Lyme neuroborreliosis (LNB) is a bacterial infection of the nervous system caused by spirochetes of the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) complex transmitted through bites from hard-shelled ticks of the Ixodes genus. With an approximate incidence in endemic countries between 3.2 and 6.3 per 100,000 persons/year (ed.: this is based on reported cases, which significantly underestimate the actual number of cases due to diagnostic difficulties). LNB is among the most frequent bacterial infections of the nervous system in Europe. LNB can cause a wide range of clinical neurological conditions, but most frequently presents as a subacute painful meningo-radiculitis with radiating pain from the spine to neck, extremities, thorax or abdomen, lymphocytic meningitis and/or cranial neuropathies, e.g., facial nerve palsy. If relevant antibiotic therapy is administered at an early stage of disease, LNB has a favorable long-term prognosis. However, delayed treatment is associated with an increased risk of residual symptoms and long-term sequelae. In countries where LNB is endemic, the average time from onset of neurological symptoms to diagnosis is typically around 3 weeks and has remained unchanged for the last four decades.
The cause of the diagnostic delay is multifactorial. Overlapping symptomatology with other more common diseases and the fact that only around 40% of patients with LNB report a tick bite and only 25% report a history of the classic skin rash erythema migrans make it less likely that physicians and patients consider LNB as a differential diagnosis, especially in the absence of facial nerve palsy.
However, even when LNB is clinically suspected at an early stage, analyses of cerebrospinal fluid (CSF) are currently required to establish the diagnosis. A lumbar puncture is an uncomfortable and expensive procedure that may require hospitalization and general anesthesia for children. Direct pathogen identification of B. burgdorferi s.l. with polymerase chain reaction (PCR), cultivation, or a combination has retained an exceedingly poor level of sensitivity both in blood and CSF despite several attempts to improve tools and techniques over the years. Further, the serological response in LNB is not detectable early in the course of disease, and antibodies may remain elevated for months to several years after full recovery of well-treated infections, making it impossible to discriminate between past and current infection. Furthermore, the B. burgdorferi s.l.-specific IgG and IgM in blood poorly predict nervous system involvement.
Thus, in order to reduce the diagnostic delay in LNB, the need for novel diagnostic tools is evident. Especially improved blood-based diagnostic tests would be extremely valuable as they would both potentially help reduce the diagnostic delay and offer a less invasive diagnostic tool.
(C) Lyme Borreliosis Foundation
