Lajmska neuroborelioza (LNB) nastaje hematogenim rasapom borelija u središnji živčani sustav (SŽS), a opisan je i prodor putem
perifernog živca. Razvija se serozni meningitis sa ili bez pareze kranijalnog živca što je prevladavajuća klinička slika. Najčešće je
zahvaćen n. facialis. Za razliku od Sjeverne Amerike, u Europi mogu biti zahvaćeni i drugi kranijalni živci, što se povezuje s prevaliranjem različitih vrsta borelija - u Europi najčešće B. garinii, B. bavariensis i B. afzelii, a u Sjevernoj Americi samo B. burgdorferi sensu stricto. Meningoradikulitis ili Bannwarthov sindrom tipična je slika LNB samo u Europi. Simptomi LNB većinom nisu tipični i mogu sličiti različitim neurološkim bolestima, pa dijagnozu često nije jednostavno definirati. Dijagnostika LNB mora uključivati
analizu likvora u kojem je značajan nalaz pleocitoze, što upućuje na serozni meningitis kojem je potrebno dokazati povezanost s borelijama. Mikrobiološka dijagnostika LNB obuhvaća kultivaciju, zahtjevnu i dugotrajnu metodu (9-12 tjedana) koja se radi isključivo u referentnim centrima, te molekularnu (PCR) i serološku dijagnostiku. Zbog malog broja borelija u likvoru kao i relativno
male količine likvora koja se šalje za analizu, molekularna je dijagnostika često lažno negativna. Stoga je serološka dijagnostika
ključna za dokazivanje LNB. Serologija se radi iz istovremeno uzetih uzoraka seruma i likvora u kojima se određuju specifična protutijela IgM i IgG te ukupni imunoglobulini i/ili albumini. Serum i likvor moraju se analizirati istom metodom u istim uvjetima kako bi se mogla odrediti intratekalna sinteza specifičnih protutijela, tj. izračunati indeks protutijela (antibody index, AI). Specifična protutijela u lajmskoj boreliozi nastaju relativno sporo, a s duljinom trajanja infekcije njihova količina se povećava. U ranoj LNB protutijela u likvoru ne može se uvijek otkriti, iako je prisutna pleocitoza. Kasnu LNB u pravilu prati jaki imunosni odgovor i uz pleocitozu često se nalazi pozitivan AI. Nakon infekcije, vremenom se likvor normalizira i pleocitoza se više ne nalazi, iako specifična protutijela u likvoru mogu ostati dugo prisutna, čak i uz pozitivan AI. Stoga je potrebno pratiti imunosni odgovor u krvi i likvoru od dana kada se bolesnik javi zbog simptoma i zatim nakon npr. jednog, tri, šest i dvanaest mjeseci, radi procjene korelacije nalaza i bolesti. Dijagnoza LNB mora biti u skladu s kliničkim, epidemiološkim i anamnestičkim podatcima te laboratorijskim nalazima, posebno u likvoru. LNB je 1) potvrđena ako uz kliničku sliku postoji pleocitoza i intratekalna sinteza specifičnih protutijela; 2) vjerojatna ako intratekalna sinteza nije potvrđena, a specifična protutijela su prisutna u krvi bolesnika; 3) LNB nije vjerojatna ako nema pleocitoze ili nema analize likvora, iako su prisutna specifična protutijela u krvi bolesnika, ali klinička slika i epidemiološka anamneza nisu karakteristični. CXCL13 je biljeg koji može biti koristan kao dodatni test premda nije specifičan za LNB - u likvoru je povišen i prati akutnu upalu. Ako postoji mogućnost, LNB bi trebalo potvrditi kultivacijom i molekularnom dijagnostikom. Interpretacija laboratorijskih i kliničkih nalaza zahtijeva znanje i iskustvo. Informacije se trebaju sagledati u skladu s okolnostima i specifičnosti bolesnika, tako da je svaki bolesnik poseban dijagnostički izazov.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
