Neurosyphilis

What is Neurosyphilis?

Syphilis is an infectious disease caused by a type of bacteria called Treponema pallidum. It’s often referred to as the “great imitator” because it can cause many different symptoms. The disease can switch between active phases, where symptoms are present, and latent phases, where no symptoms are noticeable.

Neurosyphilis is when the syphilis infection affects the central nervous system, which includes the brain and spinal cord. Unlike the other stages of syphilis, which follow a specific order, neurosyphilis can occur at any point after becoming infected. Research has found that the bacteria can reach the fluid surrounding the brain and spinal cord (cerebral spinal fluid or CSF) just hours after initial infection. The bacteria invading the nervous system is a common occurrence in everyone infected with syphilis. However, if the body doesn’t successfully clear out the bacteria, then the person may begin to show signs of neurosyphilis.

There are five types of neurosyphilis that range from early to late stages of the disease. The early forms may either show no symptoms at all or symptoms related to inflammation of the brain’s protective covering, known as meninges, which can show up less than a year from the infection. The later stages may involve symptoms like poor muscle coordination and numbness that can appear five to twelve years or even decades after the initial infection. Problems with vision or hearing can also happen due to neurosyphilis at any stage of the disease.

What Causes Neurosyphilis?

T pallidum is a type of bacteria that can spread throughout the body in just minutes after infection. This bacteria causes syphilis, which mainly spreads through sexual contact. However, it can also be transmitted from a mother to her baby during pregnancy, and very rarely, through blood transfusions.

This bacteria can enter your body through the thin protective layers that line certain parts of your body (like the inside of your mouth or nose) or through small cuts in your skin. Having unprotected sex increases the risk of getting this infection, especially for men who have sex with men and people who are infected with HIV.

The bacteria can penetrate the central nervous system (the brain and spinal cord) in almost every infected individual very quickly. Nonetheless, most people infected with the bacteria will never develop neurosyphilis, a condition that occurs when the syphilis infection affects the brain and spinal cord.

The body has the natural ability to get rid of T pallidum from the central nervous system. This might happen due to enhanced activity of specific immune system cells, called macrophages and helper T cells type 1.

Medical studies have found that the bacteria can reach the brain and spinal cord early on in around 40% of people diagnosed with the initial stage of syphilis, 23% with the second stage, and 20% in those carrying the bacteria without showing any symptom. Before antibiotics were introduced, 25% to 35% of people with early-stage syphilis and 13.5% with late-stage disease had neurosyphilis without showing any symptom.

Risk Factors and Frequency for Neurosyphilis

According to a global health study, the number of syphilis cases around the world increased by 60% between 1990 and 2019, resulting in approximately 50 million people infected in 2019 alone. After the creation of penicillin, the rate of syphilis fell to historic lows by the end of the 20th century. Despite this, the rate of syphilis has been steadily rising, especially in men who have sex with men (MSM) and those living with HIV. MSM individuals are 15 to 20 times more likely to have syphilis than other men, and they account for over 80% of all new syphilis diagnoses in the US. It’s also reported that nearly half of MSM individuals with syphilis also have HIV.

Before antibiotics were developed, neurosyphilis, a severe form of the disease, was found in about a third of all syphilis patients. Today, it’s more common in people with HIV, in particular those who are untreated or have low CD4+ counts or detectable HIV RNA levels. People with high-risk sexual behavior can potentially contract both HIV and syphilis.

The chances of getting neurosyphilis are 2 to 3 times higher in Whites compared to Blacks, even though Blacks are 5 times more likely to have other forms of syphilis.
Men are twice as likely as women to have neurosyphilis.
In the US, between 3% and 5% of all individuals with syphilis may develop neurological, ocular, or auditory complications.

Signs and Symptoms of Neurosyphilis

Neurosyphilis is a serious condition that affects the nervous system, often related to a syphilis infection. The symptoms can take different forms, depending on what stage of the disease you’re in. Early neurosyphilis doesn’t usually cause symptoms. But if it progresses, it can lead to damage to the brain and spinal cord.

The most common symptoms of neurosyphilis are changes in personality, cognition, or behavior. Other symptoms can include difficulty moving and balancing, strokes, vision problems, bladder control issues, headache, dizziness, and seizures. Physical signs of this disease might also show up, such as a loss of reflexes, changes in the eyes, and nerve damage.

Changes in personality, cognition, or behavior

Difficulty moving and balancing

Strokes

Vision problems

Bladder control issues

Headache

Dizziness

Seizures

Loss of reflexes

Changes in the eyes

Nerve damage

Approximately one-third of all untreated syphilis cases that develop into neurosyphilis will not show any symptoms. Unfortunately, without the right treatment, neurosyphilis can have serious consequences, such as the development of mental disorders, spinal diseases, and other neurological symptoms.

Neurosyphilis has different forms, including asymptomatic, meningeal, and meningo-vascular neurosyphilis. Each form has unique characteristics and progresses at different rates. Asymptomatic neurosyphilis, for example, can occur before any other symptoms of syphilis appear. Meanwhile, meningeal neurosyphilis affects the membranes surrounding the brain and spinal cord, and meningo-vascular syphilis involves inflammation of the brain and spinal cord.

If not treated promptly, neurosyphilis can progress into more serious forms, such as syphilitic paresis and tabes dorsalis, which can cause severe mental and physical problems. Understanding the symptoms and seeking medical help early can help manage the progression of the disease better.

Testing for Neurosyphilis

Syphilis can affect many body systems, including the nervous system, where it is known as neurosyphilis. It’s important that a general syphilis infection is confirmed or suspected before diagnosing neurosyphilis.

The first step to diagnose syphilis involves blood tests, usually both a treponemal and nontreponemal test. However, the nontreponemal tests can turn normal or negative over time, especially in later stages of neurosyphilis.

Diagnosing neurosyphilis can be challenging because there are no definitive standardized tests for it. The diagnosis relies on a combination of clinical findings, symptoms, medical history, imaging and lab testing, and analysis of cerebrospinal fluid (the fluid around your brain and spinal cord, or CSF). Patients with neurosyphilis who have dementia or seizures often respond positively to antibiotic treatments, so it’s important to diagnose and treat the condition as early as possible.

Usually, neurosyphilis can’t be diagnosed properly without analyzing CSF. However, if doing so would not change the treatment approach or if a patient refuses a spinal tap to obtain the CSF, it may be more beneficial to treat them for neurosyphilis anyway.

In the early stages, neurosyphilis usually shows positive results for both treponemal and nontreponemal tests in blood or CSF. Different types of testing can include methods like fluorescent treponemal antibody absorption, T pallidum particle agglutination assay, and enzymatic immunoassays, which are highly sensitive but nonspecific in the CSF. These tests are positive for life and are unlikely to be negative in cases of neurosyphilis.

Additional testing like the Venereal Disease Research Laboratory and rapid plasma reagin tests can also be used as they tend to decrease over time and can thus track the disease progress and the body’s response to therapy.

There are also several specific scenarios in which a doctor may consider analyzing a patient’s CSF, including if the patient has untreated syphilis of unknown duration, has been untreated for a year or more, has neurological symptoms, has demonstrated complications from late syphilis, or has not responded to syphilis treatments.

Using an MRI scan for neuroimaging can be useful in diagnosing and managing neurosyphilis. The common findings include frontal and temporoparietal atrophy or shrinkage in the frontal and temporoparietal regions of the brain. However, these findings are generally nonspecific, and there are no unique signs that confirm neurosyphilis. Neuroimaging is generally not required for diagnosing neurosyphilis and is only used if there are reasons to suspect other neurological conditions.

The process of diagnosing neurosyphilis is complex and relies heavily on the usage of quite a few lab tests. As such, there are also various biomarkers, or indicators of a condition, being studied to help aid in the diagnosis of neurosyphilis.

As a point of interest, this process of diagnosis has not changed much since 1944 when Stokes, a renowned researcher, stated in his book on ‘Modern Clinical Syphilology’ that the frequency of neurosyphilis in general medical practice depends greatly on the accuracy of the search for signs of neuraxis involvement and the frequency of spinal fluid examinations. This simply means that the frequency of diagnosing neurosyphilis depends greatly on the precision and regularity of checking signs related to the nervous system and conducting spinal fluid tests.

Finally, the diagnosis of neurosyphilis in newborns and infants is thoroughly explained in the StatPearls’ companion reference, “Congenital Syphilis”.

Treatment Options for Neurosyphilis

The CDC recommends the use of penicillin, an antibiotic, to treat all stages of neurosyphilis. This is due to its proven effectiveness and its ability to penetrate into the cerebrospinal fluid (CSF), a liquid that protects your brain and spinal cord. Penicillin works by hindering an essential enzyme for bacteria growth, causing the bacteria to weaken and eventually die.

Because Treponema pallidum, the bacteria that causes syphilis, reproduces slowly, treatment for neurosyphilis needs to be extended, often lasting at least seven days. However, there is no definitive consensus on the ideal duration of treatment.

In most cases, patients with neurosyphilis will be hospitalized to start antibiotic treatment. Steroids are not recommended as part of the treatment.

Penicillin is used in different forms. For instance, aqueous crystalline penicillin G is given intravenously or as a steady infusion for 10 to 14 days. An alternative option, procaine penicillin G, is injected into the muscle and given along with a medication called probenecid, and is suggested for highly compliant patients only.

If a patient is allergic to penicillin, it’s advised to undergo penicillin desensitization if possible. When desensitization is not possible, an alternative antibiotic called ceftriaxone is recommended. It’s also effective against the syphilis bacteria and can penetrate the blood-brain barrier well.

Effectiveness of treatment is usually tracked using tests known as VDRL or RPR serum assays, which measure the presence of antibodies in the blood. These tests are recommended at intervals of 3, 6, 9, 12, 18, and 24 months after treatment.

If there’s no improvement after two years of treatment, the patient may need to be treated again. The return to normal of the CSF may take longer in patients who are also diagnosed with HIV.

Lastly, treating the psychological symptoms of neurosyphilis can be challenging due to the lack of specific treatment guidelines. However, medications such as olanzapine, valproate, quetiapine, and gabapentin have proven effective.

Neurosyphilis, often known as the “great imitator,” can be mistaken for a wide variety of other conditions due to its diverse symptoms. Here are some key conditions a doctor would think about when diagnosing neurosyphilis:

Acute basal meningitis: Especially when there’s a symptom like cranial nerve palsy, doctors would also need to rule out other causes of acute meningitis and tuberculosis.
Acute psychiatric illnesses: In cases where people show symptoms like delirium, mania, psychosis, personality change, dementia, or depression, a diagnosis of general paresis might be considered.
Brain tumors/abscesses: Any tumors or abscesses found on brain scans might also be due to a condition called gumma.
Drug toxicity: Various drugs can cause symptoms that may resemble neurosyphilis.
Electrolyte imbalances: Sometimes, an imbalance of minerals in the body can cause similar symptoms to neurosyphilis.
Herpes encephalitis: This is an inflammation of the brain caused by the herpes virus, which can also present similar symptoms.
Multiple sclerosis: Symptoms of neurosyphilis can sometimes resemble those of multiple sclerosis.
Subacute combined degeneration of the spinal cord: This condition is usually due to a lack of vitamin B12 and causes the deterioration of certain areas in the spinal cord, leading to symptoms that are similar to a form of neurosyphilis, known as tabes dorsalis.
Subarachnoid hemorrhage: This involves bleeding around the brain which can mimic some symptoms of neurosyphilis.
Wernicke encephalopathy: This condition, typically caused by heavy alcohol use, can also present similar symptoms.

What to expect with Neurosyphilis

The National Institute of Health says that how well someone recovers from neurosyphilis depends largely on the specific type of the disease, which parts of the nervous system got affected, how much damage was done, and how early the disease was detected. Neurosyphilis is a stage of syphilis, an infection caused by bacteria, affecting the nervous system.

For people who have neurosyphilis without symptoms or those who have it in the lining of their brain and spinal cord, they usually go back to normal health if treated properly and in a timely manner. However, for those who have types of neurosyphilis that affects the blood vessels in the brain, causes general loss of physical abilities, or affects the spine (like Charcot spine), may see some improvement but usually do not return to their previous level of health or functionality.

Moreover, people who receive treatment many years after the initial infection tend to have much poorer outcomes.

Possible Complications When Diagnosed with Neurosyphilis

Neurosyphilis refers to when syphilis, a sexually transmitted disease, affects the nervous system. If left untreated, it can lead to severe health problems including the possibility of permanent paralysis, dementia, backward movement of the spine, and even death. The good news is that treatment with antibiotics could potentially reverse some symptoms and complications if started as early as possible. But keep in mind that success of treatment in reversing neurological symptoms is less likely the longer the infection remains untreated.

Body conditions/diseases include:

Permanent Paralysis
Dementia
Spinal degeneration
Death

Potential Reversible symptoms / complications include:

Some neurological symptoms

Remember, the longer the infection remains untreated, the harder it would be to reverse the symptoms and complications.

Preventing Neurosyphilis

Individuals who have been diagnosed with syphilis should be given advice about how the disease can spread and how to decrease the risk through safe sex practices. For those who are pregnant, they should be advised about the potential of passing the disease to their baby, a process known as vertical transmission. It’s also essential for everyone to understand the symptoms of advanced forms of syphilis that can affect the nervous system, namely neurosyphilis and tabes dorsalis.

Those undergoing treatment for syphilis should know about the importance of regular blood tests that measure the disease progress in their body. These tests, known as titers, are a way to monitor how well the treatment is working. Besides, these patients should also be made aware about a common reaction to syphilis treatment called the Jarisch-Herxheimer reaction. While uncomfortable, they should be assured that this reaction does not mean they are allergic to penicillin, the antibiotic often used for treatment.

If patients notice that their blood tests do not show significant improvement in their disease status within 6 to 12 months after treatment, this may be a sign of a more serious condition called neurosyphilis. In such cases, they may need to undergo additional testing and possibly a stronger treatment plan. Additionally, all patients diagnosed with neurosyphilis should also be tested for HIV, as the two conditions often co-exist.

Frequently asked questions

Neurosyphilis is when the syphilis infection affects the central nervous system, which includes the brain and spinal cord.

Neurosyphilis is found in about a third of all syphilis patients.

The signs and symptoms of Neurosyphilis include: - Changes in personality, cognition, or behavior - Difficulty moving and balancing - Strokes - Vision problems - Bladder control issues - Headache - Dizziness - Seizures - Loss of reflexes - Changes in the eyes - Nerve damage In addition, physical signs of Neurosyphilis might also show up, such as a loss of reflexes, changes in the eyes, and nerve damage. It is important to note that approximately one-third of all untreated syphilis cases that develop into Neurosyphilis will not show any symptoms. Without the right treatment, Neurosyphilis can have serious consequences, such as the development of mental disorders, spinal diseases, and other neurological symptoms. Neurosyphilis has different forms, including asymptomatic, meningeal, and meningo-vascular Neurosyphilis. Each form has unique characteristics and progresses at different rates. If not treated promptly, Neurosyphilis can progress into more serious forms, such as syphilitic paresis and tabes dorsalis, which can cause severe mental and physical problems.

Neurosyphilis can occur as a result of a syphilis infection that spreads to the central nervous system, including the brain and spinal cord. It can be acquired through sexual contact, including unprotected sex, especially for men who have sex with men and people who are infected with HIV. Neurosyphilis can also be transmitted from a mother to her baby during pregnancy, and very rarely, through blood transfusions.

The other conditions that a doctor needs to rule out when diagnosing Neurosyphilis are: 1. Acute basal meningitis 2. Acute psychiatric illnesses (general paresis) 3. Brain tumors/abscesses (gumma) 4. Drug toxicity 5. Electrolyte imbalances 6. Herpes encephalitis 7. Multiple sclerosis 8. Subacute combined degeneration of the spinal cord (tabes dorsalis) 9. Subarachnoid hemorrhage 10. Wernicke encephalopathy

The types of tests needed for diagnosing neurosyphilis include: 1. Blood tests: Both treponemal and nontreponemal tests are usually performed to confirm or suspect a general syphilis infection. The nontreponemal tests can turn normal or negative over time, especially in later stages of neurosyphilis. 2. Analysis of cerebrospinal fluid (CSF): Analyzing the CSF is crucial for diagnosing neurosyphilis. This involves a spinal tap to obtain the CSF, which can help determine the presence of syphilis infection in the nervous system. 3. Additional testing: Other tests such as fluorescent treponemal antibody absorption, T pallidum particle agglutination assay, and enzymatic immunoassays can be used to test the CSF for neurosyphilis. The Venereal Disease Research Laboratory and rapid plasma reagin tests can also track the disease progress and the body's response to therapy. 4. Neuroimaging: An MRI scan can be useful in diagnosing and managing neurosyphilis, although it is generally not required for diagnosis. Common findings include frontal and temporoparietal atrophy or shrinkage in the brain, but these findings are nonspecific. It is important to note that the diagnosis of neurosyphilis relies on a combination of clinical findings, symptoms, medical history, imaging and lab testing, and analysis of CSF.

Neurosyphilis is treated with the use of penicillin, an antibiotic, which is recommended by the CDC. Penicillin is effective in treating all stages of neurosyphilis and can penetrate into the cerebrospinal fluid to target the bacteria that causes syphilis. Treatment typically lasts at least seven days, but the ideal duration is not definitively established. Hospitalization is often required to initiate antibiotic treatment, and steroids are not recommended. If a patient is allergic to penicillin, penicillin desensitization is advised if possible. If not, an alternative antibiotic called ceftriaxone can be used. Treatment effectiveness is monitored using tests that measure the presence of antibodies in the blood. Psychological symptoms of neurosyphilis can be challenging to treat due to the lack of specific guidelines, but certain medications have shown effectiveness.

The text does not mention any specific side effects when treating Neurosyphilis.

The prognosis for neurosyphilis depends on several factors, including the specific type of the disease, which parts of the nervous system are affected, the extent of damage, and how early the disease is detected. Individuals with neurosyphilis without symptoms or with involvement limited to the lining of the brain and spinal cord can usually return to normal health with proper and timely treatment. However, those with neurosyphilis that affects blood vessels in the brain, causes general loss of physical abilities, or affects the spine may see some improvement but typically do not fully recover their previous level of health or functionality. Delayed treatment after the initial infection tends to result in poorer outcomes.

A neurologist or an infectious disease specialist.