Lyme neuroborreliosis

Abstract

Neuroborreliosis, an infection of the nervous system caused by spirochetes of the genus Borrelia, has achieved worldwide attention in the last decade as part of the clinical spectrum of Lyme disease. This disorder, caused by Borrelia burgdorferi, has increased in incidence to become the most frequent arthropod-borne infection in North America and Europe. As a result of this rapid rise in incidence and of its protean neurological manifestations, this disease has created an important challenge to modern neurology. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. This review takes a chronological approach to clinical neuroborreliosis to summarize its most important aspects. The limitations as well as the benefits of laboratory diagnosis are also considered, with the aim of providing assistance in this area. Recent advances in neuroimmunology regarding the pathogenesis of neuroborreliosis that may elucidate its protean clinical spectrum are summarized.

Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A

“…Therefore, any degree of OspA-salivary gland binding is not likely to be functionally relevant. These studies also indicate that OspAOspA interactions may increase spirochete adherence in the gut through self-binding, particularly at high B. burgdorferi density, and this phenomenon may partially explain the reported in vivo aggregation of B. burgdorferi in the tick gut or on cell lines in vitro (29)(30)(31)(32)(33). The downregulation of OspA by spirochetes during the bloodmeal may also facilitate dissemination to the tick salivary glands and the host's dermis by preventing the bacteria from clumping to one another during transmission.…”

Heterozygous Arg753Gln Polymorphism of Human TLR-2 Impairs Immune Activation by Borrelia burgdorferi and Protects from Late Stage Lyme Disease

“…Incidence increased significantly over the last years, with Ͼ23,000 cases in the U.S. in 2002 (2). LD displays different clinical stages: erythema chronicum migrans (ECM) is associated with early localized infection; early disseminated infection commonly may include facial palsy as well as meningoencephalitis, the latter occurring more frequently in Europe as compared with the U.S. (3). Lyme arthritis is the most common manifestation of late disseminated or late stage LD in the U.S., while acrodermatitis chronica atrophicans (ACA) is more often observed in Europe (4).…”

“…Osps are anchored within the outer membrane via a triacylated lipid anchor structure comprising a N-palmitoyl-S- [2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)cysteinyl moiety at the amino terminus, also referred to as Pam 3 Cys, shown to induce cytokines in mononuclear phagocytes via TLR-2 in vitro (10 -12). To interact with a rather wide spectrum of ligands, TLR-2 forms heterodimers with TLR-1 and TLR-6 (13).…”

Borrelia burgdorferi supercoiled plasmids encode multicopy tandem open reading frames and a lipoprotein gene family

“…Now recognized as the most common arthropod-borne infection in the United States (10), Lyme disease typically proceeds in stages characterized by a wide range of clinical manifestations (47). When left untreated, the disease may become chronic, culminating in debilitating arthritis and various neurologic disorders (17,27,47). During the development of these clinical manifestations, there are vigorous cellular and humoral immune responses which, for unclear reasons, fail to entirely eradicate the spirochetes.…”