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The Clinical Spectrum of Lyme Neuroborreliosis
M Elamin, T Monaghan, G Mulllins, E Ali, G Corbett-Feeney, S OConnell, TJ CounihanDepartment of Neurology, University Hospital Galway, Newcastle Rd, Galway Abstract
Lyme disease is a multisystem infectious disease, endemic in parts of Europe, including the West of
Ireland. Neurological manifestions (neuroborreliosis) are variable. Presenting neurological
syndromes include meningitis, cranial neuropathies, myeloradiculitis and mononeuritis multiplex. A
lack of specificity in serological diagnosis may add to diagnostic confusion. We reviewed thirty
cases of acute Lyme disease in the West of Ireland and found neurological syndromes in 15 (50%),
with painful radiculopathy (12 patients; 80%) and cranial neuropathy (7 patients;46%) occurring
frequently. Neuroborreliosis needs to be considered in the differential diagnosis of these
neurological syndromes in the appropriate clinical context.
Introduction
Lyme disease is a multisystem infectious disease caused by the Borrelia spirochaete genus. The
predominant species in North America is Borrelia burgdorferi sensu stricto, and in Europe the
predominant species are B. afzelli and B. garinii. Deer and other mammals are the intermediate
. Lyme disease is the most frequently reported arthropodborne infection of the nervous system in Europe and the USA1. Erythema migrans (EM) is regarded as the most common clinical marker of infection and is estimated to occur in 60-80% of patients disease (neuroborreliosis; NB) comprise an array of both central and peripheral neurological syndromes, mimicking a variety of common disorders . Typical neurological presenting syndromes include include meningitis, cranial neuropathies (with a predilection for the facial nerve), myeloradiculitis and mononeuritis multiplex . Difficulties in the diagnosis and management of patients with Lyme NB may be compounded by a lack of specificity and sensitivity of serological Seroprevalence studies report the Republic of Ireland as having one of the highest rates of Lyme . Lyme disease is considered endemic in the West of Ireland studies have explored the clinical presentation and natural history of Lyme NB in Ireland therefore undertook a retrospective analysis of the clinical characteristics of Lyme NB in the Westof Ireland. We conducted a retrospective review of the clinical presentation of patients withserologically confirmed Lyme disease diagnosed over a five-year period at a single referral centrein the West of Ireland. We identified the proportion of patients presenting with NB, we define theneurological syndromes at presentation, and report the clinical outcomes.
Methods
The study population included those patients who had serological testing consistent with Lyme
disease, based on referrals to the Department of Medical Microbiology, University Hospital Galway.
The study period extended from January 1999 to August 2004. During that period, approximately 2100
sera were tested using the screening ELISA. A two-tier diagnostic process was utilized in accordance
, comprising an initial screening enzyme-linked immunosorbant assay (ELISA) for anti Borrelia antibodies. In those patients who had positive screening ELISA tests,antibody positivity was confirmed by a positive IgG and/or IgM immunoblot assay at the LymeBorreliosis Unit, Southampton, UK. We identified 42 samples over the sixty-six month study periodwith serology consistent with Lyme disease.
After obtaining Ethics Committee approval and written informed consent from the referring physician,we then obtained clinical data for 32 patients. Data was collected by chart review and includeddemographic characteristics, potential exposure to tick bite, clinical presentation and results ofimaging and cerebrospinal fluid analysis. Patients were included in the study in whom there was aclear temporal relationship between the onset of a clinical syndrome known to be associated withLyme disease, (such as EM) and serological testing. Exclusion criteria were equivocal serologicalresults or positive tests that were deemed to represent convalescence serology. Two patients wereexcluded; both had IgG anti B. burgdorferi antibodies but their clinical presentation and imagingstudies were compatible with alternative diagnoses (multiple sclerosis and brain neoplasm). Data onthe remaining 30 patients was analyzed as pooled data.
Results
Baseline characteristics
Antibody subtypes directed against B burgdorferi in the thirty patients included in the study were
detected as follows: seventeen patients (57%) had both IgM and IgG antibodies; six patients (20%)
exhibited anti IgM antibodies only, and seven patients (23%) had only IgG anti-Borrelia antibodies.
Patients ranged from 26 to 80 years of age, with a mean of 52.5 years; 60% were male. Twenty
patients (67%) were resident of western counties of Ireland. Only one patient was resident outside
the state. Recent travel outside Ireland was documented in seven cases. Nine patients (30%) had
documented potential exposure to heavily wooded areas due to occupation or leisure activities. A
history of tick bite was elicited in only one third of the patients. Lyme serology was requested by
the patients general practitioner in twelve cases, by a consultant physician in thirteen cases
and by a neurologist in five cases.
Clinical PresentationThe majority of patients (25/27, 93 %) presented between the months of May and October. Whiletwenty-two patients (71%) had a rash at presentation, only 43% of patients presented with EM rash.
Fatigue was a prominent symptom in more than half of the patients (16/30), but fever >38 degrees Cwas reported in only four patients (13%). Seven patients (23%) had polyarthralgia at presentation;one patient had anterior uveitis. None of the patients had cardiovascular symptoms.
Neurological ManifestationsFifteen patients (50%) had neurological manifestations at presentation (Table). The most commonsymptom was radiculitis (12/15 patients; 80%). Cranial neuropathy occurred in seven patients, amongwhom unilateral facial palsy was present in six patients (40% of patients with neurologicalmanifestations). Bilateral facial palsies were documented in only one patient. Four patients hadheadache at presentation. Psychiatric disturbances, in the form of marked irritability and reducedconcentration, were noted in one patient.
Laboratory Findings in NB patientsEleven patients with Lyme NB had both anti-Borrelia antibodies for IgM and IgG; two patients wereIgM positive only, and two were IgG positive only. Cerebrospinal fluid (CSF) analysis was carriedout in five of the fifteen patients with NB and was abnormal in all five (Table). All had raised CSFprotein levels ranging from 0.6 g / l to greater than 1g/l. Four had CSF pleocytosis (>6 white ), predominantly a lymphocytosis. Oligoclonal bands were present in one patient. Lyme serology in CSF was positive for IgM and IgG antibodies in the only patient in whom it wasrequested. MRI brain scans were abnormal in two out seven cases in which it was performed. In bothcases, the abnormalities found were considered to be incidental findings (acoustic schwannoma;hypertensive leukoencephalopathy).
Treatment and Follow upDoxycycline was used in three patients; seven patients received intravenous cefotaxime/ceftriaxone,and two patients received oral amoxicillin, one patient received vibramycin while treatment was notdocumented in two patients. Follow up of the fifteen patients with Lyme NB was as follows: fourpatients showed definite clinical improvement, defined as complete resolution of symptoms (three hadreceived intravenous ceftriaxone/cefotaxime and one had received oral doxycyline; five patientsshowed partial improvement or relapse (two patients received oral doxycyline, two received oralamoxicillin and one received oral vibramycin); five patients were lost to follow up and one patientwho had received only steroids showed no response.
Discussion
We identified forty-two patients with serological evidence of acute Lyme disease over a five-year
period presenting to a single referral laboratory in the West of Ireland. Fifty percent of the
patients on whom clinical data was available had evidence of Lyme NB. Both the incidence of Lyme
disease as well as the proportion of patients with NB in our study appears to be higher than in
. The first reported cases of Lyme disease in Ireland appeared in the late 1980s . The West of Ireland has been identified as a high-risk area because of high rates of sero-prevalence among asymptomatic adults ; the highest seroprevalence was documented in the western area of Portumna (8.7%) compared to a national average of 3.4% study, only 13 of 483 serum samples were seropositive for Lyme antibodies, mainly from patientsattending Dublin hospitals, but Galway area patients formed the second largest group despite its . Given the apparent high incidence of Lyme disease in Ireland, information regarding Lyme NB in this region is sparse. Reilly and Hutchinson in 1991 described theclinical presentation of six cases of NB diagnosed in Ireland over a 4 year period, five of whom contracted the disease in the West of Ireland . The authors recommended further epidemiological studies to establish the prevalence and pattern of infection with B. burgdorferi in Ireland. Thelarger number of patients in our study may reflect a combination of higher awareness amongphysicians, as well as more reliable serological diagnostic techniques.
The Clinical Spectrum of Lyme Neuroborreliosis The proportion of patients with Lyme NB in our cohort is high, amounting to 50% of patientspresenting with confirmed Lyme disease. Although estimates vary, previous studies in Ireland and Europe report rates of neurologic involvement in Lyme disease ranging from 18% -31% sensory-motor radiculitis and facial palsy were the two most common neurological presentations inthese patients; we have recently reported perineuritis as a pathological finding in one of this . Lymphocytic meningoradiculitis (Bannwarth’s syndrome) is a radicular neuralgia associated with a chronic lymphocytic pleocytosis in cerebrospinal fluid and frequently with unilateral orbilateral peripheral facial palsy) is one of the commonest neurological manifestations of Lyme disease in clinical studies conducted in Ireland and other parts of Europe in one of our patients was severe enough to prompt investigation for a cardiac cause. All patientswith Lyme facial palsy in our cohort had additional neurological symptoms, and 87% reportedconstitutional complaints. This highlights the fact that while NB may be responsible for up to 10% , Lyme disease should be considered in a patient with facial palsy when it is associated with other signs or symptoms of borreliosis.
A relatively small number of our patients had symptoms of meningism. Meningitis in NB seems to cause less pronounced meningitic symptoms than aseptic meningitis with symptoms suggestive of NB had a lumbar puncture and cerebrospinal fluid analysis; however, CSFwas abnormal in all of these cases. Oligoclonal bands were present in cerebrospinal fluid and notserum in one case. Current guidelines consider the presence of intrathecal specific antibodies asessential laboratory evidence for the diagnosis of early Lyme NB and the presence of specific CSF . Given the relatively high yield of CSF for identification of Lyme antibodies physicians should be encouraged to carry out CSF analysis in allpatients with symptoms suggestive of NB even in the absence of meningism.
This study has some inherent limitations due to its retrospective design and potential forascertainment bias. However the potential for overestimation of disease incidence through the use ofserology as part of patient selection is more than offset by the fact that only about 40-60% of patients with early disease EM have positive serology . Moreover, serology may not be requested in these patients as current guidelines recommend diagnosis and treatment of EM on clinical grounds However in patients in whom the duration of illness is 4 weeks or more, the sensitivity and specificity of IgG response is very high (range of 95%-99%) as determined by the 2 test approach and thus a single test (for IgG only) is usually sufficient for diagnosis if the clinical picture is . We believe our results indicate a relatively high incidence of neurological complications in patients with Lyme disease, particularly in patients with serologically confirmeddisease. There is a high incidence of Lyme NB among patients with Lyme disease in the West ofIreland, higher than that suggested by previous studies. The absence of a history of tick bite,potential exposure to ticks or EM is not reliable in the exclusion of the diagnosis. CSF analysisand serology testing is recommended in all suspected cases of neuroborreliosis, even in the absenceof meningeal symptoms.
Correspondence: TJ CounihanDepartment of Neurology, University Hospital Galway, Newcastle Rd, GalwayEmail: References
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The Clinical Spectrum of Lyme Neuroborreliosis

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