Clinical presentation of neurosyphilis – a single-center retrospective data analysis

Abstract Background As cases of neurosyphilis are rising worldwide – especially in people living with HIV (PLWH) – current data on clinical presentation, diagnostics and management of neurosyphilis in Europe are of high interest. Methods Clinical data from adult patients, who had been treated for neurosyphilis at a university hospital in Germany from 2005 to 2024, were retrospectively analyzed. Probable diagnosis was based on corresponding signs and symptoms, positive syphilis serology, Cerebrospinal fluid (CSF) abnormalities, and/or improvement after antibiotic therapy. In asymptomatic patients, diagnosis was based on CSF abnormalities with positive serology. A positive CSF/serum treponemal antibody index confirmed the diagnosis. Results 77 patients with neurosyphilis were identified, the majority being male (95%), with a high proportion of HIV co-infection (43%). Clinical presentation was most frequently asymptomatic or ocular neurosyphilis (both 26%), other common symptoms were cognitive deficits, headache, and psychiatric symptoms. CSF abnormalities and additional co-infections were more pronounced among PLWH. CSF cell count and protein concentration were significantly lower in asymptomatic (latent) neurosyphilis compared to symptomatic cases, yet between various symptomatic manifestations of neurosyphilis only minor differences were observed. CSF VDRL-test was negative in nearly half of patients with confirmed neurosyphilis. Penicillin G was the predominant treatment (71%), with ceftriaxone used as the main alternative (21%), and doxycycline in 3 patients mostly due to penicillin allergy. Clinical improvement was observed in 88% of symptomatic patients. Discussion Our findings align with recent reports describing neurosyphilis as a heterogeneous infection strongly linked to HIV-infection. The limited sensitivity of CSF VDRL reinforces the need for multimodal diagnostics. Current CSF testing criteria may miss asymptomatic cases, warranting heightened clinical vigilance.