Neurosyphilis refers to infection of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

in a patient with

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...

. In the era of modern

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

s the majority of neurosyphilis cases have been reported in HIV-infected patients.

Meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

is the most common neurological presentation in early syphilis.

Tertiary syphilis Tertiary ( ) is a widely used but obsolete term for the geologic period from 66 million to 2.6 million years ago. The period began with the demise of the non-avian dinosaurs in the Cretaceous–Paleogene extinction event, at the start ...

symptoms are exclusively neurosyphilis, though neurosyphilis may occur at any stage of infection. To diagnose neurosyphilis, patients undergo a

lumbar puncture Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to ...

to obtain

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

(CSF) for analysis. The CSF is tested for

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

for specific ''

Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacterium with various subspecies that cause the diseases syphilis, bejel (also known as endemic syphilis), and yaws. It is transmitted only among humans. It is ...

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s. The preferred test is the

VDRL test The Venereal Disease Research Laboratory test (VDRL) is a blood test for syphilis and related non-venereal treponematoses that was developed by the eponymous lab. The VDRL test is used to screen for syphilis (it has high sensitivity), whereas oth ...

, which is sometimes supplemented by

fluorescent treponemal antibody absorption test The fluorescent treponemal antibody absorption (FTA-ABS) test is a diagnostic test for syphilis. Using antibodies specific for the ''Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacter ...

(FTA-ABS). Historically, the disease was studied under the

Tuskegee study The Tuskegee Study of Untreated Syphilis in the Negro Male (informally referred to as the Tuskegee Experiment or Tuskegee Syphilis Study) was a study conducted between 1932 and 1972 by the United States Public Health Service (PHS) and the Cente ...

, a notable example of

unethical human experimentation Unethical human experimentation is human experimentation that violates the principles of medical ethics. Such practices have included denying patients the right to informed consent, using pseudoscientific frameworks such as race science, and tortu ...

. The study was done on approximately 400

African-American African Americans (also referred to as Black Americans and Afro-Americans) are an Race and ethnicity in the United States, ethnic group consisting of Americans with partial or total ancestry from sub-Saharan Africa. The term "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 Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...

of the subjects and was continued by the

United States Public Health Service The United States Public Health Service (USPHS or PHS) is a collection of agencies of the Department of Health and Human Services concerned with public health, containing nine out of the department's twelve operating divisions. The Assistant S ...

until 1972. The researchers failed to notify and withheld treatment for patients despite knowing

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

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

. 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.

is the most common neurological presentation in early syphilis. It typically occurs in the secondary stage, arising within one year of initial infection. The symptoms are similar to other forms of meningitis. The most common associated with neurosyphilitic meningitis is

cranial nerve Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and ...

palsy Palsy is a medical term which refers to various types of paralysisDan Agin, ''More Than Genes: What Science Can Tell Us About Toxic Chemicals, Development, and the Risk to Our Children;; (2009), p. 172. or paresis, often accompanied by weakness a ...

, especially of the

facial nerve The facial nerve, also known as the seventh cranial nerve, cranial nerve VII, or simply CN VII, is a cranial nerve that emerges from the pons of the brainstem, controls the muscles of facial expression, and functions in the conveyance of tas ...

. Nearly any part of the eye may be involved. The most common form of ocular syphilis is

uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...

. Other forms include

episcleritis Episcleritis is a benign, self-limiting inflammatory disease affecting part of the eye called the episclera. The episclera is a thin layer of tissue that lies between the conjunctiva and the connective tissue layer that forms the white of the e ...

, vitritis,

retinitis Retinitis is inflammation of the retina in the eye, which can permanently damage the retina and lead to blindness. The retina is the eye's "sensing" tissue. Retinitis may be caused by a number of different infectious agents. Its most common form, ...

, papillitis,

retinal detachment Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blin ...

, and

interstitial keratitis Interstitial keratitis (IK) is corneal scarring due to chronic inflammation of the corneal stroma. Interstitial means space between cells i.e. corneal stroma which lies between the epithelium and the endothelium. Keratitis means corneal inflammati ...

Meningovascular syphilis Neurosyphilis refers to infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurolo ...

usually occurs in late syphilis but may affect those with early disease. It is due to

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

of the vasculature supplying the

, that results in

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

. It typically occurs about 6–7 years after initial infection and it may affect those with early disease. It may present as

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

or spinal cord infarct. Signs and symptoms vary with vascular territory involved. The

middle cerebral artery The middle cerebral artery (MCA) is one of the three major paired cerebral artery, cerebral arteries that supply blood to the cerebrum. The MCA arises from the internal carotid artery and continues into the lateral sulcus where it then branches an ...

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

tabes dorsalis Tabes dorsalis is a late consequence of neurosyphilis, characterized by the slow degeneration (specifically, demyelination) of the neural tracts primarily in the dorsal root ganglia of the spinal cord (nerve root). These patients have lancinating n ...

, because of a degenerative process of the posterior columns of the spinal cord. The constellation includes

Argyll Robertson pupil Argyll Robertson pupils (AR pupils) are bilateral small pupils that reduce in size on a near object (i.e., they accommodate), but do ''not'' constrict when exposed to bright light (i.e., they do not react). They are a highly specific sign of neu ...

, ataxic wide-based gait,

paresthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...

s, bowel or bladder

incontinence Incontinence or Incontinent may refer to: *Fecal incontinence, the involuntary excretion of bowel contents *Urinary incontinence, the involuntary excretion of urine * Lack of moderation or self-control, especially related to sexual desire - see I ...

, loss of position and vibratory sense, loss of deep pain and temperature sensation, acute episodic gastrointestinal pain,

Charcot joints Neuropathic arthropathy (or neuropathic osteoarthropathy), also known as Charcot joint (often Charcot foot) after the first to describe it, Jean-Martin Charcot, refers to progressive degeneration of a weight-bearing joint, a process marked by b ...

, and general paresis.

Gummatous A gumma (plural gummata or gummas) is a soft, non-cancerous growth resulting from the tertiary stage of syphilis (and yaws). It is a form of granuloma. Gummas are most commonly found in the liver (''gumma hepatis''), but can also be found in br ...

disease may also present with destructive inflammation and space-occupying lesions. It is caused by

granuloma A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious ...

tous destruction of

visceral In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a ...

organs. They most often involve the

frontal Front may refer to: Arts, entertainment, and media Films * ''The Front'' (1943 film), a 1943 Soviet drama film * ''The Front'', 1976 film Music * The Front (band), an American rock band signed to Columbia Records and active in the 1980s and e ...

and

parietal lobe The parietal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The parietal lobe is positioned above the temporal lobe and behind the frontal lobe and central sulcus. The parietal lobe integrates sensory informa ...

s of the brain. Movement disorders can be found in a small percentage of individuals with neurosyphilis. The abnormal movements already reported were tremor, chorea, parkinsonism, ataxia, myoclonus, dystonia, athetosis, and ballism.

Neuropsychiatric

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 Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wit ...

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

, depression, and

delirium Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...

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

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

lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...

s that are released from dead and dying organisms following antibiotic treatment. It is typically characterized by fever, headache,

myalgia Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...

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

antipyretic An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which r ...

s and nonsteroidal anti-inflammatory medications.

Risk factors

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

antiretroviral therapy The management of HIV/AIDS normally includes the use of multiple Antiviral drug, antiretroviral drugs as a strategy to control HIV/AIDS, HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life- ...

(ART) suppresses HIV transmission, but not syphilis transmission. It may also be associated with recreational drug use.

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 lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessel ...

. 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 The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

anterior chamber The anterior chamber ( AC) is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Hyphema, anterior uveitis and glaucoma are three main pathologies in this area. In hyphema, blood f ...

, vitreous and

choroid The choroid, also known as the choroidea or choroid coat, is a part of the uvea, the vascular layer of the eye, and contains connective tissues, and lies between the retina and the sclera. The human choroid is thickest at the far extreme rear ...

, and

optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...

) and cause local inflammation and edema. In primary or secondary syphilis, invasion of the meninges may result in

lymphocytic A lymphocyte is a type of white blood cell (leukocyte) in the immune system of gnathostomata, most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated immunity, cell-mediated, cytotoxicity, cytotoxic innate imm ...

and

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...

infiltration of

perivascular space A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain blood vessels in several organs, including the brain, potentially having an immunological function, but more broadly a dispersive role fo ...

s (Virchow-Robin spaces). The extension of cellular immune response to the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

and

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

causes inflammation and necrosis of small meningeal vessels. In tertiary syphilis, reactivation of chronic latent infection may result in meningovascular syphilis, arising from

endarteritis obliterans Obliterating endarteritis is severe proliferating endarteritis (inflammation of the intima The tunica intima (New Latin "inner coat"), or intima for short, is the innermost tunica (layer) of an artery or vein. It is made up of one layer of end ...

of small, medium, or large arteries supplying the CNS. The parenchymal syphilis, presents as

and general paresis. Tabes dorsalis thought to be due to irreversible degeneration of nerve fibers in posterior columns of the spinal cord involving the

lumbosacral The vertebral column, also known as the backbone or spine, is part of the axial skeleton. The vertebral column is the defining characteristic of a vertebrate in which the notochord (a flexible rod of uniform composition) found in all chordates ...

and lower

thoracic The thorax or chest is a part of the anatomy of humans, mammals, and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main divisions of the crea ...

levels. The general paresis is caused by meningeal vascular inflammation and

ependyma The ependyma is the thin Neuroepithelial cell, neuroepithelial (Simple columnar epithelium, simple columnar ciliated epithelium) lining of the ventricular system of the brain and the central canal of the spinal cord. The ependyma is one of the fou ...

tous infiltration may lead to neuronal loss, along with

astrocytic Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endot ...

and microglial proliferation and damage may preferentially occur in the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...

striatum The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

, and

meninges In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in th ...

. Concurrent infection of ''T. pallidum'' with

human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...

(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 and limited access to penicillin.

Diagnosis

To diagnose neurosyphilis,

(CSF) analysis is required.

Lumbar puncture Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to ...

("spinal tap") is used to acquire CSF. The

Venereal Disease Research Laboratory test The Venereal Disease Research Laboratory test (VDRL) is a blood test for syphilis and related non-venereal treponematoses that was developed by the eponymous lab. The VDRL test is used to screen for syphilis (it has high sensitivity), whereas othe ...

of the CSF is the preferred test for making a diagnosis of neurosyphilis. A positive test confirms neurosyphilis but a negative result does not rule out neurosyphilis. Due to the low sensitivity of the CSF VDRL,

(FTA-ABS) can be used to supplement VDRL. Reported sensitivity is variable. False-negative antibody test result occurring when antibody concentration is so high that

agglutination In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...

reaction cannot occur, which is typically seen during secondary stage and can be overcome by diluting test sample 1:10. CSF

white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...

count is often elevated in the early stages of neurosyphilis, ranging from about 50 to 100 white blood cells/mcL with a

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

predominance. Cell counts are typically lower in late syphilis. Regardless of syphilis disease stage, the absence of CSF white blood cells rules out neurosyphilis.

Treatment

Penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

is used to treat neurosyphilis. Two examples of penicillin therapies include: * Aqueous

penicillin G Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, and in military slang "Peanut Butter Shot" is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enteroco ...

3–4 million units every four hours for 10 to 14 days. * One daily

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

and

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or or ...

probenecid Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia. Probenecid was developed as an alternative to caronamide to competitive ...

four times daily, both for 10 to 14 days. Follow-up blood tests are generally performed at 3, 6, 12, 24, and 36 months to make sure the infection is gone. 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. 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. The treatment success is measured with a 4-fold 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. In people who cannot take penicillin it is uncertain if other antibiotic therapy is effective for treating neurosyphilis.

References

{{reflist, refs= {{cite book, author=Walter George Bradley, title=Neurology in Clinical Practice: The neurological disorders, url=https://books.google.com/books?id=l9wtYZ_iCCIC&pg=PA1497, year=2004, publisher=Taylor & Francis, isbn=9789997625892, page=1497 {{cite encyclopedia , url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001722/ , title=Neurosyphilis , encyclopedia=A.D.A.M. Medical Encyclopedia on PubMed Health , date=6 October 2012 , access-date=2014-10-23 , others=Reviewed by David C. Dugdale, Jatin M. Vyas, David Zieve {{cite journal , vauthors = Gordon SM, Eaton ME, George R, Larsen S, Lukehart SA, Kuypers J, Marra CM, Thompson S , title = The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection , journal = N. Engl. J. Med. , volume = 331 , issue = 22 , pages = 1469–73 , date = December 1994 , pmid = 7969296 , doi = 10.1056/NEJM199412013312201 {{cite web , last=Kennard , first=Christine , title=Neurosyphilis , url=http://alzheimers.about.com/od/typesofdementia/a/neurosyphilis.htm , website=About.com , date=10 September 2014 , access-date=2014-10-23 {{cite journal , vauthors = Mehrabian S, Raycheva M, Traykova M, Stankova T, Penev L, Grigorova O, Traykov L , title = Neurosyphilis with dementia and bilateral hippocampal atrophy on brain magnetic resonance imaging , journal = BMC Neurol , volume = 12 , pages = 96 , date = September 2012 , pmid = 22994551 , pmc = 3517431 , doi = 10.1186/1471-2377-12-96 {{cite journal , vauthors = Musher DM , title = Syphilis, neurosyphilis, penicillin, and AIDS , journal = J. Infect. Dis. , volume = 163 , issue = 6 , pages = 1201–6 , date = June 1991 , pmid = 2037785 , doi = 10.1093/infdis/163.6.1201 {{cite web , title=Syphilis CDC Fact Sheet , url=https://www.cdc.gov/std/syphilis/STDFact-Syphilis-detailed.htm , publisher=Centers for Disease Control and Prevention , date=4 September 2012 , access-date=2014-10-23 Sexually transmitted diseases and infections Syphilis Disorders causing seizures Syndromes affecting the nervous system