Lyme. Diagnosis .

Recognition of the symptoms of Lyme borreliosis is essential for prompt diagnosis and treatment.  

North American Lyme borreliosis generally manifests itself in three distinct clinical stages . Well-characterized neurological symptoms attributable to Lyme borreliosis include a primarily lymphocytic meningitis with or without painful cranial neuritis or polyradiculitis, encephalomyelitis, and peripheral neuropathy . 

Importantly, the clinical features of European Lyme borreliosis are different from those of North American disease . Erythema migrans is often slower spreading and appears less intensely inflamed in European cases and so may be less readily recalled by patients. The most common presentation of European Lyme neuroborreliosis is the triad of Banworth's syndrome (lymphocytic meningitis, cranial neuropathy, and painful radiculitis) rather than aseptic meningitis, which is seen more commonly in North American disease. Additionally, if left untreated, infections caused by European Borrelia genospecies are more likely to progress to chronic low-grade encephalitis. The most common clinical presentation of Lyme neuroborreliosis in children is peripheral facial nerve palsy, occurring in up to 71% of patients, followed by aseptic meningitis . Transverse myelitis, other cranial neuropathies, and ataxia have been rarely reported in children . Nonspecific symptoms such as fatigue, headache, and myalgias are common, and neurological examination was normal in 21% of children in one Dutch study .

Although the clinical features of our patient were highly suggestive of Lyme neuroborreliosis, investigations using diagnostic methods optimized for North American B. burgdorferi sensu stricto were largely negative. Specific testing for an immune response to European strains of the organism was suggestive but not conclusive for an acute infection. While our patient did have serum anti-Borrelia IgM antibodies detectable by Western blotting, she did not subsequently develop IgG seropositivity by this procedure. The VlsE C6 peptide used in the Immunetics ELISA is a conserved sequence found in Borrelia burgdorferi and the European genospecies B. afzelii and B. garinii, which provides an extremely Borrelia-specific assay. Positive results in a C6 ELISA often precede the development of a positive IgG Western blot (presence of five or more significant bands), which appears to be the case for this patient. While the absence of detectable Western blot IgG antibodies is quite surprising given the extent of neurological involvement at the time of presentation, the lack of a Western blot IgG antibody response after treatment is not. Studies have clearly demonstrated the negative impact of antimicrobial treatment on the production and subsequent detection of Western blot IgG antibodies . Alternatively, isolated elevations in anti-Borrelia IgM serum antibodies are present in up to 20% of children with other neurological diagnoses, including viral meningitis and headache .

There is no “gold standard” diagnostic test for Lyme neuroborreliosis. Direct culture of Borrelia species and PCR are of low sensitivity; therefore, laboratory diagnosis instead relies on the detection of anti-Borrelia antibodies. 

In North America, testing follows a two-step algorithm . Serum samples are screened for antibodies with an ELISA, a relatively sensitive, but not specific test. Confirmatory testing is then performed using Western blotting, which is specific, but not sensitive. The sensitivity of the two-step approach is well described to increase in later stages of the disease for both European - and North American -acquired borreliosis. While sensitivity may be less than 40% in cases of acute stage 1 Lyme disease, both retrospective  and prospective  studies from New England have found the sensitivity of the two-step approach to be 85% to 100% in cases of stage 2 acute neuroborreliosis. It has been noted that European Borrelia strains induce variable host antibody responses leading to reduced reliability of serum Western blot analysis . For the diagnosis of European Lyme neuroborreliosis, examination of the ratio of intrathecal to serum antibodies may be a more sensitive test (5, 6). In this case, diagnostic testing was initiated in accordance with Canadian Public Health Laboratory Network guidelines, which recommend consideration of CSF PCR, and not intrathecal antibody testing, in patients with neurological symptoms (8). Although determination of a CSF-to-serum antibody index is a more sensitive test for Lyme neuroborreliosis acquired in Europe, no residual CSF remained for this analysis.

Lyme neuroborreliosis should be considered in the differential diagnosis of new neurological symptoms in children and adults with histories of travel to areas of Lyme endemicity both within and outside of North America. The geographic site of potential exposure must be disclosed to the diagnostic laboratory so that the appropriate assays may be employed. Timely recognition and treatment are imperative in order to facilitate recovery and to prevent long-term sequelae.