Review article
SPECIFICITY OF LYME NEUROBORRELIOSIS DIAGNOSTICS
EVA RUŽIĆ-SABLJIĆ
; Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
OKTAVIJA ĐAKOVIĆ RODE
; Dr. Fran Mihaljević University Hospital for Infectious Diseases, Zagreb, Croatia; School of Dental Medicine, University of Zagreb, Zagreb, Croatia
*
* Corresponding author.
Abstract
Lyme neuroborreliosis (LNB) is caused by hematogenous spread of Borrelia into the central nervous system (CNS), but entry
through a peripheral nerve has also been described. Aseptic meningitis develops with or without cranial nerve palsy, which is
the predominant clinical presentation. Facial nerve is most frequently affected. Unlike North America, other cranial nerves can be
affected in Europe, which is related to the prevalence of different types of Borrelia. Borrelia (B.) garinii, B. bavariensis, and less
frequently B. afzelii are most common in Europe, while B. burgdorferi sensu stricto is the only North American strain. Meningoradiculitis or Bannwarth syndrome is a typical LNB presentation described only in Europe. The symptoms of LNB can resemble
various neurological diseases, which makes the diagnosis of LNB difficult. The diagnosis of LNB must include analysis of cerebrospinal fluid (CSF) in which pleocytosis is significant to support aseptic meningitis, and the association with Borrelia must
be proven. Microbiological diagnosis of LNB includes cultivation, a demanding and long-term method (9-12 weeks), which is
performed exclusively in reference centers, and molecular (polymerase chain reaction, PCR) and serological diagnostics. PCR
is often false-negative due to the low number of strands in the CSF. Thus, serological diagnosis remains crucial to confirm LNB.
Serology is performed on simultaneously collected serum and CSF samples, from which specific IgM and IgG antibodies, total
immunoglobulins and/or albumins need to be determined. Serum and CSF samples must be analyzed by the same method under the same conditions in order to assess the intrathecal synthesis of specific antibodies, i.e., to calculate the antibody index
in CSF (antibody index, AI). In patients with Lyme borreliosis, specific antibodies are produced relatively slowly, and their quantity increases with the duration of the infection. In early LNB, antibodies in the CSF are not always detectable while pleocytosis
is present. In late LNB, a strong immune response is present in the CSF, as well as pleocytosis, and a positive AI can be determined. Over time, CSF normalizes and pleocytosis is no longer detected, but CSF antibodies can remain present for a long period of time. Therefore, the immune response in the blood and CSF has to be monitored from the day the patient presented with
symptoms, and then, for example, at one, three, six and twelve months to assess the correlation of laboratory findings with the
disease. The diagnosis of LNB must be in accordance with clinical, epidemiological and history data and laboratory findings, especially in CSF. LNB is confirmed if the clinical picture is accompanied by pleocytosis and intrathecal synthesis of specific antibodies; LNB is probable if intrathecal synthesis is not confirmed while specific antibodies are present in the patient’s blood; and LNB is unlikely if there is no pleocytosis or no CSF analysis, although specific antibodies are present in the patient’s blood but the clinical picture and epidemiological history are not characteristic. If there is a possibility, LNB should be confirmed by culture and molecular diagnostics. CXCL13 is a marker that can be useful as an additional test, even though it is not specific for LNB as
it is elevated in CSF and observed during acute inflammation. Interpretation of laboratory and clinical findings in LNB requires
knowledge and experience. The findings should be interpreted in accordance with the circumstances and condition of the patient, and therefore each patient represents a special diagnostic challenge.
Keywords
Lyme neuroborreliosis; Borrelia burgdorferi; microbiological diagnostics; serological diagnostics; cerebrospinal fluid; cerebrospinal fluid antibody index
Hrčak ID:
310551
URI
Publication date:
22.11.2023.
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