Initial symptoms and late complication in Lyme neuroborreliosis from the perspective of patients and relatives: a qualitative study.

BACKGROUND: Lyme borreliosis is by far the most common vector-borne infection in Western Europe. The most severe manifestation of Lyme borreliosis is Lyme neuroborreliosis (LNB). In LNB symptoms vary from mild to severe and may include late complications that involve both physical and/or neurocognitive constraints. An estimated 25-28% of the LNB population suffers from late complications. This study investigates patient and relative perspectives on everyday life with LNB symptoms, diagnosis, and treatment to identify areas for improvement of healthcare. METHODS: A focus group was conducted at Odense University Hospital, Denmark. The focus group comprised 16 participants, nine patients diagnosed with LNB who had been treated at the Clinical Center for Emerging and Vector-borne Infections, and seven relatives of the patients' choice. The focus group lasted 2 ½ hours and was audio recorded as well as documented in field notes. RESULTS: Data analysis was grounded in the conceptual framework of critical psychology and resulted in three main themes: (1) Burden of LNB symptoms in everyday life, (2) A break in the conduct of everyday life caused by LNB and (3) Need for transparent pathways to specialist knowledge. CONCLUSIONS: Before diagnosis and treatment, each patient reported varying degrees of non-treatable pain, and cognitive and/or musculoskeletal symptoms. Visible physical symptoms were rare. All patients had experienced that their bodily symptoms remained unaddressed throughout numerous encounters with the healthcare system. The course of LNB comes with a break in patients' everyday lives and self-understandings affecting their ability to work and manage everyday activities. Patients and relatives strongly recommend a specialised LNB clinic.

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.

Sensorineural hearing loss in Lyme neuroborreliosis.

BACKGROUND: Sensorineural hearing loss (SNHL) has been suggested to occur in patients with Lyme neuroborreliosis (LNB); however, a clear association has never been documented. The present study prospectively investigated the development of SNHL in patients admitted for treatment of LNB using distortion-product-oto-acoustic emissions (DPOAE) as a measure of cochlear function. METHODS: DOAE were measured in patients with LNB on the day of diagnosis, during treatment, and 30-60 days after discharge. Frequencies were categorized as Low (1, 1.5, 2 kHz), Mid (3, 4, 5 kHz), Mid-high (6, 7, 8 kHz), and High (9, 10 kHz). Pure Tone Audiometry (PTA3) was performed at discharge and 60 days after. Patients were treated with i.v. ceftriaxone or oral doxycycline for 14 days according to guidelines. RESULTS: DPOAE measurements were obtained in 25 patients with LNB at admission and in 18 patients at follow-up. Median age was 56 years (IQR, 48-64 years), and 16 (67%) were men. Fourteen (78%) of 18 patients showed improvement in Emission Threshold Levels (ETL) from admission to follow-up in low, mid-, and mid-high frequency categories, where ETLs increased by median levels of 3.2 (-4.1 to 8.3), 7.5 (-2.8 to 9.8), and 4.7 dB (-4.3 to 10.1). A decline was observed in the high frequency category, median -3.3 dB (-9.1 to 6.7). SNHL defined by pure tone average (PTA3) >20 dB was present in 11 out of 23 (48%) at discharge and in 9 out of 16 patients (56%) 60 days after discharge, which differed significantly from matched controls (Mann-Whitney test, p = 0.036). CONCLUSION: LNB can lead to cochlear outer-hair cell dysfunction, resulting in temporary and long-term SNHL.

[Bilateral facial palsy: an atypical presentation of Lyme disease (a case report)]. / Paralysie faciale bilatérale : une présentation atypique d'une maladie de Lyme (cas clinique).

Lyme neuroborreliosis is a rare zoonosis which can be difficult to diagnose, in particular in low endemic areas. We here report the case of a 35-year-old man presenting with disabling back pain preceded by facial monoplegia, which was wrongly treated as Bell's palsy (paralysis a frigore) and then as post-traumatic lumbosciatica. The onset of facial diplegia allowed for a definitive diagnosis. The patient was treated with ceftriaxone and symptoms gradually improved.

Diagnostic patterns of serum inflammatory protein markers in children with Lyme neuroborreliosis.

Definite diagnosis of Lyme neuroborreliosis (LNB) requires investigation of serum and cerebrospinal fluid (CSF). Thus, lumbar puncture is necessary, and requires administration of sedating drugs in children. This study aimed to investigate if a pattern of different inflammatory biomarkers in serum could contribute to the selection of children for lumbar puncture in suspected LNB. Patients were included from a cohort of children who was previously investigated for LNB including serum and CSF sampling during the years 2010-2014. The multiplex proximity extension assay (PEA) inflammation panel Target 96 (Olink Bioscience, Uppsala, Sweden) was used to examine 92 biomarkers in serum. Based on the presence of CSF pleocytosis and Borrelia-specific antibodies, patients were divided into a definite LNB group (n=61) and a non-LNB control group (n=58). Following PEA and statistical analysis with multivariate logistic regression, five biomarkers remained significant (p < 0.001), which were included in a calculation of protein index. The index biomarkers were CST5, IL-15RA, CXCL10, DNER and CX3CL1. A receiver operating characteristic curve was constructed from the index, which showed an 80 % sensitivity and 81 % specificity. Area under the curve was 0.889. We offer evidence that, with further refinements, patterns of serum biomarkers might help identify those children more or less likely to have LNB, perhaps ultimately decreasing the need for lumbar punctures.

Characteristics of patients consulted for suspected Lyme neuroborreliosis in an endemic area.

INTRODUCTION: Some patients with unexplained neurological symptoms sought care for presumed Lyme neuroborreliosis (LNB). We aimed to compare patients' characteristics with and without LNB. MATERIAL AND METHODS: All patients consulting for LNB suspicion and having a lumbar puncture between 2014 and 2020 in a high endemic area of Lyme borreliosis were included in the study. RESULTS: One hundred fifty-five patients were included. Forty-five patients (29 %) had LNB (mean age: 57.6 years, 28.9 % of women) including 17 with isolated intrathecal synthesis. One hundred and ten patients had no LNB (mainly neurological (29 %) and rheumatological diseases (19 %)). Non-neurological symptoms were similar in patients with LNB and patients with no LNB (asthenia, 31 % vs. 46 %, p = 0.14, arthralgia 20 % vs. 31 %, p = 0.14) with the exception of myalgia, which was less frequent in patients with LNB (4.4 % vs. 19.1 % p = 0.02). In multivariable analysis, factors associated with LNB were presence of facial nerve palsy (OR = 5.7), radiculopathy (OR = 11.3), positive Lyme serology (OR = 5.4) and duration of symptoms less than 3 months (OR = 4.48). Patients with isolated intrathecal synthesis had a longer duration of symptoms (3 vs 1 months) than patients with pleocytosis. Asthenia (5.9 % vs. 32.1 %), headaches (0 % vs. 39.3 %) neuropathic pain (17.6 % vs. 50 %) and facial palsy (11.8 % vs. 39.3 %) were less frequent in patients with isolated intrathecal synthesis than patients with pleocytosis. The presence of isolated subjective neurological symptoms (paresthesia, memory disorders, insomnia, irritability, asthenia, headaches) was reported in 7/17 (41 %) of patients with isolated intrathecal synthesis, 2/28 (7.1 %) in patients with pleocytosis and 75/110 (68 %) in patients without LNB (p < 0.001). CONCLUSION: More than one quarter of patients consulted for suspected LNB had non-neurologic symptoms, whether or not they have a LNB. Concerning patients with isolated intrathecal synthesis, the question of presence of sequelae with a spontaneously cured disease or an active Lyme borreliosis requiring antibiotic remain.

Spectrum of MRI findings in central nervous system affection in Lyme neuroborreliosis.

Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020-December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms.

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.

Neuroborreliosis interpreted as multiple sclerosis by MRI.

Lyme neuroborreliosis (LNB) is the most prevalent nervous system bacterial infection in Denmark. In a young man with LNB, brain MRI and cerebrospinal fluid (CSF) demonstrated findings compatible with multiple sclerosis. This case report underlines the requirement for testing for intrathecal Borrelia antibody production when the number of cells in the CSF is low or even normal. It also demonstrates the unchanged diagnostic delay of NBL observed during the last 20 years.

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.

Atypical Acute Neuroborreliosis With Leg Paresis and Constipation.

BACKGROUND/AIM: An 80-year-old male patient had complained of proximal paresis of the left leg, pain and sensory disturbances in the left abdomen, exanthema in the left lower abdomen, coprostasis, and severe abdominal pain, as well as a progressive deterioration of his general condition for weeks. The patient had already presented to three other medical centers. Colonoscopy and computed tomography of the abdomen could not explain the pronounced symptomatology. In addition, there was acute elevator paresis of the left leg and severe pruritic rash on both sides of the trunk. CASE REPORT: At the Israelitisches Krankenhaus Hamburg (IKH), laboratory parameters of urine, stool, and blood, ultrasound, electrocardiogram, and transthoracic echocardiography diagnosis showed no abnormalities. Esophago-gastro-duodenoscopy revealed patchy erythema and moderately severe chronic low-activity Helicobacter-positive gastritis. Colonoscopically, two polyps were ablated. A neurological examination with magnetic resonance imaging and electroneurography also showed normal findings. Evidence of autoimmune or rheumatoid disease was also absent. Finally, analysis of the cerebrospinal fluid revealed a lympho-granulocytic cell count (32/3 lymphocytes, 21/3 granulocytes) and an elevated Borrelia-specific IgG index (Ai) of 20.82. This finding was confirmed by a complementary serological diagnosis, in which Borrelia-specific IgM and IgG antibodies were detected. In sum, Bannwart's syndrome was assumed to be the cause of the neurological symptoms. The 21-day borreliosis therapy included doxycycline administration and analgesia with novaminsulfone and pregabalin as needed. CONCLUSION: A complex symptomatology of leg paresis, lower abdominal pain and sensory disturbances, exanthema, and coprostasis in combination with a long-lasting poor general condition were found to be the consequences of atypical neuroborreliosis.

Isolated Intracranial Hypertension as a Presentation of Pediatric Lyme Borreliosis: A Case Report and Literature Review.

BACKGROUND: It is extremely rare for Lyme borreliosis to present solely with features of increased intracranial pressure. The treatment of pediatric Lyme neuroborreliosis with oral versus intravenous antibiotics remains controversial. METHODS: Case report and literature review. RESULTS: A 13-year-old male presented with five days of binocular diplopia, several weeks of headache, and a history of multiple tick bites six weeks prior. His examination showed a left eye abduction deficit and bilateral optic disc edema. Magnetic resonance imaging (MRI) of the brain with contrast showed tortuosity of the optic nerves, prominence of the optic nerve sheaths, and enhancement of the left fifth and bilateral sixth cranial nerves. Lumbar puncture showed an elevated opening pressure and a lymphocytic pleocytosis. Lyme IgM and IgG antibodies were positive in the serum and cerebrospinal fluid. The patient was treated with intravenous ceftriaxone for two days empirically followed by doxycycline by mouth for 19 days. Symptoms began improving after 48 hours. The strabismus resolved after two weeks, and the papilledema improved slowly with complete resolution at six months. CONCLUSIONS: Lyme neuroborreliosis can present as isolated intracranial hypertension in the pediatric population; it can be differentiated from idiopathic intracranial hypertension on MRI, and lumbar puncture and can be confirmed with serum antibody testing. Oral doxycycline can be considered for Lyme neuroborreliosis in children.

Serum neurofilament light chain associates with symptom burden in Lyme neuroborreliosis patients: a longitudinal cohort study from Norway.

OBJECTIVES: Serum neurofilament light chain (sNfL), an indicator of neuronal damage, is increasingly recognized as a potential biomarker for disease activity in neurodegenerative disorders. In this study, we wanted to investigate sNfL as a prognostic marker in a large, well-defined population of 90 patients with Lyme neuroborreliosis (LNB). In addition, we sought to explore associations between symptoms and sNfL levels during the acute phase of LNB. MATERIALS AND METHODS: Patients diagnosed with definite or possible LNB were recruited from a double-blinded, placebo-controlled, multi-center trial, in which the participants were randomly assigned to 2 or 6 weeks of oral doxycycline treatment. The sNfL levels were measured using a single molecule array assay at both diagnosis and 6-month follow-up, and analysed against clinical parameters, variations in symptom burden and long-term complaints as assessed by a composite clinical score. RESULTS: At the time of diagnosis, approximately 60% of the patients had elevated sNfL levels adjusted for age. Notably, mean sNfL levels were significantly higher at diagnosis (52 pg/ml) compared to 6 months after treatment (12 pg/ml, p < 0.001), when sNfL levels had normalized in the majority of patients. Patients with objective signs of spinal radiculitis had significantly higher baseline sNfL levels compared to patients without spinal radiculitis (p = 0.033). CONCLUSION: Our findings suggest that sNfL can serve as a biomarker for peripheral nerve tissue involvement in the acute phase of LNB. As found in an earlier study, we confirm normalization of sNfL levels in blood after treatment. We found no prognostic value of acute-phase sNfL levels on patient outcome.

Paretic complications of tick-borne encephalitis and Lyme neuroborreliosis in the Czech Republic: Characteristics and clinical outcome.

Tick-borne encephalitis (TBE) and Lyme neuroborreliosis (LNB), the most common tick-borne diseases of the central nervous system in Central Europe, are frequently associated with pareses. The aim of this study was to characterise paretic complications in patients with TBE and LNB, including their severity, persistence and impact on the patients' quality of life. Our retrospective observational study included patients with aseptic CNS infection due to TBE virus or Borrelia burgdorferi sensu lato. Paretic complications were evaluated in the acute phase and the patients were followed up until complete regression or long-term stabilisation of any neurological deficit. The severity of the neurological deficit was graded according to the modified Rankin Scale (mRS). A total of 823 patients (582 with TBE, 241 with LNB) was included. Paretic complications were diagnosed in 63 TBE patients (10.8 %) and in 147 LNB patients (61.0 %). In TBE, the most common neurological deficit was brachial plexus paresis in 21 patients (33 %) and bulbar symptoms in 18 patients (29 %). In LNB patients, facial nerve palsy was the most frequent neurological deficit (117patients; 79.6 %), followed by lower limb paresis in 23 patients (15.6 %). Forty-nine TBE patients and 134 LNB paretic patients completed follow-up. Paresis resolved within 3 weeks in 16 TBE patients (33 %) and 53 LNB patients (39.5 %), but the proportion of patients with paresis persisting for more than 12 months was significantly higher in TBE (34.7 vs. 3.7 %, p < 0.001). The mean mRS was significantly higher in TBE paretic patients compared to LNB (p < 0.001). Paretic complications are significantly more common in LNB than in TBE but pareses associated with TBE last longer than in LNB and considerably reduce the quality of life of patients. Prevention remains the only way to influence the long-term motor deficits of TBE.

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.

Clinical and epidemiological features of Lyme neuroborreliosis in adults and factors associated with polyradiculitis, facial palsy and encephalitis or myelitis.

The clinical course of Lyme neuroborreliosis (LNB) is highly variable. Delayed diagnosis and treatment still remain actual challenges. Moreover, there is a lack of studies analyzing the factors associated with different LNB syndromes. We aimed to analyze clinical and epidemiological features of LNB in hospitalized adults in eastern Lithuania. A retrospective study was performed for patients presenting in the years 2010-2021. A total of 103 patients were included in the study, 100 with early, and three with late LNB. Patients with early LNB most often presented polyradiculitis [75/100, (75%)], which was also the most common initial neurological syndrome. Peripheral facial palsy was diagnosed in 53/100 (53%) patients, in 16/53 (30.2%) cases both facial nerves were affected. Encephalitis or myelitis was diagnosed in 14% of patients with LNB. A total of 76/103 (73.8%) patients were discharged with residual symptoms or signs. One patient presenting encephalomyelitis died because of bacterial complications. The absence of observed erythema migrans (EM) was the predictor of peripheral facial palsy, while female sex and EM untreated with antibiotics were predictors of isolated polyradiculitis. A fever of ≥ 38 ° °C and pleocytosis of ≥ 300 × 106/l were associated with the development of encephalitis or myelitis in patients with early LNB.

Enteroviral central nervous system infections in patients with Lyme neuroborreliosis.

Patients with Lyme neuroborreliosis (LNB) are rarely tested for the presence of neurovirulent viruses other than tick-borne encephalitis virus (TBEV); however, such coinfections could be of clinical importance. The aim of the study was to search for the presence of neurotropic viruses in a LNB patients. Fourteen patients admitted with signs and symptoms of neuroinfection who were eventually diagnosed to have LNB (according to the guidelines of the European Federation of Neurological Societies) were subjects of the study. Sera and cerebrospinal fluid (CSF) collected at the time of initial presentation were tested for viral pathogens most common in our geographical area: human enteroviruses (EV), herpes simplex virus type 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus type 6, human adenoviruses, and TBEV using PCR/RT-PCR and serological assays. RNA and DNA-based metagenomic next-generation sequencing (mNGS) was used to detect other viral pathogens. EV was detected in CSF from two (14 %) LNB patients and viral loads were similar (220 and 270 copies/ml). The mMGS analysis were performed on CSFs from 10 patients and generated a total 213,750,885 NGS reads, 0.05 % of which were viral. However, none of potential pathogens fulfilled the criteria for positive viral detection by mNGS. Using a number of PCR/RT-PCR assays and mNGS we identified EV infection in two out of 14 LNB patients. The possible co-occurrence of enterovirus and Lyme neuroborreliosis infections may warrant further research.

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.

Cerebrospinal fluid CXCL13 in non-borrelial central nervous system infections: contribution of CXCL13 to the differential diagnosis.

BACKGROUND: The chemokine CXCL13 in cerebrospinal fluid (CSF) is used as a diagnostic marker of Lyme neuroborreliosis (LNB). However, the elevated levels in other non-borrelial CNS infections and the lack of a clearly defined cut-off value are limitations of the test. METHODS: In our prospective study, we evaluated CSF CXCL13 levels in patients with LNB (47 patients), tick-borne encephalitis (TBE; 46 patients), enteroviral CNS infections (EV; 45 patients), herpetic CNS infections (HV; 23 patients), neurosyphilis (NS; 11 patients) and controls (46 patients). The correlation of CXCL13 with CSF mononuclears was determined in all groups. RESULTS: Median CXCL13 was significantly higher in LNB group; however, the cut-off value of 162 pg/mL was also exceeded in 22% of TBE patients, 2% EV patients, 44% HV patients and in 55% patients with NS. Sensitivity and specificity were 0.83 and 0.78, respectively, with a Youden index of 0.62. CXCL13 was significantly correlated with CSF mononuclears (p = .0024), but the type of infectious agent had a greater influence on CXCL13 levels. CONCLUSIONS: Increased CXCL13 levels are useful for LNB diagnostics, but other non-purulent CNS infections causes should be considered if intrathecal synthesis of borrelia specific antibodies is not confirmed or clinical manifestations are atypical.

Lyme radiculopathy in a septuagenarian.

A man in his 70s presented to hospital in early summer with a 5-week history of progressive lower back and right thigh pain, sensory deficit and right leg weakness. There had been limited response to analgesics in the community. Primary investigations on admission revealed no cause for his symptoms. Five days into admission, history emerged of a possible tick bite with subsequent rash sustained 3 months earlier, raising the possibility of neuroborreliosis leading to radiculopathy. Cerebrospinal fluid demonstrated a lymphocytic pleocytosis. An elevated Borrelia burgdorferi antibody index confirmed a diagnosis of Lyme neuroborreliosis. The patient was treated successfully with 28 days of intravenous ceftriaxone, analgesia and physiotherapy. Within the literature, Lyme radiculopathy is a common presentation of neuroborreliosis and should be considered and investigated in patients without radiological evidence of a mechanical cause of worsening lower back pain in settings with endemic Lyme disease.