Neurosyphilis

Home » MEDCLIN530 » Virtual Neurology Clinical Case Studies: MEDCLIN530 » Neurosyphilis
Headshot of Dawn Elise DeWitt, MD, MSc, CMedEd, MACP, FRACP, FRCP-London · Senior Associate Dean, Collaboration for InterProfessional Health Education Research & Scholarship (CIPHERS)
Dawn Elise DeWitt
MD, MSc, CMedEd, MACP, FRACP, FRCP-London · Senior Associate Dean, Collaboration for InterProfessional Health Education Research & Scholarship (CIPHERS)
envelope icon
Table of Contents

Author

Liana Bloom

Editor

Dawn DeWitt, MC, MSc, MACP, FRACP

Tap the arrow to view the case.
John Doe is a 40 yo AMAB presenting for routine PrEP follow up. Prior to seeing him together, your preceptor mentions John’s last visit was 6 months ago.
You learn the following:
John has been on PrEP for a couple years. He takes the medication daily, very rarely missing a dose. He has had two new sexual partners since his last appointment, one female and one male. John does not have any concerns regarding the medication and requests a refill.
Then, John mentions that he has been experiencing episodes of blurry vision, which he originally attributed to an old contact lens prescription. In the last month, he has had trouble with his peripheral vision, particularly noticeable when driving. He has also noticed significant hair thinning in the last 1–2 months and wonders if there is anything he can take for this.
John's history reveals:
PMHx: Pre-diabetes (last A1c 5.9%)
Surgical Hx: None
Medications: Oral PrEP, multi-vitamin
Allergies: None
Social: John is a middle school vice principal. His work has been incredibly stressful the last six months due to budget cuts in the school district.
John's test results

Image credits

Unless otherwise noted, images are from Adobe Stock.

Clinical correlation

HIV PrEP Management of therapy

Syphilis stages

Citation 1

Neurosyphilis spans all stages.

Primary

  • Incubation: 10–90 days  (median 21–25 days).
  • Solitary, painless chancre.
  • Painless, regional LAD.
  • Resolution: 3–6 weeks, w/o treatment.

Secondary

  • Hematogenous, lymphatic spread.
  • Onset: 2–8 weeks after chancre resolves.
  • Systemic: Fever, malaise, weight loss, HA.
  • Pharyngitis, myalgias, arthritis, patchy alopecia.
  • Cutaneous: Diffuse maculopapular rash palms + soles. Condyloma lata.
  • Resolution: Within a few weeks w/o treatment.

Latent

  • Primary and secondary lesions resolve without treatment.
  • No clinical manifestations.
  • Duration: Months–Years.

Tertiary (Late)

  • Onset: Months–years later.
  • Cardiovascular.
  • Systemic gummas.
  • Neuro.
    • Early.
    • Late.

(Via rabbit inoculation tests) “Investigations revealed pathogen in the CSF in 30% of those examined in the secondary stage of syphilis; CSF pleocytosis was found at this stage in 40% of those examined. Only 5–10% of those affected develop neurosyphilis years later in the natural course of syphilis, spontaneous ‘healing’ in the CNS is possible.”

author

Neurosyphilis: Early stages

Citations 2,3,4

  • (+) syphilis serology, CSF lymphocytic pleocytosis and protein elevation and/or (+) VDRL.
  • No clinical symptoms.
  • Within 12 mo primary infection, up to a few years.
  • HA, N/V, neck stiffness.
  • Cranial neuropathies: VII, VIII, III, II.
  • Within 5–12 yrs primary infection.
  • Endarteritis and perivascular inflammation luminal narrowing.
    • Consider: Relatively young, healthy adult with stroke. MCA and basilar artery branches common.
  • Gummas: Invasion into cortex.

Neurosyphilis: Late stages

Citations 2,3,4,5

  • 20–30 yrs after primary infection.
  • Inflammation progressive destruction thoracolumbar dorsal column and dorsal nerve roots.
  • Diminished vibration, proprioception, pain sensation.
  • Lancinating pain (sudden lightening-like pain).
  • Sensory ataxia: wide-based, unsteady gait and “foot slapping.”
  • Decreased DTRs, usually lower extremities.
  • Rare.
  • Chronic, progressive joint degradation 2/2 sensory innervation.
  • Neurosyphilis: Vertebrae, hips, knees, ankles.
  • Miotic pupils, accommodation, no light reflex.
  • “Light-near dissociation.”
    • Central: Dorsal midbrain lesion, sparing ventral accommodation pathway.
    • Peripheral: Ciliary ganglion or nerves of the orbit.
  • 30–40 yrs after primary infection.
  • Chronic, progressive meningoencephalitis.

Personality

Affect

  • Depression.
  • Apathy.
  • Mania.

Reflexes

  • Hyperactive.

Eye

Sensorium

  • Delusions.
  • Hallucinations.

Intellect

  • Memory.
  • Judgment.
  • Insight.

Speech

Management

Citations 1,7,8,9

  • Non-treponemal
    • Use: Screening, monitor disease progress and treatment response.
    • “Reactive” or “Non-reactive”, quantification via serial dilutions (4-fold).
    • VDRL and RPR.
  • Treponemal-specific antibody assay.
    • Use: Confirmation, positive for life.
    • FTA-ABS, TPPA, TPHA, CIA.

Rec: Clinical manifestations; significance of CSF abnormalities w/o SX is questioned:

  • CSF: VDRL > RPR. FTA-ABS. WBC. Protein.
    • CSF VDRL sensitivity 49–87% and specificity 74–100%.
    • CSF RPR sensitivity 51–82% and specificity 81–100%.
    • CSF FTA-ABS higher sensitivity, lower specificity.
  • IV aqueous crystalline penicillin G 18–24 million units daily for 10–14 days.
  • Late disease > 12 mo: Add 1x IM benzathine penicillin G 2.4 million units.

Today: Syphilis

Citations 10,11,12

2019 2020 2021 2022 2023
Washington
2,186
2,079
3,366
4,410
4,481
  • From 2018–2022, reported cases of syphilis rose 80% in the United States.
  • In 2022, congenital syphilis rates were 10x higher than in 2012.
  • Disproportionately affecting African American and American Native populations.

200 mg doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by ~50%.

CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024. Recommendations and Reports/ June 6, 2024/73(2);1–8

Text citations

  1. Tudor ME, Al Aboud AM, Leslie SW, et al. Syphilis. In: StatPearls [Internet], StatPearls Publishing. Updated August 17, 2024. Accessed January 29, 2025. 
  2. Klein, M., Angstwurm, K., Esser, S. et al. German guidelines on the diagnosis and treatment of neurosyphilis. Neurol. Res. Pract. 2020;2(33). doi: 10.1186/s42466-020-00081-1
  3. Knudsen RP, Singh NN, Thomas FP, Talavera F. Neurosyphilis overview of syphilis of the CNS. Medscape. Updated October 2, 2023. Accessed January 29, 2025. 
  4. Piura Y, Mina Y, Aizenstein O, Gadoth A. Neurosyphilis presenting as cranial nerve palsy, an entity which is easy to miss. BMJ Case Rep. 2019;12(2):e226509. doi: 10.1136/bcr-2018-226509
  5. Wang M, Huang R, Wang L, Yu N, Li L. Syphilis with charcot arthropathy: a case report. Dermatologic Therapy. 2019;32(3). doi: 10.1111/dth.12862
  6. Thompson HS, Karson RH. The Argyll Robertson pupil. Journal of Neuro-Ophthal. 2006;26(2):p 134–138. doi: 10.1097/01.wno.0000222971.09745.91
  7. Marra CM. Neurosyphilis. In: UpToDate, Connor RF (Ed), Wolters Kluwer. 
  8. Boog, G.H.P., Lopes, J.V.Z., Mahler, J.V. et al. Diagnostic tools for neurosyphilis: a systematic review. BMC Infect Dis. 2021; 21,568. doi: 10.1186/s12879-021-06264-8
  9. Tuddenham S, Katz SS, Ghanem KG. Syphilis Laboratory Guidelines: Performance Characteristics of Nontreponemal Antibody Tests. Clinical Infectious Diseases. 2020;71(1):p S21–S42. doi: 1093/cid/ciaa306
  10. Sexually Transmitted Infections Surveillance, 2023. Table 3. Total syphilis—reported cases and rates of reported cases by state/territory and region in alphabetical order, United States. CDC.gov. Accessed January 30, 2025. 
  11. Winny A. The U.S. syphilis spike has been brewing for decades. Johns Hopkins Bloomberg School of Public Health. March 2024. Accessed January 30, 2025. 
  12. Bachmann LH, Barbee LA, Chan P, et al. CDC clinical guidelines on the use of doxycycline postexposure prophylaxis for bacterial sexually transmitted infection prevention, United States, 2024. MMWR Recomm Rep. 2024;73(No. RR-2):p 1–8.

Image citations

Krakower DS, Mayer KH. HIV pre-exposure prophylaxis. In: UpToDate, Connor RF (Ed), Wolters Kluwer. 

Warning: Copyright restrictions

This course content and all writings and materials provided to you at the Elson S. Floyd College of Medicine are protected by federal copyright law and Washington State University policy. The content is copyrighted by the Washington State University Board of Regents or licensed to the Elson S. Floyd College of Medicine by the copyright owner. Limited access to this content is given for personal academic study and review purposes of registered students and faculty of Elson S. Floyd College of Medicine. You shall not otherwise copy, share, distribute, modify, transmit, upload, post, republish, reuse, sell, gift, rent, lend or otherwise disseminate any portion of this course content without permission in writing, signed by an individual authorized by Washington State University.

 

The Digital Publishing team makes every effort to ensure these educational materials are accessible to all learners. If you run into problems, please contact us with your concerns at medicine.digipub@wsu.edu. We will respond within 2 business days.

Site Menu