| Neurosyphilis | |
|---|---|
 | |
| Section of human skull damaged by late stages of neurosyphilis | |
| Specialty | Neurology,infectious diseases |
| Symptoms | Headache,stiff neck,paresthesia,loss of bladder control, personality andmood changes |
| Causes | Treponema pallidum |
| Risk factors | HIV infection,unprotected sex |
| Treatment | Antibiotics (generallypenicillin) |
Neurosyphilis is the infection of thecentral nervous system byTreponema pallidum, the bacterium that causes thesexually transmitted infectionsyphilis. In the era of modernantibiotics, the majority of neurosyphilis cases have been reported inHIV-infected patients.[1]
There is a wide variety of symptoms that neurosyphilis can present with depending on the affected structure of the central nervous system. While early neurosyphilis is often asymptomatic,meningitis is the most common neurological presentation of the early stage. Late neurosyphilis typically involves thebrain andspinal cordparenchyma, manifesting astabes dorsalis andgeneral paresis.Tertiary syphilis can involve several different organ systems, though neurosyphilis may occur at any stage of infection.[2]
Clinical history, a physicalneurological examination, and alumbar puncture to obtaincerebrospinal fluid (CSF) for analysis are crucial for diagnosing neurosyphilis. There is no single laboratory test to confirm the diagnosis of neurosyphilis in all cases.[3] A positiveCSF-VDRL test in the presence of neurological symptoms is sufficient for a diagnosis, but additional tests may be needed in certain instances.[4]
Standard treatment is an infusion of intravenouspenicillin G for 10 to 14 days. Patients with neurosyphilis should also be evaluated forHIV, and their sexual partners should be properly evaluated by a medical professional.[5]
While the stages ofsyphilis are categorized as primary, secondary, latent, and tertiary, neurosyphilis is typically categorized into early, intermediate, and late stages. It is important to note that neurosyphilis may occur any time after initial infection.[3]
Early neurosyphilis often has no clinical symptoms.Meningitis is the most-common neurological presentation in early syphilis, typically arising within one year of initial infection.[6] Symptoms of syphilitic meningitis are similar to other forms of meningitis, including headache, neck stiffness,photophobia, confusion, nausea, and vomiting.[7] Meningeal inflammation may also affect thecranial nerves, most commonly thefacial nerve, presenting asfacial paralysis.[6] Cerebralgummas, which are caused bygranulomatous destruction of the brain from syphilis, can also cause symptoms of meningitis.[8]
Meningovascular syphilis is often in the intermediate stage of neurosyphilis, typically presenting 5 to 12 years after infection.[6] It is due toinflammation of the blood vessels supplying thecentral nervous system, resulting in the death of brain tissue calledischemia. It may present asstroke orspinal cord injury. Signs and symptoms vary with the blood vessel that is affected. Themiddle cerebral artery is most often affected, causing a variety of symptoms including weakness, sensory loss, eye deviation, andhemineglect syndrome.[9]
Parenchymal syphilis occurs in the late stage of neurosyphilis, with average presentation occurring 15 to 25 years after initial infection.[3] This stage of the disease is generally in the form oftabes dorsalis orgeneral paresis. Tabes dorsalis, also called locomotor ataxia, describes a constellation of symptoms resulting from a degenerative process of theposterior columns of the spinal cord. Symptoms include pain, ataxic wide-based gait,paresthesias, bowel or bladderincontinence, loss of position and vibratory sense, acute episodic gastrointestinal pain,Charcot joints, and reducedreflexes.[6] TheArgyll Robertson pupil, which is a condition where the pupils do not constrict to bright light but constrict when focusing on a near object (accommodation reflex), is another feature that may be present.[10]
Another late form of neurosyphilis isgeneral paresis, which is a slow degenerative process of the brain. Neuropsychiatric symptoms might appear due to overall damage to the brain. These symptoms can make the diagnosis more difficult and can include symptoms ofdementia,[11][12]mania,psychosis,depression,[13] anddelirium.[14] These symptoms are may progress to the point of where a patient becomes bedridden.[3][15]
Nearly any part of the eye may be involved in neurosyphilis, resulting in ocular syphilis. The most common form of ocular syphilis isuveitis. Other forms includeepiscleritis,vitritis,retinitis,papillitis,retinal detachment, andinterstitial keratitis.[16][17] Patients typically present with worsening vision.[18]
Otosyphilis refers to a type of neurosyphilis that affects thevestibulocochlear nerve, causing issues withhearing and balance. Signs include loss of hearing,tinnitus,vertigo, andgait instability.[19]
Ocular syphilis and otosyphilis may occur at any point after initial infection, and its presentation can overlap with other symptoms of neurosyphilis.[3]
There are several risk-factors of neurosyphilis that overlap with the risk factors forsyphilis and otherSTIs, including high-risk sexual behavior, i.e. unprotected sex, and multiple sexual partners.[2] A significant proportion of syphilis cases are seen among males, especiallymen who have sex with men.[1] There is also an association between patients who are infected with syphilis andHIV.[20] The link between syphilis and HIV is thought to be because of shared risk factors. Another possibility is that a weakenedimmune system, such as those in people with HIV, may decrease the body's ability to clear the infection from the central nervous system.[21] It is important to note that the HIV infectionantiretroviral therapy (ART) suppresses HIV transmission but not syphilis transmission.
Treponema pallidum is thespirochete-shaped bacteria that causes neurosyphilis. The pathogenesis is not fully known, in part due to fact that the organism is not easilycultured, making scientific experiments difficult.[22] Within days to weeks after initial infection,T. pallidum spreads throughout the body via blood andlymphatic vessels. The organism may proliferate in theperivascular spaces of nearly any organ, including the central nervous system (CNS).[21] It is unclear why some patients with syphilis develop a persistent CNS infection and others do not. Scientists have also debated if neurosyphilis is the result the bacterial invasion of the CNS or the immune system responding to bacteria in the CNS.[3]
In primary or secondary syphilis, invasion of the protective membrane of the brain called themeninges may result inlymphocytic andplasma cell infiltration ofperivascular spaces. The immune response may affect thebrain andspinal cord through inflammation and necrosis of small blood vessels. In tertiary syphilis, reactivation of a chronic latent infection causes severe inflammation of CNS arteries calledendarteritis obliterans, leading to meningovascular syphilis.[23]
The parenchymal syphilis, present late in neurosyphilis astabes dorsalis andgeneral paresis. Tabes dorsalis thought to be due to irreversible loss ofmyelin in nerve fibers of theposterior columns of the spinal cord involving thelumbosacral and lowerthoracic levels.[6] General paresis is caused by chronic inflammation of meninges and brain, leading tofibrosis of the meninges,atrophy of the cerebral cortex, and the formation ofdemyelinating plaques, particularly in thefrontal andparietal lobes.[6] Rarely,T. pallidum may invade any structures of the eye (such ascornea,anterior chamber,vitreous andchoroid, andoptic nerve) and cause local inflammation and edema.[24]
There is no single test that is sufficient on its own to make a diagnosis of neurosyphilis in every case.[3]Serum studies are used to determine if a patient has preexisting syphilis.[2] Common serum studies to diagnose syphilis include therapid plasma reagin and theVenereal Disease Research Laboratory (VDRL) test. To diagnose neurosyphilis, aclinical history,physical examination, andcerebrospinal fluid (CSF) analysis are required.Lumbar puncture ("spinal tap") is the procedure to obtain CSF. The VDRL test of the CSF is a common test for making a diagnosis of neurosyphilis. A positive VDRL test in the presence of neurological symptoms is sufficient to confirm a diagnosis of neurosyphilis.[4] However, a negative VDRL result does not rule out neurosyphilis. Due to the lowsensitivity of the VDRL test, CSF analyses that specifically look for antibodies againstT. pallidum, such as thefluorescent treponemal antibody absorption test (FTA-ABS) and theT. pallidum particle agglutination assay (TPPA), are also used in certain cases. The FTA-ABS test is more sensitive but lessspecific than the VDRL test.[4] Reported sensitivity of different tests for neurosyphilis are variable.[3][25]
Other components of CSF analysis can be helpful for diagnosing neurosyphilis. The CSFwhite blood cell count is often elevated in neurosyphilis, but this finding is nonspecific and can be unreliable in patients with other infections such as HIV. Similarly, an elevated CSF protein may be suggestive of neurosyphilis, but it is a nonspecific result.[6]
Penicillin is used to treat neurosyphilis. TheCenters for Disease Control and Prevention recommend the following regimen:
Alternatively:
Follow-up blood serum tests are generally performed at 3, 6, 12, and 24 months to ensure successful treatment.[6] The CDC states that repeated CSF studies are unnecessary for people with intact immune systems and people with HIV who are on adequateART.[5] All patients with syphilis should be tested for HIV infection.[5] 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.[26]
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.[27]
In people who are allergic to penicillin, initiation ofpenicillin desensitization is advised. If desensitization is not possible, the CDC recommends ceftriaxone as an alternative.[5] Doxycycline or tetracycline may be considered in select patients for treating neurosyphilis.[6][28]
TheJarisch–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 treponemallipoproteins 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 withantipyretics andnonsteroidal anti-inflammatory medications.[29]
Historically, syphilis was studied under theTuskegee study, often cited as an example ofunethical human experimentation. The study began withoutinformed consent of the subjects and was continued by theUnited States Public Health Service until 1972. The researchers failed to notify and withheld treatment for patients despite knowingpenicillin was found as an effective cure for syphilis. After four years of follow-up, neurosyphilis was identified in 26.1% of patients vs. 2.5% of controls.[30] After 20 years of follow-up, 6.5% showed signs of neurosyphilis and 40% had died from other causes.[31]
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