Plasma Exchange for Lyme Neuroborreliosis delayed diagnosis: A case report.

Lyme neuroborreliosis (LNB) is a rare infectious disease, caused by Borrelia burgdorferi spirochetes and responsible for a variety of neurological manifestations. The most common manifestations of LNB in children are cranial nerve involvement, especially facial nerve palsy often accompanied by lymphocytic meningitis. In this article, we present a case of a 4-year-old boy presented to our emergency department with abdominal pain evolving for a week and symmetrical ascending progression of weakness responsible for severe respiratory failure. Diagnosis of Guillain-Barré syndrome (GBS) was initially suspected. Although our patient had received 2 courses (each of 5 days) of Intravenous immunoglobulin (IVG) treatment, no clinical improvement was observed. The diagnosis of LNB was confirmed by detection of both IgG and IgM specific antibodies in serum. The patient's muscle weakness got better after a 2- week course of Ceftriaxone but respiratory muscle failure didn't improve with two extubation failures. Consequently, we decided to conduct plasmapheresis procedures. We managed to extubate the child and discharge him after a good recovery of his symptoms. Pediatricians must consider LNB disease in the differential diagnosis of GBS, especially when the patient didn't recover after IVG treatment. This case shows that plasmapheresis could be effective for pediatric neuroborreliosis cases with severe neurological disorders.

An intervention in general practice to improve the management of Lyme borreliosis in Denmark.

BACKGROUND: Our objectives were to improve the following outcomes in patients with Lyme borreliosis (LB) through an educational intervention in general practice: (i) increase the number of hospital referrals on suspicion of LB, (ii) increase the number of cerebrospinal fluid (CSF) tests examined for Borrelia burgdorferi antibody index, (iii) decrease the number of serum-B. burgdorferi antibody tests ordered, (iv) shorten delay from symptom onset to hospital in Lyme neuroborreliosis (LNB) patients, (v) increase LB knowledge among general practitioners. METHODS: A prospective non-blinded non-randomized intervention trial on the island of Funen, Denmark. The intervention included oral and written education about LB and was carried out in areas with an LNB incidence ≥4.7/100.000 between 22 January 2019 and 7 May 2019. Results were compared between the intervention group (49 general practices) and the remaining general practices in Funen (71 practices) 2 years before and after the intervention. RESULTS: In the study period, 196 patients were referred on suspicion of LB, a 28.9% increase in the intervention group post-intervention, 59.5% increase in the control group (P = 0.47). The number of CSF-Borrelia-antibody index tests increased 20.8% in the intervention group, 18.0% in the control group (P = 0.68), while ordered serum-B. burgdorferi antibody tests declined 43.1% in the intervention group, 34.5% in the control group (P = 0.30). 25.1% had the presence of serum-B. burgdorferi antibodies. We found no difference in LNB pre-hospital delay before and after intervention or between groups (P = 0.21). The intervention group performed significantly better on a follow-up questionnaire (P = 0.02). CONCLUSION: We found an overall improvement in LB awareness and referrals among general practitioners but could not show any effect of the intervention on clinical outcomes of LNB.

Assessment of the Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication Among Patients With Lyme Neuroborreliosis in Denmark.

Importance: The association of Lyme neuroborreliosis with the development of psychiatric disease is unknown and remains a subject of debate. Objective: To investigate the risk of psychiatric disease, the percentage of psychiatric hospital inpatient and outpatient contacts, and the receipt of prescribed psychiatric medications among patients with Lyme neuroborreliosis compared with individuals in a matched comparison cohort. Design, Setting, and Participants: This nationwide population-based matched cohort study included all residents of Denmark who received a positive result on an intrathecal antibody index test for Borrelia burgdorferi (patient cohort) between January 1, 1995, and December 31, 2015. Patients were matched by age and sex to a comparison cohort of individuals without Lyme neuroborreliosis from the general population of Denmark. Data were analyzed from February 2019 to March 2020. Exposures: Diagnosis of Lyme neuroborreliosis, defined as a positive result on an intrathecal antibody index test for B burgdorferi. Main Outcomes and Measures: The 0- to 15-year hazard ratios for the assignment of psychiatric diagnostic codes, the difference in the percentage of psychiatric inpatient and outpatient hospital contacts, and the difference in the percentage of prescribed psychiatric medications received among the patient cohort vs the comparison cohort. Results: Among 2897 patients with Lyme neuroborreliosis (1646 men [56.8%]) and 28 970 individuals in the matched comparison cohort (16 460 men [56.8%]), the median age was 45.7 years (interquartile range [IQR], 11.5-62.0 years) for both groups. The risk of a psychiatric disease diagnosis and the percentage of hospital contacts for psychiatric disease were not higher among patients with Lyme neuroborreliosis compared with individuals in the comparison cohort. A higher percentage of patients with Lyme neuroborreliosis compared with individuals in the comparison cohort received anxiolytic (7.2% vs 4.7%; difference, 2.6%; 95% CI, 1.6%-3.5%), hypnotic and sedative (11.0% vs 5.3%; difference, 5.7%; 95% CI, 4.5%-6.8%), and antidepressant (11.4% vs 6.0%; difference, 5.4%; 95% CI, 4.3%-6.6%) medications within the first year after diagnosis, after which the receipt of psychiatric medication returned to the same level as the comparison cohort. Conclusions and Relevance: In this population-based matched cohort study, patients with Lyme neuroborreliosis did not have an increased risk of developing psychiatric diseases that required hospital care or treatment with prescription medication. The increased receipt of psychiatric medication among patients with Lyme neuroborreliosis within the first year after diagnosis, but not thereafter, suggests that most symptoms associated with the diagnosis subside within a short period.

Abdominal pain as first manifestation of lyme neuroborreliosis in children, case report and review of literature.

BACKGROUND: Lyme neuroborreliosis can cause a variety of neurological manifestations. European children usually present facial nerve palsy, other cranial nerve palsies and aseptic meningitis. CASE PRESENTATION: We hereby report a case of Lyme neuroborreliosis in a 9-year-old boy with abdominal pain as first symptom and subsequent onset of attention deficit and ataxia. Diagnosis was made by detection of specific antibody in both serum and cerebrospinal fluid with neuro-radiological images suggestive for this infectious disease. A 12-months follow-up was performed during which no relevant neurological sequelae were revealed. CONCLUSION: This case report shows that abdominal radiculitis, although extremely rare, could be the first manifestation of early Lyme neuroborreliosis in pediatric patients. Pediatricians must consider Lyme disease in the differential diagnosis of abdominal pain of unknown origin in children, especially in countries where the infection is endemic.

[A story of neuroborreliosis†: case report]. / Histoire de neuroborréliose†: étude d'un cas.

Neuroborreliosis affects approximately 15 % of people infected with Borrelia burgdorferi. The symptoms are very varied, which can sometimes delay the diagnosis. We can diagnose a neuroborreliosis in front of a compatible clinic and laboratory examinations, in particular a lumbar puncture showing a pleocytosis, an intrathecal synthesis of antibodies against B. burgdorferi, and an increased level of chemokine CKCL13. We present the case of a patient in whom the diagnosis was delayed in connection with non-specific symptoms and we review the latest recommendations in terms of treatment of neuroborreliosis.

La neuroborréliose touche entre 10 et 15 % des personnes infectées par Borrelia burgdorferi. Les symptômes sont très variés, ce qui peut parfois retarder le diagnostic. Celui-ci est posé en présence d'une clinique compatible et des examens de laboratoire, notamment une ponction lombaire montrant une pléocytose, une synthèse intrathécale d'anticorps contre B. burgdorferi et une augmentation de la chimiokine CXCL13. Nous présentons le cas d'un patient chez qui le diagnostic a mis du temps à être posé en lien avec des symptômes peu spécifiques et revoyons les dernières recommandations en termes de traitement de la neuroborréliose.

Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance.

Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.

Guidelines for diagnosis and treatment in neurology - Lyme neuroborreliosis.

Lyme borreliosis is the most common tick-borne infectious disease in Europe. A neurological manifestation occurs in 3-15% of infections and can manifest as polyradiculitis, meningitis and (rarely) encephalomyelitis. This S3 guideline is directed at physicians in private practices and clinics who treat Lyme neuroborreliosis in children and adults. Twenty AWMF member societies, the Robert Koch Institute, the German Borreliosis Society and three patient organisations participated in its development. A systematic review and assessment of the literature was conducted by the German Cochrane Centre, Freiburg (Cochrane Germany). The main objectives of this guideline are to define the disease and to give recommendations for the confirmation of a clinically suspected diagnosis by laboratory testing, antibiotic therapy, differential diagnostic testing and prevention.

Occurrence of Lyme disease infection in a non-endemic area in Northern Italy.

BACKGROUND: In Italy, the incidence of human tick-borne disease has increased over the last decades. Since 2015 a multidisciplinary group has been established in Sacco Hospital for the management of the patients affected by Lyme disease (LD). A retrospective evaluation (2015-2017) was performed for LD in non-endemic areas. METHODS: Retrospective analysis of all 1000 samples for 800 patients screened for LD antibodies at the Sacco Hospital in 3 years (2015-2017). Clinical and epidemiological data were collected and compared with the serological results. RESULTS: Among the 800 patients screened, 134 of them were diagnosed with borreliosis during 2015 (37 cases), 2016 (31 cases) and 2017 (66 cases). Localized LD was diagnosed 100 out of 134 cases (69%): in most of them (N.=63) erythema migrans has been documented; in 37 out of 100 it was not possible to detect it. In only three cases, patients complained of different clinical symptoms such as headache, arm and facial pain respectively. 23 out of 134 cases (16%) showed a persistence of serological positivity and symptoms with osteomuscular involvement and fatigue, despite the therapy (late LD). In that same study 11 out of 134 patients (7%) received a diagnosis of neuroborreliosis. CONCLUSIONS: Our data reported a high percentage of LD infection (19%) in a non-endemic area. The definition of a Multidisciplinary Working Group and a clinical care pathway allowed a better clinical management of LD cases treated in Sacco Hospital, Milan.

Functional signs in patients consulting for presumed Lyme borreliosis.

INTRODUCTION: Little is known about the functional symptoms associated with Lyme borreliosis (LB) in Europe. We aimed to assess functional symptoms associated with presumed LB and to compare patients with and without confirmed LB. MATERIALS AND METHODS: We performed a retrospective monocenter study. Patients consulting for presumed LB were included. RESULTS: Between November 2015 and June 2018, 355patients were included (mean age: 51years, 52% of women) of which 48had LB: erythema migrans (42%), early disseminated LB (50%; 35% of neuroborreliosis cases), and late disseminated LB (8%). The most frequently reported functional symptoms were neuropathic pain (23%), arthralgia (23%), and asthenia (17%). Other functional symptoms were rare (≤10%). Three hundred and seven (86%) patients did not have LB. Patients with confirmed LB reported fewer functional symptoms than patients without LB (1.8 (±1.7) vs. 3.6 (±2.5), P<0.001) with a shorter duration of symptoms (< 3 months in 48% vs. 16% of cases, P<0.001). They less often reported asthenia (17% vs. 59%, P<0.001), widespread pain (10% vs. 31%, P=0.003), myalgia (10% vs. 32%, P=0.002), memory disorders (4% vs. 16%, P=0.03), irritability (2% vs. 23%, P±0.001), and sadness (0% vs. 16%, P=0.003). CONCLUSION: In patients consulting for presumed LB, patients diagnosed with LB had fewer and shorter functional symptoms than patients without LB.

Comparison of Neuroborreliosis Between Children and Adults.

BACKGROUND: Lyme neuroborreliosis (NB) is a tick-borne infectious disorder of the nervous system caused by Borrelia burgdorferi spirochetes. There are not many data available regarding the differences in the course of NB in children and adults. The aim of our study was to compare the clinical course of NB between children and adults. METHODS: Retrospective analysis of medical documentation of 181 patients with NB was performed. The patients were divided into 2 groups: Group I: 57 children with NB; Group II: 124 adults with NB. Medical data, such as patients' age, sex, place of living (residence), time from a tick bite, subjective complaints, general examination results, laboratory parameters and treatment were analyzed. RESULTS: In children, the most common symptoms were headache (89.5%), neck stiffness (64.9%) and nausea and vomiting (56.1%). In adults, the most common symptoms were headache (77.4%), facial nerve palsy (59.7%), neck stiffness (59.7%), vertigo (41.9%) and lumbosacral region pain (37.1%). Bannwarth's syndrome was observed in 10.5% of children and 36.3% of adults. In cerebrospinal fluid (CSF) in children, the pleocytosis at admission was higher than in adults, but protein concentration was significantly lower. There were no differences in percentage of mononuclear cells in CSF smear between the groups. In CSF examination after treatment, a decrease in pleocytosis and protein concentration was observed in both groups. Analysis of effectiveness of treatment mostly with third generation cephalosporins (defined as complete recovery) between the groups, calculated by the Kaplan-Meier method and compared with the use of the log-rank test, showed no significant differences between children and adults (log-rank P = 0.619). CONCLUSIONS: In children, NB more frequently presented as meningitis, and in adults in the form of Bannwarth's syndrome. CSF pleocytosis in children with NB was higher than in adults, while the protein concentration in children was lower. Outcomes in children and adults were favorable and did not differ after standard NB treatment.

Neuroborreliosis ­ clinical presentation ­ Current state of knowledge

Neuroborreliosis is one of the manifestations of Lyme disease involving central and peripheral nervous system. It is caused by infection with Borrelia burgdorferi spirochete which is transmitted by tick bites. Neuroborreliosis can affect both adults and children. The clinical course in children is often different than in adults. The article discusses the most common clinical symptoms, complications, diagnostics and treatment of neuroborreliosis in children.

Psychosis in Borrelia burgdorferi infection - part I: epidemiology, pathogenesis, diagnosis and treatment of neuroborreliosis. / Zaburzenia psychotyczne w przebiegu zakazenia Borrelia burgdorferi ­ czesc I: epidemiologia, patogeneza, diagnostyka i leczenie neuroboreliozy.

Borreliosis is a multisystem, bacterial, zoonotic infectious disease with diversified spectrumof symptoms, which may also include psychotic disorders. Clinical picture of the disease is often unspecific, which makes the diagnosis relatively difficult. Uncharacteristic process of borreliosis is a result of complex molecular strategies used by spirochetes to infect, disseminate and survive in host organism. Part I of the article is focused on the current knowledge about pathogenesis of Lyme Borreliosis (LB), especially neuroborreliosis. Additionally, epidemic situation in Poland and in Europe was presented. Also, typical clinical manifestations of LB were described. In the article, the crucial pathogenic cell mechanisms were depicted. The processes of infection and dissemination of Borrelia in host were presented. The most important strategies of evading the response of host immune system were also discussed. These mechanisms are probable cause of the chronic and uncharacteristic clinical picture of the disease, as they significantly impair host immune response to bacteria. Also, there were presented molecular processes of neural cells impairment, which may lead to observed clinical symptoms of neuroborreliosis. Furthermore, diagnostic methods, treatment guidelines and some of diagnostic problems were discussed.

Lyme Neuroborreliosis: Clinical Outcomes, Controversy, Pathogenesis, and Polymicrobial Infections.

Lyme borreliosis is the object of numerous misconceptions. In this review, we revisit the fundamental manifestations of neuroborreliosis (meningitis, cranial neuritis, and radiculoneuritis), as these have withstood the test of time. We also discuss other manifestations that are less frequent. Stroke, as a manifestation of Lyme neuroborreliosis, is considered in the context of other infections. The summary of the literature regarding clinical outcomes of neuroborreliosis leads to its controversies. We also include new information on pathogenesis and on the polymicrobial nature of tick-borne diseases. In this way, we update the review that we wrote in this journal in 1995. ANN NEUROL 2019;85:21-31.

Treatment-Related Complications in Children Hospitalized With Disseminated Lyme Disease.

We describe here treatment approaches and treatment-related complications in 138 hospitalized children with disseminated Lyme disease. The patients who received parenteral antibiotics had a higher rate of complications than those who received oral therapy (15.4 vs 4.2 per 1000 days of therapy, respectively; P < .05). Oral therapy should be used preferentially if either route is supported by current guidelines.

[Neuroborreliosis - Diagnostics, treatment and course]. / Neuroborreliose ­ Diagnostik, Therapie und Verlauf.

Lyme neuroborreliosis is a tick-borne infectious disease caused by the spirochete bacterium Borrelia burgdorferi sensu lato. Clinical manifestations are classified as early and late Lyme neuroborreliosis. Early manifestations are much more common than late manifestations. Serological testing should only be performed when typical neurological symptoms are present because false positive results are common due to a high seroprevalence in the population. Cerebrospinal fluid (CSF) analysis should be performed if Lyme neuroborreliosis is suspected. A systematic review found similar effects of beta-lactam antibiotics and doxycycline regarding the outcome of neurological symptoms and adverse effects. The prognosis after antibiotic treatment is usually favorable and residual symptoms can rarely persist. Impairments in quality of life, fatigue, depression and cognitive impairment are not more frequent in patients after treatment of Lyme neuroborreliosis than in the normal healthy population.

[Challenge of neuroborreliosis]. / Herausforderung Neuroborreliose.

Lyme borreliosis is the most frequent tick-borne infection in Europe. It is a multisystemic disease affecting the skin, joints, heart, in rare cases the eyes and regularly the nervous system. Taking current clinical and microbiological guidelines into account, neuroborreliosis can in general be diagnosed and treated successfully. An appropriate guideline-conform antibiotic treatment is effective and in most cases recovery from acute neuroborreliosis is complete. Nevertheless, the evidence base regarding pharmacological treatment needs reform and improvement. Contrary to this scientifically based medical opinion, divergent opinions presented in the media cause uncertainty and confusion among patients and also some physicians. The currently available scientific data on epidemiology, treatment and performance of microbiological testing reveals gaps and therefore a large scope for interpretation. In clinical practice, diagnostics and therapeutic methods that do not fulfill the criteria of evidence-based medicine are widely used due to the uncertain data situation. The Clinical Network Neuroborreliosis (KNN) is a publicly funded network of clinicians and clinical laboratory physicians with the goal to improve knowledge for disease-oriented evaluation of diagnostic and therapeutic methods. In addition, the Robert Koch Institute (RKI) and the KNN are performing an epidemiological study for collation and estimation of the number of neuroborreliosis cases in Germany (aNBorD study).

Clinical management of infectious cerebral vasculitides.

A wide range of infections (virus, bacteria, parasite and fungi) may cause cerebral vasculitides. Headache, seizures, encephalopathy and stroke are common forms of presentation. Infection and inflammation of intracranial vessels may cause pathological vascular remodelling, vascular occlusion and ischemia. Vasculitis in chronic meningitis may cause ischemic infarctions, and is associated with poor outcome. Appropriate neuroimaging (CT-angiography, MR-angiography, conventional 4-vessel angiography) and laboratory testing (specific antibodies in blood and CSF, CSF culture and microscopy) and even brain biopsy are needed to quickly establish the aetiology. Enhancement of contrast, wall thickening and lumen narrowing are radiological signs pointing to an infectious vasculitis origin. Although corticosteroids and prophylactic antiplatelet therapy have been used in infectious cerebral vasculitis, there are no randomized clinical trials that have evaluated their efficacy and safety. Stable mycotic aneurysms can be treated with specific antimicrobial therapy. Endovascular therapy and intracranial surgery are reserved for ruptured aneurysms or enlarging unruptured aneurysms.

Treatment of Lyme neuroborreliosis with plasmapheresis.

Lyme disease is a rare tick-borne multisystemic infection caused by Borrelia burgdorferi. Different neurological conditions were reported in the disease. In this article, we present a 15-year-old patient hospitalized with ataxia who was diagnosed with Lyme neuroborreliosis. Intravenous immunoglobulin and ceftriaxone treatment was applied to the patient for 4 weeks. However, ataxia did not recover, upper and lower muscle weakness developed, and deep tendon reflexes diminished during follow-up. The patient was diagnosed with Guillain-Barre syndrome arising from B. burgdorferi. Second dose of intravenous immunoglobulin treatment was started for 5 days but the patient didn't recover. Therefore administration of plasmapheresis was decided. All symptoms relieved following the plasmapheresis. The effect of plasmapheresis in pediatric neuroborreliosis has not been documented before. This study highlights that plasmapheresis could be a useful alternative for pediatric neuroborreliosis cases. J. Clin. Apheresis 31:476-478, 2016. © 2015 Wiley Periodicals, Inc.

Lyme neuroborreliosis-epidemiology, diagnosis and management.

Lyme disease, caused by the Borrelia burgdorferi bacterium, is the most common vector-borne disease in the northern hemisphere. The clinical presentation varies with disease stage, and neurological manifestations (often referred to as Lyme neuroborreliosis) are reported in up to 12% of patients with Lyme disease. Most aspects of the epidemiology, clinical manifestation and treatment of Lyme neuroborreliosis are well known and accepted; only the management of so-called chronic Lyme disease is surrounded by considerable controversy. This term is used for disparate patient groups, including those who have untreated late-stage infection (for example, late neuroborreliosis), those with subjective symptoms that persist after treatment (termed 'post-treatment Lyme disease syndrome' [PTLDS]), and those with unexplained subjective complaints that may or may not be accompanied by positive test results for B. burgdorferi infection in serum (here called 'chronic Lyme disease'). The incidence of PTLDS is still a matter of debate, and its pathogenesis is unclear, but there is evidence that these patients do not have ongoing B. burgdorferi infection and, thus, do not benefit from additional antibiotic therapy. Chronic Lyme disease lacks an accepted clinical definition, and most patients who receive this diagnosis have other illnesses. Thus, a careful diagnostic work-up is needed to ensure proper treatment.