Search Results (53)

CXCL12 is a chemokine acting via CXCR4 that plays a key role in inflammatory processes by regulating leukocyte migration and immune responses, making it an important focus of research in neuroinfections. In this study, the CXCL12 chemokine was evaluated as a potential diagnostic marker of different neuroinfections with particular emphasis on tick-borne encephalitis (TBE). A group of 214 patients with confirmed meningitis and/or encephalitis was included and divided according to etiology into TBE, aseptic meningitis, neuroborreliosis, and purulent meningitis. CXCL12 concentration and other inflammatory parameters were measured in cerebrospinal fluid (CSF). CXCL12 levels were compared with those of controls (N = 25) and analyzed statistically. In addition, serum was used to determine albumin concentrations. CXCL12 concentrations were significantly higher in patients with neuroinfections compared to controls and showed good diagnostic performance in the overall study group (AUC = 0.791), with a more moderate diagnostic performance observed in individual etiological groups, except in the purulent meningitis group, where the effect was not statistically significant, likely due to the small sample size. CXCL12 also demonstrated some utility in differentiating between specific etiologies; however, this effect was limited. Better diagnostic performance was observed when CXCL12 was combined with pleocytosis in a composite model differentiating between the TBE group and aseptic meningitis (AUC = 0.761). The presented results indicate the role of CXCL12 in neuroinflammation while simultaneously highlighting its potential in the development of novel diagnostic approaches for viral neuroinfections. Despite higher levels in TBE, its standalone diagnostic value is limited; however, it may enhance diagnostic accuracy when combined with other markers such as pleocytosis. Full article

Background: Measurements of the B-cell attracting chemokine CXCL13 in cerebrospinal fluid (CSF) has become increasingly popular in the diagnostic work-up for Lyme neuroborreliosis (LNB). ReaScan is a point-of-care test for CXCL13 with a short turnaround-time. However, the diagnostic cut-off value for LNB has not been firmly established. Methods: We conducted a retrospective cohort study including all ReaScan CXCL13 measurements performed on CSF samples at Copenhagen University Hospital, Rigshospitalet, from patients of all ages suspected for LNB in 2020–2025. Patients were categorized in accordance with the European Federation of Neurological Societies (EFNS) diagnostic guidelines for LNB as definite, possible, or non-LNB based on a retrospective review of patient records. The manufacturer-informed cut-off value for positive test results was applied and the diagnostic accuracy was calculated based on the ability to identify patients with possible and definite LNB. In addition, a Youden-index optimized cut-off value was calculated and evaluated on the cohort. Results: A total of 1181 ReaScan CXCL13 measurements from children and adults were evaluated against final diagnoses. Using the manufacturer-informed cut-off value (14 AU/mL) ReaScan CXCL13 reached a sensitivity of 38% and a specificity of 98% for identifying cases of possible and definite LNB. A Youden-index optimized cut-off value (1.79 AU/mL) significantly improved the diagnostic accuracy reaching a sensitivity value of 71% and a specificity of 92%. Conclusions: These real-world clinical data suggest that the current cut-off value for the ReaScan CXCL13 analysis is not optimal for diagnosing LNB. Lowering the cut-off level would significantly increase the diagnostic accuracy. Full article

Background: Guillain–Barré syndrome (GBS) is a rare, immune-mediated disorder affecting the peripheral nerves, often presenting with ascending muscle weakness and possible respiratory failure, usually following an infection. Borrelia burgdorferi, the causative agent of Lyme neuroborreliosis, is an uncommon trigger of GBS. Case presentation: We report the case of a 13-year-old girl with Lyme neuroborreliosis who developed sensorimotor GBS. She presented with progressive, symmetrical weakness, initially in the lower limbs and subsequently in the upper limbs, accompanied by absent deep tendon reflexes. Peripheral demyelination, confirmed in this case, is exceptionally rare. Results: Prompt diagnosis and appropriate treatment, together with rehabilitation measures, prevented further nerve damage. Seven months after onset, she was able to walk with support and had no sensory or cognitive deficits. Conclusions: Lyme neuroborreliosis can rarely trigger GBS with peripheral demyelination. Early recognition, timely intervention, and effective interprofessional collaboration limited the extent of nerve damage and promoted neurological recovery. Full article

Lyme borreliosis (LB), the most common European tick-borne disease, can manifest as an erythema migrans (EM) rash or as disseminated LB. The prospective Burden of Lyme Disease (BOLD) study evaluated the frequency of LB clinical manifestations, including signs, symptoms, and treatment patterns in 14 healthcare practices in endemic regions of six European countries: the Czech Republic, Germany, Poland, Slovakia, Slovenia, and Sweden. Between April 2021 and December 2022, patients with suspected LB were evaluated using predefined case definitions that were applied by investigators to identify medically attended LB cases. Enrolled cases were interviewed about their symptoms. Among the 797 LB cases, 615 (77.2%) had EM and 182 (22.8%) had disseminated disease; 154 of the disseminated cases had Lyme arthritis (LA), five had Lyme neuroborreliosis, and three had Lyme carditis. Geographically, the proportion of disseminated disease varied by country, from 1.1% in Slovenia to 78.0% in Slovakia. Overall, 76.3% of all LB cases in Slovakia were LA. Antibiotic use varied by country, although every country prescribed doxycycline. The frequency of LB manifestations varied substantially between countries. EM was the most common manifestation in all countries except Slovakia, where LA was most common. This study underscores the need for improved prevention strategies. Full article

Background: Macrophages play a key role in clearing Borrelia burgdorferi infection and express somatostatin receptor subtype 2 (SSTR2), a potential imaging target. This study investigates immune activation in neuroborreliosis (NB) and assesses the diagnostic value of ⁶⁴Cu-DOTATATE positron emission tomography/computed tomography (PET/CT) alongside magnetic resonance imaging (MRI). Methods: Prospective cohort study (2024–2025) enrolling patients with suspected NB from four Danish hospitals. NB was defined by the following ≥2 criteria: neurological symptoms, cerebrospinal fluid (CSF) pleocytosis, and intrathecal B. burgdorferi-specific antibodies; patients not meeting these criteria served as controls. Results: The study included 20 participants: 15 NB patients (75%) and 5 controls (25%). PET/CT was performed after a median of 9.5 days of antibiotic treatment. Symmetric ⁶⁴Cu-DOTATATE uptake in dorsal root and paravertebral ganglia was observed in 10 of 15 patients, with cervical involvement in 8 and lumbosacral in 9. All of them had symptoms that corresponded to the anatomical distribution of the uptake. No controls had lumbosacral involvement (p = 0.04). One control with erythema migrans and systemic symptoms showed cervical ganglia uptake. MRI showed cranial or spinal nerve enhancement in five patients. Only one patient had focal PET uptake matching MRI findings and clinical facial palsy. Conclusions: Symmetric ⁶⁴Cu-DOTATATE ganglionic uptake in NB patients may reflect immune activation or altered ganglionic physiology. One patient had focal ⁶⁴Cu-DOTATATE uptake corresponding with palsy and MRI and ⁶⁴Cu-DOTATATE PET/CT did not contribute additional diagnostic value beyond standard clinical evaluation. Full article

Lyme neuroborreliosis (LNB) may mimic other neurological diseases, while neurological diseases may be misdiagnosed as LNB. The aims of the study were to contribute to the knowledge regarding the epidemiology and clinical manifestations of LNB, discuss differential diagnosis, and compare characteristics in patients with and without LNB. We present patients evaluated for suspected LNB by the multidisciplinary team of a “Lyme Borreliosis Centre” in a highly endemic area in Romania. A retrospective study was performed between January 2011 and October 2023 on patients referred for suspected LNB based on neurological manifestations and positive serology for Borrelia burgdorferi antibodies using two-tier testing. A lumbar puncture was performed for diagnosis, and the European LNB definition was used for classification. Of three hundred and three LNB suspected patients, five (1.65%) were classified as definite LNB, eighty-three (27.39%) as possible LNB, and in two hundred and fifteen patients (70.95%), LNB was excluded. Comparing the definite/possible to excluded LNB patients, there was no significant difference in neurological symptoms/manifestations. The patients presented fifty-one neurological, twelve rheumatological, and seven psychiatric diagnoses, with significantly more meningitis/encephalitis/myelitis diagnoses in the definite/possible LNB group, and more demyelinating disease and discopathy in the LNB-excluded group. Considering the complex differential diagnoses, access to laboratory diagnostics and multidisciplinary management should be available in centres that evaluate suspected LNB patients. Comparing results with data from the national surveillance system, we conclude that LNB is underdiagnosed/underreported in Romania. Full article

Background: We report an uncommon presentation of Lyme disease and highlight the importance of a detailed history in a patient with new-onset sixth nerve palsy. Methods: Case report and literature review. Results: A 46-year-old man receiving infliximab presented to the ophthalmology emergency department with horizontal binocular diplopia. History revealed a diffuse headache that had begun three weeks earlier. Ophthalmologic examination demonstrated a left sixth cranial nerve palsy. The workup showed positive Borrelia serum IgG, which was interpreted as a likely false-positive result given the limited specificity of serologic testing. At follow-up, the patient reported left-sided peripheral facial palsy, and worsening headache and diplopia. Further history revealed prior erythema migrans treated with doxycycline four months earlier. Considering these new findings, a lumbar puncture was performed and demonstrated intrathecal production of Borrelia antibodies. Neuroborreliosis, a neurologic involvement secondary to systemic infection by the spirochete Borrelia burgdorferi, was diagnosed. The patient was treated with oral doxycycline for 28 days with complete resolution of symptoms. Conclusions: Lyme disease may present with progressive neuro-ophthalmologic symptoms, underscoring the crucial role of ophthalmologists in its diagnosis. Moreover, immunosuppression may delay diagnosis and allow neurological progression, highlighting the need for careful history taking and close follow-up. Full article

Background/Objectives: Tick-borne diseases (TBDs) are increasingly recognized as causes of both systemic and neurologic illness. While their impact on vascular health is established, their role in cerebrovascular disease remains underexplored. This review aims to synthesize clinical evidence linking TBDs with cerebrovascular events, focusing on mechanisms of injury, pathogen-specific associations, and treatment outcomes. Methods: A narrative review was conducted using Boolean keyword searches across PubMed, Scopus, EMBASE, and Web of Science. Relevant literature on ischemic and hemorrhagic stroke, cerebral vasculitis, and stroke mimics associated with TBDs was examined. The review included case reports, observational studies, and mechanistic research. Pathogen-specific data and disease characteristics were extracted and summarized. Results: Several tick-borne pathogens were associated with cerebrovascular complications. Borrelia burgdorferi was most commonly implicated and typically presented with large-vessel vasculitis. Rickettsia, Ehrlichia, and Anaplasma species caused endothelial injury through immune-mediated inflammation. Powassan virus and Crimean–Congo hemorrhagic fever virus exhibited central nervous system involvement and hemorrhagic potential. Babesia species contributed to vascular injury through thrombocytopenia and embolic complications. Neuroimaging frequently demonstrated multifocal stenoses and vessel wall inflammation. Antimicrobial treatment, particularly with doxycycline or ceftriaxone, was often effective, especially when administered early. Supportive care for stroke symptoms varied by presentation and underlying pathogen. Conclusions: Cerebrovascular disease caused by tick-borne pathogens is an underrecognized but potentially reversible condition. Despite diverse etiologies, most pathogens share a final common pathway of endothelial dysfunction. Early recognition and targeted antimicrobial therapy, combined with supportive stroke care, are essential to improving patient outcomes. Full article

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