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, and the decision to perform an LP should be based on the presence of clinical signs or symptoms of neurologic or ophthalmic involvement. The diagnosis of neurosyphilis requires both serologic evidence of syphilis infection and cerebrospinal fluid (CSF) abnormalities, which can only be obtained through LP 1. However, according to the most recent guidelines, LP is not recommended for routine evaluation of patients with primary or secondary syphilis unless clinical signs or symptoms of neurologic or ophthalmic involvement are present 1.

Key Considerations

• The CSF analysis should show elevated white blood cells (typically >5 cells/μL), elevated protein, and a positive CSF-VDRL (Venereal Disease Research Laboratory) test 1.
• The CSF-VDRL is highly specific but not very sensitive, so a negative result doesn't rule out neurosyphilis if clinical suspicion is high and other CSF abnormalities are present 1.
• Treatment for neurosyphilis consists of intravenous penicillin G (18-24 million units daily, administered as 3-4 million units every 4 hours) for 10-14 days 1.
• For penicillin-allergic patients, desensitization is preferred over alternative antibiotics 1.
• Follow-up LP is recommended at 6-month intervals until the CSF cell count normalizes, but this may not be necessary for HIV-uninfected patients or HIV-infected patients on antiretroviral therapy who exhibit appropriate serologic and clinical responses after treatment for neurosyphilis 1.

Clinical Implications

• The decision to perform an LP should be based on the presence of clinical signs or symptoms of neurologic or ophthalmic involvement, as the risk of neurosyphilis is low in patients without these symptoms 1.
• The LP is essential because neurosyphilis treatment differs from early syphilis treatment, and missing the diagnosis can lead to irreversible neurological damage, as the spirochete Treponema pallidum can directly invade the central nervous system and cause inflammation and tissue damage 1.

From the Research

Diagnostic Approach to Neurosyphilis

• The diagnosis of neurosyphilis can be challenging, and a lumbar puncture (LP) is often necessary to confirm the diagnosis 2, 3, 4, 5, 6.
• Current guidelines recommend LP in patients with syphilis who have neurologic symptoms, as the presence of these symptoms may indicate neurosyphilis 3.
• However, the absence of symptoms does not guarantee that the cerebrospinal fluid (CSF) test will be nonreactive, regardless of HIV status 3.

Role of Lumbar Puncture in Diagnosis

• LP is essential in evaluating the effectiveness of treatment for neurosyphilis, in addition to its diagnostic value 2.
• The CSF test can help identify asymptomatic neurosyphilis, which is present in a significant proportion of patients with asymptomatic late syphilis or syphilis of unknown duration 4.
• A reactive CSF-Venereal Disease Research Laboratory (VDRL) test is a key indicator of neurosyphilis, and LP is necessary to obtain this test result 3, 5, 6.

Indications for Lumbar Puncture

• Patients with syphilis and serum VDRL ≥ 1:32 may be at higher risk of neurosyphilis and may require LP to confirm the diagnosis 5.
• LP is also indicated in patients with atypical movement disorders, as neurosyphilis can present with a range of movement disorders 6.
• Routine serologic testing for syphilis should be part of the evaluation of patients with atypical presentations or in whom alternative diagnoses are not forthcoming, and LP should be performed when serology is positive 6.