Cranial nerve involvement, visual complications and headache syndromes in Lyme disease.

PURPOSE OF REVIEW: To provide a summary of the visual manifestations and cranial neuropathies seen in Lyme disease. RECENT FINDINGS: Lyme facial palsy remains the most common manifestation of Lyme neuroborreliosis. Recent investigations show likely evidence of vagal involvement in Lyme disease. SUMMARY: The literature on Lyme neuroborreliosis continues to evolve. Lyme disease can affect nearly any cranial nerve in addition to causing various headache syndromes. The most common manifestation is Lyme disease facial palsy, occurring in up to 5-10% of patients with documented Lyme disease. Headache syndromes are common in the context of facial palsy but can occur in isolation, and more specific headache syndromes including trigeminal and geniculate neuralgias can occur rarely. Signs and symptoms indicative of vestibulocochlear nerve involvement are relatively common, although it could be that these represent other vestibular involvement rather than a specific cranial neuropathy. Optic neuritis is a controversial entity within Lyme disease and is likely overdiagnosed, but convincing cases do exist. Physicians who see any cranial neuropathy, including optic neuritis, in an endemic area can consider Lyme disease as a possible cause.

Optic nerve involvement in patients with Lyme neuroborreliosis: an electrophysiological study.

PURPOSE: The aim of this neurophysiological study was to retrospectively analyze visual evoked potentials (VEPs) acquired during an examination for diagnosing optic nerve involvement in patients with Lyme neuroborreliosis (LNB). Attention was focused on LNB patients with peripheral facial palsy (PFP) and optic nerve involvement. METHODS: A total of 241 Czech patients were classified as having probable/definite LNB (193/48); of these, 57 were younger than 40 years, with a median age of 26.3 years, and 184 were older than 40 years, with a median age of 58.8 years. All patients underwent pattern-reversal (PVEP) and motion-onset (MVEP) VEP examinations. RESULTS: Abnormal VEP results were observed in 150/241 patients and were noted more often in patients over 40 years (p = 0.008). Muscle/joint problems and paresthesia were observed to be significantly more common in patients older than 40 years (p = 0.002, p = 0.030), in contrast to headache and decreased visual acuity, which were seen more often in patients younger than 40 years (p = 0.001, p = 0.033). Peripheral facial palsy was diagnosed in 26/241 LNB patients. Among patients with PFP, VEP peak times above the laboratory limit was observed in 22 (84.6%) individuals. Monitoring of patients with PFP and pathological VEP showed that the adjustment of visual system function occurred in half of the patients in one to more years, in contrast to faster recovery from peripheral facial palsy within months in most patients. CONCLUSION: In LNB patients, VEP helps to increase sensitivity of an early diagnostic process.

Diagnosis and management of suspected Lyme neuroborreliosis-related facial nerve palsy in children by paediatricians and general practitioners: a French survey.

The diagnosis and management of facial nerve palsy in children in Lyme borreliosis endemic area can be complex. The objective of this study was to evaluate the diagnosis and management of children with suspected Lyme neuroborreliosis (LNB)-related facial nerve palsy by general practitioners (GP) and paediatricians. We conducted a prospective national survey of clinical practice between September 2018 and January 2020. The questionnaire was intended for GPs and paediatricians. It is based on two distinct clinical situations (a 10-year-old child and a 5-year-old child) and contains questions about the diagnosis and management of facial nerve palsy in children with a recent tick bite. We obtained 598 responses (350/4125 paediatricians and 245/577 GPs). For a 10-year-old child with a facial nerve palsy in the context of a tick bite, more than half of GPs (52%) required a paediatric infectious consultation and 18% an admission to the hospital for lumbar puncture before the result of Lyme serology. The most prescribed antimicrobial therapies were amoxicillin (32%) and ceftriaxone (29%). For a 5-year-old child, there is no difference in the diagnosis of LNB and treatment except for doxycycline which was less prescribed. Concerning treatment, 18% of practitioners prescribed antibiotic therapy only (14% of GPs vs 21% of paediatricians, p = 0.09), and 17% prescribed antibiotic therapy combined with corticosteroids (14% of GPs vs 19% of paediatricians, p = 0.15). Finally, 93% of GPs and 75% of paediatricians reported to be uncomfortable with the diagnosis of LNB in children. CONCLUSION: Most participants were uncomfortable with the diagnosis of LNB. There was a limited difference in the management of LNB in children between GPs and paediatricians. WHAT IS KNOWN: • Lyme neuroborreliosis (LNB) is the second cause of facial nerve palsy in Europe, and its diagnosis is based on neurological symptoms and a lumbar puncture. However, no clinical criteria could be used to differentiate Bell's palsy and LNB. Moreover, data on the adjunctive corticosteroid treatment and outcome in patients with LNB-related facial nerve palsy are controversial. WHAT IS NEW: • Most participants were uncomfortable with the diagnosis of LNB. Its management was heterogeneous and most often not consistent with guidelines. Only 28% of participants requested a lumbar puncture in cases of suspected LNB, and 17% prescribed antibiotics with corticosteroids. • This study highlights the need for new specific guidelines in management (need for lumbar puncture and/or LB serology) and treatment (time to antibiotic initiation, probabilistic therapy, role of corticosteroids, doxycycline in children younger than 8 years) of LNB in children.

Rituximab leading to an atypical presentation of neuroborreliosis and false negative serology.

Two patients, recently treated with the B-cell-depleting monoclonal antibody, rituximab, had 2-3 months of progressive systemic symptoms; comprehensive investigations did not clarify the diagnosis. Transient radicular pain at disease onset had suggested neuroborreliosis, but seronegativity and an atypical clinical course made this unlikely. However, PCR identified Borrelia burgdorferi DNA in cerebrospinal fluid, establishing the diagnosis of neuroborreliosis. Both the clinical picture and the laboratory findings can be atypical in people with neuroborreliosis who have recently been treated with rituximab. In B-cell depleted patients living in endemic areas, one should suspect neuroborreliosis even when the typical symptoms are drowned out by more atypical symptoms; PCR should be used as a diagnostic supplement when the serological response is uncertain or absent.

Association of Persistent Symptoms after Lyme Neuroborreliosis and Increased Levels of Interferon-α in Blood.

Patients who have Lyme neuroborreliosis (LNB) might experience lingering symptoms that persist despite antibiotic drug therapy. We tested whether those symptoms are caused by maladaptive immune responses by measuring 20 immune mediators in serum and cerebrospinal fluid (CSF) in 79 LNB patients followed for 1 year. At study entry, most mediators were highly concentrated in CSF, the site of the infection. Those responses resolved with antibiotic therapy, and associations between CSF cytokines and signs and symptoms of LNB were no longer observed. In contrast, subjective symptoms that persisted after use of antibiotics were associated with increased levels of serum interferon-α (IFN-α), which were already observed at study entry, and remained increased at each subsequent timepoint. Highest IFN-α levels corresponded with severe disease. Although the infection serves as the initial trigger, sequelae after antibiotic therapy are associated with unremitting systemic IFN-α levels, consistent with the pathogenic role of this cytokine in interferonopathies in other conditions.

Olfactory reference plus Truman symptoms in one patient with Gilbert syndrome and antiphospholipid antibodies (Hughes disease) secondary to probable chronic Lyme neuroborreliosis.

After reading an article in the journal, regarding affective disorders in patients with rare illnesses, the authors would like to discuss a case of non-affective psychosis, presenting with olfactory reference and Truman symptoms, in a patient with three unusual conditions: Gilbert disease, Hughes syndrome and Lyme neuroborreliosis.

Lyme neuroborreliosis with antibodies in cerebrospinal fluid but not in serum.

BACKGROUND AND PURPOSE: To diagnose Lyme neuroborreliosis (LNB), cerebrospinal fluid (CSF) is tested for pleocytosis and intrathecal antibody production. The Dutch guideline for Lyme borreliosis indicates a lumbar puncture in the case of positive Borrelia serology or a strong clinical suspicion of LNB. This suggests that LNB might be underdiagnosed in patients with negative Borrelia serology and/or a minor clinical suspicion. The objective was to assess how often negative Borrelia serology occurs in the case of LNB. METHOD: A retrospective study was performed among patients with LNB visiting Gelre Hospitals between January 2007 and December 2020. Electronic medical records of patients with pleocytosis were reviewed to identify patients with LNB. Data were collected from medical records. RESULTS: Included were 127 patients with LNB, 58 of whom were children. In 67 patients Borrelia antibodies were present in both serum and CSF. In 53 of 67 patients there was intrathecal antibody production. In 28 patients there was intrathecal antibody production but serum antibodies were absent. Of patients with positive serology 77% had antibodies in CSF versus 83% of patients with negative serology (p = 0.435). Of patients with positive serology 61% had intrathecal antibody production versus 78% of patients with negative serology (p = 0.073). CONCLUSIONS: Twenty-eight LNB patients had intrathecal antibody production but no antibodies in serum. In this specific patient population, positive serum serology was not associated with antibodies in CSF nor with intrathecal antibody production. In Lyme endemic areas, in patients with symptoms suggestive for LNB, there is a need to lower the threshold for a lumbar puncture.

Plasma neurofilament light significantly decreases following treatment in Lyme neuroborreliosis and is not associated with persistent symptoms.

BACKGROUND AND PURPOSE: Currently there is an unmet need for a highly standardized blood biomarker test to monitor treatment response in Lyme neuroborreliosis (LNB). Differentiating between active or past infection is challenged by the relatively high frequency of persistent symptoms after the end of antibiotic treatment (estimated 15%-20%), the variable clinical course and the long-lasting Borrelia burgdorferi antibodies. The aim was therefore to evaluate plasma neurofilament light chain (pNfL) as a marker for disease activity in LNB. METHODS: This was a prospective cohort of definite LNB (N = 36) with blood samples and clinical evaluation including Glasgow Outcome Score at treatment initiation and 3 and 6 months' follow-up. Consecutive plasma was retrospectively analysed for the content of neurofilament light chain by Quanterix® kits (Simoa® NF-light Kit). RESULTS: Plasma neurofilament light chain significantly decreased between treatment initiation and the 3-month follow-up (median 83 pg/ml vs. median 14 pg/ml (25 pairs), p < 0.0001). No significant change was observed between 3 and 6 months' follow-up (median 14 pg/ml vs. median 12 pg/ml (21 pairs), p = 0.33). At treatment initiation 90% had pNfL above the age-defined reference compared to only 23% and 7% respectively at 3 and 6 months' follow-up. Decreases in pNfL were mirrored by increasing Glasgow Outcome Score. Reporting persistent symptoms at the 6-month follow-up was not associated with pNfL (relative change from reference or actual values) at baseline or at 6 months' follow-up. CONCLUSION: Plasma neurofilament light chain decreases following antibiotic treatment in LNB and is not associated with reporting persistent symptoms. It was therefore speculated that it may prove useful as a treatment response biomarker in LNB.

Lyme neuroborreliosis: An unusual case with extensive (peri)vasculitis of the middle cerebral artery.

Lyme disease is a tick-borne infection caused by Borrelia burgdorferi sensu latu. Neuroborreliosis is reported in approximately 10% of patients with Lyme disease. We report a patient with central nervous system (CNS) large vessel vasculitis, ischemic stroke, and tumefactive contrast-enhancing brain lesions, an unusual complication of neuroborreliosis. A 56-year-old man presented with headache and disorientation for 1 month. Magnetic resonance imaging revealed basal meningitis with rapidly progressing frontotemporoinsular edema and (peri)vasculitis. Transcranial ultrasound confirmed stenosed medial cerebral arteries. [18 F]GE-180 microglia positron emission tomography (PET) showed frontotemporoinsular signal more pronounced on the right. [18 F]FET amino acid PET demonstrated low tracer uptake, suggesting an inflammatory process. Cerebrospinal fluid (CSF) showed lymphomonocytosis (243/µl), intrathecal anti-Borrelia IgM (CSF/serum index = 15.65, normal < 1.5) and anti-Borrelia IgG (CSF/serum index = 6.5, normal < 1.5), and elevated CXCL13 (29.2 pg/ml, normal < 10 pg/ml). Main differential diagnoses of neurotuberculosis and perivascular CNS lymphoma were ruled out by biopsy and Quantiferon enzyme-linked immunosorbent assay. Ceftriaxone (28 days), cortisone, and nimodipine (3 months) led to full recovery. Neuroborreliosis is an important differential diagnosis in patients with CNS large vessel vasculitis and tumefactive contrast-enhancing brain lesions, mimicking perivascular CNS lymphoma or neurotuberculosis as main neuroradiological differential diagnoses. Vasculopathy and cerebrovascular events are rare in neuroborreliosis but should be considered, especially in endemic areas.

Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis: An updated systematic review.

BACKGROUND: Evidence-based recommendations for treatment of Lyme neuroborreliosis (LNB) should rely on the available literature. As new data emerges, close review and evaluation of the recent literature is needed to build evidence-based recommendations to inform clinical practice and management of LNB. We performed an update of a previous systematic review on treatment of LNB. METHODS: A systematic literature search of Medline and CENTRAL was performed for published studies from 2015 to 2023 to update a previous systematic review. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs; NRS were assessed using the ROBINS-I-tool. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data were integrated into an existing meta-analysis of the available literature. RESULTS: After screening 1530 records, two RCTs and five NRS with new and relevant data were additionally identified. Meta-analysis showed no statistically significant difference between doxycycline and beta-lactam antibiotics regarding residual neurological symptoms after 12 months. Meta-analysis showed no benefit of extended antibiotic treatment of LNB. Three NRS show no benefit for additional steroid use in LNB with facial palsy. DISCUSSION: Additional incorporated recent research corroborates existing guideline recommendations for treatment of LNB. New RCTs add to the certainty of previous analysis showing similar efficacy for doxycycline and beta-lactam antibiotics in LNB. Available evidence shows no benefit for extended antibiotic treatment in LNB. NRS do not suggest a role for steroids in facial palsy due to LNB.

Positive intrathecal anti-Borrelia antibody synthesis: what are the implications for clinical practice? Clinical features and outcomes of 138 patients in a French multicenter cohort study.

We aimed to describe the clinical characteristics, management, and residual symptoms (RS) in patients with definite and possible Lyme neuroborreliosis (LNB). We conducted a retrospective French multicenter cohort study (2010-2020). Cases of LNB were defined as clinical manifestations attributed to LNB and a positive Borrelia-specific intrathecal antibody index (AI) ("possible" LNB) and with pleocytosis ("definite" LNB). Risk factors of RS were determined using a logistic regression model. We included 138 adult patients with a positive AI. Mean age was 59.5 years (± 14.7). The median duration of symptoms before diagnosis was 1.0 [0.5-4.0] months. The most frequent manifestation was radicular pain (n = 79, 57%). Complete cerebrospinal fluid (CSF) leukocyte analysis was available in 131 patients, of whom 72 (55%) had pleocytosis. Patients with definite LNB had a shorter duration of symptoms (median 1.0 [0.5-2.6] vs. 3.0 [0.6-7.0] months, p < 0.01) and more radicular pain (74% vs 44%, p < 0.01) than patients with possible LNB. At the last visit (median duration of follow-up: 70 [30-175] days), 74/124 patients (59.7%) reported RS, mostly radicular pain (n = 31, 25%). In multivariate analysis, definite LNB (OR = 0.21 [0.05-0.931], p = 0.039) and duration of symptoms less than 3 months (OR = 0.04 [0.01-0.37], p = 0.005) were protective factors against RS at last follow-up. Our study highlights the challenges of LNB management, especially for patients with a positive AI without pleocytosis, questioning whether LB is still ongoing or not. Early diagnosis and treatment are important to improve outcomes and to lower potential RS.

A case report of unilateral cerebral vasculitis in adults: keep in mind Lyme neuroborreliosis.

BACKGROUND: Lyme neuroborreliosis (LNB), due to infection of the nervous system by the spirochete Borrelia burgdorferi, occurs in 15% of Lyme disease cases. However, neurovascular involvement is uncommon, especially recurrent stroke related to cerebral vasculitis in the absence of CSF pleocytosis. CASE PRESENTATION: We report the case of a 58-year-old man without any medical history who exhibited recurrent strokes in the same vascular territory (left internal carotid). Multiple biological screening, neuroimaging methods, and cardiovascular examinations failed to provide a diagnosis and treatment that could have prevented recurrences. Finally, B. burgdorferi sensu lato serology testing in blood and cerebrospinal fluid enabled diagnosis of LNB, in relation to a cerebral vasculitis. The patient experienced no further stroke after four weeks of doxycycline treatment. CONCLUSION: B. burgdorferi central nervous system infection must be considered in case of unexplained recurrent and/or multiple strokes, especially if cerebral vasculitis is suspected or demonstrated on neuroimaging.

Clinical manifestations of Lyme neuroborreliosis in children: a review.

Lyme neuroborreliosis (LNB) is a manifestation of Lyme disease involving the central and peripheral nervous system. It is caused by the spirochete Borrelia burgdorferi, transmitted by tick bites to a human host. Clinical signs of LNB develop after the dissemination of the pathogen to the nervous system. The infection occurs in children and adults, but the clinical manifestations differ. In adults, painful meningoradicultis is the most common manifestation of LNB, while children often present with facial nerve palsy and/or subacute meningitis. Subacute headache can be the only manifestation of LNB in children, especially during the summer months in Lyme disease-endemic regions. Non-specific symptoms, such as loss of appetite, fatigue or mood changes, may also occur, especially in young children. A high level of suspicion and early recognition of the various clinical manifestations presented by children with LNB is essential to minimize delay in diagnosis and optimize management. This review provides an overview of the spectrum of clinical manifestations, and discusses diagnosis, antibiotic treatment, and clinical outcome of LNB in children.

Clinical characteristics of Lyme neuroborreliosis in Dutch children and adults.

Lyme neuroborreliosis (LNB) is a tick-borne infection caused by Borrelia burgdorferi which can affect the nervous system in adults and children. The clinical course of LNB in adults is often different than in children. Studies comparing these differences are scarce. The aim of this study was to compare the clinical characteristics and outcome of LNB between children and adults. We performed an observational retrospective study among patients with LNB who presented at Gelre Hospital from 2007 to 2020 and had cerebrospinal fluid pleocytosis. Data were collected from electronic medical records. A total of 127 patients with LNB were identified. Included were 58 children (median age 8 years) and 69 adults (median age 56 years). The incidence of LNB was 3.2 per 100,000 inhabitants per year. The most common neurological manifestation in adults and in children was facial nerve palsy (67%). Unilateral facial nerve palsy was more prevalent in children (85%) than in adults (42%) (P < 0.001). Headache was also more prevalent in children (59%) than in adults (32%) (P = 0.003). (Poly)radiculitis was more prevalent in adults (51%) than in children (3%) (P < 0.001), encephalitis was not reported in children. In children, the time between symptom onset and diagnosis was 10 days versus 28 days in adults (P < 0.001). Complete recovery was reported significantly more often in children (83%) compared to adults (40%) (P < 0.001).    Conclusion: In a Lyme-endemic area in the Netherlands, LNB commonly presents with facial nerve palsy. Facial nerve palsy and headache are more prevalent in children, while radiculitis and encephalitis are mostly reported in adults. What is Known: • The clinical course of Lyme neuroborreliosis in adults is often different from children. . • The aim of this study was to compare the clinical characteristics and outcome of LNB between children and adults. What is New: • Lyme neuroborreliosis in the Netherlands commonly presents with facial nerve palsy. • Facial nerve palsy and headache are more prevalent in children than in adults. Radiculitis and encephalitis are mostly reported in adults.

Bilateral facial nerve palsy as a presentation of coexisting neuroborreliosis and post-acute COVID-19 syndrome.

Bilateral simultaneous facial nerve palsy is an extremely rare condition that may be induced by infection (bacterial, viral, or fungal) or noninfective causes (autoimmune, traumatic, or structural). The treatment depends on the underlying disorder, and, if it is introduced on time, the disease is in most cases completely reversible. We report on a patient with bilateral simultaneous facial nerve palsy without an obvious cause. The possible causes were SARS-CoV-2 infection and postvaccination syndrome. After we excluded the SARS-CoV-2 infection, a wide range of diagnostic tests were conducted. Magnetic resonance imaging after gadolinium intravenous application showed bilateral facial nerve enhancement. Serological tests revealed Borrelia burgdorferi, and the result was confirmed by an enzyme-linked immunosorbent assay (IgM positivity). After 14 days of antibiotic therapy, the symptoms resolved completely without sequelae. This report shows that the symptoms of bilateral simultaneous facial nerve palsy may completely resolve if thorough clinical investigation and an appropriate early treatment are applied.

Diagnosis of neuroborreliosis in the context of local seroprevalence: A chart review study and a methodological overview.

Background & objectives: In neuroborreliosis (NB) serology might objectively differentiate ongoing from past infection when the intrathecal space is involved. The hierarchy of the parallel serum-CSF (cerebrospinal fluid) methods is seldom discussed and remains elusive in daily practice. We compared the efficacy of certain methods and assessed the prevalence of anti-Borrelia antibodies in the local population. Methods: We summarized standard two-tier test results in all ELISA-reactive samples of patients with suspected NB (n=152) since 2017 and tested 122 unrelated sera for anti-Borrelia antibodies from central Hungary. Results: The most common central nervous system symptom was a cranial nerve palsy (27.6% of all subjects). CSF was available in 25 cases. A serum-CSF IgG-matched line immunoassay (LIA) detected intrathecal antibody production correctly in 6 of 8 samples when compared to the ELISA-based antibody-index (AI). Among the 122 random sera the prevalence of specific anti-Borrelia IgG antibodies (on LIA, not including anti-p41) were 6.8% above 30 and 10% above 60 years. Our results enable us to assume the predictive values of serological results according to the pretest probability of neuroborreliosis. Interpretation & conclusion: Our results suggest that recombinant antigen-based two-tier serology from solely the sera might have sufficient positive predictive value to verify NB in young individuals with characteristic anamnestic data in our region. When parallel serum-CSF testing is warranted, AI should have priority. IgG and albumin concentrations in the both serum and the CSF, the potential time of exposure and the nature and duration of symptoms form the bare minimal set of data for conclusive testing.

PROGRESSIVE PARAPARESIS IN A 66-YEAR-OLD MAN - A CASE STUDY.

The paper presents a case of progressive paraparesis in a 66-year-old man with no history of tick bite, who was finally diagnosed with neuroborreliosis on the basis of the performed tests. Proper diagnosis and introduction of causal treatment resulted in rapid improvement of the patient's condition.

Early identification of Lyme disease complications.

ABSTRACT: Complications of Lyme disease including Lyme arthritis, Lyme carditis, and Lyme neuroborreliosis, typically occur during the early disseminated and late phases of the disease. Clinicians must maintain a high index of suspicion so they can recognize and treat complications promptly. Early treatment with appropriate antibiotics often leads to improved clinical outcomes.

Unique Clinical, Immune, and Genetic Signature in Patients with Borrelial Meningoradiculoneuritis1.

Lyme neuroborreliosis (LNB) in Europe may manifest with painful meningoradiculoneuritis (also known as Bannwarth syndrome) or lymphocytic meningitis with or without cranial neuritis (peripheral facial palsy). We assessed host immune responses and the prevalence of TLR1 (toll-like receptor 1)-1805GG polymorphism to gain insights into the pathophysiology of these conditions. Regardless of LNB manifestation, most mediators associated with innate and adaptive immune responses were concentrated in cerebrospinal fluid; serum levels were unremarkable. When stratified by specific clinical manifestation, patients with meningoradiculoneuritis had higher levels of B-cell chemoattractants CXC motif chemokine ligand (CXCL) 12 and CXCL13 and T-cell-associated mediators CXCL9, CXCL10, and interleukin 17, compared with those without radicular pain. Moreover, these patients had a higher frequency of TLR1-1805GG polymorphism and more constitutional symptoms. These findings demonstrate that meningoradiculoneuritis is a distinct clinical entity with unique immune and genetic pathophysiology, providing new considerations for the study of LNB and borrelial meningoradiculitis.

Brain damage markers neuron-specific enolase (NSE) and S100B in serum in children with Lyme neuroborreliosis-detection and evaluation as prognostic biomarkers for clinical outcome.

Lyme borreliosis (LB) is the most common tick-borne infection in Europe, with Lyme neuroborreliosis (LNB) its second most frequent clinical manifestation. Prognostic factors for clinical outcomes in LNB have not been identified. Elevated serum levels of the brain damage markers neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have been associated with poor clinical outcomes in other disorders of the central nervous system. The aim of this study is to assess NSE and S100B in serum as prognostic biomarkers for clinical outcomes in paediatric LNB patients. Children evaluated for LNB (n = 121) in Sweden were prospectively included during 2010-2014, serum samples were collected on admission, and all children underwent a 2-month follow-up. Patients with pleocytosis and anti-Borrelia antibodies in cerebrospinal fluid (CSF) were classified as having LNB (n = 61). Controls were age- and gender-matched non-LNB patients (n = 60). NSE was elevated in 38/61 (62%) LNB patients and in 31/60 (52%) controls. S100B was elevated in 3/60 (5%) LNB patients and 0/59 (0%) controls. NSE and S100B concentrations did not differ significantly when comparing LNB patients with controls. No differences were found in the concentrations when comparing the clinical recovery of LNB patients at the 2-month follow-up. NSE was detectable in the majority of LNB patients and controls, whereas S100B was detectable in only a few LNB patients and no controls. NSE and S100B in serum cannot be recommended as prognostic biomarkers for clinical outcomes in children with LNB.