Abstract
BackgroundNeuroborreliosis is a tick-borne infectious disease of the nervous system caused by Borrelia burgdorferi. Common clinical manifestations of neuroborreliosis are cranial nerve dysfunctions, polyradiculoneuritis, and meningitis. Diagnosis is usually based on clinical presentation, serologic testing, and analysis of cerebrospinal fluid. Many aspects of pharmacological treatment, such as choice of drug, dosage, and duration are subject of intense debate, leading to uncertainties in patients and healthcare providers alike. To approach the questions regarding pharmacological treatment of neuroborreliosis, we will perform a systematic review.MethodsWe will perform a comprehensive systematic literature search for potentially eligible studies that report outcomes after pharmacological interventions. To adequately consider the wealth of research that has been conducted so far, this review will evaluate randomized controlled trials (RCTs) and non-randomized studies on treatment of neuroborreliosis. We will assess potential risk of bias for each RCT meeting our selection criteria using the Cochrane risk of bias tool for RCTs. For non-randomized studies, we will use the Newcastle-Ottawa Scale and the recently piloted Cochrane risk of bias tool for non-randomized studies. Our primary outcome of interest will be neurological symptoms and the secondary outcomes will be disability, patient-reported outcomes (quality of life, and, if reported separately from other neurological symptoms, pain, fatigue, depression, cognition, and sleep), adverse events, and cerebrospinal fluid pleocytosis. Pooling of data and meta-analysis will only be deemed justified between studies with similar design (e.g., RCTs are only combined with other RCTs), characteristics (e.g., similar populations), and of acceptable heterogeneity (I2 < 80%). Pooled estimates will be calculated using RevMan software. Prespecified subgroup analyses will evaluate groups of antibiotics, length of antibiotic treatment, and different doses of doxycycline. We will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.DiscussionThis systematic review will summarize the available evidence from RCTs and non-randomized studies regarding pharmacological treatment of neuroborreliosis. The available evidence will be summarized and discussed to provide a basis for decision-making for patients and healthcare professionals.Systematic review registrationPROSPERO registration number: CRD42014008839
Highlights
Neuroborreliosis is a tick-borne infectious disease of the nervous system caused by Borrelia burgdorferi
Common clinical manifestations of neuroborreliosis are polyradiculoneuritis (Bannwarth’s syndrome, 63.75% of all cases), in 60% accompanied by cranial nerve dysfunctions, and meningitis (23.75%) [3,4]
Diagnosis of neuroborreliosis is usually based on clinical presentation, serologic testing, and analysis of cerebrospinal fluid (CSF) [10]
Summary
Neuroborreliosis is a tick-borne infectious disease of the nervous system caused by Borrelia burgdorferi. IDSA, EFNS, and AAN guidelines usually recommend cephalosporin antibiotics, doxycycline, or penicillin antibiotics, whereas some authors recommend treatment with other substances, like carbapenem antibiotics, metronidazole, or antimalarial drugs such as hydroxychloroquine for certain subgroups of patients [17]. The IDSA and EFNS guidelines recommend doxycycline doses of 200 mg, whereas the guidelines of the Deutsche Gesellschaft für Neurologie (DGN) and AAN guidelines suggest applying higher doses of up to 400 mg [10,15,16,21] These various, partly contradicting recommendations lead to a considerable ambiguity and doubt in patients and healthcare providers alike when facing treatment decisions for neuroborreliosis. Non-randomized studies seem to be more suitable for the detection of adverse events than RCTs and may have longer follow-up periods [22]
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