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Neurosyphilis - a Potentially Serious Infection

Published on Sep 11, 2020 and last reviewed on Sep 14, 2020   -  4 min read



Neurosyphilis is the infection of the brain and spinal cord in patients with syphilis, a sexually transmitted bacterial infection. Read the article to know about its types, diagnosis, and treatment.


What Is Neurosyphilis?

Neurosyphilis is a chronic, life-threatening infection of the central nervous system (CNS), involving the brain and spinal cord. It is caused by the spirochete bacterium Treponema pallidum.

Despite the absence of a definitive diagnostic test, several sets of criteria are used for diagnosis of neurosyphilis, including high CSF (cerebrospinal fluid), WBC (white blood cells) count, and/or a reactive CSF, VDRL (Venereal Disease Research Laboratory) with clinical symptoms. Early and adequate treatment is the key factor in the prevention of active neurosyphilis. The intravenous administration of aqueous crystalline Penicillin G 18 to 24 million units (MU) per day every 4 hours or continuously for 10 to 14 days is the first-line regimen in the treatment of neurosyphilis.

It is believed that, in most cases, the dissemination into the central nervous system occurs in the early stage of the infection. However, the neurological presentation of the infection could appear at any stage of syphilis.

Most commonly, neurosyphilis develops in untreated individuals who progress to the tertiary stage of syphilis, 10 to 30 years following the primary infection.

Despite the rare prevalence of early neurosyphilis, it has been detected that the rate of occurrence is significantly related to the treatment and is ten times higher in people receiving inappropriate therapy compared to those who are not treated.

Types of Neurosyphilis and Clinical Manifestation:

Once the bacteria infects the central nervous system, the body response could vary from asymptomatic to symptomatic, including a variety of manifestations. Neurosyphilis compromises five types with different clinical manifestations:

  1. Asymptomatic neurosyphilis.

  2. Meningeal neurosyphilis.

  3. Meningovascular neurosyphilis.

  4. General paresis.

  5. Tabes dorsalis.

Meningeal Neurosyphilis:

In the case of meningeal syphilis, symptoms could usually appear during the first year following the bacterial invasion, though the duration can extend from a couple of weeks to a couple of years. The clinical features of meningeal syphilis include signs of meningeal irritation, such as headache, nausea, vomiting, stiff neck, and of cranial neuropathies affecting cranial nerves VII, VIII, VI, and II, which could lead to visual and hearing impairment. Adequate treatment is required for active infection in order to prevent the progression to more serious types of neurosyphilis.

Meningovascular Syphilis:

Meningovascular syphilis is another form of neurosyphilis, characterized by the presence of endarteritis (inflammation of the inner lining of the artery) and perivascular (surrounding the blood vessel) inflammation. The inflammation of the tunica intima and the surrounding artery causes a narrowing within the lumen of vessels, which eventually could contribute to the formation of cerebrovascular thrombosis, vessel occlusion, ischemia, and infraction. Usually, clinical manifestation starts to develop about seven years after individuals get infected. However, it could appear as early as a few months or delayed to several years following the initial infection.

The symptoms of meningovascular syphilis comprise the signs of meningeal syphilis with the presence of stroke syndrome, which mostly affects the middle cerebral artery and the branches of the basilar artery in young adults. In addition, it could be associated with subacute encephalitis presentation, including headache, insomnia, vertigo, and psychological disorders as decreased memory, mood change, and personality disorders.

Parenchymatous Syphilis:

Parenchymatous syphilis is composed of general paresis (general paralysis) and tabes dorsalis (locomotor ataxia), which are relatively rare regarding other forms of neurosyphilis, due to developed medical prevention, screening, and treatment. Typically, it develops as a result of cortical parenchymal damage following chronic meningoencephalitis. It occurs within several years after infection, usually 3 to 30 years in general paresis and 5 to 50 years in tabes dorsalis with an average of 15 to 20 and 20 to 25 years, respectively.

The presentation of general paresis is subdivided into early and late symptoms including headaches, irritability, decreased memory, personality changes, and insomnia in early manifestations, and emotional lability, memory loss, confusion, disorientation, delusions, and seizures in late manifestations. It is found to be as well associated with psychiatric disorders like depression, hallucinations, mania, and psychosis.

General paresis is a severe form of neurosyphilis, and patients could die within an average of 5 years if they are left untreated. Regarding tabes dorsalis, the clinical features could range from ataxic gait, pains in the limbs, balance problem, paraesthesia to bladder dysfunction, and vision loss.

Diagnosis of Neurosyphilis:

There is no definitive diagnostic test for neurosyphilis. However, several sets of case definition criteria were reported by the CDC to assist the classification of neurosyphilis into three groups: possible, likely, or verified. The diagnosis of neurosyphilis is considered possible when a reactive nontreponemal test (as VDRL, RPR) with a reactive treponemal test (as EIA, CIA, TP-PA) and clinical manifestations of neurosyphilis are detected without the presence of other possible causes for these findings.

While it is defined likely when all the above criteria are associated with elevated cerebrospinal fluid (CSF) protein or leucocyte count without other possible causes. Verified neurosyphilis is confirmed by the presence of reactive nontreponemal and treponemal tests with characteristic clinical symptoms and reactive VDRL in CSF without significant bloody contamination of the CSF.

Management of Neurosyphilis

Regarding the available treatments provided to patients with neurosyphilis, aqueous crystalline Penicillin G is used as first-line regimens, given intravenously at 18 to 24 million units (MU) either every 4 hours or continuously for 10 to 14 days. An alternative therapy could be offered instead of the recommended treatment and includes 2.4 MU of Procaine Penicillin administered by intramuscular injection once daily plus 500 mg of Probenecid given four times a day orally for a total duration of 10 to 14 days.

However, for late syphilis, an additional dose of 2.4 MU of intramuscular Benzathine Penicillin is recommended once a week for three weeks following previous regimens to establish an adequate duration of therapy. A follow-up after treatment is required to ensure a complete resolution of the infection. For that reason, a CSF examination should be performed every six months until normal results are detected. If CSF results remain abnormal within the next two years, patients need to be re-treated for neurosyphilis.


The latest data shows an increase in the total number of reported syphilis cases, including all stages, by 13.3 % from 2017 to 2018. Regarding the continuous rise of the overall syphilis rate, further public health interventions are required to reduce the numbers, control the spread, and prevent the progression of disease, especially with the absence of gold standard lab test methods. However, early application of adequate treatment could provide sufficient protection against active neurosyphilis and associated complications as neurological disorders, disability, and even death.


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Last reviewed at:
14 Sep 2020  -  4 min read


Dr. Tonina Sleiman

Dr. Tonina Sleiman

MD, MMed (infection and immunology)

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