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Current guidelines suggest that success of neurosyphilis treatment be assessed by performing a lumbar puncture 6 months after completion of therapy and repeating the procedure until the cerebrospinal fluid (CSF) profile is normal. Parameters measured are CSF white blood cell (WBC) count, CSF protein concentration, and CSF VDRL titer. However, lumbar punctures are logistically difficult to perform in an outpatient setting, and many patients refuse them. Researchers in Seattle sought to determine whether normalization of serum rapid plasma reagin (RPR) titer might serve as a surrogate for normalization of CSF profile.
The study involved 110 patients who were treated for neurosyphilis. Thirty-seven of them had symptomatic syphilitic meningitis, and 23 had syphilitic eye disease; 86 were HIV-infected. The patients had follow-up visits 3, 6, and 12 months after treatment. At 3 months, all participants underwent lumbar puncture; at 6 and 12 months, only those with abnormal CSF profiles at the previous visit repeated the procedure. Serum samples were obtained at all visits.
By 13 months after therapy, serum RPR titer had normalized (defined as a 4-fold decrease in titer or reversion of the test to nonreactive) in 97 participants (88%). The odds that CSF WBC count, protein concentration, and VDRL titer would normalize, and that neurosyphilis symptoms would resolve, were 28- to 57-fold higher if the serum RPR titer had normalized than if it had not (P=0.001 for each). Normalization of serum RPR titer without resolution of CSF abnormalities was more likely in HIV-infected patients who were not receiving potent antiretroviral therapy than in those who were (P=0.007).
Marra CM et al. Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis. Clin Infect Dis 2008 Oct 1; 47:893.
Comment
Relapse is the major concern when treating neurosyphilis, particularly in HIV-infected patients. The study does not directly address this clinical endpoint. Nonetheless, it demonstrates that CSF parameters of inflammation do correlate with serum RPR. The findings add support to what has probably become standard practice — that is, to follow serum RPR titer alone.