Lyme CNS Infection IgG Screen, CSF
Lyme CNS Infection IgG, S
Reflex test: Lyme CNS Infection, IgG Ab Index
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.
Aiding in the diagnosis of neuroinvasive Lyme disease or neuroborreliosis due to Borrelia species associated with Lyme disease (eg, B. burgdorferi, B. garinii, or B. afzelli).
This test should be ordered in patients with suspected neuroinvasive Lyme disease.
Although a small percentage of patients with neuroinvasive Lyme disease may be seronegative, it is recommended that all patients test by the Lyme Antibody Index assay also have standard 2-tiered testing for Lyme disease performed on serum.
This test compares the level of IgG antibodies to Lyme disease-causing Borrelia species in spinal fluid (CSF) and serum. The level of anti-Borrelia species IgG is normalized to total IgG and albumin in CSF and serum.
This test can help identify whether the presence of IgG to Borrelia species in the CSF is due to true intrathecal antibody synthesis, suggesting neuroinvasive Lyme disease, 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.
Both cerebrospinal fluid (CSF) and serum are required for this test. CSF and serum must be collected within 24 hours (maximum) of each other.
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.
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. Label as serum.
3. Band specimens together.
CSF contaminated with blood
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 Centers for Disease Control and Prevention (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.
False-reactive results may occur in patients with syphilis or Leptospira infections. Patient management decisions should not be made on a single reactive result.
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 (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 Centers for Disease Control and Prevention. Briefly, the LYME test includes testing of serum specimens by an anti-Bbsl antibody enzyme-linked immunosorbent assay (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 (AI) 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 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.