Chronic or late lyme neuroborreliosis: analysis of evidence compared to chronic or late neurosyphilis

Abstract

Whether spirochetes persist in affected host tissues and cause the late/chronic manifestations of neurosyphilis was the subject of long-lasting debate. Detection of Treponema pallidum in the brains of patients with general paresis established a direct link between persisting infection and tertiary manifestations of neurosyphilis. Today, the same question is in the center of debate with respect to Lyme disease. The goal of this review was to compare the established pathological features of neurosyphilis with those available for Lyme neuroborreliosis. If the main tertiary forms of neurosyphilis also occur in Lyme neuroborreliosis and Borrelia burgdorferi can be detected in brain lesions would indicate that the spirochete is responsible for the neuropsychiatric manifestations of late/chronic Lyme neuroborreliosis. The substantial amounts of data available in the literature show that the major forms of late/chronic Lyme neuroborreliosis (meningovascular and meningoencephalitis) are clinically and pathologically confirmed. Borrelia burgdorferi was detected in association with tertiary brain lesions and cultivated from the affected brain or cerebrospinal fluid. The accumulated data also indicate that Borrelia burgdorferi is able to evade from destruction by the host immune reactions, persist in host tissues and sustain chronic infection and inflammation. These observations represent evidences that Borrelia burgdorferi in an analogous way to Treponema pallidum is responsible for the chronic/late manifestations of Lyme neuroborreliosis.Late Lyme neuroborreliosis is accepted by all existing guidelines in Europe, US and Canada. The terms chronic and late are synonymous and both define tertiary neurosyphilis or tertiary Lyme neuroborreliosis. The use of chronic and late Lyme neuroborreliosis as different entities is inaccurate and can be confusing. Further pathological investigations and the detection of spirochetes in infected tissues and body fluids are strongly needed.

Keywords: Borrelia burgdorferi; Chronic Lyme disease; Chronic infection; Late Lyme disease; Lyme neuroborrelisosis; Neurosyphilis; Syphilis; Treponema pallidum..

Fig. (1)

The presence of high number of Treponema pallidum in late/chronic neurosyphilis. Numerous spirochetes accumulated in the cerebral cortex of a patient suffering from general paresis. Immunostaining was performed using a polyclonal anti-Treponema pallidum antibody (Biodesign, B65210R). Bar corresponds to 20 µm. The illustration was done in relation with a previously published study, where the material and methods used were described in detail [34].

Fig. (2)

Arteritis in meningovascular Lyme neuroborreliosis. The proliferation of the intima is well visible in panel A and arrows in panel B point to lymphocytic infiltrates in the thickened adventitia. Magnification: x 50. The photomicrographs were taken from a previously published study, which reported the detailed clinical and neuropathological findings of this case [47]. Compare panels A and B of this figure with those illustrated for Heubner’s arteritis in neurosyphilis (Greenfield’s Neuropathology, Figs 6 and 8, page 257 [25]).

Fig. (3)

B. burgdorferi cultivated and detected in the brain in the atrophic form of Lyme neuroborreliosis. Spirochetes cultivated (A) and detected by silver-impregnation technique (B) in the brain of a patient with slowly progressive dementia who suffered from Lyme neuroborreliosis. Bars A: 20 µm; B: 30 µm. The illustrations were taken from previous studies, which were the subject of several publications [34, 68, 99]. Compare the distribution of B. burgdorferi in B with that of T. pallidum in general paresis in Fig. (1).