Neurosyphilis is what happens when Treponema pallidum, the bacterium that causes syphilis, invades the brain, spinal cord, or surrounding fluid. It can appear at any stage of infection, not just late disease. Diagnosis usually relies on a spinal-fluid (lumbar puncture) analysis, and treatment is intravenous penicillin rather than the single shot used for early syphilis.
~3 wks; 10–90 days
by stage
| Item | Value |
|---|---|
| Primary sore | painless — ~3 wks; 10–90 days |
| Testing | 2 blood tests |
| Treatment | penicillin — by stage |
| Symptoms fade | ≠ cured |
The essentials
Syphilis is a staged bacterial infection caused by Treponema pallidum, curable with the right antibiotics CDC. Most people picture a slow march from a painless sore to a body rash to silent latent infection, and that's the usual path. But the spirochete can cross into the central nervous system early, sometimes within weeks or months of infection, so neurosyphilis isn't simply "end-stage" disease.
Neurosyphilis differs in how it's confirmed and how it's treated. Ordinary early syphilis is treated with a single intramuscular (IM) injection. Neurosyphilis penetrates a part of the body that IM penicillin doesn't reliably reach in high enough levels, so it requires aqueous crystalline penicillin G given intravenously (IV) over a stretch of days. That distinction between IV and IM, and between spinal fluid and blood, runs through this whole page.
It matters because syphilis is climbing. The U.S. recorded about 53,000 primary-and-secondary cases in 2023, and late or unknown-duration disease nearly doubled, rising from 14 to close to 30 per 100,000 between 2020 and 2023 CDC AtlasPlus, 2023. More untreated and under-treated infection means more chances for the bacterium to reach the nervous system.
Symptoms of neurosyphilis
Neurosyphilis can be dramatic or nearly silent, depending on which part of the nervous system is affected and how long the infection has been present. Because syphilis can invade the eyes or nervous system at any stage, new vision changes or neurological symptoms in someone with syphilis are treated as a medical emergency CDC.
Early neurosyphilis
Early in infection the bacterium can inflame the meninges (the membranes wrapping the brain and cord) or the blood vessels feeding the brain. That can cause headache, neck stiffness, confusion, or even stroke-like symptoms in a younger person. Some people have no symptoms at all and are picked up only on testing.
Ocular syphilis
Ocular syphilis is infection involving the eye, most often uveitis (inflammation inside the eye), and it can cause eye pain, redness, floaters, blurred vision, or sudden vision loss. It's frequently grouped with neurosyphilis because the eye is an extension of the central nervous system, and untreated it can lead to permanent blindness.
Otosyphilis
Otosyphilis affects the inner ear and hearing pathways, producing hearing loss, ringing in the ears (tinnitus), or vertigo (a spinning sensation). Like ocular disease, it can progress quickly and is treated on the same urgent footing as neurosyphilis.
Late neurosyphilis
When syphilis goes untreated for years, late neurosyphilis can emerge as part of tertiary disease, the stage that classically appears 10 to 30 years after infection, though some manifestations come sooner. Two long-recognized syndromes are general paresis (a slow decline in memory, personality, and judgment that can resemble dementia) and tabes dorsalis (degeneration of the spinal cord causing shooting pains, an unsteady wide-based walk, and loss of position sense). These reflect irreversible nerve damage, so catching syphilis early matters.
How neurosyphilis is tested
Diagnosing neurosyphilis is a two-layer process: first establish that the person has syphilis, then determine whether it has reached the nervous system.
The blood work is a simple draw, and a syphilis diagnosis requires two serologic tests, a nontreponemal test (RPR or VDRL) and a treponemal test (TP-PA, FTA-ABS, EIA, or CIA) CDC Lab Recs, 2024. Labs run these in one of two acceptable orders: the traditional algorithm (nontreponemal first, treponemal confirms) or the reverse-sequence algorithm (treponemal first, then a quantitative nontreponemal test). Either is valid. Early after exposure the blood test can be falsely negative; antibodies may take up to two weeks after the chancre appears, and the chancre itself shows up roughly three weeks after exposure, so if your risk was recent, retest rather than trusting a single negative. See the practical guide on when to test after exposure.
Confirming neurosyphilis usually means a lumbar puncture (spinal tap), in which a needle draws cerebrospinal fluid (CSF) from the lower back. The lab examines the CSF for white-cell count, protein, and a CSF-VDRL; a reactive CSF-VDRL strongly supports neurosyphilis, though a negative one doesn't rule it out. In someone with clear ocular or otosyphilis and matching eye or ear findings, clinicians often treat without a tap. The procedure sounds frightening but is done routinely at the bedside with local anesthetic.
If you only need baseline syphilis screening, you can get tested through a clinic or at-home blood test; the CSF workup happens in a medical setting once syphilis is confirmed and neurological involvement is suspected.
Treatment: why neurosyphilis needs IV penicillin
Penicillin G is the preferred drug for every stage of syphilis, and for neurosyphilis the route changes CDC Tx Guidelines. The standard regimen is aqueous crystalline penicillin G, 18–24 million units per day, given as 3–4 million units IV every 4 hours (or as a continuous infusion) for 10–14 days. An accepted alternative is procaine penicillin G 2.4 million units IM once daily plus probenecid 500 mg by mouth four times daily, both for 10–14 days. These high-dose, frequent regimens keep penicillin levels high enough across the blood-brain barrier, which the single benzathine IM shot used for early syphilis does not achieve.
That single-shot regimen is worth contrasting so the difference is clear:
| Stage | Penicillin regimen | Route |
|---|---|---|
| Primary, secondary, early latent | Benzathine penicillin G 2.4 million units, single dose | IM |
| Late latent / unknown duration, tertiary | Benzathine penicillin G 7.2 million units total (3 weekly doses of 2.4 million units) | IM |
| Neuro / ocular / otosyphilis | Aqueous crystalline penicillin G 18–24 million units/day for 10–14 days | IV |
One product safety note carries over from early syphilis: the correct benzathine product is benzathine penicillin G (Bicillin L-A). The combination product Bicillin C-R (benzathine plus procaine) is not an acceptable substitute and has caused treatment-failure errors.
A Jarisch-Herxheimer reaction can happen within the first day of treatment, with fever, chills, headache, and muscle aches as the dying bacteria release inflammatory signals StatPearls. It's most common when treating earlier disease (it affects roughly 95% of people treated for secondary syphilis) and usually settles within about 24 hours. It is not a penicillin allergy, and patients should be counseled not to mistake it for one.
If you're allergic to penicillin
For neurosyphilis specifically, there's no well-validated oral substitute, so managing a true allergy generally means penicillin desensitization, a supervised process that lets the drug be given safely. Most penicillin allergy is mislabeled: over 90% of people who think they're allergic are not. The oral alternatives used in early syphilis (doxycycline for primary, secondary, or latent disease) are options for those stages, not a dependable cure for nervous-system infection, and azithromycin is not recommended because of resistance. If a penicillin allergy is on your chart, read the options on syphilis penicillin allergy before assuming you can't be treated.
In pregnancy the rule is firm: a pregnant person with syphilis at any stage who reports penicillin allergy should be desensitized and treated with penicillin, because there is no safe alternative that protects the baby.
Confirming the cure
Feeling better doesn't equal cure. Response is tracked with quantitative nontreponemal titers (RPR/VDRL) over time; a fourfold or greater drop (for example, 1:32 falling to 1:8) confirms the treatment worked, while a fourfold rise signals reinfection or failure. For neurosyphilis, clinicians may also repeat the CSF analysis to confirm the inflammation is resolving. If your titers climb after treatment, that's a flag to revisit whether this is can you get syphilis again after treatment? versus inadequate treatment.
Preventing syphilis (and neurosyphilis)
You don't prevent neurosyphilis directly. You prevent syphilis and treat it early before it reaches the nervous system. Correct and consistent condom use, mutual monogamy with a partner who's tested negative, and routine screening are the foundation. DoxyPEP, 200 mg doxycycline within 72 hours after sex, reduced syphilis acquisition by about 73% and is recommended through shared decision-making for gay and bisexual men and transgender women who've had a bacterial STI in the past year CDC DoxyPEP, 2024. For the full playbook, see how to prevent syphilis.
Pregnancy is its own priority. Untreated syphilis in pregnancy harms the baby in 50 to 80% of cases, and congenital syphilis nearly doubled from 2,163 cases in 2020 to 3,882 in 2023, its highest level in decades, and nearly all of it preventable with prenatal screening plus penicillin.
When to see a clinician
Seek urgent care if you have known or suspected syphilis and develop any new vision change, hearing loss, ringing in the ears, severe headache, confusion, weakness, or trouble walking; these can signal ocular, oto-, or neurosyphilis and shouldn't wait. The first sore is the classic trap. It's painless, often hidden, and heals on its own, which can feel like recovery while the infection moves inward. A healed chancre is not a cured infection. If you've had a possible exposure or a positive screen, get evaluated promptly.