BACKGROUND: Neuroborreliosis is the disseminated form of Lyme borreliosis and refers to the involvement of the central nervous system by Borrelia burgdorferi sensu lato spirochetes. Several reports suggest its emergence as a potential cause of cerebral vasculitis and stroke in children and young adults. The objective of this paper is to highlight endovascular treatment options within this context.
METHODS: The medicinal and endovascular treatments of three patients-two adults and one child-with ischemic stroke resulting from neuroborreliosis-associated severe cerebral vasculitis were retrospectively assessed. Detailed descriptions of the clinical course, treatments, and follow-up data for each patient are provided. Additionally, a literature review focusing on endovascular treatment options within this topic was conducted.
RESULTS: Both endovascular and medicinal treatments resulted in excellent clinical outcomes in all three patients, with no observed periprocedural complications. Significant clinical improvement was noted during mid-term follow-up. Follow-up angiographies confirmed stent patency.
CONCLUSIONS: Endovascular interventions as a bailout strategy may enhance clinical outcomes in patients with vascular complications of neuroborreliosis, especially when medicinal therapy alone fails to achieve further improvement. In the setting of severe ischemic stroke with sub-occlusive large vessel stenosis or occlusion, the cause of which is often unknown, it should be considered to prioritize prompt endovascular treatment, even if neuroborreliosis is suspected on admission.

OBJECTIVE: Residual symptoms after treatment of Lyme disease, sometimes called post-treatment Lyme disease symptoms (PTLDs), are a matter of ongoing controversy. To guide treatment recommendations, a systematic review was performed of the available literature on specific treatment for PTLDs.
METHODS: A systematic literature search of MEDLINE and CENTRAL was performed. No restrictions on case definitions, study types or specific interventions were applied to enable a comprehensive overview of the available literature. Risk of bias was assessed using the Cochrane risk of bias tools for randomized controlled trials. Certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Outcomes of interest were quality of life, fatigue, depression and cognition as well as adverse events.
RESULTS: After screening 1274 records, eight eligible randomized controlled trials were included. Heterogeneity was observed regarding inclusion criteria, intervention, length of treatment and outcome measures. For efficacy outcomes, results are presented narratively due to heterogeneity. Eligible studies show no statistically significant difference between antibiotics and placebo regarding quality of life, cognition and depression. Results for fatigue were inconsistent whilst studies with low risk of bias showed no statistically significant difference between antibiotics and placebo. Meta-analysis of safety outcomes showed statistically significantly more adverse events for antibiotics compared to placebo.
CONCLUSIONS: Available literature on treatment of PTLDs is heterogeneous, but overall shows evidence of no effect of antibiotics regarding quality of life, depression, cognition and fatigue whilst showing more adverse events. Patients with suspected PTLDs should not be treated with antibiotics.

BACKGROUND: It is extremely rare for Lyme borreliosis to present solely with features of increased intracranial pressure. The treatment of pediatric Lyme neuroborreliosis with oral versus intravenous antibiotics remains controversial.
METHODS: Case report and literature review.
RESULTS: A 13-year-old male presented with five days of binocular diplopia, several weeks of headache, and a history of multiple tick bites six weeks prior. His examination showed a left eye abduction deficit and bilateral optic disc edema. Magnetic resonance imaging (MRI) of the brain with contrast showed tortuosity of the optic nerves, prominence of the optic nerve sheaths, and enhancement of the left fifth and bilateral sixth cranial nerves. Lumbar puncture showed an elevated opening pressure and a lymphocytic pleocytosis. Lyme IgM and IgG antibodies were positive in the serum and cerebrospinal fluid. The patient was treated with intravenous ceftriaxone for two days empirically followed by doxycycline by mouth for 19 days. Symptoms began improving after 48 hours. The strabismus resolved after two weeks, and the papilledema improved slowly with complete resolution at six months.
CONCLUSIONS: Lyme neuroborreliosis can present as isolated intracranial hypertension in the pediatric population; it can be differentiated from idiopathic intracranial hypertension on MRI, and lumbar puncture and can be confirmed with serum antibody testing. Oral doxycycline can be considered for Lyme neuroborreliosis in children.

UNASSIGNED: In neuroborreliosis (NB) serology might objectively differentiate ongoing from past infection when the intrathecal space is involved. The hierarchy of the parallel serum-CSF (cerebrospinal fluid) methods is seldom discussed and remains elusive in daily practice. We compared the efficacy of certain methods and assessed the prevalence of anti-Borrelia antibodies in the local population.
UNASSIGNED: We summarized standard two-tier test results in all ELISA-reactive samples of patients with suspected NB (n=152) since 2017 and tested 122 unrelated sera for anti-Borrelia antibodies from central Hungary.
UNASSIGNED: The most common central nervous system symptom was a cranial nerve palsy (27.6% of all subjects). CSF was available in 25 cases. A serum-CSF IgG-matched line immunoassay (LIA) detected intrathecal antibody production correctly in 6 of 8 samples when compared to the ELISA-based antibody-index (AI). Among the 122 random sera the prevalence of specific anti-Borrelia IgG antibodies (on LIA, not including anti-p41) were 6.8% above 30 and 10% above 60 years. Our results enable us to assume the predictive values of serological results according to the pretest probability of neuroborreliosis.
UNASSIGNED: Our results suggest that recombinant antigen-based two-tier serology from solely the sera might have sufficient positive predictive value to verify NB in young individuals with characteristic anamnestic data in our region. When parallel serum-CSF testing is warranted, AI should have priority. IgG and albumin concentrations in the both serum and the CSF, the potential time of exposure and the nature and duration of symptoms form the bare minimal set of data for conclusive testing.

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

Evidence-based recommendations for treatment of Lyme neuroborreliosis (LNB) should rely on the available literature. As new data emerges, close review and evaluation of the recent literature is needed to build evidence-based recommendations to inform clinical practice and management of LNB. We performed an update of a previous systematic review on treatment of LNB.
A systematic literature search of Medline and CENTRAL was performed for published studies from 2015 to 2023 to update a previous systematic review. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs; NRS were assessed using the ROBINS-I-tool. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data were integrated into an existing meta-analysis of the available literature.
After screening 1530 records, two RCTs and five NRS with new and relevant data were additionally identified. Meta-analysis showed no statistically significant difference between doxycycline and beta-lactam antibiotics regarding residual neurological symptoms after 12 months. Meta-analysis showed no benefit of extended antibiotic treatment of LNB. Three NRS show no benefit for additional steroid use in LNB with facial palsy.
Additional incorporated recent research corroborates existing guideline recommendations for treatment of LNB. New RCTs add to the certainty of previous analysis showing similar efficacy for doxycycline and beta-lactam antibiotics in LNB. Available evidence shows no benefit for extended antibiotic treatment in LNB. NRS do not suggest a role for steroids in facial palsy due to LNB.

OBJECTIVE: Less than 1 % of patients with Lyme Neuroborreliosis (LNB) present with a cerebrovascular event. Ischaemic strokes occur more commonly than parenchymal or subarachnoid haemorrhages. If cerebral vasculitis due to LNB is suspected, antibiotic treatment should be started immediately, which will normally lead to remission. Very rarely progression and recurrent strokes are observed despite sufficient antibiotic therapy, even if steroids are added. Currently there are no guidelines on the adequate treatment of cerebral vasculitis due to LNB which is not responsive to antibiotics and steroids, but in very few reported cases cyclophosphamide led to disease stabilisation. We reviewed the literature regarding cyclophosphamide treatment in these patients and want to share our experience of cyclophosphamide therapy in progressive cerebral vasculitis due to LNB.
RESULTS: We report a 71-year-old female patient with cerebral vasculitis and multiple strokes as a complication of LNB. Progression could only be halted by additional immunosuppressive treatment using cyclophosphamide. However, at that point the patient had already suffered severe ischaemic brain damage. Similarly, in existing case reports cyclophosphamide had been administered only at a time when patients already showed serious neurological deficits.
CONCLUSIONS: Cerebral vasculitis in patients with LNB is very rare and normally responds to antibiotic treatment. A minority of patients show disease progression despite antibiotics and steroids. Our case report strengthens the recommendation that in those patients - even if signs of progressive vasculitis are only detectable on imaging and not clinically - cyclophosphamide should be considered without delay to prevent further cerebrovascular events.

Lyme neuroborreliosis (LNB) is a manifestation of Lyme disease involving the central and peripheral nervous system. It is caused by the spirochete Borrelia burgdorferi, transmitted by tick bites to a human host. Clinical signs of LNB develop after the dissemination of the pathogen to the nervous system. The infection occurs in children and adults, but the clinical manifestations differ. In adults, painful meningoradicultis is the most common manifestation of LNB, while children often present with facial nerve palsy and/or subacute meningitis. Subacute headache can be the only manifestation of LNB in children, especially during the summer months in Lyme disease-endemic regions. Non-specific symptoms, such as loss of appetite, fatigue or mood changes, may also occur, especially in young children. A high level of suspicion and early recognition of the various clinical manifestations presented by children with LNB is essential to minimize delay in diagnosis and optimize management. This review provides an overview of the spectrum of clinical manifestations, and discusses diagnosis, antibiotic treatment, and clinical outcome of LNB in children.

The safety and efficacy of hyperacute reperfusion therapies in childhood stroke due to focal cerebral arteriopathy (FCA) with an infectious and inflammatory component is unknown. Lyme neuroborreliosis (LNB) is reported as a rare cause of childhood stroke. Intravenous thrombolysis (IVT) and endovascular therapy (EVT) have not been reported in LNB-associated stroke in children. We report two children with acute stroke associated with LNB who underwent hyperacute stroke treatment. A systematic review of the literature was performed to identify case reports of LNB-associated childhood stroke over the last 20 years. Patient 1 received IVT within 73 min after onset of acute hemiparesis and dysarthria; medulla oblongata infarctions were diagnosed on magnetic resonance imaging (MRI). Patient 2 received successful EVT 6.5 hr after onset of progressive tetraparesis, coma, and decerebrate posturing caused by basilar artery occlusion with bilateral pontomesencephalic infarctions. Both patients exhibited a lymphocytic cerebrospinal fluid (CSF) pleocytosis and elevated antibody index (AI) to Borrelia burgdorferi. Antibiotic treatment, steroids, and platelet inhibitors including tirofiban infusion in patient 2 were administered. No side effects were observed. On follow-up, patient 1 showed good recovery and patient 2 was asymptomatic. In the literature, 12 cases of LNB-associated childhood stroke were reported. LNB-associated infectious and inflammatory FCA is not a medical contraindication for reperfusion therapies in acute childhood stroke. Steroids are discussed controversially in inflammatory FCA due to LNB. Intensified antiplatelet regimes may be considered; secondary prophylaxis with acetyl-salicylic acid (ASA) is recommended because of a high risk of early stroke recurrence.

BACKGROUND: Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described.
OBJECTIVE: To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study.
METHODS: Medline, Embase, Scopus, Cochrane library.
METHODS: There was no discrimination on study type, time of publication or language.
METHODS: Review: All articles with definite LNB and confirmed/possible encephalitis. Cohort: LNB cohorts from Denmark, Sweden and Norway 1990-2019 were screened for patients with encephalitis.
METHODS: Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. Cohort: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered.
RESULTS: Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2-90 days). Of 38 patients with available follow-up after median 12 months (IQR 5-13), 32 had fully or partially recovered, two had died. Cohort: Thirty-five patients (median age 67 years, IQR 48-76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2-4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7-34), with further 7 days (IQR 3-34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113-389), 65.6% had residual symptoms. None had died.
CONCLUSIONS: This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered.