Table 3.

Important unanswered questions in neurosyphilis.

Area	Questions
Epidemiology	•How high is the authentic incidence and mortality of neurosyphilis?
		•What is the probability of the ANS patients progressing to symptomatic neurosyphilis?
Pathogenesis	•What is the mechanism of T. pallidum invading the CNS? • What is the mechanism of the CNS damage mediated by neurosyphilis?
		•Will HIV infection affect the susceptibility to neurosyphilis?
		•What genetic factors make humans susceptible to neurosyphilis?
Diagnosis	•When do syphilis patients need lumbar puncture to evaluate neurosyphilis?
		•How are specific antibodies produced in CSF of patients with neurosyphilis? How to accurately detect?
		•How to early identify neurosyphilis?
Administration	•What tests can be used to monitor the treatment response of patients with neurosyphilis?
		•Can standard penicillin treatment improve the long-term prognosis of neurosyphilis?
		•Will the increase in gene mutations related to penicillin resistance gradually accumulate, leading to the emergence of penicillin-resistant T. pallidum?
		•What are the indications for stopping treatment for neurosyphilis?
		•How to develop a vaccine against neurosyphilis?

ANS, asymptomatic neurosyphilis; CNS, central nervous system; CSF, cerebrospinal fluid.