Neurosyphilis

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Neurosyphilis
Antibiotics (generally penicillin
)

Neurosyphilis is the infection of the

Tertiary syphilis
symptoms are exclusively neurosyphilis, though neurosyphilis may occur at any stage of infection.

To diagnose neurosyphilis, patients undergo a lumbar puncture to obtain cerebrospinal fluid (CSF) for analysis. The CSF is tested for antibodies for specific Treponema pallidum antigens. The preferred test is the VDRL test, which is sometimes supplemented by fluorescent treponemal antibody absorption test (FTA-ABS).[1][2][3]

Historically, the disease was studied under the

Tuskegee study, often cited as an example of unethical human experimentation. The study was done on approximately 400 African-American men with untreated syphilis who were followed from 1932 to 1972 and compared to approximately 200 men without syphilis. The study began without informed consent of the subjects and was continued by the United States Public Health Service until 1972. The researchers failed to notify and withheld treatment for patients despite knowing penicillin
was found as an effective cure for neurosyphilis. After four years of follow up, neurosyphilis was identified in 26.1% of patients vs. 2.5% of controls. After 20 years of followup, 14% showed signs of neurosyphilis and 40% had died from other causes.

Signs and symptoms

The signs and symptoms of neurosyphilis vary with the disease stage of syphilis. The stages of syphilis are categorized as primary, secondary, latent, and tertiary. It is important to note that neurosyphilis may occur at any stage of infection.[citation needed]

palsy, especially of the facial nerve.[4][5]

Nearly any part of the eye may be involved. The most common form of ocular syphilis is uveitis. Other forms include episcleritis, vitritis, retinitis, papillitis, retinal detachment, and interstitial keratitis.[2][6]

Meningovascular syphilis usually occurs in late syphilis but may affect those with early disease. It is due to inflammation of the vasculature supplying the central nervous system, that results in ischemia. It typically occurs about 6–7 years after initial infection and it may affect those with early disease. It may present as stroke or spinal cord infarct. Signs and symptoms vary with vascular territory involved. The middle cerebral artery is most often affected.[7]

Parenchymal syphilis occurs years to decades after initial infection. It presents with the constellation of symptoms known as

Charcot joints
, and general paresis.

visceral organs. They most often involve the frontal and parietal lobes of the brain.[citation needed
]

Neuropsychiatric

idiocy
secondary to syphilis

Although neurosyphilis is a neurological disease, neuropsychiatric symptoms might appear due to overall damage to the brain. These symptoms can make the diagnosis more difficult and can include symptoms of dementia,[8][9] mania, psychosis, depression,[10] and delirium:[11]

These symptoms are not always present, and when they are, they usually appear in more advanced stages of the disease.[12]

Complications

The Jarisch–Herxheimer reaction is an immune-mediated response to syphilis therapy occurring within 2–24 hours. The exact mechanisms of reaction are unclear, however most likely caused by proinflammatory treponemal lipoproteins that are released from dead and dying organisms following antibiotic treatment. It is typically characterized by fever, headache, myalgia and possibly intensification of skin rash. It most often occurs in early-stage syphilis (up to 50%–75% of patients with primary and secondary syphilis). It is usually self-limiting and managed with antipyretics and nonsteroidal anti-inflammatory medications.

Risk factors

There are several risk factors: high-risk sexual behavior from unprotected sex and multiple sexual partners.[

antiretroviral therapy (ART) suppresses HIV transmission, but not syphilis transmission. It may also be associated with recreational drug use.[citation needed
]

Pathophysiology

The pathogenesis is not fully known, in part due to fact that the organism is not easily cultured. Within days to weeks after initial infection, Treponema pallidum disseminates via blood and lymphatics. The organism may accumulate in perivascular spaces of nearly any organ, including the central nervous system (CNS). It is unclear why some patients develop CNS infection and others do not. Rarely, organisms may invade any structures of the eye (such as cornea, anterior chamber, vitreous and choroid, and optic nerve) and cause local inflammation and edema. In primary or secondary syphilis, invasion of the meninges may result in lymphocytic and plasma cell infiltration of perivascular spaces (Virchow–Robin spaces). The extension of cellular immune response to the brainstem and spinal cord causes inflammation and necrosis of small meningeal vessels.[citation needed]

In tertiary syphilis, reactivation of chronic latent infection may result in meningovascular syphilis, arising from

lumbosacral and lower thoracic levels. The general paresis is caused by meningeal vascular inflammation and ependymal granulomatous infiltration may lead to neuronal loss, along with astrocytic and microglial proliferation and damage may preferentially occur in the cerebral cortex, striatum, hypothalamus, and meninges.[citation needed
]

Concurrent infection of T. pallidum with human immunodeficiency virus (HIV) has been found to affect the course of syphilis. Syphilis can lie dormant for 10 to 20 years before progressing to neurosyphilis, but HIV may accelerate the rate of the progress. Also, infection with HIV has been found to cause penicillin therapy to fail more often. Therefore, neurosyphilis has once again been prevalent in societies with high HIV rates[2] and limited access to penicillin.[13]

Diagnosis

To diagnose neurosyphilis,

False-negative antibody test result occurring when antibody concentration is so high that agglutination reaction cannot occur, which is typically seen during secondary stage and can be overcome by diluting test sample 1:10. CSF white blood cell count is often elevated in the early stages of neurosyphilis, ranging from about 50 to 100 white blood cells/mcL with a lymphocyte predominance. Cell counts are typically lower in late syphilis. Regardless of syphilis disease stage, the absence of CSF white blood cells rules out neurosyphilis.[citation needed
]

Treatment

Penicillin is used to treat neurosyphilis.[2] Two examples of penicillin therapies include:[1]

Follow-up blood tests are generally performed at 3, 6, 12, 24, and 36 months to make sure the infection is gone.[1] Lumbar punctures for CSF fluid analysis are generally performed every 6 months until cell counts normalize. All patients with syphilis should be tested for HIV infection.[15] All cases of syphilis should be reported to public health authorities and public health departments can aid in partner notification, testing, and determining need for treatment.[16]

The treatment success is measured with a fourfold drop in the nontreponemal antibody test. In early-stage syphilis drop should occur in 6–12 months; in late syphilis drop can take 12–24 months. Titers may decline more slowly in persons who have previously had syphilis.[citation needed]

In people who cannot take penicillin it is uncertain if other antibiotic therapy is effective for treating neurosyphilis.[17]

References

  1. ^ a b c d "Neurosyphilis". A.D.A.M. Medical Encyclopedia on PubMed Health. Reviewed by David C. Dugdale, Jatin M. Vyas, David Zieve. 6 October 2012. Retrieved 2014-10-23.{{cite encyclopedia}}: CS1 maint: others (link)
  2. ^
    PMID 22994551
    .
  3. ^ "Syphilis CDC Fact Sheet". Centers for Disease Control and Prevention. 4 September 2012. Retrieved 2014-10-23.
  4. ^ Radolf JD, Tramont EC, Salazar JC. Syphilis (Treponema pallidum).
  5. ^ Bennett J, Dolin R, Blaser M, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 8th ed. New York, NY: Saunders; 2015: 2684–2709.e4
  6. ^ Kennard, Christine (10 September 2014). "Neurosyphilis". About.com. Retrieved 2014-10-23.
  7. PMID 35321268
    .
  8. S2CID 208230186
    .
  9. S2CID 9393216
    .
  10. ^ "Neurosyphilis". MedlinePlus Medical Encyclopedia. Retrieved 2023-10-27 – via medlineplus.gov.
  11. PMID 37814742
    .
  12. ^ "Neurosyphilis: Overview of Syphilis of the CNS, Pathophysiology of Syphilis, Epidemiology of Syphilis". 19 July 2021.
  13. PMID 7969296
    .
  14. ISBN 9789997625892
    .
  15. PMID 2037785
    .
  16. PMID 1445500
    .
  17. PMID 31132142
    .
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