Is a lumbar puncture (LP) necessary to confirm a diagnosis of neurosyphilis?

From the Guidelines

A lumbar puncture (LP) is not always necessary to confirm a diagnosis of neurosyphilis, especially in asymptomatic patients, as the significance of CSF abnormalities in the absence of symptoms is unclear. The diagnosis of neurosyphilis can be challenging, and no single laboratory test is perfectly sensitive and specific for a diagnosis 1. According to the most recent and highest quality study, the sensitivity of the CSF VDRL ranged from 49–87.5% and the specificity ranged from 74–100% for diagnosing neurosyphilis 1.

Key Points to Consider

• The CSF VDRL is highly specific but not very sensitive, so a negative result doesn't exclude neurosyphilis if clinical suspicion is high 1.
• The diagnosis of neurosyphilis usually depends on various combinations of reactive serologic test results, abnormalities of cerebrospinal fluid (CSF) cell count or protein, or a reactive VDRL-CSF with or without clinical manifestations 1.
• Treatment for neurosyphilis consists of intravenous aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units every 4 hours or by continuous infusion for 10-14 days [@Example@].
• For penicillin-allergic patients, desensitization is preferred, but alternatives include ceftriaxone 2g daily for 10-14 days [@Example@].
• LP is essential in symptomatic patients because neurosyphilis requires more intensive and prolonged treatment than early syphilis, and CSF analysis is needed to monitor treatment response with follow-up LPs at 6-month intervals until CSF abnormalities normalize [@Example@].

Recent Guidelines and Recommendations

• The 2022 guidelines suggest that a diagnostic cerebrospinal fluid (CSF) examination is not necessary in patients with isolated ocular or otic signs and symptoms, reactive syphilis serologic results, and confirmed ocular/otic abnormalities at examination, as up to 40% and 90% of patients, respectively, would have no CSF abnormalities 1.
• Repeated CSF examinations are not necessary for HIV-uninfected patients or HIV-infected patients on antiretroviral therapy who exhibit appropriate serologic and clinical responses after treatment for neurosyphilis 1.

From the Research

Diagnosis of Neurosyphilis

• The diagnosis of neurosyphilis is typically confirmed by a reactive Venereal Disease Research Laboratory (VDRL) test in cerebrospinal fluid (CSF) 2, 3, 4, 5.
• A lumbar puncture (LP) is necessary to collect CSF for VDRL testing and other analyses, such as CSF protein concentration and white blood cell count 2, 3, 4, 5.

Indications for Lumbar Puncture

• Current guidelines recommend LP in patients with syphilis who have neurologic symptoms 2.
• LP is also indicated for patients with asymptomatic late syphilis or syphilis of unknown duration 3.
• In HIV-infected patients with syphilis, LP may be necessary to diagnose asymptomatic neurosyphilis, especially in those with low CD4 T-cell count, high rapid plasma reagin (RPR) titre, and lack of HIV virological suppression 6.

Diagnostic Sensitivity and Specificity

• The diagnostic sensitivity of neurologic symptoms for neurosyphilis is low, ranging from 1.5% to 38.1% 2.
• However, the diagnostic specificity of these symptoms is high, ranging from 91.6% to 100% when limited to moderate or greater severity 2.

Risk of Neurosyphilis

• People living with HIV (PLWH) are at increased risk of asymptomatic neurosyphilis 6.
• The risk of neurosyphilis is also higher in patients with high RPR titers, such as ≥ 1:128 3 or ≥ 1:32 4.
• The number needed to test (NNTT) to diagnose a single case of asymptomatic neurosyphilis is estimated to be 38, suggesting that LP may not be necessary for all patients with syphilis lacking signs or symptoms of central nervous system infection 6.