To evaluate cerebrospinal fluid (CSF) flow cytometry findings in patients with neurosyphilis (NS) and determine whether specific immune cell profiles can support this diagnosis.

Neurosyphilis remains a challenging diagnosis due to its variable neurological presentations and the limited sensitivity of conventional serologic and CSF assays. Delayed recognition can result in significant neurologic injury. CSF flow cytometry enables detailed assessment of immune cell populations and may help distinguish infectious from autoimmune neuroinflammatory processes. Only limited data exist describing characteristic CSF immune profiles in neurosyphilis. Further study could improve early diagnosis, guide management, and inform future diagnostic guidelines.

We conducted a retrospective chart review of all patients diagnosed with neurosyphilis at NYU Langone by an Infectious Disease specialist who underwent CSF flow cytometry prior to antibiotic therapy. Demographic, clinical, and laboratory data were extracted, and immune cell subset distributions were analyzed.

Four patients met inclusion criteria (mean age 55 years; all male; two HIV-positive). Presenting symptoms included decreased bilateral visual acuity, papilledema, and flashing or colorful lights. CSF analysis showed elevated white blood cell counts ranging from 8–69/µL with lymphocytic predominance (76–95%) and protein levels of 29–59 mg/dL. CSF VDRL was reactive at 1:1 in two patients and non-reactive in two. Flow cytometry demonstrated B-cell enrichment (CD19⁺ 2.7–12.9%) and modest plasmacytoid populations (0.7–2.0%). T cells were predominant (CD3⁺ 57–89%) with variable CD4⁺ (27–57%) and CD8⁺ (15–37%) subsets. NK cells were low (<1.1%), with detectable monocytes (1.8–15.2%) and granulocytes (0.75–1.9%). All patients received intravenous penicillin and experienced significant clinical improvement or complete resolution of neurological symptoms.

CSF flow cytometry, particularly B-cell enrichment, may support the diagnosis of neurosyphilis when standard CSF tests are inconclusive. These findings suggest a potential diagnostic role for flow cytometry in differentiating infectious from autoimmune neuroinflammation and warrant further study to guide clinical application and future diagnostic criteria.