Neuroborreliosis Research Articles

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

BackgroundLyme 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.MethodsA 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.ResultsData 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.ConclusionsBefore 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.

Evaluation of the Epitogen Lyme Detect IgG ELISA: a novel peptide multiplexing approach.

Lyme Borreliosis (LB), or Lyme disease, is a growing health concern caused by Borrelia burgdorferi sensu lato (Bbsl) bacteria transmitted through tick bites, and untreated cases can lead to severe health complications. Existing serology tests, while valuable, have low sensitivity in early infection stages where diagnosis is vital, interpretation variability, and false positives from cross-reactivity, while direct detection methods also suffer from low sensitivity, due to the inconsistent presence of Bbsl components in clinical samples. This study validated the diagnostic performance of the novel Epitogen Lyme Detect IgG enzyme-linked immunosorbent assay (ELISA) based on scaffold-displayed peptide antigens, using 120 specific immunodominant epitopes selected from 37 antigenic bacterial proteins corresponding to the main pathogenic Bbsl genospecies. Using 220 serum samples from Scottish patients with early, late, and disseminated LB, the assay's sensitivity was compared with that of the LIAISON Borrelia IgG CLIA, while specificity was assessed with 198 control samples, including healthy individuals and patients with diseases that are humorally similar. The Epitogen Lyme Detect IgG assay demonstrated comparable performance to the LIAISON Borrelia IgG in disseminated and late LB (Lyme neuroborreliosis, acrodermatitis chronica atrophicans, and Lyme arthritis). Notably, the Epitogen Lyme Detect IgG showed significantly higher sensitivity in patients with suspected erythema migrans, while maintaining high specificity. The Epitogen Lyme Detect IgG ELISA offers a promising advancement in LB diagnostics, demonstrating its potential for more accurate and timely diagnosis, particularly in the early stages of LB infection.IMPORTANCELyme Borreliosis (LB), caused by Borrelia burgdorferi sensu lato bacteria, poses significant health risks if undiagnosed or diagnosed late. Current diagnostic tests have limitations, especially in early-stage detection. This study validates the Epitogen Lyme Detect IgG enzyme-linked immunosorbent assay, demonstrating superior sensitivity in early LB detection while maintaining high specificity. The Epitogen Lyme Detect IgG comprises a suite of 120 immunodominant IgG epitopes/peptides from 37 bacterial antigens, covering the main LB-causing species: Borrelia burgdorferi sensu stricto, Borrelia afzelii, Borrelia garinii, and Borrelia mayonii. The novel design of multiplexing peptide antigens onto a scaffold to facilitate expression, correct folding, and orientation of the relevant peptides offers a promising advancement, potentially leading to more accurate and timely LB diagnoses and improving patient outcomes.

Bridging the gap: Insights in the immunopathology of Lyme borreliosis.

Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) genospecies transmitted by Ixodes spp. ticks, is a significant public health concern in the Northern Hemisphere. This review highlights the complex interplay between Bbsl infection and host-immune responses, impacting clinical manifestations and long-term immunity. Early localized disease is characterized by erythema migrans (EM), driven by T-helper 1 (Th1) responses and proinflammatory cytokines. Dissemination to the heart and CNS can lead to Lyme carditis and neuroborreliosis respectively, orchestrated by immune cell infiltration and chemokine dysregulation. More chronic manifestations, including acrodermatitis chronica atrophicans and Lyme arthritis, involve prolonged inflammation as well as the development of autoimmunity. In addition, dysregulated immune responses impair long-term immunity, with compromised B-cell memory and antibody responses. Experimental models and clinical studies underscore the role of Th1/Th2 balance, B-cell dysfunction, and autoimmunity in LB pathogenesis. Moreover, LB-associated autoimmunity parallels mechanisms observed in other infectious and autoimmune diseases. Understanding immune dysregulation in LB provides insights into disease heterogeneity and could provide new strategies for diagnosis and treatment.

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.

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

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. • 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. • 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 8years) of LNB in children.

Estimated incidence of symptomatic Lyme borreliosis cases in five southern coastal counties in Norway, 2022.

Lyme borreliosis (LB), the most common tick-borne disease in Europe, is endemic to southern coastal Norway. LB commonly presents as erythema migrans, which can disseminate, resulting in more severe disease such as Lyme neuroborreliosis or arthritis. In Norway, public health LB surveillance is conducted via mandatory reporting of laboratory-confirmed disseminated cases. From 2012 to 2022, Norway's surveillance-reported incidence of laboratory-confirmed disseminated LB increased by 78%. Although surveillance provides estimates of the incidence of disseminated LB, this study sought to estimate the incidence of symptomatic LB to better understand Norway's LB disease burden. Two studies were identified that, when combined, estimated an LB seroprevalence of 6.8% in the general adult population in southern Norway. Utilizing data from these seroprevalence studies, public health surveillance, and results from literature searches indicating that 37% of seroconverted LB cases are symptomatic and that the duration of LB antibody detection ranges from 10 to 20 years, we estimated that there were 315-630 symptomatic LB cases per 100,000 adult population in five southern coastal counties in Norway in 2022 and 24-48 cases of symptomatic LB for every public health surveillance-reported LB case in adults in these five counties in Norway.

Evaluation of different standard and modified two-tier testing strategies for the laboratory diagnosis of lyme borreliosis in a European setting.

Diagnosis of Lyme borreliosis (LB) relies on clinical symptoms and detection of Borrelia-specific antibodies. Guidelines recommend a two-tier testing (TTT) strategy for disseminated LB: serological screening with a sensitive enzyme immunoassay (EIA) and confirmation with a specific immunoblot. Searching for the most sensitive and specific approach, this retrospective study evaluated standard (STTT) and modified (MTTT) strategies using a well-defined study population. Cases included patients with active Lyme neuroborreliosis (LNB; n = 29) or Lyme arthritis (LA; n = 17). Controls comprised patients treated for LNB (n = 36) or LA (n = 8), healthy individuals who were either untreated (n = 75) or treated for LB (n = 15) in the past, and patients with potentially cross-reactive diseases (n = 16). Sera were subjected to three EIAs and two immunoblots. Reactive screening results were confirmed by immunoblot (STTT) or EIA (MTTT). Solitary IgM results in the screening assay and effects of antibiotic treatment on isotype-specific seropositivity rates were also assessed. Sensitivities of STTT strategies ranged from 90%-97% for LNB and were 100% for LA. MTTT strategies were 100% sensitive. Specificities ranged from 89%-95% for STTT and from 88%-93% for MTTT strategies. Differences between STTT and MTTT strategies were not statistically significant. Solitary IgM reactivity was common among controls. Antibiotic treatment significantly reduced IgM/IgG positivity for LNB patients; for LA patients, a decline was only observed for IgM. In conclusion, MTTT strategies showed a slightly higher sensitivity and similar specificity compared to STTT strategies. Since EIAs are more time- and cost-efficient, MTTT strategies seem more favorable for clinical use. IgG testing enhances specificity with minimal sensitivity loss.

Changes in the serum proteome profile of patients with neuroborreliosis, foresters, and patients treated according to ILADS method.

The aim of study was to evaluate the changes in proteomic profile of human serum induced by the development of tick-borne neuroborreliosis (NB), before/after therapy, patients treated with prolonged multidrug therapy according to ILADS (International Lyme and Associated Diseases Society), and foresters frequently exposed to tick bites. A proteomics approach was used to analyze the expression of proteins in serum of patients and sex/age-matched healthy donors. The analysis was performed using SDS-PAGE/LC-MS/MS (Q-Exactive OrbiTrap mass spectrometer). Obtained results indicated changes in the serum proteome of patients with NB putting attention to the proteins involved mainly in calcium transport/metabolism and signaling molecules that differ patients before and after classic therapy. Moreover, ILADS treated patients have different protein distribution than patients from other groups, what is the consequence of prolonged antibiotic therapy. In the case of foresters, the most important result is the increased β-secretase level. Obtained results may contribute to a better understanding of the mechanism of the development of tick-borne diseases, as well as will allow create new opportunities for its rapid and more effective therapy. However, further studies, on larger patients groups, are needed to apply them in clinical practice.

Incidence of symptomatic Lyme borreliosis in nine European countries

ObjectivesTo better understand the Lyme borreliosis (LB) burden in Europe, we aimed to estimate the incidence of symptomatic Borrelia burgdorferi sensu lato (Bbsl) infections after adjusting public health LB surveillance data for under-detection of symptomatic Bbsl infections. MethodsData from seroprevalence studies and estimates of the symptomatic proportion and duration of antibody detection in Bbsl-infected individuals, derived from reviews of the published literature, were used to adjust public health LB surveillance data to estimate the incidence of symptomatic Bbsl infection in nine European countries from 2018 to 2022. ResultsThe prevalence of anti-Bbsl antibodies ranged from 2.3% in Romania to 9.4% in Germany. Under-detection multipliers varied across surveillance systems; using 10-year duration of antibody detection, multipliers were 2.4-10.5 in countries reporting all LB cases and 54.6-722.2 in countries reporting only Lyme neuroborreliosis cases. The incidence of symptomatic Bbsl infection adjusted for under-detection was highest in Finland, Germany, Norway, Poland, and Switzerland, intermediate in the Czech Republic and Denmark, and lowest in Ireland and Romania. ConclusionAdjustment of LB surveillance for under-detection found a high incidence of symptomatic Bbsl infection in several European countries. Differences in LB surveillance systems should be considered when comparing surveillance data between countries and when estimating LB disease burden.

Clinical and laboratory characteristics during a 1‐year follow‐up in European Lyme neuroborreliosis: A prospective cohort study

AbstractBackground and PurposeWe need more knowledge on clinical presentations, time course, biomarkers, and prognosis in European Lyme neuroborreliosis (LNB).MethodsA prospective 12‐month follow‐up of predetermined clinical and laboratory parameters was undertaken in 105 patients with LNB.ResultsAt presentation, 79% had radiculopathy, 49% had facial palsy, and 13% had solely subjective symptoms (predominately pain). Intrathecally produced Borrelia burgdorferi (Bb) antibodies were demonstrated and cerebrospinal fluid (CSF) CXCL13 was positive in 85% and 82% pretreatment, in 73% and 10% at 6 months, and in 58% and 14% at 12 months, respectively. CSF Bb polymerase chain reaction (PCR) was positive in 40% pretreatment. In four patients who tested negative for Bb antibodies in both serum and CSF, the diagnosis was supported by typical clinical features, pleocytosis, CSF Bb‐PCR (n = 1), or CSF CXCL13 (n = 2). The proportion with symptoms influencing daily life was 91% pretreatment, 25% at 10 weeks, 20% at 6 months, and 15% at 12 months. Fatigue was the most common complaint at 12 months. A high burden of symptoms before and after treatment was associated with residual complaints at 12 months, whereas background data, other clinical features, and laboratory features were not.ConclusionsLNB can present with solely subjective symptoms, especially pain. Many LNB patients have persistent Bb antibodies in serum and CSF. In seronegative LNB, CSF Bb‐PCR and CXCL13 may give diagnostic support. CXCL13 may be persistently positive after treatment in some patients. Most of the clinical improvement occurs during the first 10 weeks. High initial clinical score is associated with poorer outcome.

Lyme neuroborreliosis in adults - epidemiology data and clinical findings

<p><strong>Introduction. </strong>Lyme neuroborreliosis (LNB) can manifest during the early and late stages of Lyme disease (LD). The aim of this study is to determine epidemiology and clinical findings in patients with LNB. <br /><strong>Methods.</strong> The research was conducted in Banja Luka at the University Clinical Center of Republic of Srpska (UCC RS) during a four-year period from 10/2017 to 10/2021. The research included 51 patients admitted to the hospital with some neurological symptoms that could lead to the LNB diagnosis. Patients had lumbar puncture with cytochemical analysis of cerebrospinal fluid (CSF), ELISA anti-Borrelia IgM/IgG in serum and CSF, Immunoblot anti-Borrelia IgM/IgG in serum, and other documentation about epidemiology and clinical findings in LNB.  <br /><strong>Results.</strong> A statistically significant (p=0.017) higher proportion of female patients was observed. Most patients were between 50 and 60 years old. Most of them were retirees (31.37%), farmers, medical technicians followed with forestry workers, students etc. Most of examinees did not have information on previous tick bite (64.71%). The largest number (72.55%) did not have data on previous skin changes. The largest number of neurological symptoms at admission related to the feeling of tingling and weakness in the extremities, headache, dizziness and some ophthalmological symptoms. Patients also suffered from consciousness and speech disorder, anxiety, paresis n.VII. The largest number of examinees had some neurological symptoms up to three months prior the admission to the hospital.  <br /><strong>Conclusion. </strong>Symptoms of LNB can be quite non-specific or possibly even mimic other neurological diseases. Involvement <br />of peripheral nervous system is dominant in adult patients. It is necessary to work on early diagnosis of LD and it is mandatory to report it to the national epidemiological service. </p>

Lyme Neuroborreliosis in the Context of Dementia Syndromes.

Lyme disease (LD) can affect the skin, joints, heart, and nervous system as a multisystemic condition. The cause of the illness is the spirochete of the genus Borrelia. These pathogens can affect the skin, joints, heart, and nervous system. Lyme neuroborreliosis (LNB) is the term for the disease, which occurs when the nervous system gets involved. Regarding geographical distribution, LNB is more prevalent in Europe than in North America. The most significant change in pathogenesis is inflammation of the central nervous system (CNS) and peripheral nervous system (PNS). Furthermore, clinically, it can represent a variety of neurological manifestations, such as meningitis, encephalitis, radiculopathies, and cranial neuritis. However, dementia-like syndrome is an infrequent manifestation of Lyme disease. Our review article aims to summarize the similarities and differences between dementia-like syndrome in LNB and that in primary neurodegenerative diseases, as well as to look for a correlation between the pathogenesis of the disease and the possibility of developing dementia-like syndrome. The world literature lacks sufficiently convincing data on the relationship between spirochete infection and primary dementia syndromes. However, cases of secondary dementia syndrome due to nervous system involvement as well as post-treatment have been described. A thorough examination, medical history, laboratory and imaging studies, cerebrospinal fluid (CSF) examination, MRI, and fludeoxyglucose-18-positron emission tomography (FGD-PET) are required to differentiate between these syndromes.

Assessment of three criteria to establish borrelial infection in suspected lyme neuroborreliosis.

Diagnosis of (European) Lyme neuroborreliosis has been based on clinical presentation, cerebrospinal fluid (CSF) pleocytosis and demonstration of intrathecal borrelial antibody synthesis (ITBAS) to document Borrelia burgdorferi s. l. It is not known if other criteria to document Borrelia infection may contribute to the diagnosis. We compared the sensitivity of three individual criteria (ITBAS, CSF Borrelia culture, and the presence of erythema migrans [EM]) to confirm the diagnosis of early Lyme neuroborreliosis in 280 patients ≥ 15 years of age evaluated at a Lyme borreliosis outpatient clinic in Slovenia. The patients had either radicular pain of new onset or involvement of a cranial nerve but without radicular pain, each in conjunction with CSF pleocytosis. Evaluation was of patients who had each of the three confirmatory criteria assessed, and for whom at least one criterion was positive. Analysis of 280 patients, 120 women and 160 men, median age 57 (range 15-84) years, revealed that ITBAS was the most frequently observed positive criterion (85.4%), followed by EM (52.9%), and by a positive CSF Borrelia culture (9.6%). Of the 280 patients, 154 (55%) met only one criterion (43.2% ITBAS only, 10.7% EM only, and 1.1% positive CSF culture only), whereas 42.1% met two criteria. Only 2.9% of patients were positive by all three criteria. Although ITBAS was the most frequent criterion for confirmation for Borrelia infection, the presence of EM alone confirmed an additional 10.7% of patients and a positive CSF Borrelia culture alone added another 1.1%.

Healthcare-seeking behaviour preceding diagnosis of Lyme neuroborreliosis: population-based nationwide matched nested case-control study

ObjectivesTo identify diagnostic opportunities, we investigated healthcare-seeking behaviour among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis. MethodsWe conducted a population-based, nationwide matched nested case-control study (Denmark, 2009–2021). As cases, we included all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis). We randomly selected controls from the general population and matched 10:1 on date of birth and sex. Exposures were assignment of diagnostic codes for symptoms, contact to medical specialties, medical wandering, and undergoing diagnostic procedures. We calculated the weekly and 3-month proportions of individuals with exposures and calculated absolute risk differences with corresponding 95% CI. ResultsWe included 1056 cases with LNB and 10 560 controls.Within 3 months before diagnosis, the most frequent assigned symptoms were pain (difference: 13.0%, 95% CI: 10.9–15.1). Cases with LNB exhibited increased contact with most specialties, particularly general practitioners (difference: 48.7%, 95% CI: 46.0–51.4), neurology (difference: 14.3%, 95% CI: 11.7–16.8), and internal medicine (difference: 11.1%, 95% CI: 8.7–13.5), and medical wandering (difference: 17.1%, 95% CI: 14.3–20.0). Common diagnostic procedures included imaging of the brain (difference: 10.2, 95% CI: 8.3–12.1), the spine (difference: 8.8%, 85% CI: 7.0–10.6), and the abdomen (difference: 7.2%, 95% CI: 5.4–9.1). The increase in healthcare-seeking behaviour was observed ≤12 weeks preceding diagnosis. DiscussionPain appears to be an ambiguous symptom of LNB, potentially contributing to delays in establishing the correct diagnosis. It would be difficult to identify patients with LNB more effectively as the increased healthcare-seeking behaviour preceding diagnosis is distributed across many medical specialties.

Monoclonal antibody therapy for refractory chronic migraine-like headache related Lyme disease: a case report

IntroductionLyme disease, caused by Borrelia burgdorferi, can lead to diverse neurological manifestations, including headache. While most Lyme-associated headaches resolve with antibiotics, some may evolve into a refractory chronic migraine-like syndrome. We present a case of post-Lyme chronic migraine-like headache responsive to galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody.Case ReportA 42-year-old woman developed chronic migraine-like headaches following treatment for Lyme neuroborreliosis. The headaches were refractory to standard preventive therapies and only partially responsive to onabotulinumtoxinA. Administration of galcanezumab resulted in significant reduction of headache frequency, intensity, and impact on daily activities.CommentThis case highlights the potential of CGRP-targeted therapies for persistent migraine-like headaches following Lyme neuroborreliosis. The favorable response to galcanezumab suggests a role for CGRP in the pathophysiology of post-Lyme headache. While further research is needed to establish efficacy and safety, clinicians should consider CGRP monoclonal antibodies for chronic migraine-like headaches refractory to standard treatments in the post-infectious phase of Lyme disease. The emergence of chronic migraine-like headaches following Lyme neuroborreliosis and the response to a CGRP monoclonal antibody in this case underscore the importance of considering targeted migraine therapies in the management of persistent headaches after antibiotic treatment. This report contributes to the understanding of Lyme disease sequelae and potential treatment options, warranting further investigation into the utility of CGRP-targeted therapies in this context.

Obtainment of prescribed analgesics among patients with Lyme neuroborreliosis; a nationwide, population-based matched cohort study

BackgroundRadicular pain is the most predominant symptom among adults with Lyme neuroborreliosis (LNB) but the duration preceding and following diagnosis remains unknown. We aimed to investigate whether patients with LNB have increased obtainment of analgesics before and after diagnosis and for how long. MethodsWe performed a nationwide, population-based, matched cohort study (2009–2021). all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis) were included. To form a comparison cohort, individuals from the general population were randomly extracted and matched 10:1 to patients with LNB on age and sex. Outcomes were obtainment of simple analgesics, antiepileptics, tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, tramadol, and other opioids. We calculated monthly and six-monthly proportions of individuals with obtainment of analgesics and absolute risk differences. Results1,056 patients with LNB and 10,560 comparison cohort members were included. An increased proportion of patients with LNB obtained analgesics from 3 months before study inclusion, especially simple analgesics, tramadol, and other opioids. Within the 0–1-month period after study inclusion, patients with LNB most frequently obtained simple analgesics (15 %), antiepileptics (11 %), and tramadol (10 %). Thereafter, obtainment of analgesics declined within a few months. A slightly larger proportion of patients with LNB obtained antiepileptics up to 2.5 years after diagnosis. ConclusionsUp to 3 months preceding diagnosis, LNB was preceded by increased obtainment of analgesics, which suggests diagnostic delay. Importantly, most patients with LNB did not obtain analgesics after the immediate disease course, although obtainment remained more frequent up to 2.5 years after.

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.

Tenascin-C in patients with central nervous system infections

BackgroundThe extracellular matrix protein tenascin-C has been discovered to be an important regulator of the response to tissue injury and repair in cerebrovascular diseases. This study investigated if tenascin-C is released in response to infections in the central nervous system (CNS). MethodsTenascin-C concentration in the cerebrospinal fluid (CSF) was measured in patients, (>18 years) with and without CNS infections, admitted to a department of infectious diseases in Denmark. CSF tenascin-C was measured on the Meso-scale platform. Results174 patients were included of which 140 were diagnosed with a CNS infection and 34 where this was ruled out (control group). Median CSF tenascin-C levels were significantly higher among patients with bacterial meningitis (147 pg/mL), viral meningitis (33 mg/mL), viral encephalitis (39 pg/mL) and Lyme neuroborreliosis (45 pg/mL) when compared to controls (21 pg/mL). Correlations between tenascin-C and CSF markers of inflammation and age were only moderate. ConclusionLevels of CSF tenascin-C are higher among patients with bacterial and viral neuroinfections, already on admission, but exhibit only a modest correlation with baseline indices of neuroinflammation. CSF tenascin-C is highest among patients with bacterial meningitis compared to the other CNS infections. Patients with unfavorable outcomes presented with higher median CSF tenascin-C than their counterparts.

CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

Diagnostic Challenges of Lyme Neuroborreliosis in Inpatient Neurology: A Case Series.

Lyme disease is a multisystem disorder transmitted through the Ixodes tick and is most commonly diagnosed in northeastern and mid-Atlantic states, Wisconsin, and Minnesota, though its disease borders are expanding in the setting of climate change. Approximately 10%-15% of untreated Lyme disease cases will develop neurologic manifestations of Lyme neuroborreliosis (LNB). Due to varying presentations, LNB presents diagnostic challenges and is associated with a delay to treatment. We discuss three cases of LNB admitted to our referral center in a traditionally low-incidence state to highlight clinical pearls in LNB diagnosis. Three patients from low-incidence areas with prior diagnostic evaluations presented in August with neurologic manifestations of radiculoneuritis, cranial neuropathies, and/or lymphocytic meningitis. MRI findings included cranial nerve, nerve root, and leptomeningeal enhancement leading to broad differential diagnoses. Lumbar puncture demonstrated lymphocytic pleocytosis (range 85-753 cells/uL) and elevated protein (87-318mg/dL). Each patient tested positive for Lyme on two-tiered serum testing and was diagnosed with LNB. All three cases were associated with a delay to health care presentation (mean 20days) and a delay to diagnosis and treatment (mean 54days) due to under-recognition and ongoing evaluation. With the geographic expansion of Lyme disease, increasing awareness of LNB manifestations and acquiring detailed travel histories in low-incidence areas is crucial to prompt delivery of care. Clinicians should be aware of two-tiered serum diagnostic requirements and use adjunctive studies such as lumbar puncture and MRI to eliminate other diagnoses. Treatment with an appropriate course of antibiotics leads to robust improvement in neurological symptoms.