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.
