Chronic infections are notoriously difficult challenges for the clinician. With respect to determining their clinical spectra, diagnosing them, treating them, or studying their epidemiology, they are daunting. HIV, tuberculosis, syphilis, malaria, and Lyme disease, to name just a few, continue to vex us and make us humbler and wiser physicians.
The study by Sibony et al in this issue of Journal of Neuro-Ophthalmology (citation here) is an effort to determine whether various forms of optic neuropathy are within the spectrum of Lyme disease. The authors used a retrospective chart review of patients within a patient database at SUNY Stony Brook School of Medicine; the school is located in an area endemic for Lyme disease. Out of 440 patients presenting with optic neuritis, the authors found that only five (1%) had compelling evidence that active Borrelia burgdorferi was responsible for, or contributed to, their visual deficit. This would indicate that in an academic center in an endemic area in the United States, extremely few patients with optic neuritis had Lyme disease as a cause, and that it is not a common cause of optic neuritis.
Why did I include the qualifier “in the United States” in the aforementioned sentence? Because Lyme neuroborreliosis has different clinical phenotypes for different genotypes of infecting subtypes of B. burgdorferi spirochetes. This has been an observation in the human disease (1) and its animal models (2). Thus, the conclusions drawn from the study of Sibony et al may not be readily applicable to Lyme disease in Europe, where the disease has a more aggressive neurologic presentation (3). Not surprisingly, investigators in Europe such as the Finns (4) and the Germans (5), both appropriately quoted in the study of Sibony et al, might dispute the conclusion that optic neuritis is rare in Lyme neuroborreliosis. The difference is likely because of the fact that American neuroborreliosis is caused predominantly by B. burgdorferi sensu stricto, whereas European disease is caused by B. garinii or B. afzelii, and the genetic differences between these subspecies are considerable.
Another issue that the authors did not address is the nagging question of whether our serological assays (enzyme-linked immunosorbent assay and Western blot) are so powerful that they will always be positive in cases of optic neuritis caused by B. burgdorferi. My answer is, possibly not! The concern is that in this chronic infection, it is conceivable that spirochetes can be cleared from the periphery but retained in “immune-privileged” sites such as the eye or the brain. Thus, an enzyme-linked immunosorbent assay-positive but Western blot-negative patient with optic neuritis could conceivably be infected yet have a localized process without adequate peripheral activation to become Western blot positive. A similar situation occurs in tertiary neurosyphilis, in which the CSF (cerebrospinal fluid) VDRL can be negative in a substantial percentage of cases despite a positive serum FTA-ABS.
These remarks do not detract, of course, from a very nice contribution to the literature by Sibony et al, especially in pointing out that optic nerve involvement in Lyme borreliosis in the United States is predominantly found in the child with meningitis, increased intracranial pressure, and optic disc edema. Retrobulbar neuritis remains very unlikely to be caused by Lyme disease; most likely it has another cause.
1. Steere AC, Berardi VP, Weeks KE, et al. Evaluation of the intrathecal antibody response to Borrelia burgdorferi
as a diagnostic test for Lyme neuroborreliosis. J Infect Dis
2. Pachner, AR, Dail D, Bai Y, et al. Genotype determines phenotype in experimental Lyme neuroborreliosis. Ann Neurol
3. Hansen K, Lebech AM. The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985-1990. A prospective study of 187 patients with Borrelia burgdorferi
specific intrathecal antibody production. Brain
4. Karma A, Seppala I, Mikkila H, Kaakkola, et al. Diagnosis and clinical characteristics of ocular Lyme Borreliosis. Am J Ophthalmol
5. Preac-Mursic V, Pfister HW, Spiegel H, et al. First isolation of Borrelia burgdorferi from an iris biopsy. J Clin Neuroophalmol