Neurosyphilis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

Neurosyphilis refers to a site of infection involving the central nervous system (CNS). It may occur at any stage of syphilis. Before the advent of antibiotics, it was typically seen in 25-35% of patients with syphilis. Neurosyphilis is now most common in patients with HIV infection. Reports of neurosyphilis in HIV-infected persons are similar to cases reported before the HIV pandemic. The precise extent and significance of neurologic involvement in HIV-infected patients with syphilis, reflected by either laboratory or clinical criteria, have not been well characterized. Furthermore, the alteration of host immunosuppression by antiretroviral therapy in recent years has further complicated such characterization.

During the Napeoleonic Wars, General Paresis of the Insane(GPI) first appears to be reported in Paris. In 1836, Marshall Hall an English physician found a patient with loss of postural control in darkness caused by severely compromised proprioception, but He did not develop more information about it. In 1840, Moritz Heinrich Romberg, a german physician was the first who discovered tabes dorsalis which is the most prominent manifestation of neurosyphilis. He described excessive drinking and increase sexual activity may be the causes of tabes dorsalis. He named the disease as progressive locomotor ataxia. He was unable to find the relation between syphilis and tabes doesalis. In 1858, Guillaume Duchenne a French neurologist for the first time described the association between syphilis and neurosyphilis .In 1875, Jean-Alfred Fournier, a French dermatologist conclusively described the syphilis as the main cause of tabes dorsalis. In 1888, Sir William R. Gowers a British neurologist gave accurate details of the modern Romberg’s test.

The forms of presentation of neurosyphilis can be grouped in two categories: early (asymptomatic which is the most common form, meningealand meningovascular neurosyphilis and late (progressive general paralysis and tabes dorsalis). Other less important forms are gummas, ocular forms of neurosyphilis and syphilitic amyotrophy or hypoacusis

Neurosyphilis is caused by Treponema pallidum, the bacteria that cause syphilis. It usually occurs about 10 – 20 years after a person is first infected with syphilis. Not everyone who has syphilis will develop this complication. Treponema pallidum is usually transmitted via direct contact with the infected lesion (sexual contact) or blood transfusion (rare). The incubation period varies with the size of innoculum (9-90 days). Following transmission, Treponema pallidum uses the intact or abraded mucous membrane to enter the body. It then disseminates to the lymphatics and blood stream to gain access to any organ of the body. Syphilis uses fibronectin molecules to attach to the endothelial surface of the vessels in organs resulting in inflammation and obliteration of the small blood vessels causing vasculitis (endarteritis obliterans). Organism has slow replication rate (30-33 hrs) and evades the initial host immune response. It may seed to different organs of the body especially the cardiovascular system and central nervous system resulting in tertiary syphilis. Different stages of syphilis results from the interaction between the antigen and the host immune response. The initial infection in primary syphilis is limited due to Th1 response and lack of the antibodyresponse. It is speculated that there is a shift from Th1 to Th2 response during secondary syphilis. Cytotoxic T cells and an incomplete humoral immunity response is mainly responsible for persistence of infection and tissue damage in tertiary syphilis. Ineffective type 4 delayed hypersensitivity reaction containing macrophages and sensitized T cells is mainly responsible for the gumma formation in various organs. There is no known genetic association of syphilis. However, neurosyphilis may be associated with the gene polymorphism for IL-10 production with increased levels seen in the patients with neurosyphilis. In neurosyphilis, the brain tissue and preganglionic portion of the dorsal roots of spinal nerves is infiltrated with lymphocytes and plasma cells, and invasion of treponema pallidum spirochetes to brain tissue and posterior columns of the spinal cord makes them atrophic. The demyelination of the axones of the neurons is the main cause of symptoms and it affects the neuronsin the brain, dorsal root ganglia and posterior columns of the spinal cord.

Neurosyphilis is a complication of late or tertiary syphilis infection. Syphilis is a sexually transmitted infectious disease. The infection damages the brain, spinal cord and peripheral nervous tissue.

Neurosyphilis must be differentiated from other diseases that cause abnormal gait, blindness, confusion and depression, such as multiple sclerosis, brain tumors, Wernicke’s encephalopathy, CNS abscess, electrolyte disturbance, subdural empyema, subarachnoid hemorrhage, brain stroke, conversion disorder and drug toxicity.

Neurosyphilis is not a common disease now because syphilis is usually treated early. In 2012, the incidence of syphilis was estimated to be 6 million cases worldwide. From year 2005 to 2014, the incidence of syphilis in the United States increased from 2.9 to 6.3 cases/100,000/year. The rate of reported cases increased by 15.1% between 2013 and 2014 in the United States. In 2012, the prevalence of syphilis was estimated to be approximately 18 million cases in men and women aged 15-29 worldwide. Among infected patients with Treponema pallidum only 3 to 5% develop neurosyphilis and 5% of those individuals develop tabes dorsalis, 10–20 years later.

The most potent risk factor in the development of neurosyphilis is HIV infection. Other risk factors include male gender, high serum RPR titer, advanced age, and African American race.

Screening guidelines for syphilis include all high risk non-pregnant individuals aged 15-65, all pregnant females, men who have sex with men, women who have sex with women, and HIV positive individuals. Routine screening of adolescents who are asymptomatic for syphilis is not recommended.

The symptoms of neurosyphilis usually develop secondary to long-term untreated syphilis, and include diplopia, impaired vision, hearing loss, hoarseness, persistent headache, dizziness, vertigo, lightning pains, impaired sensation and proprioception, hypesthesias, hemiparesis, homonymous hemianopsia, slurred speech and dysarthria. If left untreated, most patients with neurosyphilis may progress to develop paralysis, dementia, Charcot arthropathy, stroke and blindness. Common complications of neurosyphilis include meningitis, meningiovascular syphilis, Argyll-Robertson pupil, stroke, cranial nerve neuropathies, dementia, paralysis, Charcot arthropathy (Charcot joint) of the foot and sensory ataxic gait.

The first step laboratory test when there is a clinical suspicious toward neurosyphilis is a venereal disease research laboratory test (VDRL) or rapid plasma reagin (RPR). Fluorescent treponemal antibody absorbed (FTA-ABS) test is the gold standard test for the diagnosis of neurosyphilis.

The late forms of neurosyphilis (tabes dorsalis and general paresis) are seen much less frequently since the advent of antibiotics. The most common manifestations today are asymptomatic or symptomatic meningitis. Clinical signs of neurosyphilis (i.e., cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, loss of vibration sense, and auditory or ophthalmic abnormalities) warrant further investigation and treatment for neurosyphilis.

Patients with neurosyphilis may be asymptomatic. Physical examination of patients with neurosyphilis is usually remarkable for: Argyll-Robertson pupils, impaired vibratory and proprioception sense, broad base and sensory ataxic gait and positive romberg’s test.

Approximately 35% to 40% of persons with secondary syphilis have asymptomatic central nervous system (CNS) involvement, as demonstrated by an abnormal leukocyte cell count, protein level, or glucose level or a demonstrated reactivity to Venereal Disease Research Laboratory (VDRL) antibody test on cerebrospinal fluid (CSF) examination. Laboratory testing is helpful in supporting the diagnosis of neurosyphilis; however, no single test can be used to diagnose neurosyphilis in all instances.

There are no ECG findings associated with neurosyphilis.

X-rays are not routinely recommended to detect neurosyphilis. However, complications associated with syphilis may be detected incidentally on x-ray. Cardiovascular manifestations of syphilis may be seen as a non-specific widening of the aortic or mediastinal silhouettes on PA and lateral chest x-ray. Linear calcification of the ascending aorta is an almost pathognomonic finding of syphlitic aortitis. This may prompt the clinician to order further imaging studies for confirmation. Additionally, on chest x-ray, secondary pulmonary syphilis may be characterized by the bilateral infiltrates, pleural effusion, subpleural nodules, and lymphadenopathy. X-ray findings may also include osteolytic bone lesions.

There are no echocardiography/ultrasound findings associated with neurosyphilis.

CNS CT scan may be helpful in the diagnosis of neurosyphilis. Findings on CT scan suggestive of of neurosyoohilis include areas of decreased density suggesting cerebral infarction, syphilitic gumma (appear hypodense with precontrast), focal or diffuse extraaxial enhancement and non-specific white matter lesions.

Spinal and brain MRI may be helpful in the diagnosis of neurosyphilis. Findings on MRI suggestive of neurosyphilis include non specific white matter lesions (cerebral gummas or arteritis), hyperintensity in mesiotemporal lobes, cortical atrophy , cerebral infarction, hippocampal atrophy, hyperintensities in multiple cortical areas and thalami, intramedullary hyperintensity and spinal cord atrophy, longitudinal T2-weighted hyperintensity in the dorsal columns of the spinal cord, narrowing between the cervical intervertebral discs and partial ankylosis of the cervical disc space, bilateral high intensity signals on the T2 weighted sequence located in mesiotemporal, insular, frontal regions and calcification of the ligamentum flavum.

Other imaging findings of neurosyphilis include novel PET/CT technology, multimodal ophthalmologic imaging and bone scintigraphy. In PET/CT scan, increased FDG uptake in lymph nodes may be seen. Multimodal ophthalmologic imaging combines ophthalmoscopy with spectral domain optical coherence tomography (SD-OCT) to produce high definition imaging of the posterior chamber of the eye. Bone scintigraphy allows clinicians to visualize bone uptake of Technetium-99 (T-99m) using x-ray technology.

Biopsy may be considered in some cases of neurosyphilis if clinical findings do not correlate with negative serological tests and there is a strong index of suspicion for neurosyphilis.

CNS involvement can occur during any stage of syphilis. However, CSF laboratory abnormalities are common in persons with early syphilis, even in the absence of clinical neurological findings. No evidence exists to support variation from recommended treatment for early syphilis for patients found to have such abnormalities. If clinical evidence of neurologic involvement is observed (e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of meningitis), a CSF examination should be performed. Syphilitic uveitis or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis. Patients who have neurosyphilis or syphilitic eye disease (e.g., uveitis, neuroretinitis, and optic neuritis) should be treated with the recommended regimen for neurosyphilis; those with eye disease should be managed in collaboration with an ophthalmologist. A CSF examination should be performed for all patients with syphilitic eye disease to identify those with abnormalities; patients found to have abnormal CSF test results should be provided follow-up CSF examinations to assess treatment response.

Surgical intervention is not recommended for the management of neurosyphilis.

There is no vaccine available for prevention of syphilis. However, effective measures for the primary prevention of syphilis include abstinence from intimate physical contact with an infected person, consistent use of latex condoms, limiting number of sexual partners, avoidance of sharing sex toys, practising safe sex, routine screening in pregnant females, individuals with high risk behaviours, and those residing in highly prevalent areas. In patients with diagnosed syphilis, early treatment with penicillin can widely prevent neurosyphilis.

Secondary prevention strategies following syphilis include routine screening and follow up in patients with early syphilis to prevent complications, diagnosis and treatment of sexual partners of infected individuals, routine screening, diagnosis and treatment in pregnant females. In patients with diagnosed syphilis, early treatment with penicillin can completely prevent neurosyphlis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

Neurosyphilis is caused by Treponema pallidum, the bacteria that cause syphilis. It usually occurs about 10 – 20 years after a person is first infected with syphilis. Not everyone who has syphilis will develop this complication. Treponema pallidum is usually transmitted via direct contact with the infected lesion (sexual contact) or blood transfusion (rare). The incubation period varies with the size of innoculum (9-90 days). Following transmission, Treponema pallidum uses the intact or abraded mucous membrane to enter the body. It then disseminates to the lymphatics and blood stream to gain access to any organ of the body. Syphilis uses fibronectin molecules to attach to the endothelial surface of the vessels in organs resulting in inflammation and obliteration of the small blood vessels causing vasculitis (endarteritis obliterans). Organism has slow replication rate (30-33 hrs) and evades the initial host immune response. It may seed to different organs of the body especially the cardiovascular system and central nervous system resulting in tertiary syphilis. Different stages of syphilis results from the interaction between the antigen and the host immune response. The initial infection in primary syphilis is limited due to Th1 response and lack of the antibody response. It is speculated that there is a shift from Th1 to Th2 response during secondary syphilis. Cytotoxic T cells and an incomplete humoral immunity response is mainly responsible for persistence of infection and tissue damage in tertiary syphilis. Ineffective type 4 delayed hypersensitivity reaction containing macrophages and sensitized T cells is mainly responsible for the gumma formation in various organs. There is no known genetic association of syphilis. However, neurosyphilis may be associated with the gene polymorphism for IL-10 production with increased levels seen in the patients with neurosyphilis. In neurosyphilis, the brain tissue and preganglionic portion of the dorsal roots of spinal nerves is infiltrated with lymphocytes and plasma cells, and invasion of treponema pallidum spirochetes to brain tissue and posterior columns of the spinal cord makes them atrophic. The demyelination of the axones of the neurons is the main cause of symptoms and it affects the neurons in the brain, dorsal root ganglia and posterior columns of the spinal cord.

• Neurosyphilis is a manifestation of invasion of treponema pallidum spirochetes to the brain and dorsal column of spinal cord in tertiary syphilis.^[1][2]
• Neurosyphilis usually occurs in patients who have untreated syphilis for a long time, usually about 10 to 20 years after first infection by treponema pallidum
• Only 25%–40% of persons who are not treated with penicillin will develop neurosyphilis.

The forms of presentation of neurosyphilis can be grouped in two categories:^[3]

1. Early (asymptomatic which is the most common form, meningeal and meningovascular neurosyphilis)
2. late (progressive general paralysis and tabes dorsalis).

Other less important forms are:

• Gummas
• Ocular forms
• Syphilitic amyotrophy or hypoacusis

In neurosyphilis, the brain tissue and preganglionic portion of the dorsal roots of spinal nerves is infiltrated with lymphocytes and plasma cells, and invasion of treponema pallidum spirochetes to brain tissue and posterior columns of the spinal cord makes them atrophic.^[4]

• The demyelination of the axones of the neurons is the main cause of symptoms and it affects the neurons in the brain, dorsal root ganglia and posterior columns of the spinal cord.^[4]

The pathogenesis of neurosyphilis may be described in the following steps:^{[4][5][1][6][7][8][9][10][11][12][13]}

Treponema pallidum is usually transmitted via direct contact with the infected lesion (sexual contact) or blood transfusion (rare).

The incubation period varies with the size of innoculum (9-90 days).

• Following transmission, Treponema pallidum uses the intact or abraded mucous membrane to enter the body.
• It then disseminates to the lymphatics and blood stream to gain access to any organ of the body like brain and spinal cord.

• Syphilis uses fibronectin molecules to attach to the endothelial surface of the vessels in organs resulting in inflammation and obliteration of the small blood vessels causing vasculitis (endarteritis obliterans).
• Organism has slow replication rate (30-33 hrs) and evades the initial host immune response.
• It may seed to different organs of the body especially the cardiovascular system and central nervous system resulting in tertiary syphilis.

Different stages of syphilis results from the interaction between the antigen and the host immune response.^[4][5]

Acute response

• The initial infection in primary syphilis is limited due to Th1 response and lack of the antibody response.
• It is speculated that there is a shift from Th1 to Th2 response during secondary syphilis.
• In neurosyphilis the main immune response is caused by Th2 response.

Chronic

• Cytotoxic T cells and an incomplete humoral immunity response is mainly responsible for persistence of infection and tissue damage in tertiary syphilis.
• Ineffective type 4 delayed hypersensitivity reaction containing macrophages and sensitized T cells is mainly responsible for the gumma formation in various organs like brain and spinal cord.

There is no known genetic association of syphilis. However, neurosyphilis may be associated with the gene polymorphism for IL-10 production with increased levels seen in the patients with neurosyphilis.^[13]

Neurosyphilis is associated with increased transmission of HIV. The underlying mechanism may be related to the accumulation of dendritic cells containing CCR5 co-receptors at the site of infection, the same receptor entity binding the HIV.^[11]

• Treponema pallidum may invade the central nervous system is any stage of syphilis disease and cause neurosyphilis.

• On microscopic histopathological analysis, characteristic findings of syphilis depends on the stage of the disease:

Primary syphilis

• Mononuclear leukocytic infiltration, macrophages, and lymphocytes
• Swelling and proliferation of small blood vessels

Secondary syphilis

• Swelling and dilatation of blood vessels in the dermis
• Epidermal hyperplasia and neutrophilic infiltration
• Inflammatory cell infiltrate, predominantly plasma cell

Tertiary syphilis

• Small vessel inflammation (endarteritis obliterans)
• Granulomatous lesions (gumma) containing central necrosis, inflammatory cells, such as lymphocytes, macrophages, plasma cells and fibroblasts.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

Neurosyphilis is a complication of late or tertiary syphilis infection. Syphilis is a sexually transmitted infectious disease. The infection damages the brain, spinal cord and peripheral nervous tissue.

Neurosyphilis is a complication of late or tertiary syphilis infection. Syphilis is a sexually transmitted infectious disease. The infection damages the brain, spinal cord and peripheral nervous tissue.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]Tarek Nafee, M.D. [3]

Neurosyphilis must be differentiated from other diseases that cause abnormal gait, Blindness, confusion and depression, such as multiple sclerosis, Brain tumours, Wernicke’s encephalopathy, CNS abscess, electrolyte disturbance, Subdural empyema, subarachnoid hemorrhage, brain stroke, Conversion disorder and Drug toxicity.

• Neuroyphilis has an extensive differential diagnosis.

• Neurosyphilis must be differentiated from other diseases that cause abnormal gait, Blindness, confusion and depression, such as multiple sclerosis, Brain tumours, Wernicke’s encephalopathy, CNS abscess, electrolyte disturbance, Subdural empyema, subarachnoid hemorrhage, brain stroke, Conversion disorder and Drug toxicity.^{[1][2][3][4][5][6][7][8][9][10]}

Diseases	Diagnostic tests				Physical Examination					Symptoms			Past medical history	Other Findings
	Na+, K+, Ca2+	CT /MRI	CSF Findings	Gold standard test	Neck stiffness	Motor or Sensory deficit	Papilledema	Bulging fontanelle	Cranial nerves	Headache	Fever	Altered mental status
Neurosyphilis[3][4]		✔	↑ Leukocytes and protein	CSF VDRL-specifc CSF FTA-Ab -sensitive[5]	✔	✔	✔	✔	✔	✔	✔	✔	Unprotected sexual intercourse, STIs History of multiple sexual partners. History of genital ulcer (chancre)	Blindness confusion, epression, Abnormal gait
Multiple sclerosis			Oligoclonal bands of IgG on electrophoresis of cerebrospinal fluid	MRI	✔	✔			✔	✔		✔	History of fatigue Mood problems Spasticity Bowel and bladder dysfunction	Vision problems Balance problems Dizziness Areas of demyelination in CNS MRI
Brain tumour[1][2]		✔	Cancer cells[7]	MRI		✔	✔	✔	✔	✔		✔		Cachexia Gradual progression of symptoms
Wernicke’s encephalopathy			Normal				✔	✔			✔		History of alcohal abuse	Ophthalmoplegia confusion
CNS abscess		✔	↑ leukocytes >100,000/ul ↓ glucose and ↑ protien ↑ red blood cells lactic acid >500mg	Contrast enhanced MRI is more sensitive and specific Histopathological examination of brain tissue	✔	✔	✔		✔	✔	✔	✔	History of drug abuse endocarditis	High grade fever Fatigue Nausea vomiting
Electrolyte disturbance	↓ or ↑			Depends on the cause						✔		✔		Confusion Seizures
Subdural empyema		✔		Clinical assesment and MRI	✔	✔	✔	✔	✔			✔	History of relapses and remissions	Blurry vision urinary incontinence Fatigue
Delirium tremens		✔		Clinical diagnosis		✔	✔		✔	✔	✔	✔	Alcohol intake Sudden withdraw or reduction in consumption	Tachycardia diaphoresis hypertension tremors, mydriasis Positional Nystagmus,
Subarachnoid hemorrhage[8]		✔	Xanthochromia[9]	CT scan without contrast[11][6]	✔	✔	✔	✔	✔	✔	✔	✔	Trauma/fall	Confusion dizziness Nausea Vomiting
Stroke		✔	Normal	CT scan without contrast		✔	✔		✔	✔		✔	TIAs, hypertension, diabetes mellitus	Speech difficulty Gait abnormality
Viral encephalitis		✔	Increased RBCS or xanthochromia Mononuclear lymphocytosis High protein content Normal glucose	Clinical assesment	✔	✔	✔		✔	✔	✔	✔	Tick bite Mosquito bite Viral prodome for several days	Extreme lethargy Rash hepatosplenomegaly lymphadenopathy behavioural changes
Herpes simplex encephalitis		✔		Clinical assesment			✔	✔	✔	✔	✔		History of hypertension	Delirium Cortical blindness cerebral edema seizure
Drug toxicity											✔	✔		Lithium Sedatives phenytoin carbamazepine
Conversion disorder				Diagnosis of exclusion		✔		✔		✔	✔	✔		Tremors blindness Difficulty swallowing
Febrile convulsion			Not performed in first simple febrile seizures	Clinical diagnosis and EEG					✔	✔	✔	✔	Family history of febrile seizures Family history of gastroenteritis Family history of viral illness or	Age > 1 month,
Hypoglycemia	↓ or ↑			Serum glucose HbA1c		✔				✔		✔	History of diabetes	Palpitations sweating dizziness Low serum glucose

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

The most potent risk factor in the development of neurosyphilis is HIV infection. Other risk factors include male gender, high serum RPR titer, advanced age, and African American race.

The most potent risk factor in the development of neurosyphilis is HIV infection. Other risk factors include male gender, high serum RPR titer, advanced age, and African American race.

Common risk factors in the development of neurosyphilis include:^[1][2]

• HIV infection
• Male gender
• High serum rapid plasma reagent titer

Less common risk factors in the development of neurosyphilis include:^[2]

• Advanced age
• African American race

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

The symptoms of neurosyphilis usually develop secondary to long-term untreated syphilis, and include diplopia, impaired vision, hearing loss, hoarseness, persistent headache, dizziness, vertigo, lightning pains, impaired sensation and proprioception, hypesthesias, hemiparesis, homonymous hemianopsia, slurred speech and dysarthria. If left untreated, most patients with neurosyphilis may progress to develop paralysis, dementia, Charcot arthropathy, stroke and blindness. Common complications of neurosyphilis include meningitis, meningiovascular syphilis, Argyll-Robertson pupil, stroke, cranial nerve neuropathies, dementia, paralysis, Charcot arthropathy (Charcot joint) of the foot and sensory ataxic gait.

Neurosyphilis is one of the late manifestations of untreated syphilis disease.

• Painless chancre appears 3-4 weeks after exposure.
• Chancre typically resolves, after which the patient may develop constitutional symptoms and generalized symmetric rash in 4 to 8 weeks.
  • In less than 10% of individuals, complications such as hepatitis, iritis, nephritis, and neurological problems may develop at this stage.
• This stage is typically self limited to 4 to 8 weeks without treatment and patient enters into asymptomatic latent phase.
• Approximately 25% of patients develop recurrent symptoms in one year.^[1]
• Approximately 35% of patients develop tertiary syphilis, which includes the following complications:^[2][3][4]
  • Cardiovascular involvement after 15-30 years (80-85% of patients) including aortic aneurysm, aortic regurgitation, angina, and heart failure
  • Gummatous lesions involving skin, bone and joints, associated with significant morbidity and mortality^{[5][6][7][8][9]}
• Neurologic infection in 10-15 years (5-10% of patients) including cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, loss of vibration sense, and auditory or ophthalmic abnormalities.
• The symptoms of tabes dorsalis typically occurs 10 to 30 years after primary infection by treponema pallidum.^[10]
• If left untreated, most patients with neurosyphilis may progress to develop paralysis, dementia, charcot arthropathy, stroke and blindness.

Common complications of neurosyphilis include:

• Meningitis^[11]
• Meningiovascular syphilis^[12][13][14]
• Stroke^[15]
• Cranial nerve neuropathies ^[16]

• Dementia^[17]
• Paralysis^[18]

Prognosis varies by site of involvement and duration of disease:^[5][6][7]

• Among patients with neurosyphilis, 90% respond to treatment.
• Gummatous lesions reverse with treatment.
• Mortality rate of patients with neurosyphilis is around 20% which is mainly due to related complications.

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