar puncture.

Do not submit CSF from the first vial due to the possibility of blood contamination, which will cause specimen rejection.

4. Band specimens together.


Specimen Type: Serum

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1.2 mL

Collection Instructions:

1. A serum sample of 1.2 mL needs to be collected within 24 hours of the spinal fluid specimen, preferably at the same time.

2. Centrifuge and aliquot serum into a plastic vial.

3. Label as serum.

4. Band specimens together.

Useful For

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


Profile Information

Test ID Reporting Name Available Separately Always Performed
LNBAC Lyme CNS Infection IgG Screen, CSF No Yes
LNBAS Lyme CNS Infection IgG, S No No

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
LNBAI Lyme CNS Infection IgG, Ab Index No No

Testing Algorithm

This test begins with IgG screening of the spinal fluid 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:

-Lyme Neuroborreliosis Diagnostic Algorithm

-Acute Tick-Bourne Disease Testing Algorithm

-Meningitis/Encephalitis Panel Algorithm

Method Name

Enzyme-Linked Immunosorbent Assay (ELISA)

Reporting Name

Lyme CNS Infection IgG w/ AI Reflex

Specimen Type


Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
CSF Refrigerated (preferred) 11 days
  Frozen  35 days
Serum Refrigerated (preferred) 11 days
  Frozen  35 days

Clinical Information

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 Borrelia afzelii and Borrelia 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, 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 Centers for Disease Control and Prevention. Briefly, the LYME test includes testing of serum specimens by an anti-Bbsl antibody enzyme-linked immunosorbent assay, 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



Reference values apply to all ages.



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.



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.

Clinical Reference

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 Microbiol. 2016;54(5):1191-1196

5. Theel ES, Aguero-Rosenfeld ME, Pritt B, Adem PV, Wormser GP: Limitations and confusing aspects of diagnostic testing for neurologic Lyme disease in the United States. J Clin Microbiol. 2019 Jan 2;57(1): e01406-18. doi: 10.1128/JCM.01406-18

Day(s) Performed

Monday, Wednesday, Friday

Report Available

Same day/1 to 4 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


86618 x2 - if applicable

82040 - if applicable

82042- if applicable

82784 x2 - if applicable

LOINC Code Information

Test ID Test Order Name Order LOINC Value
LNBAB Lyme CNS Infection IgG w/ AI Reflex 92815-0


Result ID Test Result Name Result LOINC Value
LNB1 Lyme CNS Infection IgG, CSF 92813-5
LNBAS Lyme CNS Infection IgG, S 92814-3
LNB2 Lyme CNS Infection IgG Interp 69048-7


If not ordering electronically, complete, print, and send Infectious Disease Serology Test Request (T916) with the specimen.

Mayo Clinic Laboratories | Microbiology and Infectious Disease Catalog Additional Information:

mml-tickborne, mml-mbid-cnsinfections