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.

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.

Parálisis facial, la importancia de realizar una buena historia clínica / Facial palsy, the importance of taking a good medical history

La parálisis facial plantea un diagnóstico diferencial amplio en Pediatría, sobre todo cuando se acompaña de sintomatología que orienta en contra de una parálisis de Bell, por lo que resulta imprescindible realizar una correcta anamnesis. La enfermedad de Lyme es una de las posibles causas de parálisis facial, habiendo sido poco descrita en niños en España. Presentamos el caso de un varón de 11 años con diagnóstico de parálisis facial asociada a infección por B. burgdorferi con evolución favorable tras tratamiento con doxiciclina. (AU)

Facial palsy poses a wide differential diagnosis in pediatrics, especially when it is accompanied by symptoms that make it doubtful whether Bell's palsy is present. It is essential to perform a correct anamnesis to rule out diagnoses that require early detection and treatment to improve the prognosis. Lyme disease (EL) is one of the possible causes of facial palsy, having been seldom described in children in Spain. We present the case of an 11-years-old male with diagnosis of facial palsy associated with B. burgdorferi infection with favorable evolution after treatment with doxycycline. (AU)

Incidence of Lyme Borreliosis in Germany: A retrospective observational healthcare claims study.

Lyme borreliosis (LB) is the most common tick-borne disease in Germany. Although the incidence of LB in Germany has been assessed in several studies, those studies either used data from statutory surveillance, which frequently underreport cases, or data from health claims databases, which may overestimate cases due to non-specific LB case definitions. Here, using a more specific case definition, we describe the incidence of medically-attended LB by disease manifestation, age group, and federal state for the period 2015-2019. Both inpatient and outpatient cases were analyzed from a claims database. To be eligible for inclusion, patients were required to have an LB specific ICD-10 GM diagnosis code plus an antibiotic prescription, and for disseminated manifestations, a laboratory test order additionally. LB cases were classified as erythema migrans (EM), or disseminated disease including Lyme arthritis (LA), Lyme neuroborreliosis (LNB), and all other disease manifestations (OTH). Between 2015 and 2019, the incidence of medically-attended LB cases ranged from 195.7/100,000 population per year (95% confidence interval [CI], 191.0 - 200.5) to 254.5/100,000 population per year (95% CI, 249.0 - 260.0) per year. The majority of cases (92.2%) were EM, while 2.8% presented as LA, 3.8% as LNB, and 1.2% as OTH. For both EM and disseminated disease, the incidence peaked in children aged 5-9 years and in older adults. By federal state, the incidence of medically-attended EM ranged from 74.4/100,000 population per year (95% CI, 71.9 - 77.0) per year in Hamburg, to 394.1/100,000 population per year (95% CI, 370.7 - 417.6) per year in Saxony, whereas for medically-attended disseminated disease, the highest incidence was in Thuringia, Saxony, and Bavaria (range: 22.0 [95% CI, 19.9 - 24.0] to 35.7 [95% CI, 34.7 - 36.7] per 100,000 population per year). This study comprehensively estimated the incidence of all manifestations of medically-attended LB and showed a high incidence of LB throughout Germany. Results from the study support performing epidemiological studies in all federal states to measure the burden of LB and to invest in public health interventions for prevention.

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.

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.

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.

Genome-wide DNA Methylation Profiling in Lyme Neuroborreliosis Reveals Altered Methylation Patterns of HLA Genes.

Lyme neuroborreliosis (LNB) is a complex neuroinflammatory disorder caused by Borrelia burgdorferi, which is transmitted through tick bites. Epigenetic alterations, specifically DNA methylation (DNAm), could play a role in the host immune response during infection. In this study, we present the first genome-wide analysis of DNAm in peripheral blood mononuclear cells from patients with LNB and those without LNB. Using a network-based approach, we highlighted HLA genes at the core of these DNAm changes, which were found to be enriched in immune-related pathways. These findings shed light on the role of epigenetic modifications in the LNB pathogenesis that should be confirmed and further expanded upon in future studies.

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.

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.

Doxycycline for the Treatment of Lyme Disease in Young Children.

BACKGROUND: Doxycycline is considered the first-line treatment of Lyme disease in adolescents and adults, but largely disproven concerns of permanent tooth staining prevented its use and evaluation in children <8 years old. We sought to describe short-term adverse effects and treatment failures among young children receiving oral doxycycline for Lyme disease. METHODS: We completed a 2-pronged evaluation of children with Lyme disease treated with doxycycline. We performed a retrospective case series of patients <8 years old who were diagnosed with Lyme disease and treated with doxycycline. We then performed a telephone follow-up survey study of the patients' parents to gather additional details regarding clinical outcomes and adverse reactions to doxycycline. Descriptive statistics were calculated. RESULTS: A total of 32 patients were identified through the retrospective case series and 18 participated in the follow-up survey. The most common clinical diagnosis (22/32; 69%) was single erythema migrans. Seven (22%) had neurological Lyme disease. Three patients (9%) stopped doxycycline treatment prematurely due to adverse effects. During telephone follow-up, 2 children were reported to have dental staining. No patients were identified with treatment failure during the retrospective case series. On telephone follow-up, 3 patients had residual symptoms after treatment, though none were convincing of treatment failure. CONCLUSIONS: Our study suggests that doxycycline is generally well-tolerated and an effective treatment of Lyme disease in young children. Prospective, observational studies with long-term assessment of dental staining and clinical outcomes are needed. Alternative antibiotics, principally amoxicillin, remain the preferred treatment of non-neurological Lyme disease manifestations in young children, but doxycycline is likely a safe and effective alternative when needed.

IMPACT OF CLINICAL CHARACTERISTICS OF LYME BORRELIOSIS ON PATIENTS' LIFE QUALITY.

OBJECTIVE: The aim: To study the impact of clinical characteristics of the disease on the life quality of patients with Lyme borreliosis. PATIENTS AND METHODS: Materials and methods: Forty-eight (33 women and 15 men) patients with Lyme borreliosis aged 23-77 years and 48 individuals who did not have any somatic diseases that would impact the quality of life (experimental group) were examined. The MOS 36-item Short Form Health Survey (SF-36) was used to study the quality of life. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). RESULTS: Results: According to the SF-36 questionnaire, patients with Lyme borreliosis had a significant decrease in scores for all indicators of physical health (р < 0.001), as well as impaired social (р < 0.001) and emotional (p = 0.027) functioning compared with healthy individuals. The deterioration of the quality of life indicators essentially depends on the clinical characteristics of the disease, namely its duration, the presence of Lyme arthritis, neuroborreliosis, cognitive disorders, multiple organ involvement, disease stage. CONCLUSION: Conclusions: Lyme borreliosis and its certain clinical characteristics have a significant impact on the life quality of patients.

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.

Lyme neuroborreliosis presenting with urinary retention and spastic paraparesis.

Progressive myelopathy, urinary retention and gait problems are rare presenting features of Lyme neuroborreliosis. A 30-year-old man had 11 months of urinary retention and 3 months of spastic paraparesis. MR scans of the brain and the spinal cord showed leptomeningeal thickening with contrast enhancement. Cerebrospinal fluid showed mononuclear pleocytosis, decreased glucose, increased protein and chemokine ligand 13, with intrathecal Borrelia-specific IgM and IgG antibodies. He received 14 days of intravenous ceftriaxone followed by 14 days of oral doxycycline. Despite improvement at 6 months, he still had severe gait problems. Urinary retention in otherwise healthy people needs investigation, and Lyme neuroborreliosis is a rare cause.

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.

Multippel erythema migrans, borrelialymfocytom og nevroborreliose hos eit barn.

BACKGROUND: Lyme disease after a tick bite often presents as erythema migrans, yet less frequent variants of this disease, such as Borrelia lymphocytoma, multiple erythema migrans and neuroborreliosis, are also seen occasionally. CASE PRESENTATION: We report a case of a tick-bitten child who first presented with an indistinct macular erythema around the left eye and a more distinct macular erythema on and around the left ear. The next day, she developed a facial palsy. INTERPRETATION: The case was interpreted as facial multiple erythema migrans and Borrelia lymphocytoma on the ear, followed by neuroborreliosis. The diagnosis of lymphocytoma was made from clinical findings and PCR of skin biopsy. She recovered quickly after intravenous ceftriaxone and is now healthy.

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.