Neurosyphilis (Grand Rounds)

From EyeWiki
Original article contributed by: Jesse L. Berry, MD
All contributors: Jesse L. Berry, MD
Assigned editor:
Review: Assigned status Up to Date by Jesse L. Berry, MD on February 14, 2017.


Mercury Intro.JPG

History

  • 44-year-old male with a history of optic neuropathy OD in 2011
  • Presents to LAC+USC Medical Center in May 2016 with pain OS associated with superotemporal injection
    • Pain is intermittent, 10/10, shoots from the periorbital area across the left temple to the left side of the head
    • No tenderness to palpation of the left temple; no jaw claudication
    • No photophobia
  • In May 2016 patient was diagnosed with idiopathic scleritis; started on topical and oral steroids with taper
  • September 2016 patient presented with decreased vision OS with persistent (though improved) pain and injection

Exam Findings

  • VAsc
    • OD: 20/100
    • OS: 20/50 PH 20/40
  • Pupils: Round and Reactive OU, 2+ RAPD OD
  • Ishihara color plates: OD 1/8 , OS 6/8 (decreased OS from prior exam of 8/8)
  • IOP OD: 12, OS: 12
  • External exam
    • Violaceous injection of the scleral vessels (non-blanching with phenylephrine), more predominate in the superotemporal quadrant
    • No scleral thinning
  • Slit Lamp Exam (pertinent positives and negatives)
    • K: clear OS
    • AC: deep and quiet OS
    • Iris: flat, round, no nodules
    • Vitreous: syneresis, no cell OS
  • Posterior segment
    • Media: clear
    • ON: OD Pale; OS CDR 0.1, hyperemic with increased vascularity temporally and temporal swelling, no obscuration of the vessels coursing over the nerve, no hemorrhages
    • Macula: flat OU, no exudates OS
    • Vessels: normal, no vascular sheathing
    • Periphery: normal, no holes, tears or detachments
Mercury 1.JPG
Mercury 2.JPG

Differential Diagnosis

  • Elevated ICP
  • Inflammation
  • Infection
  • Demyelination
  • Sarcoidosis
  • Vasculitis
  • Compression (Foster-Kennedy syndrome)
  • Infiltration

Additional Investigations

  • Fluorescein angiogram
    • Demonstrated early disc leakage with late staining OS
Mercury 3.JPG

Visual fields (Humphrey Visual Field 24-2)

  • OD: reliable, inferior altitudinal defect, enlargement of the blind spot
  • OS: reliable, normal
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Mercury 5.JPG
  • Laboratory testing September 2016
    • RPR 1:2
    • FTA ABS +
    • CSF 5 cells, protein 30, Glucose 191 (serum 298)
    • CSF VDRL negative
    • HIV negative
    • Additional infectious/inflammatory workup negative
  • History
    • In 2011 the patient had tested positive for a “venereal disease” and was treated with 2-3 intramuscular injections

Diagnosis

  • Ocular syphilis (Neurosyphilis)

Pathophysiology

  • Syphilis is an infection of the spirochete T. Pallidum. It is spread through direct contact with a chancre; transmission occurs during sexual contact. Pregnant women can also transmit the disease through the placenta within the first 16 weeks of pregnancy.
  • Syphilis is characterized by the phases of infectious process:
    • Primary syphilis: chancre at site of inoculation
    • Secondary syphilis: fever, malaise, lymphadenopathy, rash
    • Early latent (year) and late latent (decades)
    • About 1/3 progress to tertiary syphilis
    • 2/3 of patients have subclinical disease or the infection clears
  • Tertiary syphilis: Neurosyphilis, Cardiac, Benign (gummas)
  • Ocular syphilis is considered Neurosyphilis from a management standpoint and its manifestations vary widely through the anterior and posterior segments
    • Anterior segment
      • Interstitial keratitis (congenital > acquired)
      • Posterior synechiae
      • Lens dislocation
      • Iris roseola
      • Vascularized papules (iris papulosa)
      • Large red iris nodules (iris nodosa)
      • Gummata
      • Iris atrophy
    • Posterior segment
      • Vitritis/posterior and panuveitis
      • Chorioretinitis
      • Focal retinitis
      • Retinal vasculitis
      • Exudative RD
      • Isolated papillitis
      • Neuroretinitis
    • Neuro-ophthalmologic findings of syphilis
      • Argyll Robertson pupil
      • Oculomotor nerve palsies (meningovascular syphilis)
      • Optic neuropathies
      • Retrobulbar optic neuritis
    • HIV may modify the natural course of syphilis by modulating the immunologic response to T. pallidum
      • Evidence demonstrates that the ophthalmologic manifestations significantly differ between HIV+ patients and HIV- patients
      • In addition, significant difference in patient serology:
        • Higher RPR titers in HIV+ patients
        • More likely to test positive for VDRL in CSF if HIV+

Diagnostics

  • Nontreponemal Testscardiolipin-cholesterol-lecithin antigen
    • Rapid plasma reagin (RPR)
    • Venereal Disease Research Laboratory (VDRL)
      • Toluidine Red Unheated Serum Test (TRUST)
    • Changes in titer are followed after treatment to detect therapeutic response
    • 1 to 2 percent False Positives
  • Treponemal Tests
    • Fluorescent treponemal antibody absorption (FTA-ABS)
    • Microhemagglutination test for antibodies to T. pallidum (MHA-TP)
    • T. pallidum particle agglutination assay (TPPA)
    • T. pallidum enzyme immunoassay (TP- EIA)
    • Chemiluminescence immunoassay (CLIA)
    • Positive for life
  • Negative Non-Treponemal Test
    • For most patients this precludes a diagnosis of active syphilis
    • If symptomatic consider:
      • Early empiric treatment (seroreversion)
      • In early syphilis: Testing could be prior to Antibody formation, or prozone reaction (2 percent)
      • Late syphilis: advanced immunosuppression (B cell failure), natural history
  • Interpretation of CSF
    • VDRL in CSF = highly specific; poor sensitivity
      • If positive establishes the diagnosis
    • FTA-ABS can be ordered = sensitive; not specific
    • CSF-VDRL false+: traumatic tap when serum nontreponemal titer high
    • Pleocytosis >5 and Protein >45 is consistent with the diagnosis, but is also non specific
    • Non-specific pleocytosis also occurs in setting of HIV infection and makes interpretation difficult

Treatment

  • Treat ocular syphilis as neurosyphilis
    • Aqueous crystalline penicillin G (18 to 24 million units per day)
    • 3 to 4 mil units IV q 4 H 10 to 14 days
    • Desensitization in patients with severe allergy
    • May consider doxycycline and ceftriaxone as alternatives in patients with severe allergy (excluding pregnancy)

References

  • Gajula V, Kamepalli R, Kalavakunta JK. A star in the eye: cat scratch neuroretinitis. Clinical Case Reports. 2(1):17.
  • Hicks, CB and M Clement. Syphilis: Screening and diagnostic testing, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on January 08, 2017)
  • Marra CM. Neurosyphilis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on January 15, 2017)
  • Lee SY, Cheng V, Rodger D, Rao N. Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection. J Ophthal Inflamm Infect. 2015 Dec; 5(1):56
  • Liu L, Lin L, Tong M, Zhang H, Huang S, Chen Y, et al. Incidence and Risk Factors for the Prozone Phenomenon in Serologic Testing for Syphilis in a Large Cohort. Clinical Infectious Diseases (2014);59(3):384-389.
  • Read RW, Acharya N, Levinson RD, Rao PK, Sen HN, Walker JD, et al. Section 09, Intraocular Inflammation and Uveitis. In: Cantor LB, Rapuano CJ, Cioffi GA, 2016-17 AAO, Basic and Clinical Science Course. Section 9: Intraocular Inflammation and Uveitis, 2016:359.
  • Weisenthal, RW, Afshari, NA, et al. Cantor LB, Rapuano CJ, Cioffi GA. 2016-2017 AAO, Basic and Clinical Science Course. Section 8: External Disease and Cornea, 2016:359.