What is the role of cerebrospinal fluid (CSF) in neurosyphilis (neurological manifestation of syphilis)?

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From the Guidelines

Cerebrospinal fluid (CSF) analysis is crucial in diagnosing neurosyphilis (neurolues), and patients with suspected neurosyphilis should undergo a lumbar puncture to examine their CSF, as recommended by the Centers for Disease Control and Prevention 1.

Importance of CSF Analysis

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.

  • Typical CSF findings in neurosyphilis include:
    • Pleocytosis (elevated white blood cells, usually 10-400 cells/μL with lymphocyte predominance)
    • Elevated protein levels (45-200 mg/dL)
    • Normal or slightly decreased glucose
    • Positive serologic tests

CSF Tests

The most important CSF tests include:

  • The VDRL (Venereal Disease Research Laboratory) test, which is highly specific but not very sensitive
  • The FTA-ABS (Fluorescent Treponemal Antibody Absorption) test, which is more sensitive but less specific

Treatment and Follow-up

Treatment for neurosyphilis consists of intravenous aqueous crystalline penicillin G at 18-24 million units daily, administered as 3-4 million units every 4 hours or by continuous infusion for 10-14 days, as recommended by the CDC 1. For penicillin-allergic patients, desensitization is preferred, but alternatives include ceftriaxone 2g daily for 10-14 days. Follow-up CSF examinations should be performed at 6-month intervals until cell count normalizes and VDRL becomes nonreactive, which may take years. These CSF abnormalities reflect the inflammatory response to Treponema pallidum infection in the central nervous system, and proper diagnosis and treatment are essential to prevent progressive neurological damage.

From the Research

Cerebrospinal Fluid in Neurosyphilis

  • Cerebrospinal fluid (CSF) analysis is a crucial diagnostic tool for neurosyphilis, as it can help confirm or exclude the diagnosis 2.
  • The analysis of CSF parameters, such as white cell count and protein concentration, can provide valuable information for the diagnosis of neurosyphilis 2, 3.
  • CSF sequencing, including metagenomic next-generation sequencing (mNGS), can also be used to diagnose neurosyphilis, especially in cases where the diagnosis is uncertain or the patient has atypical symptoms 4.
  • The presence of treponemal and lipoidal antibodies in CSF can also be used to support the diagnosis of neurosyphilis 3.

Treatment and Antibiotic Strategy

  • The treatment of neurosyphilis typically involves the use of antibiotics, such as penicillin, and the choice of antibiotic regimen depends on the severity of the disease and the patient's overall health 5, 3.
  • The use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin has been suggested as a potential treatment option for neurosyphilis 3.
  • However, the penetration of penicillin into the CSF can be limited, and some studies have shown that benzathine penicillin G may not achieve detectable levels in the CSF 6.

Diagnostic Challenges

  • The diagnosis of neurosyphilis can be challenging due to its atypical and progressive symptoms, and the increasing incidence of the disease underscores the need for early and accurate diagnosis 4, 5.
  • The results of routine CSF analysis in patients with a possible diagnosis of neurosyphilis are inconsistently applied in the clinical setting, and empirical neurosyphilis treatment should be considered upfront in patients with a high pre-test probability of the diagnosis 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Neurosyphilis: Concordance between cerebrospinal fluid analysis and subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of neurosyphilis.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2019

Research

State-of-the-Art Review: Neurosyphilis.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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