Lyme Neuroborreliosis: Known Knowns, Known Unknowns

John J. Halperin; Randi Eikeland; John A. Branda; Rick Dersch


Brain. 2022;145(8):2635-2647. 

In This Article


As in any nervous system infection, treatment requires organism-appropriate antimicrobials. Recommendations differentiate parenchymal (brain, spinal cord) CNS infection from all others. Parenteral treatment is recommended for the very rare parenchymal infections, not based on evidence but because other parenchymal CNS infections generally require such treatment to achieve therapeutic CNS concentrations. For all other LNB, choices include intravenous ceftriaxone, cefotaxime or penicillin G or oral doxycycline[9,60] for 14–21 days, with oral and parenteral regimens considered equally effective.

Although extensive evidence supports such treatment in clear-cut LNB, questions often arise when patients with other neurological or psychiatric disorders are found to have positive two-tier test results. Such patients raise two distinct questions: (i) do the benefits outweigh the risks of treating this particular patient for possible Lyme disease and, if so, how much treatment would be appropriate; and (ii) is a pathophysiological link between Lyme borreliosis and this neurological disorder plausible?

As detailed above, in CNS disorders without CNS inflammation, CNS LNB is extremely unlikely and aggressive antimicrobial treatment is usually not warranted. PNS involvement without CSF inflammation can be more challenging. If there is other evidence of Lyme borreliosis (EM, ACA, Lyme arthritis) recommended treatment regimens are reasonable. In less clear-cut instances this decision must consider the risk of misdiagnosis, of side effects and concerns about promoting antimicrobial resistance.