Search Results (43)

Lyme disease (LD), caused by the spirochete Borrelia burgdorferi, is the most prevalent tick-borne disease in Europe, including Romania, where endemic areas are well documented. It has a wide range of clinical manifestations and severity, including rare neurological complications. Persistent hyponatremia is an atypical presentation of Lyme neuroborreliosis and can be associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH is characterized by unregulated antidiuretic hormone release, leading to impaired water excretion, dilutional hyponatremia, and low serum osmolality. We report the case of a 16-year-old female with clinically well-tolerated, but severe, refractory hyponatremia, who was poorly responsive to intravenous sodium supplementation and fluid management. Complex investigations ruled out multiple causes of hyponatremia; neuroborreliosis was confirmed via positive Borrelia serologies, despite the absence of a suggestive history of exposure. SIADH likely symptomatology resulted from central nervous system inflammation induced by Borrelia, a mechanism rarely documented in the medical literature. Treatment with antibiotics and fluid restriction led to a gradual improvement in fluid balance and sodium homeostasis. This case emphasizes the importance of considering rare infectious causes, such as LD, in patients with unexplained SIADH, especially in endemic areas. It highlights the importance of a multidisciplinary approach in intricate, complex cases. Full article

The causative agent of Lyme disease, Borrelia burgdorferi, is endemic to Canada, the northeastern United States, northern California, and temperate European regions. It is rarely associated with a travel-related exposure. In this report, we describe a resident of southern Ontario, Canada who developed rash, fever, and cranial nerve VII and XII palsies following a 12 day trip to Ecuador and the Galapagos islands approximately four weeks prior to referral to our center. Comprehensive microbiological work-up was notable for reactive Borrelia burgdorferi serology by modified two-tier testing (MTTT), confirming a diagnosis of Lyme disease. This case highlights important teaching points, including the classic clinical presentation of acute Lyme disease with compatible exposure pre-travel in a Lyme-endemic region of Ontario, initial manifestations during travel following acquisition of arthropod bites in Ecuador, and more severe manifestations post-travel. Given the travel history to a South American country in which Lyme disease is exceedingly uncommon, consideration of infections acquired in Ecuador necessitated a broad differential diagnosis and more comprehensive microbiological testing than would have been required in the absence of tropical travel. Additionally, cranial nerve XII involvement is an uncommon feature of Lyme neuroborreliosis, and therefore warranted consideration of an alternative, non-infectious etiology such as stroke or a mass lesion, both of which were excluded in this patient through neuroimaging. Full article

Background/Objectives: diagnosis of Lyme neuroborreliosis (LNB) relies on medical history, clinical findings, and detection of pathogen-specific antibodies in the blood and cerebrospinal fluid (CSF). The chemoattractant CXCL13 serves as an additional marker for LNB acuity. During the diagnostic workup, cytomorphological examination of immune cells in CSF provides early insights. Lympho-monocytic pleocytosis with plasma cells and activated lymphocytes is usually described as a typical feature of LNB. In contrast we frequently observe a cytological cell picture featuring neutrophilic granulocytes as well as activated mononuclear cells and plasma cells in patients with LNB, which we refer to as a mixed cell picture. We, hence, investigated the presence of granulocytes to determine their role as typical findings associated with LNB. Methods: we conducted a retrospective analysis of CSF cytology in patients diagnosed with definite LNB at the Department of Neurology, Christian Doppler Medical Centre, Salzburg between 2015 and 2021. CSF results of patients with more than 10 erythrocytes/µL were excluded to avoid the presence of granulocytes due to artificial blood contamination. Additionally, CXCL13 levels were recorded, where available. Results: a total of 75 patients (42 female; 56%) met the diagnostic criteria of definite LNB. Cytology revealed the presence of granulocytes in the CSF of 91% of the patients (68/75). CXCL13 elevation was found to be significantly associated with the presence of granulocytes in CSF (p = 0.0025, or 1.009 (95% CI: 1.003–1.016). Conclusions: we confirm a mixed cell picture with granulocytes, activated mononuclear cells and plasma cells being a typical finding in the CSF cytology of LNB. The association between granulocytes and elevated CXCL13 suggests that their presence is a specific feature of the acute, untreated phase of LNB. Full article

CXCL13 is a chemokine which is upregulated within the CNS in multiple sclerosis, Lyme neuroborreliosis, and other inflammatory diseases and is increasingly clinically useful as a biomarker. This review provides background for understanding its function in the immune system and its relationship to ectopic lymphoid follicles. Also reviewed are its utility in multiple sclerosis and Lyme neuroborreliosis and potential problems in its measurement. CXCL13 has the potential to be an exceptionally useful biomarker in a range of inflammatory diseases. Full article

Lyme borreliosis (LB) is more common in the Northern Hemisphere. It is endemic mainly in North America, where the vectors are Ixodes scapularis and Ixodes pacificus, and in Eurasia, where the vectors are Ixodes ricinus and Ixodes persulcatus. Both tick-borne diseases and LB are influenced by climate change. Africa and South America are crossed by the equator and are situated in both the Northern and Southern Hemispheres. In Africa, the LB is present on the Mediterranean and the Indian Ocean coasts. Borrelia lusitaniae is prevalent in countries bordering the Mediterranean Sea, such as Tunisia, Morocco, Algeria, and Egypt. Ticks were detected in the Ixodes Ricinus, which are carried by migratory birds and the Ixodes inopinatus and captured by the Psammodromus algirus lizards. The Borreliae Lyme Group (LG) and, in particular, Borrelia garinii, have been reported in countries bordering the Indian Ocean, such as Kenya, Tanzania, and Mozambique, transported by migratory birds from North African countries, where the vector was identified as Hyalomma rufipes ticks. This review aims to document the presence of Borreliae LG and LB in Africa. Full article

(1) Introduction: This pilot study aimed to analyze neurofilament light chain levels in cerebrospinal fluid (cNfL) in a cohort of children with different acute nontraumatic neurological conditions. (2) Methods: This prospective observational cohort study consisted of 35 children aged 3 months to 17 years and was performed from November 2017 to December 2019. Patients’ clinical data were reviewed, and patients were assigned to the following groups: n = 10 (28.6%) meningitis, 5 (14.3%) Bell’s palsy, 7 (20.0%) febrile non-CNS infection, 3 (8.6%) complex febrile seizure, 4 (11.4%) idiopathic intracranial hypertension, and 6 (17.1%) others. cNfL levels were measured using a sensitive single-molecule array assay. (3) Results: The cNfL levels [median (range)] in children with meningitis were 120.5 pg/mL (58.1–205.4), in Bell’s palsy 88.6 pg/mL (48.8–144.5), in febrile non-CNS infection 103.9 pg/mL (60.1–210.8), in complex febrile seizure 56 pg/mL (53.2–58.3), and in idiopathic intracranial hypertension 97.1 pg/mL (60.1–124.6). Within the meningitis group, children with Lyme neuroborreliosis (LNB) had significantly higher cNfL concentrations (median 147.9 pg/mL; range 87.8–205.4 pg/mL) than children with enterovirus meningitis (72.5 pg/mL; 58.1–95.6 pg/mL; p = 0.048) and non-significantly higher cNfL levels when compared to Bell’s palsy (88.6 pg/mL; 48.8–144.5 pg/mL; p = 0.082). There was no correlation between cNfL levels and age. (4) Conclusions: Although the number of patients in this pilot study cohort is limited, higher cNfL levels in children with LNB compared to those with viral meningitis (significant) and Bell’s palsy (trend) may indicate the potential of cNfL as a biomarker in the differential diagnosis of pediatric meningitis and facial palsy. Full article

Tracing the profile of pediatric Lyme borreliosis (LB) in Europe is difficult due to the interregional variation in its incidence and lack in notifications. Moreover, the identification of LB can be challenging. This study is an 18-year case series of 130 children and adolescents aged under 18 years referred to the Pediatric Infectious Diseases Unit at L. Sacco Hospital, Milan, with suspicion of LB, between January 2005 and July 2023. The routine serological workup consisted of a two-step process: an initial screening test followed by Western blot (WB). Forty-four (34%) patients were diagnosed with LB. The median age was six years, and 45% were females. Of the children with erythema migrans (EM), 33 (57%) were confirmed as having true EM, and, of these, 4 (12%) were atypical. Ten (23%) patients had early disseminated/late diseases, including facial nerve palsy (n = 3), early neuroborreliosis (n = 1), arthritis (n = 3), relapsing fever (n = 2), and borrelial lymphocytoma (n = 1). No asymptomatic infections were documented. Over seventy percent of confirmed LB cases (n = 31/44) recalled a history of tick bites; in this latter group, 19 (61%) were from the area of the Po River valley in Lombardy. Almost half of the children evaluated for LB complained of non-specific symptoms (fatigue, musculoskeletal pain, skin lesions/rash, and persistent headache), but these symptoms were observed in only two patients with confirmed LB. Most LB cases in our study were associated with EM; two-tier testing specificity was high, but we found frequent non-adherence to international recommendations with regard to the timing of serology, application of the two-step algorithm, and antibiotic over-prescription. Most children were initially assessed for a tick bite or a skin lesion suggestive of EM by a family pediatrician, highlighting the importance of improving awareness and knowledge around LB management at the primary healthcare level. Finally, the strengthening of LB surveillance at the national and European levels is necessary. Full article

In prior studies, the skin lesion erythema migrans (EM) was present for a longer time period before diagnosis of concomitant borrelial meningoradiculoneuritis (Bannwarth’s syndrome) compared to EM patients without neurologic symptoms. To determine if this observation pertains to other manifestations of Lyme neuroborreliosis (LNB), we compared EM characteristics in patients with borrelial meningoradiculoneuritis (n = 122) to those with aseptic meningitis without radicular pain (n = 72 patients), and to patients with EM but without neurologic involvement (n = 12,384). We also assessed factors that might impact duration. We found that the duration of EM at diagnosis in patients with borrelial meningoradiculoneuritis was not significantly different compared with those with LNB without radicular pain (34 vs. 26 days; p = 0.227). The duration of EM for each of these clinical presentations of LNB, however, was significantly longer than in patients with EM without LNB (10 days; p < 0.001). Contributing factors to this difference might have been that patients with LNB failed to recognize that they had EM or were unaware of the importance of not delaying antibiotic treatment for EM. In conclusion, the duration of the EM skin lesion in EM patients with LNB is longer than in patients with just EM, irrespective of the type of LNB. Full article

C-X-C-motif chemokine ligand 13 (CXCL13) in cerebrospinal fluid (CSF) is increasingly used in clinical routines, although its diagnostic specificity and divergent cut-off values have been defined so far mainly for neuroborreliosis. Our aim was to evaluate the value of CSF-CXCL13 as a diagnostic and treatment response marker and its role as an activity marker in a larger disease spectrum, including neuroborreliosis and other neuroinflammatory and malignant CNS-disorders. Patients who received a diagnostic lumbar puncture (LP) (n = 1234) between July 2009 and January 2023 were included in our retrospective cross-sectional study. The diagnostic performance of CSF-CXCL13 for acute neuroborreliosis was highest at a cut-off of 428.92 pg/mL (sensitivity: 92.1%; specificity: 96.5%). In addition, CXCL13 levels in CSF were significantly elevated in multiple sclerosis with clinical (p = 0.001) and radiographic disease activity (p < 0.001). The clinical utility of CSF-CXCL13 appears to be multifaceted. CSF-CXCL13 is significantly elevated in patients with neuroborreliosis and shows a rapid and sharp decline with antibiotic therapy, but it is not specific for this disease and is also highly elevated in less common subacute neuroinfectious diseases, such as neurosyphilis and cryptococcal meningitis or in primary/secondary B-cell lymphoma. Full article

Lyme disease (LD) spirochetes are well known to be able to disseminate into the tissues of infected hosts, including humans. The diverse strategies used by spirochetes to avoid the host immune system and persist in the host include active immune suppression, induction of immune tolerance, phase and antigenic variation, intracellular seclusion, changing of morphological and physiological state in varying environments, formation of biofilms and persistent forms, and, importantly, incursion into immune-privileged sites such as the brain. Invasion of immune-privileged sites allows the spirochetes to not only escape from the host immune system but can also reduce the efficacy of antibiotic therapy. Here we present a case of the detection of spirochetal DNA in multiple loci in a LD patient’s post-mortem brain. The presence of co-infection with Borrelia burgdorferi sensu stricto and Borrelia garinii in this LD patient’s brain was confirmed by PCR. Even though both spirochete species were simultaneously present in human brain tissue, the brain regions where the two species were detected were different and non-overlapping. The presence of atypical spirochete morphology was noted by immunohistochemistry of the brain samples. Atypical morphology was also found in the tissues of experimentally infected mice, which were used as a control. Full article

Objective: In rare cases, Lyme neuroborreliosis (LNB) can induce cerebral vasculitis leading to severe stenosis of the cerebral vasculature and consecutive ischemia. Therapy is based on anti-biotic treatment of the tick-borne disease, whereas interventional therapeutic options have not been assessed yet. Material and Methods: We report on a patient with LNB and concomitant stenoses and progressive and fatal vasculitis of the cerebral vessels despite all therapeutic efforts by the departments of neurology and interventional neuroradiology. In this context, we also conducted a literature review on endovascular treatment of LNB-associated cerebral ischemia. Results: A 52-year-old female presented with transient neglect and psychomotor slowdown (initial NIHSS = 0). MRI and serology led to the diagnosis of basal meningitis due to LNB with vasculitis of cerebral arteries. Despite immediate treatment with antibiotics and steroids, neurologic deterioration (NIHSS 8) led to an emergency angiography on day 2 after admission. Hemodynamically relevant stenoses of the MCA were treated via spasmolysis and PTA, leading to almost complete neurological recovery. Despite intensified medical treatment, the vasculitis progressed and could only be transiently ameliorated via repetitive spasmolysis. On day 19, she again presented with significant neurologic deterioration (NIHSS 9), and PTA and stenting of the nearly occluded MCA were performed with a patent vessel, initially without hemorrhagic complications. Despite all therapeutic efforts and preserved stent perfusion, vasculitis worsened and the concurrent occurrence of subdural hemorrhage led to the death of the patient. Conclusion: Neuroradiological interventions, i.e., spasmolysis, PTA, and, if necessary, stenting, can and should be considered in cases of LNB-induced vasculitis and stroke that are refractory to best medical treatment alone. Key point: Neuroradiological interventions can be considered in patients with vascular complications of Lyme neuroborreliosis as an additional extension of the primary drug therapy. Full article

The aim of this study was to perform a detailed epidemiological overview of Lyme neuroborreliosis (LNB) 2008–2021 in a highly Lyme borreliosis-endemic area in Sweden using a geographic information system (GIS). Diagnosis of LNB was based on clinical symptoms and analysis of cerebrospinal fluid (CSF) according to European guidelines. From laboratory databases and medical records, we detected all patients with CSF pleocytosis and intrathecal anti-Borrelia antibody production and listed clinical features. The distribution of LNB cases within Kalmar County, Sweden was investigated using GIS. In total, 272 cases of definite LNB were confirmed with an average yearly incidence of 7.8/100,000. Significant differences in incidence were noted between children 0–17 years (16/100,000) and adults 18+ years (5.8/100,000) (p < 0.001), between rural (16/100,000) and urban areas (5.8/100,000) (p < 0.001) and between selected municipalities (p < 0.001). Distinct clinical differences in presentation of LNB were also noted between children and adults. Thus, the incidence of LNB varies significantly locally and in relation to age, and clinical presentation shows differences between children and adults. Surveillance of LNB and knowledge of local epidemiological conditions may facilitate preventive measures. Full article

Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the central and peripheral nervous system. Although most cases of LB can be cured with a course of antibiotics, some children can present prolonged symptoms, which may constitute post-treatment Lyme disease syndrome (PTLDS). The aim of our analysis was the long-term observation of children with NB and the determination of their risk of PTLDS. The clinical observation was supplemented by a laboratory study based on the assessment of the dynamics of anti-VlsE (variable major protein-like sequence, expressed) IgG antibodies in children with NB after antibiotic therapy. The prospective survey based on 40 children presented 1–2 forms of NB. The control group consisted of 36 patients with analogical symptoms for whom LB was excluded. Our long-term observation showed a low risk of developing long-term complications in children who received antibiotic therapy in accordance with the recommendations. The concentration of anti-VlsE IgG demonstrates a statistical significance for differences between the control and the study groups for each measurement period. Higher values of anti-VlsE IgG were observed in the study group, and the concentration decreased from the first measurement period to the next. The article emphasizes the importance of the long-term follow-up of children with neuroborreliosis. Full article

Laboratory analysis of basic cerebrospinal fluid (CSF) parameters is considered as essential for any CSF evaluation. It can provide rapidly very valuable information about the status of the central nervous system (CNS). Our retrospective study evaluated parameters of basic CSF analysis in cases of either infectious or non-infectious CNS involvement. Neutrophils are effector cells of innate immunity. Predominance of neutrophils was found in 98.2% of patients with purulent inflammation in CNS. Lymphocytes are cellular substrate of adaptive immunity. We found their predominance in 94.8% of patients with multiple sclerosis (MS), 66.7% of patients with tick-borne encephalitis (TBE), 92.2% of patients with neuroborreliosis, 83.3% of patients with inflammatory response with oxidative burst of macrophages in CNS and 75.0% of patients with malignant infiltration of meninges (MIM). The simultaneous assessment of aerobic and anaerobic metabolism in CSF using the coefficient of energy balance (KEB) allows us to specify the type of inflammation in CNS. We found predominantly aerobic metabolism (KEB > 28.0) in 100.0% CSF of patients with normal CSF findings and in 92.8% CSF of patients with MS. Predominant faintly anaerobic metabolism (28.0 > KEB > 20.0) in CSF was found in 71.8% patients with TBE and in 64.7% patients with neuroborreliosis. Strong anaerobic metabolism (KEB < 10.0) was found in the CSF of 99.1% patients with purulent inflammation, 100.0% patients with inflammatory response with oxidative burst of macrophages and in 80.6% patients with MIM. Joint evaluation of basic CSF parameters provides sufficient information about the immune response in the CSF compartment for rapid and reliable diagnosis of CNS involvement. Full article

Powassan virus (POWV) is a tick-borne neuroinvasive flavivirus endemic to North America. It is generally transmitted by the tick, Ixodes scapularis. This species also transmits Borrelia burgdorferi, the causative agent of Lyme disease. Infection with B. burgdorferi can result in arthritis, carditis, and neuroborreliosis. These pathogens experience sylvatic overlap. To determine the risk of human exposure to coinfected ticks, the interactions between POWV and B. burgdorferi are assessed in laboratory-infected I. scapularis. Adult male and female I. scapularis ticks are orally inoculated with either both pathogens, POWV only, B. burgdorferi only, or uninfected media. After twenty-one days, the ticks are dissected, and RNA is extracted from their midguts and salivary glands. In infected midguts, the quantity of POWV in coinfected ticks was elevated compared to those with only POWV. In addition, the salivary glands of ticks with infected midguts had increased POWV dissemination to those with only POWV. RNA sequencing is performed to identify the potential mechanism for this pattern, which varies between the organs. Ixodes scapularis ticks are found to be capable of harboring both POWV and B. burgdorferi with a benefit to POWV replication and dissemination. Full article