Neurosyphilis is a slowly progressive and destructive infection of the brain or spinal cord. It occurs in untreated syphilis many years after the primary infection.

Causes, incidence, and risk factors
Neurosyphilis occurs in 15 to 20% of all late or Tertiary syphilis infections and is a progressive, life-threatening complication. There are 4 different forms of neurosyphilis: asymptomatic, meningovascular, tabes dorsalis, and general paresis.

Asymptomatic neurosyphilis precedes symptomatic syphilis and is present in 15% of those with latent (hidden) syphilis. In this case, abnormalities may be present in the cerebrospinal fluid, but no symptoms are present.

In meningovascular neurosyphilis, cranial nerve palsies and pupil abnormalities may be among a wide variety of symptoms. This may also cause damage to blood vessels resulting in Stroke .

In tabes dorsalis, progressive degeneration of the spinal cord occurs causing an inability to walk.

In general paresis, paralysis, tremors, seizures, and mental decline occur as a result of damage to brain cells. Gummas (inflammatory lesions) may occur anywhere in the brain or spinal cord and can cause a wide variety of neurologic deficits.

Syphilitic aseptic meningitis occurs as a chronic infection and may involve headaches, cognitive changes and cranial nerve abnormalities.


  • headache  
  • Stiff neck  
  • Irritability  
  • Poor concentration  
  • Mental confusion  
  • Depression  
  • Visual disturbances  
  • Abnormal reflexes  
  • Abnormal gait (walk)  
  • Incontinence  
  • Dementia  
  • Weakness, numbness of lower extremities  
  • Muscle function/feeling loss  
  • Muscle contractions  
  • Muscle atrophy

Note: There may be no symptoms (in the asymptomatic form)

Signs and tests

Tests to detect syphilis include detection of antibodies in blood. These are non-treponemal tests (VDRL, RPR). These are not specific and are used as screening tests. If positive the diagnosis of syphilis is confirmed using treponemal tests (e.g., FTA-Abs or MHATP). In neurosyphilis, it is important to test for VDRL in the spinal fluid.
Tests to evaluate the nervous system may include:

  • Examination of cranial nerves  
  • lumbar puncture and a CSF fluid analysis.  
  • Cranial CT scan  
  • MRI scan of the brain, brainstem, or spinal cord  
  • Cerebral angiogram

The treatment of syphilis is determined by the length of time the individual has been infected. Primary, secondary or latent syphilis of less than one year duration is treated as follows:

  • Benzathine penicillin, 2.4 million units injected into a muscle (IM) as a single dose  
  • Doxycycline 100 mg (milligrams) by mouth twice per day for 15 days  
  • Tetracycline 500 mg by mouth four times per day for 15 days  
  • Erythromycin 500 mg by mouth four times per day for 2 weeks  
  • Ceftriaxone 250 mg IM daily for 10 days

For treatment of syphilis of greater than one year duration:

  • Benzathine penicillin 2.4 million units IM weekly for 3 weeks  
  • Doxycycline 100 mg by mouth twice per day for 30 days  
  • Tetracycline 500 mg by mouth twice per day for 30 days


  • Aqueous penicillin G 12 to 24 million units injected into a vein (IV) daily for 10 days followed by benzathine penicillin 2.4 million units IM once a week for 3 weeks  
  • Procaine penicillin 2.4 million units IM daily; given with oral probenecid 500 mg four times per day-both for 10 days. This is followed by benzathine penicillin 2.4 million units once a week for 3 weeks.

Syphilis during pregnancy:
Penicillin is recommended as the only real drug of choice. Tetracycline can not be used because of toxicity to the fetus and erythromycin may fail to prevent congenital syphilis in the fetus. Penicillin-allergic individuals should be desensitized and then treated with penicillin.

Several hours following treatment of early stages of syphilis individuals may undergo a febrile reaction called Jarish-Herxheimer reaction. Symptoms of this reaction include:

  • Fever  
  • Chills  
  • headache  
  • nausea  
  • General feeling of being ill (malaise)  
  • Generalized joint aches (arthralgia)  
  • Generalized muscle aches (myalgia)

These symptoms usually disappear within 24 hours.

Follow-up blood tests must be done at 3, 6, 12, and 24 months to ensure the infection has been eliminated. There must be abstinence from sexual conduct until 2 follow-up tests have indicated that the infection has been cured. Syphilis is extremely contagious in the primary and secondary stages.

Expectations (prognosis)
The outcome depends upon the type and extent of disability before treatment is begun.


Complications include a progression of symptoms.

Calling your health care provider
Call for an appointment with your health care provider if neurologic symptoms develop in a person who has had syphilis in the past.

Neurosyphilis can be prevented by the timely diagnosis and treatment of primary syphilis and secondary syphilis. Good follow-up is necessary to prove a cure and prevent neurosyphilis from developing following incomplete treatment (either by inadequate medication or non-compliance of the individual taking the medication).

Johns Hopkins patient information

Last revised: December 4, 2012
by Janet G. Derge, M.D.

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