Neuroborreliosis Research Articles

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

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

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

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

Optic nerve involvement in patients with Lyme neuroborreliosis: an electrophysiological study.

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. 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. 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. In LNB patients, VEP helps to increase sensitivity of an early diagnostic process.

Sacral Radiculitis as the First Manifestation of Lyme Neuroborreliosis (P3-13.002)

Sacral Radiculitis as the First Manifestation of Lyme Neuroborreliosis (P3-13.002)

A Rare Case of Lyme Neuroborreliosis Presenting as Bannwarth Syndrome in Texas (P3-13.005)

A Rare Case of Lyme Neuroborreliosis Presenting as Bannwarth Syndrome in Texas (P3-13.005)

Neurofilament Light Chain Concentration in Cerebrospinal Fluid in Children with Acute Nontraumatic Neurological Disorders.

(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.

Two-tiered serology in patients with Lyme neuroborreliosis

<p><strong>Introduction. </strong>Lyme borreliosis is a multisystem infectious disease caused by Borrelia burgdorferi sensu lato complex. It is transmitted by Ixodes ticks. Apart from erythema migrans, other manifestations require laboratory confirmation. The aim of our study was to analyze the results of Two-Tiered Testing in patients with possible Lyme neuroborreliosis (LNB).</p> <p><strong> Method.</strong> We conducted a prospective diagnostic study at the University Clinical Centre of Republic of Srpska from October 2017 to October 2021. The study included 51 patients exam ined and treated under suspicion of Lyme neuroborreliosis (LNB). We used Two-Tiered Testing through ELISA anti-Borrelia IgM/IgG and confirmatory Immunoblot anti-Borrelia test IgM/ IgG.</p> <p><strong> Results. </strong>ELISA anti-Borrelia IgM in serum was positive in 25.5% patients and IgG in 76.47%, while in cerebrospinal fluid (CSF) IgM was positive in 13.7% patients and IgG in 39.2%. Immuno blot test of anti-Borrelia IgM in serum was at the borderline in 7.84% patients, positive in 6.17% and no data for 35.29%, while IgG was positive in 54.9% of patients and no data for 37.25%. A strong correlation between results of ELISA anti-Borrelia IgM in serum and CSF was observed (ρ=0.802, p<0.001) and also between ELISA anti-Borrelia IgG and Immunoblot IgG in serum (ρ=0.787, p<0.001).</p> <p><strong>Conclusion.</strong> Two-Tiered Testing is very important in patients with possible LNB. False positive and false negative results are possible and test should be interpreted with caution and in correlation with the clinical manifestation and other avail able tests. More work needs to be done to develop new reli able diagnostic test for LNB, such as detection of CXCL13 in CSF, titrate the interleukin-6 (IL-6) in addition to the CXCL13 chemokine.</p>

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

ObjectivesSerum 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 methodsPatients 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.ResultsAt 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).ConclusionOur 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.

Why Is the Duration of Erythema Migrans at Diagnosis Longer in Patients with Lyme Neuroborreliosis Than in Those without Neurologic Involvement?

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.

Isolated Intracranial Hypertension as a Presentation of Pediatric Lyme Borreliosis: A Case Report and Literature Review

BackgroundIt 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. MethodsCase report and literature review. ResultsA 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. ConclusionsLyme 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.

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.

A key protein from Borrelia burgdorferi could stimulate cytokines in human microglial cells and inhibitory effects of Cucurbitacin IIa

Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by Borrelia burgdorferi (Bb) infection. However, its pathogenesis is not fully understood. We used recombinant BmpA (rBmpA) to stimulate human microglia cell HMC3, then collected the culture supernatant and extracted total RNA from cells, and used the supernatant for cytokine chip, then ELISA and qPCR technology were used to validate the results from cytokine chip. After rBmpA stimulation of microglia, 24 inflammation-related cytokines showed elevated expression. Among them, six cytokines (IL-6, IL-8, CCL2, CCL5, CXCL1, and CXCL10) increased significantly in mRNA transcription, three cytokines (IL-6, IL-8, and CXCL10) concentrations in the cell supernatant increased significantly after the rBmpA stimulation, and CuIIa could inhibit expression of these cytokines. The BmpA can stimulate human microglia to produce large amounts of cytokines, leading to the occurrence of inflammation, which may be closely related to the development of LNB. CuIIa can inhibit BmpA-induced cytokine production in microglia, which may have potential therapeutic effects on LNB.

Yearly Occurrence and Seasonality of Neuro-ophthalmic Manifestations of Pediatric Lyme Disease.

To review the neuro-ophthalmic manifestations of Lyme disease at a central Ohio pediatric tertiary care center. A retrospective chart review of patients diagnosed as having Lyme disease from September 2015 to September 2020 was completed. Demographic information, diagnosis dates, and manifestations of Lyme disease were recorded. Patients were excluded for age older than 18 years or lack of corroborated Lyme disease diagnosis. Descriptive statistics were performed. Of the 212 cases of pediatric Lyme disease reviewed, 50 patients had neuroborreliosis. The data showed an increase in Lyme disease and neuroborreliosis cases from 2018 to 2020, with a preponderance of diagnoses in the summer months. Twenty-four patients had meningitis, and 6 of these patients (25%) were diagnosed as having bilateral optic disc edema that was clinically consistent with intracranial hypertension. Papilledema in the setting of Lyme meningitis may be more common than previously reported in central Ohio. If Lyme disease meningitis is suspected, an opening pressure should be recorded at the time of lumbar puncture and, if elevated, an ophthalmologic evaluation for optic nerve edema is indicated. [J Pediatr Ophthalmol Strabismus. 2024;61(3):179-182.].

The Rrp2-RpoN-RpoS pathway plays an important role in the blood-brain barrier transmigration of the Lyme disease pathogen.

Lyme disease, caused by Borrelia (or Borreliella) burgdorferi, is a complex multisystemic disorder that includes Lyme neuroborreliosis resulting from the invasion of both the central and peripheral nervous systems. However, factors that enable the pathogen to cross the blood-brain barrier (BBB) and invade the central nervous system (CNS) are still not well understood. The objective of this study was to identify the B. burgdorferi factors required for BBB transmigration. We utilized a transwell BBB model based on human brain-microvascular endothelial cells and focused on investigating the Rrp2-RpoN-RpoS pathway, a central regulatory pathway that is essential for mammalian infection by B. burgdorferi. Our results demonstrated that the Rrp2-RpoN-RpoS pathway is crucial for BBB transmigration. Furthermore, we identified OspC, a major surface lipoprotein controlled by the Rrp2-RpoN-RpoS pathway, as a significant contributor to BBB transmigration. Constitutive production of OspC in a mutant defective in the Rrp2-RpoN-RpoS pathway did not rescue the impairment in BBB transmigration, indicating that this pathway controls additional factors for this process. Two other major surface lipoproteins controlled by this pathway, DbpA/B and BBK32, appeared to be dispensable for BBB transmigration. In addition, both the surface lipoprotein OspA and the Rrp1 pathway, which are required B. burgdorferi colonization in the tick vector, were found not required for BBB transmigration. Collectively, our findings using in vitro transwell assays uncover another potential role of the Rrp2-RpoN-RpoS pathway in BBB transmigration of B. burgdorferi and invasion into the CNS.

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.

Doxycycline for the Treatment of Lyme Disease in Young Children.

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. 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. 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. 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.

Case report: Successive ipsilateral and contralateral laryngeal nerve palsy as probable manifestation of neuroborreliosis

Neuroborreliosis is part of advanced stage of Lyme disease and often characterized by damage to the cranial and/or peripheral nerves. Involvement of one or both recurrent nerves is rare. Diagnosis is often difficult and based on a set of clinical manifestations, biological arguments, and cerebrospinal fluid (CSF) analysis. A 70-year-old man was referred to our Voice Clinic with a 3-month history of dysphonia caused by right vocal fold paralysis (VFP) without any cutaneous symptoms of tick bite or erythema migrans in the previous weeks and normal initial radiological examination (neck and thorax CT). Methylprednisolone had already been prescribed but without any clinical improvement. Late biological investigation 3 months after initial symptoms of VFP showed high IgG (93 U/mL; reference <10 U/mL) against Borrelia burgdorferi (BB), which was confirmed by two immunoblot markers (VIsE, p39 antigens). Therefore, a possible manifestation of Lyme disease with involvement of the right inferior laryngeal nerve was suspected, namely Lyme neuroborreliosis. However, given the spontaneous recovery of the patient after 7 months without any adapted antimicrobial regimen treatment, the diagnosis of neuroborreliosis was not confirmed by a lumbar puncture. Nineteen months later, the patient presented again for the same symptomatology but as left VFP. High IgG (68 U/mL) and IgM (>6, reference <0.90) levels against BB were confirmed by immunoblot. Subsequently, lumbar puncture was performed and revealed IgG against BB at 46.1 UA/mL (reference<5.5 UA/mL) in the CSF, with an extremely high IgG intrathecal synthesis antibody index (281.33, positive if > 1.5). Intrathecal antibody synthesis is the gold standard for Lyme neuroborreliosis demonstrating a specific immune response to BB in the central nervous system, but with the limitation of persistence for years after eradication. Our patient did not exhibit pleocytosis in the CSF. Therefore, two criteria of the European Federation of Neurological Societies (EFNS) guidelines are fulfilled for possible neuroborreliosis. Doxycycline treatment led to rapid recovery in less than 8 weeks and normal mobility of the left vocal fold. Because of this very uncommon clinical presentation with two successive episodes of VFP for no other obvious reason and serological evidence from the serum and CSF during the second episode, we consider it possible that the first episode of VFP could also have been a manifestation of neuroborreliosis. This case is the first report of possible relapse of laryngeal palsy successively on the right, and then the left side as a manifestation of Lyme neuroborreliosis.

Vasculitis and Ischemic Stroke in Lyme Neuroborreliosis-Interventional Management Approach and Literature Review.

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. 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. 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. 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. Neuroradiological interventions can be considered in patients with vascular complications of Lyme neuroborreliosis as an additional extension of the primary drug therapy.