Lyme Neuroborreliosis: Current Insights into Diagnosis and Management – A Narrative Review

Abstract

Introduction and purpose: Lyme neuroborreliosis is a neurological manifestation caused by Borrelia burgdorferi infection, characterized by a wide range of clinical symptoms. The purpose of this narrative review is to provide an overview of this condition, focusing specifically on current challenges in diagnosis, neuroimaging and treatment. A comprehensive literature search was conducted across databases spanning the years 2015–2026. This review focuses on current international guidelines, meta-analyses of diagnostic parameters, as well as pivotal studies on advanced neuroimaging and the management of Lyme neuroborreliosis. 

Description of the state of knowledge: Definitive diagnosis is often complicated by the limited early sensitivity of standard two-tiered serology. While the intrathecal antibody index (AI) remains the European diagnostic "gold standard," it may yield false-negative results in a proportion of early cases. The B-cell chemoattractant CXCL13 has emerged as a highly sensitive biomarker for early neuroinflammatory infection, often preceding the humoral response. Conversely, PCR exhibits restricted clinical utility due to its low sensitivity. Neuroimaging frequently reveals cranial nerve enhancement, while 3.0T proton magnetic resonance spectroscopy can detect subclinical metabolic dysfunction, such as reduced N-acetylaspartate levels, in radiographically normal brain tissue. Management necessitates antibiotics with high central nervous system penetration. Summary: The long-term prognosis for LNB is generally favorable with prompt intervention. However, Post-Treatment Lyme Disease Syndrome (PTLDS) develops in a subset of patients, who suffer from persistent fatigue, "brain fog" and musculoskeletal pain despite the resolution of active infection. Managing these persistent symptoms remains a clinical challenge, as they significantly impact the quality of life despite successful spirochetal eradication.