All forms of neurosyphilis begin as meningitis (and meningeal inflammation) are the invariable accompaniment of all forms of neurosyphilis. The early clinical syndromes are aseptic meningitis and meningovascular syphilis; the late (secondary) ones are vascular syphilis (1 to 12 years), followed even later by tertiary syphilis, general paresis, tabes dorsalis, optic atrophy, or subacute myelitis. In all cases of tertiary neurosyphilis, the pathologic sequence results from chronic syphilitic meningitis and subpial recruitment of microglia and other inflammatory cells. The clinical syndromes are the result of chronic and progressive damage to subadjacent neurons and supporting tissues. The intermediate mechanisms, whereby transformation occurs from persistent asymptomatic syphilitic meningitis or relapsing meningitis, to the late forms of parenchymal neurosyphilis are unknown.
From a clinical point of view, asymptomatic neurosyphilis is perhaps the most important form because, if discovered and adequately treated, the symptomatic varieties would be prevented in most instances. Asymptomatic neurosyphilis can be recognized only by the changes in the CSF.
Clinical syndromes such as syphilitic meningitis, meningovascular syphilis, general paresis, tabes dorsalis, optic atrophy, and meningomyelitis often exist in mixed form. Because all of them appear to have a common origin in chronic meningitis, there is usually a combination of two or more syndromes with one predominating, for example, meningitis and vascular syphilis, tabes and paresis. Even though the patient’s symptoms may have been referable to only one part of the nervous system, postmortem examination usually discloses diffuse changes, in both brain and spinal cord, which were of insufficient severity to be detected clinically.
The clinical syndromes and pathologic reactions of congenital syphilis are similar to those of the late-acquired forms, differing only in the age at which they occur. All the aforementioned biologic events are equally applicable to congenital and childhood neurosyphilis.
The CSF is a sensitive indicator of the presence of active neurosyphilitic infection. The CSF abnormalities consist of (1) a pleocytosis of up to 100 cells/mm3, sometimes higher, mostly lymphocytes and a few plasma cells and other mononuclear cells (the counts may be lower in patients with HIV and those with leukopenia); (2) elevation of the total protein, from 40 to 200 mg/dL; (3) an increase in gamma globulin (IgG), usually with oligoclonal banding; and (4) positive serologic tests for syphilis. Elevated gamma globulin in the CSF is produced intrathecally and has been shown to be adsorbed to T. pallidum (Vartdal et al). Hence the gamma globulin represents a specific antibody response to this organism. The glucose content is usually normal.
Later, the CSF changes may vary. With either spontaneous or therapeutic remission of the disease, the cells disappear first; next the total protein returns to normal; then the gamma globulin concentration is reduced. The positive serologic tests are the last to revert to normal. Some caution is advisable in interpreting the CSF results in patients with concurrent HIV. On the one hand, an aseptic reaction may be the result of HIV alone; on the other hand, those with profound leukopenia or T-cell deficiencies may show little or no cellular reaction in the CSF (see Katz and Berger). In congenital (but not adult) neurosyphilis, the earliest changes in the CSF, consisting of pleocytosis and an elevation of protein, may occur in the first few weeks of the infection, before the serologic tests become positive.